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1 52 2 53 3 54 4 Abstracts 55 5 56 6 57 7 Scientific Poster Abstracts Selected for the National Lipid 58 8 59 9 Association 2019 Scientific Sessions, May 16-19, 2019, 60 10 61 11 Miami, FL 62 12 63 13 64 14 2019 Program Planners: Alan S. Brown, MD, FNLA; Clinical Applications of Biomarkers, Lipoprotein 65 15 Anne C. Goldberg, MD, FNLA; Sergio Fazio, MD, PhD, Testing 66 16 FNLA; Edward Gill, MD, FNLA; Antonio M. Gotto, Jr., 67 17 MD, DrPhil, FNLA; Elizabeth Jackson, MSN, ACNS-BC, 259 68 18 CLS, FNLA; Peter H. Jones, MD, FNLA; Carol Kirkpa- Establishing reference parameters for total 69 19 trick, PhD, RDN, MPH, CLS, FNLA; Pamela B. Morris, and active PCSK9 levels: A pilot study 70 20 MD, FNLA; Carl E. Orringer, MD, FNLA; Joseph J. 71 21 Saseen, PharmD, CLS, FNLA; Daneil E. Soffer, MD, Diane Allen, PhD, Catherine Wooten, BS, 72 22 FNLA Quantil Melendez, PhD, K. Kimbro, PhD, 73 23 2019 Abstracts Committee: Pamela B. Morrs, MD, Undi Hoffler, PhD, Dayami Lopez, PhD, (Fort Bragg, NC) 74 24 FNLA (Chair); Dean A. Bramlet, MD, FNLA; Deborah S. Lead Author’s Financial Disclosures: None. 75 25 Croy, DNP, CLS, FNLA; Dave L. Dixon, PharmD, CLS, 76 Study Funding: Support for work at Womack Army 26 FNLA; John Casey Elkins, DNP, MEd, CLS, FNLA; Peter 77 Medical Center (WAMC), Fort Bragg, NC was supported 27 H. Jones, MD, FNLA; and Thomas White, MD, FNLA; 78 from an AMEDD Advanced Medical Technology Initiative 28 The National Lipid Association (NLA) is pleased to 79 (AAMTI) Rapid Innovation Award. 29 announce that 87 abstracts were accepted for presenta- 80 Support for the work at NCCU: The work at NCCU was 30 tion in the poster format for the NLA 2019 Scientific 81 supported by funds from the State of North Carolina, the 31 Sessions. Each abstract was reviewed by the NLA 82 BRITE Institute, an AAMTI Rapid Innovation Award from 32 Scientific Sessions Abstracts Committee prior to 83 WAMC (Fort Bragg, NC), a research contract from Quest 33 acceptance. 84 Diagnostics (Secaucus, NJ), and a Technology Enhance- 34 Posters may be viewed from Thursday, May 16 at 6 p.m., 85 ment Grant from the North Carolina Biotechnology Center. 35 through 2 p.m. on Saturday, May 18. The NLA Young 86 36 Investigator Awards Ceremony will take place on Saturday, Background/Synopsis: Genetic testing for PCSK9 is 87 37 May 18 from 12:45-1:15 p.m. Posters were judged on complicated and expensive, but it is an excellent tool to 88 38 quality of science, originality, interest to the field of predict resistance or sensitivity to statins and qualify 89 39 lipidology, and overall impression with cash awards of patients for new drugs. Several assays that measure total 90 40 $1,000 for first place, $750 to second place, and $500 to PCSK9 levels in human serum are currently available, but 91 41 third place. The first place Young Investigator winner also they are unable to provide information on the functionality 92 42 was selected to give an oral presentation during the of PCSK9 (active PCSK9). A simple, inexpensive blood 93 43 sessions. test that could identify patients with gain-of-function 94 44 (GOF) or loss-of-function (LOF) PCSK9 mutations is 95 45 Three additional abstracts are selected to give an oral needed. 96 46 presentation during the abstract session. Objective/Purpose: The objective of this study was to 97 47 Note: Young Investigator abstract titles are marked establish reference parameters for active PSCK9 levels in 98 48 with an asterisk.* Encore abstracts are marked with a healthy individuals using a novel ELISA assay. 99 49 dagger symbol.† The Foundation of the NLA Methods: A cross-sectional study using a defined popu- 100 50 Hunninghake FH Abstract award winner is marked lation at a single time point was done. Demographics such 101 51 with a caret.‡ as age, ethnicity, and the use of medication, alcohol, and 102

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103 tobacco were collected during recruitment. Measurements 300 159 104 of blood pressure (BP), height, weight, glucose, hemoglo- Nontraditional Lipoprotein Biomarkers: 160 105 bin A1c, and lipid panel were performed. Total and active Predictive Power and Risk Stratification* 161 106 PCSK9 were measured using ELISA assays. 162 107 Results: Forty participants (50% Caucasian Americans or Mary Michael, MS, 163 108 CAs; 50% African Americans or AAs) who met the Nikolas Parisis, MS III, Mark Best, MD, (Miami, FL) 164 109 165 inclusion criteria were recruited. The median age of the Lead Author’s Financial Disclosures: None. 110 population was 22.0 years, and the median BMI was 23.2 166 Study Funding: None. 111 kg/m2. Participants had healthy blood pressure and levels 167 . 112 of total cholesterol, triglycerides, hemoglobin A1c, and Background/Synopsis: Dyslipidemia exists in 70% 168 113 glucose. Median values for LDL (99.5 mg/dL) and HDL patients with premature coronary heart disease and cardio- 169 114 (55.0 mg/dL) were just outside of normal ranges. CAs had vascular disease (CVD) remains the number one cause of 170 115 significantly lower HDL than AAs (p 5 0.0059), but death in the USA. Fasting lipid panel screening with total 171 116 significantly higher triglycerides (p 5 0.0305). The popu- cholesterol (TC), low-density lipoprotein cholesterol (LDL- 172 117 lation mean for total PCSK9 was 453 ng/mL whereas the C), high-density lipoprotein cholesterol (HDL-C), and 173 118 mean for active PCSK9 was 160 ng/mL. The ratio of active triglycerides (TG) is commonly done in the primary care 174 119 to total PCSK9 was used to identify participants with GOF setting to assess CVD risk. 175 120 (ratio.0.7) and LOF (ratio,0.2) mutations. 50% of the Objective/Purpose: We explore the predictive power 176 121 participants had wild-type PCSK9. 43% had LOF muta- of LDL-C subfractions and lipoprotein ratios in order to 177 122 tions whereas 7% had GOF mutations. Glucose levels further stratify risk in particular patient demographics. 178 123 were significantly directly correlated with active PCSK9 Methods: We searched Google Scholar, ERIC, MED- 179 124 (p 5 0.042) and the ratio of active to total PCSK9 LINE, UpToDate, and Merck Manuals for our systematic 180 125 (p 5 0.017). review of the literature. Inclusion criteria key words are: 181 126 182 Conclusions: Reference parameters for total and active LDL, HDL, triglycerides, particle size, particle density, 127 183 PCSK9 levels in a healthy population were established. The Lp(a), lipoprotein, lipid panel, cholesterol, and clinical 128 184 assays proved to be useful in identifying participants with laboratory science. Exclusion criteria is non-English 129 185 GOF and LOF PCSK9 mutations. publications. 130 186 131 187 132 188 133 Table 1 Sample Characteristics 189 134 190 5 5 5 135 Characteristics Overall N 40 Black n 20 White n 20 P-value 191 136 Age (years) 22.0 [21.0-23.0] 22.5 [21.0-23.0] 21.5 [20.0-23.0] 0.1241 192 137 Height (in) 70.0 [68.5-72.0] 69.0 [67.0-72.0] 70.0 [69.0-73.0] 0.0966 193 138 Weight (lb) 162.9 [151.7-173.6] 156.5 [144.4-171.4] 164.8 [156.6-178.9] 0.0819 194 2 139 BMI (kg/m ) 23.2 [21.8-24.1] 23.2 [21.8-24.1] 23.2 [22.3-24.1] 0.8297 195 140 Alcohol Use 0.3962 196 141 None 14 (35.0) 7 (35.0) 7 (35.0) 197 1-7 times/week 23 (57.5) 13 (65.0) 10 (50.0) 142 198 8-14 times/week 2 (5.0) 0 (0.0) 2 (10.0) 143 15+ times/week 1 (2.5) 0 (0.0) 1 (5.0) 199 144 Tobacco Use 0.1274 200 145 None 31 (77.5) 18 (90.0) 13 (65.0) 201 146 ,1 Pack/day 9 (22.5) 2 (10.0) 7 (35.0) 202 147 1-2 Packs/day 0 (0.0) 0 (0.0) 0 (0.0) 203 148 3+ Packs/day 0 (0.0) 0 (0.0) 0 (0.0) 204 149 Systolic BP (mmHg) 111.5 [107.5-120.0] 113.5 [107.5-121.0] 111.0 [107.0-119.5] 0.6670 205 150 Diastolic BP (mmHg) 63.0 [59.0-69.5] 64.0 [61.0-69.5] 62.0 [57.5-68.0] 0.1658 206 151 Total Cholesterol (mg/dL) 161.5 [148.0-194.0] 164.0 [148.5-202.0] 160.0 [139.5-185.5] 0.3165 207 152 Low Density Lipoprotein (mg/dL) 99.5 [82.0-121.5] 104 [79.0-127.0] 95.5 [86.5-118.5] 1.0000 208 High Density Lipoprotein (mg/dL) 55.0 [46.5-59.0] 57.0 [54.5-69.0] 48.5 [44.5-55.5] 0.0059 153 209 Triglycerides (mg/dL) 64.0 [51.0-102.0] 56.0 [48.5-81.0] 89.0 [58.0-123.0] 0.0305 154 Hemoglobin A1c (%) 5.2 [5.0-5.4] 5.2 [5.1-5.4] 5.1 [5.0-5.3] 0.1974 210 155 Glucose (mg/dL) 93.0 [87.5-96.5] 90.5 [85.0-96.5] 95.0 [90.5-97.0] 0.1403 211 156 Taking Medications 36 (90.0) 19 (95.0) 17 (85.0) 0.6050 212 157 4 (10.0) 1 (5.0) 3 (15.0) 213 158 Data reported in N (%) or Median [Q1-Q3] 214

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215 Results: Within the LDL-C sub-fraction a nuclear magnetic 271 216 Table 1 Lipoprotein(a) Levels measured in an outpatient 272 resonance (NMR) or ion mobility (IM) laboratory tests can Preventive Cardiology clinic on 121 patients presenting with 217 273 assess the total LDL-C particle concentration and particle size family history of premature cardiovascular disease and no 218 (small, intermediate, or large). It is thought that smaller, dense personal history of CVD. 274 219 LDL particles are more atherogenic than the larger, ’buoyant’ 275 220 LDL particles because they can infiltrate a damaged endo- Total Patients Males Females 276 Lp(a) Level N5121 N519 N5102 221 thelium with greater ease and contribute to plaque formation. 277 222 A systematic review of 24 studies demonstrated that high ,30 mg/dL 72 (59.5%) 14 58 278 223 LDL particle number is indeed associated with increased 30-49 mg/dL 13 (10.7%) 0 13 279 224 CVD risk. This is relevant because within the physiology of 50-99 mg/dL 23 (19.0%) 2 21 280 225 insulin resistance there is a disconnect between LDL-C and 100-149 mg/dL 9 (7.4%) 2 7 281 .150 mg/dL 4 (3.3%) 1 3 226 LDL particle concentration; LDL-C levels do not change with 282 227 more insulin resistance, however small LDL particle count 283 228 increases with increasing severity of insulin resistance. clinic between 2/2016-11/2018 for evaluation of strong family 284 229 Many epidemiological studies use the ratio of TC or to HDL- history of premature CVD. Patients were 40-75 years old, 285 230 C to stratify populations into higher and lower risk classes. with 19 males (average age560) and 102 females (average 286 231 There is consistent literature demonstrating that non-HDL-C age558) with no personal history of previous CVD. 287 232 288 (TC minus HDL-C) or TC to HDL-C ratio is a better CHD Results: Of 121 patients with strong family history of 233 289 risk predictor than LDL-C on its own: to support this notion premature CVD, 72 patients (59.5%; 14 males, 58 females) 234 290 here we cite a prospective cohort study using the Framingham had Lp(a) levels , 30 mg/dL, 13 patients (10.7%; 0 males, 235 291 data (n53322), a meta-analysis of 68 long-term prospective 13 females) had levels 30-49, 23 patients (19.0%; 2 males, 236 292 studies (n5302,430), and second meta-analysis of patients 21 females) had levels 50-99, 9 patients (7.4%; 2 males, 7 237 293 allocated to statin therapy from 8 trials (n538,153). females) had levels 100-149 and 4 patients (3.3%; 1 male, 3 238 294 Conclusions: In patients with metabolic syndrome risk females) had levels . 150. Thirty-six patients (29.8%; 5 239 295 factors we propose measuring LDL particle size to develop males, 31 females) had Lp(a) levels . 50, indicating 240 296 more nuanced CVD risk stratification and guide statin further consideration of statin. Additionally, 13 patients 241 297 therapy. We also recommend the clinician’s judicious use of (10.7%; 0 male, 13 females) had Lp(a) levels between 30- 242 298 either TC:HDL-C or non-HDL-C:HDL-C ratios over the 49 mg/dL, and would not be considered for statin, unless 243 299 current use of TC, HDL-C, or LDL-C. otherwise indicated, by the current ACC/ AHA Guideline 244 300 on the Management of Blood Cholesterol despite an 245 301 increased risk of future CVD. Forty-two percent (51 of 246 329 302 121) had elevated Lp(a) of 30 mg/dL or higher supporting 247 The Impact of Lipoprotein(a) Levels on 303 the data that Lp(a) is common and a significant contributor 248 Cardiovascular Risk and Statin Recommendation* 304 to genetic/ familial causes of CVD. 249 305 250 Bianca Wheyoung Yoo, MD, Conclusions: The addition of elevated Lp(a) to the 306 251 Gina Lundberg, MD, (Atlanta, GA) Guideline on the Management of Blood Cholesterol pro- 307 vides another marker to assess CVD risk . Over a quarter of 252 Lead Author’s Financial Disclosures: None. 308 253 patients with strong family history of premature CVD met 309 None. 254 Study Funding: criteria for consideration for statin based on elevated Lp(a) 310 255 Background/Synopsis: Background: The ACC/ AHA levels alone. Previous research suggests that an additional 311 256 2018 Guideline on the Management of Blood Cholesterol 11% of these patients have increased risk due to Lp(a) 312 257 recommends consideration of statin in patients 40-75 years levels over 30 mg/dl. Additionally, testing Lp(a) is a one 313 258 old whose Lipoprotein(a) [Lp(a)] levels are greater than 50 time, low-cost biomarker for increased CVD risk, espe- 314 259 mg/dL for primary cardiovascular disease (CVD) prevention. cially when family history is a contributing risk factor. 315 Inclusion of elevated Lp(a) in cholesterol management 260 348 316 261 guidelines provides another biomarker for clinicians to 317 identify risk factors and potentially augment treatment with Implementation of cholesterol screening at 2 262 years of age 318 263 statins. The Copenhagen City Heart Study found increased 319 264 CVD events with Lp(a) levels greater than 30 mg/dL and risk Luke Hamilton, MS, Alejandro de la Torre, MD, 320 265 rises with increasing levels of Lp(a). Lisa Guerra, RN, 321 266 Objective/Purpose: We studied a group of outpatients Amelia Vinson, RN, Don Wilson, MD, (Fort Worth, TX) 322 267 to determine the impact of the inclusion of elevated 323 268 Lipoprotien(a) in the new cholesterol guidelines for starting Lead Author’s Financial Disclosures: None. 324 269 statin therapy. Study Funding: None. 325 270 Methods: We examined 121 outpatients presenting to an Background/Synopsis: In 2011, the NHLBI published 326 academic-affiliated Atlanta-based preventative cardiology guidelines recommending routine cholesterol screening of

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327 all children from ages 9 to 11 years. However, Wald et al, 350 383 328 suggested screening of children from ages 1 to 9 years Lipoprotein (a) testing in youth 384 329 provided the most optimal balance of high detection and 385 330 low false positive rates. These authors initiated a choles- Luke Hamilton, MS, 386 331 terol screening program of children aged 1 to 2 years in the Alejandro de la Torre, MD, 387 332 United Kingdom, screening over 13,000 participants to Don Wilson, MD, (Fort Worth, TX) 388 333 assess feasibility of screening at a younger age. 389 Lead Author’s Financial Disclosures: None. 334 Based upon these findings, Cook Children’s Medical Center 390 335 has initiated a program providing point-of-care cholesterol Study Funding: None. 391 336 screening for 2-year-old children seen one of its 6 Background/Synopsis: Observational and genetic ev- 392 337 neighborhood general pediatric ambulatory clinics. idence strongly support a causal relationship between high 393 338 Screening was incorporated into the 2-year health mainte- plasma concentrations of Lp(a) and increased risk of 394 339 nance visit. cardiovascular disease (CVD). 395 340 Objective/Purpose: The purpose of this study was to In 2011, the NHLBI Expert Panel on Integrated Guidelines 396 341 summarize the results of cholesterol testing and describe for Cardiovascular Health and Risk Reduction in Children 397 342 the challenges that were encountered. and Adolescents recommend only selective measurement of 398 343 Lp(a) in youth: 1) those with ischemic or hemorrhagic 399 Methods: At the time of a patient’s 2-year health mainte- 344 stroke; and 2) youth with a parental history of CVD not 400 nance visit, point-of-care cholesterol testing is conducted in 345 explained by classical risk factors. The lack of a recom- 401 each of the seven Cook Children’s sponsored ambulatory 346 mendation for universal testing, in part, is due to a lack of 402 clinics that provide care for children in a 6 county area in 347 data demonstrating that lowering Lp(a) will reduce current 403 Dallas Fort-Worth. Data is reported from 4/1/2017 to 2/1/2018. 348 or future CVD-related risk independent of LDL-C, as well 404 349 Results: 4,954 children underwent a 2-year-old health as the availability of an effective and safe means of medical 405 350 maintenance visit from 4/1/2017 - 2/1/2018. Of the total intervention. However, it is not clear how well healthcare 406 351 population seen, 2,247 (45%) underwent cholesterol testing. profession who provide services to youth (,18 years of 407 352 Of the 2,247 screened, the median LDL-C level was 78 mg/ age) adhere to these limited indications for Lp(a) testing 408 353 dL. To assess criteria for referral to Cook Children’s and intervention. 409 354 Medical Center’s REACH clinic, multiple LDL-C value Despite Lp(a) levels being determined genetically, fully 410 355 thresholds were assessed (Table 1). expressed by the 2nd year of life, and the availability of 411 356 Conclusions: Successful implementation of a cholesterol reliable and affordable testing, the benefits of and current 412 357 screening program at 2-years-of-age is not without challenges. practice related to measuring Lp(a) during childhood are 413 358 In addition to initial and ongoing efforts to educate the unknown. 414 359 medical and clinic support staff, logistics, cost and clinical Objective/Purpose: The objective of this study is to 415 360 work-flow need to be very carefully considered when survey healthcare professionals who provide care to youth 416 361 implementing additional testing in a busy ambulatory Pediat- (,18 years of age) with a special interest in lipid and 417 362 ric Clinic. While guidelines for clinical management were lipoprotein metabolism, to gain a better understanding of 418 363 helpful, PCP’s often did not follow through with the current clinical practices involving measurement of Lp(a) 419 364 appropriate recommendation for dietary counseling or referral. in this unique population. 420 Information obtained from this study will provide important 365 Methods: The Lp(a) survey will be distributed to health- 421 information to facilitate process and quality improvement. 366 care professionals who provide care to youth who are 422 367 participants of either 1) the Pediatric Atherosclerosis Pre- 423 368 Table 1 Population percentages and estimated prevalence vention and Lipidology Group (PeDAL), a working com- 424 369 based on LDL-C value thresholds. mittee within the NLA; or 2) the Pediatric Endocrine 425 370 426 LDL-C value (mg/dL) Percent of population Prevalence Society’s Lipid Special Interest Group (SIG). Surveys will 371 427 a be distributed electronically and all responses collected 372 $119 5.8* 1:17 428 b anonymously. The study was approved by the Cook 373 $122 5.2% 1:29 429 $ c Children’s Medical Center Institutional Review Board. 374 130 3.1% 1:32 430 $139d 1% 1:83 Results: The results, which are incomplete at the time of 375 431 $160c 0.5% 1:200 this abstract submission, will be describe in detail. 376 $ e 432 185 0.1% 1:1,000 Conclusions: Although there is agreement that a signif- 377 $190c 0.1% 1:1,000 433 378 icantly elevated level of Lp(a) is an independent risk factor 434 a1.53 Multiple of the Median (MoM). for premature CVR-related events, recommendations for 379 b 435 95% of population. testing of both adults and children are limited. Although 380 cestimated 95% of the general population , 20 years, 20 – 29 436 381 years, and 30+ years, respectively (JCL, 2011). testing is widely available and affordable, no medical 437 382 d99% of population. intervention is currently available for selective Lp(a) 438 e99.9% of population. lowering. Understanding the current practices of pediatric

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439 healthcare providers may help inform current educational in Lp(a) exceded the 46% reduction in LDL-C, the 45% 495 440 needs and future recommendations for clinical practice reduction in LDL particle count and 50% reduction in 496 441 guidelines. Apolipoprotein B. 497 442 Conclusions: 498 443 499 444 362 1. Individual reductions in Lp(a) can exceed 50% in some 500 445 Marked reduction of Lipoprotein (a) with individuals, making PCSK9i a more optimal second ther- 501 446 PCSK9 Inhibition in a statin intolerant apy to statin baseline, when reductions in Lp(a) are addi- 502 447 patient: An Illustrative Case Report tionally desired by the patient/clinician collaboration 503 448 2. Pitavastatin in this case was tolerated in low doses 504 Dean A. Bramlet, MD, FNLA, (St. Petersburg, FL) 449 even in the setting of unfavorable SCLO1B1 genetic 505 polymorphism 450 Lead Author’s Financial Disclosures: None. 506 3. Advanced cardiovascular diagnostics were useful in iden- 451 Study Funding: None. 507 452 tifying root cause of predisposition to statin intolerance, 508 Elevated levels of Lipopro- 453 Background/Synopsis: in this case, and in identifying potentially useful targets 509 tein(a) (Lp(a)) are not uncommon in patients with ASCVD 454 of residual risk to consider for management alternatives. 510 and are not typically screened for with standard US lipid 455 511 panels. Reports of 25-30% typical reductions in levels of 456 512 Lp(a) are attributed to PCSK9 inhibitor therapy, and often 457 513 are discordant with the 50-60% reduction seen in LDL-C Diabetes, Insulin Resistance and Dyslipidemia 458 514 with PCSK9i therapy. Potentially, elevated Lp(a) may be 459 515 especially clinically important in cases when statin intol- 460 287 516 erance leads to inadequately controlled levels of LDL-C. 461 A Randomized Study of Evolocumab in 517 462 Objective/Purpose: This case report illustrates the Patients With Type 2 Diabetes and 518 463 insight gained from advanced cardiovascular diagnostic Dyslipidemia on Background Statin: Primary 519 464 testing utilization in identifying a root cause predisposition Results of the BERSON Clinical Trial 520 465 to statin intolerance, and the important recognition of 521 466 previously overlooked genetic elevation of Lp(a) for over Alberto J. Lorenzatti, MD, Freddy Eliaschewitz, MD, 522 467 25 years post myocardial infarction treated elsewhere, Yundai Chen, MD, Juming Lu, MD, Alexis Baass, MD, 523 468 including multiple subsequent stent deployments. It also Maria Laura Monsalvo, MD, Nan Wang, PhD, 524 469 demonstrates that in select individuals a much greater Andrew Hamer, MD, Junbo Ge, MD, (Cordoba, Argentina) 525 response in Lp(a) reduction can be seen with PCSK9I 470 Lead Author’s Financial Disclosures: Advisory 526 471 therapy, and that low dose pitavastatin can be tolerated in 527 some individuals with even genetically predisposed statin board and steering committee member for and has received 472 research grants and speaker fees from Amgen Inc. 528 473 intolerance. 529 Study Funding: This study was funded by Amgen Inc. 474 Methods: An 81 year old white male with remote 530 475 myocardial infarction and small abdominal aortic aneu- Background/Synopsis: BERSON was a phase 3, 531 476 rysm, had 3 coronary stents deployed 2 years previously, double-blind trial designed to evaluate the lipid-lowering 532 477 with ongoing low dose aspirin and clopidogril therapy.. He efficacy and safety of the proprotein convertase subtilisin/ 533 478 also has chronic obstructive pulmonary disease, corrected kexin type 9 inhibitor evolocumab in patients with type 2 534 479 hypothyroidism, hypertension controlled with lisinopril and diabetes mellitus (T2DM) and hyperlipidemia or mixed 535 480 amlodipine, and became intolerant or simvastatin, rosuvas- dyslipidemia on background statin. 536 481 tatin, and atorvastatin due to myalgias. Despite identifica- Objective/Purpose: We report the preliminary results 537 482 tion of T/C genotype for SCLO1B1, he was able to tolerate of BERSON. 538 483 pitavastatin 1 mg. three times a week.. Advanced cardio- Methods: Patients $ 18 to # 80 years with T2DM, on 539 484 vascular diagnostic testing was performed utilizing Boston stable pharmacotherapy for diabetes for $ 6 months, and a 540 485 Heart Diagnostics (TM) to assist in cardiac risk assessment screening low-density lipoprotein cholesterol (LDL-C) 541 486 and management. level of $ 100 mg/dL or $ 130 mg/dL, and with or 542 487 Results: On pitavastatin his direct LDL-C was 114, mg/ without statin treatment at screening, respectively, were 543 488 dl, Non-HDL-C 137 mg/dl, HDL-C 60 mg/dl. Elevated enrolled and started on atorvastatin 20 mg/day for at least 4 544 489 Lp(a) level of 85 mg/dl was identified along with LDL weeks. Patients were then randomized 2:2:1:1 to daily 545 490 particle count of 1533 nmol/L and Apolipoprotein B of 109 atorvastatin 20 mg plus either evolocumab 140 mg every 2 546 491 mg/dl. After addition of evolocumab 140 mg. subcutaneous weeks (Q2W), evolocumab 420 mg every month (QM), 547 492 injections every 2 weeks, his values 14 weeks later were: placebo Q2W, or placebo QM. Co-primary outcome 548 493 direct LDL-C 61 mg/dl, Non-HDL-C 70 mg/dl, HDL-C 67 measures were percentage change from baseline in LDL- 549 494 mg/dl, LDL particle count 843 nmol/L, and Apolioprotein C at week 12 and percentage change from baseline in LDL- 550 B 55 mg/dl. Lp(a) dropped to 40 mg/dl. This 53% reduction C at the mean of weeks 10 and 12. Additional measures

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551 607 552 Table 608 553 Evolocumab Q2W Placebo Q2W Evolocumab QM Placebo QM 609 554 (N 5 325) (N 5 164) (N 5 332) (N 5 160) 610 555 Baseline LDL-C (mg/dL), mean (SD) 92.4 (33.8) 92.2 (32.0) 93.5 (33.6) 91.0 (30.7) 611 556 Baseline non-HDL-C (mg/dL), mean (SD) 121.3 (38.1) 119.2 (38.2) 121.2 (37.0) 119.4 (36.0) 612 557 Safety 613 558 Any adverse event (AE), n (%) 137 (42.2) 72 (43.9) 151 (45.5) 66 (41.3) 614 559 Serious AE, n (%)a 10 (3.1) 6 (3.7) 22 (6.6) 5 (3.1) 615 560 Leading to discontinuation of IP 1 (0.3) 0 (0.0) 1 (0.3) 1 (0.6) 616 561 Mean of Weeks 10 and 12 617 562 Lipids 618 Percent change from baseline in LDL-C, 265.35 (3.1)c 4.94 (3.5) 269.05 (3.0)c 0.99 (3.3) 563 b 619 564 mean (SE) 620 Percent change from baseline in 256.57 (2.7)c 4.33 (3.1) 259.08 (2.6)c 0.33 (3.0) 565 621 non-HDL-C, mean (SE)b 566 Achievement of LDL-C , 70 mg/dL, n (%) 281 (90.1)c 34 (21.7) 292 (91.3)c 30 (19.4) 622 567 Week 12 623 568 Lipids 624 569 Percent change from baseline in LDL-C, 264.66 (3.2)a 7.1 (3.7) 262.3 (3.0)c 2.6 (3.4) 625 570 mean (SE)b 626 571 Percent change from baseline in 255.76 (2.8)a 5.87 (3.2) 252.92 (2.7)a 1.30 (3.0) 627 572 non-HDL-C, mean (SE)b 628 c a 573 Achievement of LDL-C , 70 mg/dL, n (%) 254 (88.2) 31 (20.9) 266 (90.2) 32 (21.3) 629 574 Glycemic Control 630 2 2 2 2 575 Change from baseline in FSG in mg/dL, 1.8 ( 12.6, 19.8) 3.6 ( 12.6, 16.2) 2.7 ( 12.6, 21.6) 1.8 ( 9.0 16.2) 631 median (Q1, Q3) 576 632 Change from baseline in HbA1c in 0.10 (20.30, 0.60) 0.10 (20.10, 0.50) 0.10 (20.30, 0.50) 0.10 (20.30, 0.50) 577 percent, median (Q1, Q3) 633 578 a 634 579 Serious AEs were reported in 4.9% of patients in the overall evolocumab group and 3.4% in the overall placebo group. No serious AEs were reported in 635 $ 1% of patients in either the overall evolocumab or the overall placebo groups 580 bValues reflect LS means (SE) from a repeated-measures linear effect model 636 581 cP , 0.0001 for evolocumab versus placebo comparison 637 582 IP, investigational product; FSG, fasting serum glucose; HbA1c, glycated hemoglobin; LDL-C, low-density lipoprotein cholesterol; non-HDL-C, 638 583 non-high-density lipoprotein cholesterol; SE, standard error 639 584 Funding: Amgen Inc. 640 585 641 586 642 587 643 588 included non-high-density lipoprotein cholesterol (non- Maria Laura Monsalvo, MD, Nan Wang, MD, 644 589 645 HDL-C), LDL-C goals, and measures of glycemic control. Andrew Hamer, MD, Junbo Ge, MD, (Beijing, China) 590 646 Results: The mean age (SD) of patients was 61.3 (8.6) 591 Lead Author’s Financial Disclosures: None. 647 years, 57.3% were women, and 42% white. Key data is 592 648 reported in the Table. Study Funding: This study was funded by Amgen Inc. 593 649 Conclusions: In patients with T2DM and hyperlipidemia Background/Synopsis: Most studies investigating the 594 benefits of proprotein convertase subtilisin/kexin type 9 650 595 or mixed dyslipidemia on statin therapy, evolocumab 651 significantly reduced LDL-C and non-HDL-C, was gener- inhibitors have focused on American and/or European 596 patient populations. 652 597 ally well tolerated, and had no notable impact on glucose or 653 This study is the first to evaluate 598 hemoglobin A1c levels. Objective/Purpose: 654 the lipid-lowering effects of evolocumab in patients in 599 655 China with type 2 diabetes mellitus (T2DM) and 600 294 656 dyslipidemia. 601 Evolocumab in Patients With Type 2 Diabetes 657 $ # 602 and Dyslipidemia on Background Statin: Methods: Patients 18 to 80 years with T2DM, on 658 $ 603 Primary Results of the China Population from stable pharmacotherapy for diabetes for 6months,and 659 604 the BERSON Clinical Trial a screening low-density lipoprotein cholesterol (LDL-C) 660 $ $ 605 level of 100 mg/dL or 130 mg/dL, and with or 661 606 Yundai Chen, MD, Juming Lu, MD, without statin treatment at screening, respectively, were 662 Freddy Eliaschewitz, MD, Alberto Lorenzatti, MD, enrolled and started on atorvastatin 20 mg/day for at least

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663 719 664 Table 1 720 665 Evolocumab Q2W Placebo Q2W Evolocumab QM Placebo QM 721 666 (N 5 150) (N 5 75) (N 5152) (N 574) 722 667 Baseline LDL-C (mg/dL), mean (SD) 86.9 (32.9) 88.9 (34.7) 90.3 (33.1) 82.7 (27.1) 723 668 Baseline non–HDL-C (mg/dL), mean (SD) 113.5 (36.5) 116.0 (41.7) 116.8 (34.1) 109.5 (30.2) 724 669 Safety 725 670 Any adverse event (AE), n (%) 85 (56.7) 39 (52.0) 89 (58.6) 40 (54.1) 726 671 Serious AE, n (%)a 8 (5.3) 2 (2.7) 16 (10.5) 4 (5.4) 727 672 Leading to discontinuation of IP 1 (0.7) 0 (0.0) 0 (0.0) 1 (1.4) 728 673 Mean of Weeks 10 and 12 729 674 Lipids 730 Percent change from baseline in LDL-C, 272.0 (1.9)c 8.4 (2.7) 273.2 (1.6)c 7.8 (2.3) 675 b 731 676 mean (SE) 732 Percent change from baseline in non-HDL-C, 261.0 (1.8)c 7.1 (2.5) 263.1 (1.4)c 5.5 (2.0) 677 733 mean (SE)b 678 Achievement of LDL-C , 70 mg/dL, n, % 139 (97.2)c 18 (24.3) 141 (95.3)c 17 (23.6) 734 679 Week 12 735 680 Lipids 736 681 Percent change from baseline in LDL-C, 273.0 (0.3)c 12.0 (0.2) 265.4 (4)c 9.5 (5.7) 737 682 mean (SE)b 738 683 Percent change from baseline in non-HDL-C, 261.1 (1.1)c 9.2 (2.9) 256.2 (2.6)c 6.7 (7.3) 739 684 mean (SE)b 740 c c 685 Achievement of LDL-C , 70 mg/dL, n, % 132 (96.4) 17 (23.6) 137 (95.1) 18 (25.0) 741 686 Glycemic Control 742 2 2 2 687 Change from baseline in FSG in mg/dL, 5.4 ( 11.7, 22.5) 2.7 ( 7.2, 16.2) 1.8 ( 16.2, 17.1) 0 (-9.0, 10.8) 743 median (Q1, Q3) 688 744 Change from baseline in HbA1c in percent, 0.30 (20.20, 0.80) 0.20 (20.10, 0.70) 0.10 (20.40, 0.80) 0.10 (-0.30, 0.60) 689 median (Q1, Q3) 745 690 a 746 691 Serious AEs were reported in 7.9% of patients in the overall evolocumab group and 4.0% in the overall placebo group. No serious adverse events were 747 reported in $1% of patients in either the overall evolocumab or the overall placebo groups. 692 b Values reflect LS means (SE) from a repeated-measures linear effect model. 748 693 c P , 0.0001 for evolocumab versus placebo comparison. 749 694 IP, investigational product; FSG, fasting serum glucose; HbA1c, glycated hemoglobin; LDL-C, low-density lipoprotein cholesterol; non-HDL-C, 750 695 non-high-density lipoprotein cholesterol; SE, standard error. 751 696 Funding: Amgen Inc. 752 697 753 698 754 699 4 weeks. Patients were then randomly assigned 2:2:1:1 to 312 755 700 daily atorvastatin 20 mg plus either evolocumab 140 mg Identifying patient perceptions and attitudes 756 701 every 2 weeks (Q2W), evolocumab 420 mg every regarding statin-associated diabetes mellitus 757 702 month (QM), placebo Q2W, or placebo QM. Co-primary 758 Cheryl A. Gibson, PhD, Rebecca Mount, MS, 703 outcome measures were the % change from baseline in 759 Jaehoon Lee, PhD, Jim Backes, PharmD, (Kansas City, KS) 704 LDL-C at week 12 and the % change from baseline in 760 LDL-C at the mean of weeks 10 and 12. Additional 705 Lead Author’s Financial Disclosures: None. 761 measures included change in non-high-density lipopro- 706 Study Funding: Kowa Pharmaceuticals America, Inc. 762 707 tein cholesterol (non-HDL-C), proportion achieving 763 # Background/Synopsis: In 2012, the FDA published a 708 LDL-C 70 mg/dL, and measures of glycemic control. 764 communication on statin safety label changes in response to 709 Results: In total, 451 (46%) of patients that were 765 reports that statin use can result in increases in glucose 710 randomized and dosed were from China. The mean age 766 levels. It is not known how the FDA communication 711 (SD) of these patients was 60.0 (8.4) years and 51% were 767 influenced patients attitudes towards and perceptions of 712 women. Table 1 reports baseline and end-of-study efficacy 768 statin therapy. In our clinical setting, patients often express 713 results and safety data. 769 apprehension about statin therapy and the potential risk of 714 Conclusions: This study demonstrated that evolocumab 770 diabetes mellitus (DM). Despite these concerns, formal 715 administered every two or four weeks significantly reduced 771 data have not been captured to assess patient perceptions 716 LDL-C and was well tolerated in Chinese patients with type 772 about statin-induced DM. 717 2 diabetes and dyslipidemia, with no notable impact on 773 718 glycemic control. Objective/Purpose: To evaluate attitudes and percep- 774 tions of statin-associated DM among patients receiving a

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775 statin or those who are candidates for statin therapy; and be effective in improving cardiovascular outcomes in 831 776 to determine how these beliefs might influence patients not adequately responding to statin and other 832 777 adherence. cholesterol lowering therapies. Over time some patients 833 778 Methods: A mixed methods design, using surveys and change from one PCSK9 inhibitor to the other. 834 779 semi-structured interviews among patients who were taking Objective/Purpose: We sought to determine the extent 835 780 a statin or potentially statin-eligible, was employed. of patients changing PCSK9 inhibitor medications and their 836 781 Patients completed an adapted Beliefs about Medicines characteristics. 837 782 838 Questionnaire (aBMQ) to ascertain concerns about poten- Methods: A retrospective review of electronic medical 783 839 tial adverse effects of statins, the necessity of therapy, and records from our heart center showed PCSK9 inhibitors 784 840 how these beliefs might influence adherence. Scores were were prescribed 371 times for 332 individual patients from 785 841 used to calculate a necessity-concerns differential about the time of commercial launch until November 2018. 786 patients beliefs about statin therapy. Interviews explored 842 787 Results: Most PCSK9 inhibitors prescriptions origi- 843 factors influencing medication beliefs over the course of nated from the lipidologist on staff; recently other 788 treatment. 844 789 cardiologists have begun prescribing as well. 39 patients 845 Results: Seventy-three (49 females; mean age 57 years) 790 (11.7%) patients changed from one medication to the 846 individuals completed the aBMQ. Current statin users 791 other during this time. All patients switching medica- 847 had stronger beliefs about the necessity of statin therapy 792 tions had atherosclerotic heart disease and 4 patients had 848 (p,0.01), and indicated fewer concerns (p,0.01) and 793 definite familial hypercholesterolemia by Dutch Lipid 849 less cost than benefit (p,0.001) compared to candidate 794 Clinics score or genetic testing. They were 12 females 850 users. Participants with higher cholesterol levels had 795 and 27 males, average age 63.5 years. 21 patients were 851 weaker beliefs about the necessity of statin therapy 796 not on a statin, 8 were on high, 2 on intermediate and 8 852 (p,0.001) and more concerns (p,0.01), and perceived 797 on low dose statin therapy. 15 patients were on ezetimibe 853 greater cost than benefit (p,0.001) compared to those 798 10 mg daily. None of the patients changing medications 854 with lower cholesterol levels. Among the 73 participants, 799 were on advanced therapies such as lomitipide or 855 14 completed interviews. Most interviewees had con- 800 apheresis. 13 patients started on alirocumab 75 mg SQ 856 cerns about statin side effects but indicated their pre- 801 q 2 wks, 8 started on alirocumab 150 mg SQ q 2wks and 857 scriber did not share any information about potential 802 18 patients started on evolocumab 140 mg SQ q 2 wks. 858 adverse effects of statins, including how statins might 803 The average duration on the first PCSK9 inhibitor was 859 affect glucose control. However, most interviewees 804 6.3 months (range 17 to 1 months). Reasons for changing 860 believed the benefits of statins outweigh the potential 805 between medications included insurance coverage (33), 861 risk of DM and this risk would not prevent them from 806 cost (5) and side effects (1). No changes occurred 862 initiating or continuing statin therapy. Further, most 807 because of medication ineffectiveness. 30 of the 39 863 indicated they also would be willing to start or continue , 808 patients were noted to achieve LDL-C 70 mg/dl 864 their statin medication if the risk of raising their blood 809 (average 60, range 171 to 5mg/dl) on the second 865 glucose was less with a lower dose. 810 PCSK9medicationcomparedtopre-treatmentLDL-C 866 811 Conclusions: There are significant differences in the (average 167, range 309 to 107mg/dl). Pre and post 867 812 perceived need and benefit of statin therapy in relation to LDL-C levels with alirocumab (152 to 62mg/dl, 59% 868 813 the potential risk of statin-associated DM. The need for reduction) and evolocumab (173 to 58 mg/dl, 70% 869 814 prescribers to address patients concerns and beliefs about reduction) were noted. Because of numerous extraneous 870 815 statin therapy is warranted. variables, incomplete lab testing and the small numbers 871 816 of patients, the effectiveness of the respective medica- 872 817 tions should not be compared. The one patient having 873 818 Enhancing Adherence, Compliance to Therapies PCSK9 inhibitor side effects later concluded that her 874 819 hair loss was not from evolocumab but from the 875 820 268 simultaneous steroid therapy administered for a pulmo- 876 nary disease exacerbation. 821 Changing Between PCSK9 Inhibitor Medications 877 822 Conclusions: Changing between PCSK9 inhibitors oc- 878 823 James Trippi, MD, FNLA, curs frequently in clinical practice. Unfortunately, insur- 879 824 Billie Jones, RN, (Indianapolis, IN) ance coverage and cost leading to switching medications, 880 825 decreases patient compliance to medical therapy, consistent 881 Lead Author’s Financial Disclosures: Speaker - 826 lipid reduction and convenience. Changing PCSK9 medi- 882 Sanofi, Amgen, Amarin, Pfizer. 827 cations creates additional work and time burdens on 883 828 Study Funding: None. medical staff as well. As insurance coverage stabilizes 884 829 Background/Synopsis: PCSK9 inhibitors (alirocumab and familiarity with insurers preferred medication in- 885 830 and evolocumab) became commercially available in July creases, fewer changes between PCSK9 inhibitors will 886 and August of 2015, respectively. They have been shown to improve patient care.

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887 352 943 888 Perceived fatigue may be an overlooked 944 889 barrier to successful therapeutic lifestyle 945 890 change 946 891 947 892 Todd Jarvis IV, OMS, Ben Bopp II, OMS, 948 893 Tyler Hamby, PhD, 949 894 Luke Hamilton, MS, Don Wilson, MD, (Fort Worth, TX) 950 895 951 896 Lead Author’s Financial Disclosures: None. 952 897 Study Funding: None. 953 898 Background/Synopsis: Children and adolescents at- 954 899 risk of developing premature cardiovascular disease (CVD) 955 900 due to genetic disorders and acquired conditions, such as 956 901 obesity and insulin resistance, are often referred to a 957 902 pediatric lipid clinic. While adoption of a lifelong, heart- 958 903 hearty lifestyle is encouraged, those with genetic disorders 959 904 may benefit from lipid-lowering medications. Recommen- 960 905 dations for therapeutic lifestyle change in those who are 961 906 obese, especially the need for less sedentary time and 30-60 962 Figure 1 Fatigue scores of study subjects vs reported obese and 907 min/d of moderate-to-vigorous physical activity, may be 963 healthy controls. 908 hindered by a perception of fatigue. An increased percep- 964 909 tion of fatigue in obese youth vs healthy controls has barriers to implementation of lifestyle modification, such as 965 910 previously been reported in those referred to an obesity perception of fatigue, when recommending less sedentary 966 911 clinic. time and 30-60 min/d of moderate-to-vigorous physical 967 912 Objective/Purpose: The purpose of this study was to activity to improve health. 968 913 examine perceived fatigue in a sample of obese youth (,18 969 914 yrs. of age; BMI 95th percentile) with acquired CVD risk Epidemiology of Cardiovascular Disease 970 915 factors, who were referred to a pediatric lipid clinic. 971 916 972 Methods: This study was a retrospective chart review of 256 917 237 youth referred to the Risk Evaluation to Achieve 973 918 Enhanced Prediction of the Population at Risk 974 Cardiovascular Health (REACH) clinic at Cook Children’s of Atherothrombotic Disease† 919 Medical Center between January 1, 2014 and August 31, 975 920 2018. During the initial clinic visit, each subject and the W. E. Feeman Jr, MD, (Bowling Green, OH) 976 921 child’s parent independently completed the PedsQL Multi- 977 922 dimensional Fatigue Scale, a validated survey with 18 items Lead Author’s Financial Disclosures: None. 978 923 divided into 3 subscales - General, Sleep/Rest, and Study Funding: None. 979 924 Cognitive - each containing 6 questions. A total score Background/Synopsis: The prediction of the popula- 980 925 was computed, the range of possible scores ranging from tion at risk of atherothrombotic disease(ATD) is essential to 981 926 0 to 100 for each subscale. Higher scores indicate less the prevention of clinical ATD. The chief ATD risk factors 982 927 perception of fatigue. A t-test was used to compare study for ATD are cigarette smoking, dyslipidemia, and hyper- 983 928 subjects to previously reported obese youth (N543) tension, with some contribution by the very high blood 984 929 referred to an obesity clinic and normal weight, healthy sugar levels of uncontrolled diabetes. These risk factors do 985 930 controls (N5157). A p-value ,0.05 was used to determine not act in a vacuum, but rather are interdependent. 986 931 statistical significance. Combining these three risk factors into a single predictive 987 932 988 Results: The study population consisted of 200 subjects, tool enhances the ability to predict the population at risk of 933 989 50.5% of whom were morbidly obese (99th percentile). ATD. Dyslipidemia is best interpreted as a ratio between 934 990 Study subjects had statistically significantly more percep- LDL- and HDL-cholesterol, in the form of the Cholesterol 935 991 tion of fatigue for each sub- and total scale for both self- Retention Fraction, or CRF. Hypertension’s contribution to 936 992 and parent-reported scales (p ,0.001) compared to healthy ATD risk is best made by the systolic blood pressure (SBP). 937 993 controls. However, there were no statistically significant Objective/Purpose: The purpose of this presentation is 938 994 differences between our study subjects and the obese youth to present an updated version of the prediction of the 939 995 previously reported (Figure). population at risk of ATD, such that it is possible to stratify 940 996 ATD risk in terms of higher ATD risk ( patients aged 64 941 Conclusions: Obese youth with and without reported 997 years or less at time of ATD onset), middle risk ( patients 942 acquired CVD risk-factors experience greater perceived 998 fatigue than healthy controls. It is important to consider aged 65-74 years at time of ATD onset), and lower risk

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999 (patients aged 75 years of older at time of ATD presenta- 1055 1000 tion). A comparison with a similar graph using LDL- 1056 1001 cholesterol instead of the CRF will be shown. 1057 1002 Methods: Chart review of the ATD database of the 1058 1003 author’s medical practice. 1059 1004 1060 Results: When the CRF is graphed against SBP (blood 1005 1061 pressures at presentation levels, which include blood 1006 1062 pressures which have been treated), one notes a layering 1007 1063 effect with virtually all of the higher risk patients lying 1008 1064 above the CRF of 0.70 or higher zone, most of the middle 1009 1065 risk patients lying in the CRF50.60-0.69 zone, and those 1010 1066 lower risk patients mostly lying in the CRF of 0.59 or lower 1011 1067 zone. Some zonal overlap is present. This layering effect is 1012 1068 eradicated by cigarette smoking, is more pronounced in ex- 1013 1069 smokers, and marked in never smokers. This layering effect 1014 1070 is not seen when LDL-cholesterol is used instead of the 1015 1071 CRF. 1016 1072 1017 Conclusions: It is possible to predict the population at 1073 1018 risk of ATD with high accuracy using factors readily 1074 1019 available to practicing physicians. This in turn affords the 1075 1020 abilitay to prevent clinical ATD events. 1076 1021 1077 1022 1078 1023 1079 1024 1080 1025 1081 1026 1082 1027 1083 1028 1084 1029 1085 1030 1086 1031 1087 1032 1088 1033 1089 1034 1090 1035 1091 1036 1092 1037 1093 1038 1094 1039 1095 1040 1096 1041 1097 1042 1098 1043 1099 1044 1100 1045 1101 1046 1102 1047 1103 1048 1104 1049 1105 1050 1106 1051 1107 1052 1108 1053 1109 1054 1110

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1111 274 Sanofi, Astra Zeneca and the Fondation Leducq. He has 1167 1112 Predicting Cardiovascular Disease in Familial participated in clinical research protocols from Pfizer, 1168 1113 Hypercholesterolemia: Risk Factors Counting Regeneron Pharmaceuticals Inc., The Medecines Company, 1169 1114 Amgen, Acasti Pharma Inc., Novart. 1170 1115 Alexis Baass, MD, Study Funding: None. 1171 1116 Martine Paquette, MSc, 1172 Background/Synopsis: Familial dysbetalipoproteine- 1117 Sophie Bernard, MD, PhD, (Montreal, QC) 1173 mia (FDBL), also referred as Type III hyperlipoproteine- 1118 1174 mia, is an autosomal recessive disorder associated with a 1119 Lead Author’s Financial Disclosures: A.B. 1175 reduced clearance of remnant lipoproteins from the cir- 1120 received research grants from Merck Frosst, Amgen, 1176 culation. The resulting accumulation of cholesterol-en- 1121 Sanofi, Astra Zeneca and the Fondation Leducq. He has 1177 riched IDL and remnant chylomicrons particles is 1122 participated in clinical research protocols from Pfizer, 1178 associated with a very high cardiovascular risk. The 1123 Regeneron Pharmaceuticals Inc., The Medecines Company, 1179 most frequent genetic predisposition of FDBL is apoE2 1124 Amgen, Acasti Pharma Inc., Novart. 1180 homozygosity. However, the penetrance of this genetic 1125 Study Funding: None. 1181 defect is low and secondary factors such as obesity, insulin 1126 Background/Synopsis: Due to the important lifelong 1182 resistance or alcohol consumption must be present to 1127 LDL cholesterol burden, patients with familial hypercho- 1183 precipitate FDBL. Unfortunately, this disease is largely 1128 lesterolemia (FH) have a high risk of cardiovascular disease 1184 underdiagnosed and untreated. Furthermore, little is 1129 (CVD). In recent years, many clinical and genetic factors 1185 known about the cardiovascular risk factors in this 1130 have been shown to modulate the CVD risk in FH. It is thus 1186 population. 1131 essential to better stratify the CVD risk in this population. 1187 Objective/Purpose: The objective of this study is to 1132 Objective/Purpose: The objective of this study is to 1188 describe the clinical characteristics of an FDBL cohort and 1133 verify whether simple risk factor counting could efficiently 1189 to investigate what are the predictors of cardiovascular 1134 stratify the risk of prevalent CVD in a large cohort of FH 1190 disease in this population. 1135 patients. 1191 Methods: Inclusion criteria were the following: age $ 18 1136 Methods: A total of 1412 adult patients diagnosed with 1192 years, apoE2/2 phenotype, triglycerides (TG) . 1.5 mmol/ 1137 FH from the FH Canada registry were included in the 1193 L (or 133 mg/dL) and VLDL-C/ TG ratio . 0.69 (in mmol/ 1138 analysis. The risk factors used for the risk factor count (RFC) 1194 L, or . 0.3 in mg/dL). Clinical data were collected 1139 are the five variables of the Montreal-FH-SCORE (MFHS), 1195 retrospectively to the baseline visit at the lipid clinic. 1140 namely age, HDL-C, sex, hypertension and smoking. 1196 1141 Results: A total of 224 FDBL patients were included in 1197 Results: Both the MFHS (AUC 0.805 [0.779-0.831]) and 1142 the analysis. The cohort was comprised of 59% of men and 1198 the RFC (AUC 0.797 [0.770-0.823]) were good predictors of 1143 the average age was 52 years. The vast majority (94%) had 1199 prevalent CVD events and were not statistically different 1144 the presence of broad-beta band on electrophoresis. A total 1200 (P50.20 for difference). Furthermore, we observed a signif- 1145 of 51 subjects (23%) had history of CVD. The univariate 1201 icant difference in the prevalence of CVD events between the 1146 predictors of CVD were hypertension (b50.323, 1202 low risk group (0 to 2 risk factors) and the high risk group (3 1147 P50.00003), diabetes (b50.191, P50.01), tuberous xan- 1203 to 6 risk factors) (7% vs 37%, respectively, P,0.0001). 1148 thomas (b50.250, P50.004) and tuberoeruptive xanthoma 1204 1149 Conclusions: Even if the RFC represents a simplified (b50.165, P50.03), whereas only hypertension (b50.299, 1205 1150 method to assess the CVD risk in FH, it is a good predictor P50.0002) and tuberous xanthomas (b50.217, P50.02) 1206 1151 of prevalent CVD events. FH patients with multiple CVD remained significantly associated with CVD in multivariate 1207 1152 risk factors would likely benefit from further risk factor analysis. 1208 reduction. Larger prospective studies are required to validate 1153 Conclusions: The presence of hypertension or tuberous 1209 if RFC in FH is associated with better patient outcomes. 1154 xanthomas are independently associated with a significant 1210 1155 increase of CVD risk in FDBL subjects. Due to the high 1211 1156 prevalence of cardiovascular disease in FDBL, aggressive 1212 1157 1213 275 treatment should be initiated in these patients. 1158 1214 1159 Hypertension and Tuberous Xanthomas 1215 predict Cardiovascular Disease in Familial 1160 293 1216 Dysbetalipoproteinemia 1161 LDL-C Values and Lipid Lowering Therapy 1217 1162 1218 Alexis Baass, MD, Utilization in a Medicare Fee For Service (FFS) 1163 1219 Martine Paquette, MSc, Population 1164 1220 Sophie Bernard, MD, PhD, (Montreal, QC) 1165 Nihar Desai, MD, MPH, Stefan DiMario, PharmD, 1221 1166 Lead Author’s Financial Disclosures: A.B. Kiran Philip, MD, Allison Petrilla, PhD, 1222 received research grants from Merck Frosst, Amgen, Xian Shen, PhD, Kevin Dietz, BA, BS, (New Haven, CT)

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1223 Lead Author’s Financial Disclosures: Research and Females and African Americans had higher levels of LDL- 1279 1224 consulting: Amgen Inc., Boehringer Ingelheim, Cytoki- C across cohorts. 1280 1225 netics, Relypsa. Conclusions: Among Medicare beneficiaries with 1281 1226 1282 Study Funding: Amgen, Inc. ASCVD, one third are not treated with any LLT and nearly 1227 $ 1283 Background/Synopsis: LDL-C is a causal risk factor 7 out of 10 had an LDL-C value 70 mg/dL. Intensifying 1228 LLT among this group of patients remains a priority for 1284 1229 for atherosclerotic cardiovascular disease (ASCVD). CVD 1285 is the leading cause for morbidity, mortality, and health care performance improvement efforts, especially when consid- 1230 ering over half of patients with an AMI had LDL-C $70 1286 1231 spending among Medicare beneficiaries. In patients with 1287 clinical ASCVD, the 2018 ACC/AHA Guidelines recom- mg/dL. 1232 LDL-C Distribution in Medicare FFS: 1288 1233 mends decreasing LDL-C with high intensity or maximally 1289 1234 tolerated statin therapy. Little is known about contemporary 1290 1235 patterns of LDL-C values and lipid lowering therapy (LLT) 1291 1236 utilization among Medicare FFS beneficiaries. 313 1292 1237 Objective/Purpose: To assess LDL-C values and LLT A lost decade: No Meaningful Changes in LDL 1293 1238 utilization in the overall Medicare FFS population, patients Cholesterol in the United States, 2008-2017: 1294 1239 with ASCVD, and those with a recent acute myocardial Insights from a National Reference Laboratory 1295 1240 infarction (AMI). 1296 1241 Methods: This retrospective cohort study used the 100% Harvey Kaufman, MD, MBA, FCAP, 1297 1242 Medicare Parts A/B/D claims linked to the Prognos LDL-C Kathryn Schurr, MS, 1298 1243 database. Patients were indexed on their latest LDL-C value James Underberg, MD, (Needham, MA) 1299 1244 in calendar year 2017 and were required to have one year of Lead Author’s Financial Disclosures: Employee of 1300 1245 continuous enrollment pre-index. Use of LLT was assessed Quest Diagnostics. 1301 1246 in the 30-day pre-index period. LLT included statin, 1302 Study Funding: None. 1247 ezetimibe, and/or PCSK9i. Three cohorts were defined; 1303 1248 all Medicare FFS beneficiaries, those with clinical ASCVD Background/Synopsis: In the US, cholesterol levels 1304 1249 as defined by the 2018 ACC/AHA guidelines, and those have declined for 50 years, until 2008, remaining flat from 1305 1250 with an AMI hospitalization in the one year pre-index. 2008-2011. From 2001-2008 low-density lipoprotein 1306 1251 LDL-C values and LLT utilization were assessed for each (LDL) cholesterol declined an average 2 mg/dL/year. 1307 1252 cohort. Objective/Purpose: We describe more recent LDL 1308 1253 Results: A total of 3.8 million patients were included in cholesterol trends, from 2010 to 2017. 1309 1254 the overall cohort, 1.4 million in the ASCVD cohort, and Methods: LDL results from adults 20-99 years, tested at 1310 1255 23,064 in the AMI cohort. For the overall cohort, the mean Quest Diagnostics, 2010-2017, were included, using the 1311 1256 age was 71 years, 43% were male, 40% had diabetes, and first result for each patient in each calendar year. Testing 1312 1257 78% and hypertension. Forty seven percent were not was performed on Olympus AU analyzers. LDL was 1313 1258 receiving LLT, 37% low- or moderate-intensity, and 12% calculated by Friedewald until 09/2017 and then by Mar- 1314 1259 high-intensity statin therapy. Mean (SD) LDL-C was 96 tin-Hopkins. In addition, the population percent at varying 1315 1260 mg/dL (35), and 77% had an LDL-C $70 mg/dL. Among levels of LDL was compared for each year, over time. 1316 1261 patients with ASCVD, 34% were not receiving LLT, 41% Results: 126,000,570 LDL results were obtained in 1317 1262 low- or moderate-intensity, and 20% high-intensity statin 50,386,603 US adults (56% women, mean + SD age 1318 1263 therapy. The mean LDL-C was 87 mg/dL (35), and 67% 52+17; 44% men, mean + SD age 52+16). Mean population 1319 1264 had an LDL-C $70 mg/dL. Among patients with an AMI, LDL did not change meaningfully over the study period, for 1320 1265 19% were not receiving LLT, 29% low- or moderate- men (103-105 mg/dL) or women (107-109 mg/dL), across 1321 1266 intensity, and 47% high-intensity statin therapy. The mean all age ranges (not shown). Similarly, there were no 1322 1267 LDL-C was 77 (36), and 52% had an LDL-C $70 mg/dL. meaningful distribution changes across LDL ranges 1323 1268 (Table). 1324 1269 Conclusions: In this study, mean LDL remained essen- 1325 1270 tially constant from 2010-2017, for both men and women, 1326 1271 across age ranges, with no meaningful distribution changes 1327 1272 1328 1273 1329 1274 Year 2010 2011 2012 2013 2014 2015 2016 2017 1330 1275 Mean LDL Cholesterol (mg/dL) 1331 1276 Overall 105.3 105.3 106.8 107 107 105.7 106.7 106.7 1332 1277 Men 103.5 103.4 104.6 104.8 104.8 103.1 104.5 104.4 1333 1278 Women 106.8 106.9 108.6 108.8 108.7 107.8 108.5 108.5 1334

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1335 across LDL ranges. In light of clinical data suggesting of LDL-C goals in NHS2016-2017 based on national 1391 1336 lower LDL is associated with improved clinical outcomes, guidelines was only 56.9%. In this latter survey, attainment 1392 1337 the lack of progress over the past decade suggests that of LDL-C objectives was 83.1% in subjects at low CVD 1393 1338 efforts to lower LDL need to be re-examined. This has risk, 42.1% in moderate risk, and 19.6% at the high risk 1394 1339 significant public health implications in the US. subgroup. Prevalence of LDL-C ,70 mg/dl in individuals 1395 1340 with known CVD was 8.5% in NHS2009-2010 versus 1396 1341 27.5% in NHS2016-2017. 1397 315 1342 Overall, these findings indicate a signifi- 1398 Trends and goal achievement in LDL Conclusions: 1343 cant reduction in LDL-C levels in Chile over a 14-year 1399 cholesterol according to cardiovascular risk in 1344 period with better LDL-C goal achievement and higher 1400 1345 Chile: Overview from 2003 to 2016-2017 1401 National Health Surveys lipid lowering drug use. Drug therapy in high CVD risk 1346 population and CVD survivors have also improved but still 1402 1347 1403 Guadalupe Echeverria, MSc, Paulina Mendoza, MD, shows unacceptably low coverage. There is need for a more 1348 1404 Salinas Lorena, MD, Valentina Serrano, MD, MSc, intensive approach in high risk groups in order to increase 1349 1405 Alvaro Passi, MSc, Alberto Maiz, MD, cost effectiveness of healthcare investment in CVD pre- 1350 1406 Attilio Rigotti, MD, PhD, vention in Chile. 1351 1407 Paula Margozzini, MD, MSc, (Santiago, Chile) 1352 Genetics, Gene Therapy and Atherosclerosis 1408 1353 Lead Author’s Financial Disclosures: None. 1409 1354 1410 Study Funding: None. 263 1355 1411 Background/Synopsis: High levels of LDL choles- 1356 Prevalence of Pathogenic Variants of 1412 terol (LDL-C) are an established risk predictor of cardio- 1357 Lipoprotein Metabolism Genes in a Single 1413 vascular disease (CVD) and the main target in dyslipidemia 1358 Lipidology Clinic* 1414 treatment for atherosclerosis management. Thus, trend 1359 1415 assessments of LDL-C are needed to set and adjust lipid Lane B. Benes, MD, 1360 1416 intervention priorities as well as to evaluate achievement of Kent Brummel, MD, Michael Davidson, MD, (Chicago, IL) 1361 1417 therapeutic lipid goals proposed by national clinical 1362 1418 guidelines. Lead Author’s Financial Disclosures: None. 1363 Study Funding: None. 1419 1364 Objective/Purpose: To determine changes from 2003 1420 Background/Synopsis: Mendelian randomization and 1365 to 2016-2017 in LDL-C levels, lipid lowering therapy use 1421 genome-wide association studies have identified genes 1366 and LDL-C goal achievement according to CVD risk 1422 causally related to and associated with dyslipidemia and 1367 among Chilean adult population. 1423 coronary artery disease (CAD), however genetic testing is 1368 Methods: Chilean National Health Surveys (NHS) are 1424 not routinely performed in the management of most lipid 1369 cross-sectional household surveys performed by complex 1425 disorders. 1370 design random selection in non-institutionalized adults 1426 1371 aged $18 years. In randomly selected subsamples, fasting Objective/Purpose: To determine the prevalence of 1427 1372 total cholesterol, HDL cholesterol, and triglycerides were pathogenic variants predisposing to dyslipidemia in a single 1428 1373 directly measured, whereas LDL and non HDL cholesterol lipidology clinic. 1429 1374 were calculated. Study analysis samples were as follows: Methods: Patients in a single lipidology clinic were 1430 1375 2003 (NHS2003) n51,813; 2009-2010 (NHS2009-2010) chosen by a lipidologist to undergo genetic testing based on 1431 1376 n52,581); and NHS 2016-2017 (NHS2016-17), n53,382. the presence of at least one of the following: hyper- 1432 . 1377 Lipid lowering drug use was defined using ATC-WHO code triglyceridemia (defined as fasting serum triglycerides 1433 1378 C10 of nurse drug inventory. Local national guidelines 150 mg/dL), elevated low-density lipoprotein-cholesterol 1434 . 1379 were used for CVD risk stratification. Weighted 2003, (LDL-C) 190 mg/dL, low high-density lipoprotein- 1435 , 1380 2009-2010 and 2016-2017 NHS LDL cholesterol means cholesterol (HDL-C) 40 mg/dL, elevated lipoprotein a 1436 1381 were compared using age-sex adjusted linear regression. (Lp(a)) .50 mg/dL or . 100 nmol/L or history of 1437 1382 Results: From NHS2003 to NHS2009-10, LDL-C levels premature CAD (defined as an acute coronary syndrome 1438 1383 remained stable, but they decreased by 12 mg/dl in 2016- or revascularization before age 40 years in men and 50 1439 1384 2017 (from 115 mg/dl in 2003 to 103 mg/dl in 2016-2017, years in women). Genetic testing was performed using 1440 1385 p,0,001 adjusted by sex and age). This change in LDL-C GBinsight Comprehensive Dyslipidemia Panel that uses 1441 1386 levels was seen in all subgroups (sex, age, educational next-generation DNA sequencing (NGS) to analyze 127 1442 1387 level, and urban/rural areas). Lipid lowering drug use genes known or suspected to be associated with dyslipide- 1443 1388 increased from 1.9% in NHS2003 to 12.1% in NHS2016- mia or CAD. 1444 1389 17 in the total adult population as well as from 27.3% in Results: Data for 84 patients are currently available, 82 1445 1390 NHS2009-2010 to 42.1% in NHS2016-2017 in subjects (97.6%) of which were found to have at least one genetic 1446 with previous CVD events. However, overall achievement variant predisposing to dyslipidemia or CAD. Known

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1447 pathogenic variants or those with a strong effect on lipid Conclusions: Patients with monogenic FH are at 1503 1448 levels included those of apolipoprotein A-5 (14 patients), increased risk of CVD compared to those with polygenic 1504 1449 intron variants associated with elevated Lp(a) (rs10455872 FH or those without an FH-causing variant. Genetic testing 1505 1450 or rs3798220, 25 patients), LDL-receptor (15 patients) and for FH can identify patients at greatest risk of CVD who 1506 1451 lipoprotein lipase (9 patients). may derive the most benefit from intensive lipid-lowering 1507 1452 Conclusions: The majority of patients presenting to a therapies. 1508 1453 lipidology clinic for treatment of dyslipidemia or premature 1509 1454 CAD had at least one pathogenic variant of lipoprotein 1510 1455 1511 metabolism, the most common of which included apolipo- 280 1456 protein A-5, intron variants associated with elevated Lp(a) 1512 Incorporation of Genetic Testing for Familial 1457 and LDL-receptor variants. 1513 1458 Hypercholesterolemia Nearly Doubles 1514 1459 Diagnosis Rate^ 1515 1460 267 1516 1461 Impact of Monogenic Familial Emily Brown, MGC, Kathleen Byrne, CRNP, 1517 1462 Hypercholesterolemia and Polygenic Dorothy Davis, RN, Rebecca McClellan, MGC, 1518 1463 Hypercholesterolemia Cardiovascular Disease Thorsten Leucker, MD, 1519 1464 Risk* Steven Jones, MD, Seth Martin, MD, (Baltimore, MD) 1520 1465 1521 Liam R. Brunham, MD, PhD, Mark Trinder, MSc, Lead Author’s Financial Disclosures: None. 1466 1522 Lubomira Cermakova, MSc, Study Funding: None. 1467 1523 Gordon Francis, MD, G. B. Mancini, MD, (Vancouver, BC) 1468 Background/Synopsis: Familial hypercholesterolemia 1524 (FH) is a hereditary condition characterized by elevated 1469 Lead Author’s Financial Disclosures: None. 1525 1470 LDL-C from birth leading to premature coronary artery 1526 Study Funding: Canadian Foundation for Innovation disease and physical sequelae of lipid deposition in tissues. 1471 and Genome British Columbia. 1527 1472 Early diagnosis is critical since timely treatment can 1528 In 30-80% of patients with 1473 Background/Synopsis: prevent atherosclerosis and coronary heart disease. Never- 1529 clinically-diagnosed Familial Hypercholesterolemia (FH), a 1474 theless, less than 10% of prevalent cases of FH in the 1530 pathogenic variant can be detected in the LDLR, APOB, or 1475 United States have been diagnosed. Low rates of diagnosis 1531 PCSK9 genes. Alternatively, w20% of clinical FH is 1476 may be attributable in part to affected patients not meeting 1532 thought to be due to a polygenic cause. The cardiovascular 1477 the clinical diagnostic criteria of the Dutch Lipid Clinic 1533 disease (CVD) risk associated with polygenic versus 1478 Network (DLCN), Simon Broom diagnostic criteria, or 1534 monogenic FH has not been previously determined. 1479 MEDPED diagnostic criteria. 1535 1480 Objective/Purpose: We evaluated the impact of mono- Objective/Purpose: To assess the utility of incorpo- 1536 1481 genic and polygenic causes of FH on CVD risk in a cohort rating genetic testing into a patient’s evaluation for FH. 1537 1482 of patients with clinically-diagnosed FH. Methods: We retrospectively reviewed patients seen in 1538 1483 Methods: We prospectively recruited patients with the Advanced Lipids Disorders Clinic at Johns Hopkins 1539 1484 ‘possible’, ‘probable’ or ‘definite’ FH, according to Dutch Hospital between January 2015 and May 2018. Between 1540 1485 Lipid Clinic Network Criteria (n5555). We performed June 2018 and December 2018, patients were consented to 1541 1486 targeted sequencing of genes known to cause FH, and to a prospective registry. DLCN, Simon Broom, and 1542 1487 detect common variants known to influence LDL levels to MEDPED criteria were applied to each patient, before 1543 1488 calculate polygenic risk scores. Cardiovascular events and after genetic testing. Genetic testing included 1544 1489 included premature unstable angina, myocardial infarction, sequencing and deletion duplication analysis of four genes 1545 1490 cardiovascular revascularization, or stoke. (LDLR, PCSK9, APOB, and LDLRAP1).Variants were 1546 1491 Results: We identified an FH-causing variant in 8.2% of classified according to the 2015 ACMG guidelines. 1547 1492 possible, 25.6% of probable, and 51.0% of definite FH Results: The retrospective review and prospective study 1548 1493 patients. A high polygenic risk score (.80th percentile) identified 135 adult, probands who were seen in our clinic 1549 1494 was identified in 33.5% of patients). Patients with an FH- for evaluation for heterozygous FH. Twenty-six individuals 1550 1495 causing variant had significantly higher levels of low- (19%) were determined to be heterozygous for a pathogenic 1551 1496 density lipoprotein cholesterol (LDL-C) than those without or likely pathogenic variant. Using the DLCN criteria, 15 1552 1497 an FH-causing variant. A monogenic cause of FH was (57.7%) individuals met criteria for a definite diagnosis of 1553 1498 associated with significantly greater risk of CVD, whereas FH prior to genetic testing. Thirteen patients (50%) met 1554 1499 the risk of CVD in patients with polygenic FH was not criteria using Simon Broom, and 16 (61.5%) patients met 1555 1500 significantly different than that of patients without an FH- criteria using MEDPED prior to genetic analysis. None of 1556 1501 causing variant. Interestingly, the presence of a high LDL- the patients who did not meet DLCN or Simon Broom 1557 1502 C polygenic risk score further increased risk among criteria had xanthomas or corneal arcus upon physical 1558 patients with monogenic FH. exam. Three patients who did not meet MEDPED criteria

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1559 did have a history of xanthomas, and one patient also had reductions in ANGPTL3 of 96% were achieved and 1615 1560 corneal arcus prior to age 45 years. All of the patients not persisted for at least 8 weeks. Reductions in TGs and 1616 1561 meeting criteria prior to genetic testing had a history of LDL-C were also observed. In DIO mice, improvements in 1617 1562 statin therapy. glucose tolerance and reduction in hepatic steatosis were 1618 1563 Conclusions: Incorporating genetic testing nearly observed. Compared to LDLr KO mice treated with 1619 1564 doubled the rate when of FH diagnosis compared to atorvastatin or ARO-ANG3 alone, reductions in TGs and 1620 1565 classification solely on clinical grounds. Affected individ- LDL-C showed additive benefits when ARO-ANG3 and 1621 1566 uals may not have originally met diagnostic criteria for a atorvastatin were administered in combination. ARO- 1622 1567 variety of reasons including having a mild phenotype or APOC3 was evaluated in human APOC3 transgenic mice 1623 1568 prior lipid lowering therapy modifying the clinical pheno- where dose-dependent reductions in serum human APOC3 1624 1569 type. Therefore, our data support genetic testing in protein (maximum 91%) and liver mRNA were observed 1625 1570 evaluation for FH, as a definitive diagnosis has important along with reductions in TGs and LDL-C. In a dyslipidemic 1626 1571 implications for patients and their relatives. NHP model, reductions in serum APOC3 (up to 80%), TGs 1627 1572 and LDL-C were observed, and the magnitudes of re- 1628 1573 ductions correlated to the degree of dyslipidemia in the 1629 1574 NHPs. Both ARO-ANG3 and ARO-APOC3 were well- 1630 324 1575 tolerated in animal safety studies. 1631 Personalized Medicine for Dyslipidemias by 1576 Conclusions: Our results support an RNAi therapeutic 1632 RNA Interference-Mediated Reductions in 1577 targeting APOC3 or ANGPTL3 as a treatment for dyslipi- 1633 Apolipoprotein C3 or Angiopoietin-Like 1578 demia. ARO-ANG3 may also provide metabolic benefits in 1634 Protein 3 1579 the liver and impact LDL in familial hypercholesterolemia. 1635 1580 1636 So C. Wong, PhD, Zhen Li, PhD, Bruce Given, MD, Both development candidates can be used to target specific 1581 patient populations depending on underlying genetic and 1637 1582 Mark Seefeld, PhD, Aaron Andersen, BS, Rui Zhu, PhD, 1638 Peter Havel, PhD, James Hamilton, MD, metabolic profiles. ARO-APOC3 and ARO-ANG3 have 1583 recently entered human clinical trials. 1639 1584 James Graham, PhD, Tao Pei, PhD, Julia Hegge, BS, 1640 1585 Casi Schienebeck, BS, Gary Christensen, BS, 1641 1586 Lucas Trilling, BS, Holly Hamilton, PhD, Qili Chu, PhD, 1642 Jeremy Briggs, BS, 1587 325 1643 Meredith Hinkes, BS, Stephan Bertin, BS, (Madison, WI) 1588 Familial Hypercholesterolemia GENEtic 1644 1589 Lead Author’s Financial Disclosures: Employee of evaluation of Minority patients with an LDL-C 1645 1590 Arrowhead Pharmaceuticals. .190mg/dL: FH GENE-Minority Study 1646 1591 1647 Study Funding: None. 1592 Mary Katherine Cheeley, PharmD, CLS, FNLA, 1648 1593 Background/Synopsis: Human genetic analysis has Allison Hester, PharmD, Adrian Brown, PharmD, 1649 1594 identified that individuals with loss-of-function mutations Julianne Padgett, PharmD, 1650 1595 in either apolipoprotein-C3 (APOC3) or angiopoietin-like Terry Jacobson, MD, FNLA, (Atlanta, GA) 1651 1596 protein 3 (ANGPTL3) have very low plasma levels of 1652 1597 triglycerides (TGs) and low-density lipoprotein (LDL-C), Lead Author’s Financial Disclosures: Speakers 1653 1598 and a reduced risk of cardiovascular disease. bureau- Regeneron/Sanofi; Investigator Initiated Study 1654 1599 Objective/Purpose: ANGPTL3 and APOC3 are pri- Grant- Regeneron/Sanofi. 1655 1600 marily expressed in hepatocytes. An RNA interference Study Funding: Funded by an investigator initiated 1656 1601 (RNAi) based therapy using Arrowhead Pharmaceuticals’ study grant from Sanofi/Regeneron. 1657 1602 TRiM platform to reduce APOC3 or ANGPTL3 production Background/Synopsis: Diagnosis of Familial Hyper- 1658 1603 in the liver by gene silencing may be an effective approach cholesterolemia (FH) can include use of multiple validated 1659 1604 to treat dyslipidemias and metabolic diseases (AHA 2018). clinical tools that may rely on family history and/or genetic 1660 1605 Methods: Highly potent and specific RNAi conjugates testing as well as other criteria. However, it was identified 1661 1606 were identified targeting human and non-human primate in an earlier study of patients at Grady Health System 1662 1607 (NHP) APOC3 transcripts (ARO-APOC3) or ANGPTL3 (GHS), an indigent health care system with a predomi- 1663 1608 transcripts (ARO-ANG3). Rodent or NHP (high fructose nately minority population, that their family history is 1664 1609 diet-fed rhesus macaques) dyslipidemic animal models largely unknown; thus, making it difficult to accurately give 1665 1610 were used to study pharmacodynamic effects in target a clinical diagnosis of FH. 1666 1611 protein reduction and reductions in TGs and LDL-C. Genetic prevalence of FH, in a primary prevention popu- 1667 1612 Results: ARO-ANG3 was evaluated in LDL receptor lation, has been shown to be about 2%; it has not been 1668 1613 knockout (LDLr KO) mice, diet-induced obese (DIO) mice, characterized in a predominately minority population. 1669 1614 and leptin receptor defective mice, as well as a dyslipi- Objective/Purpose: Data regarding FH in minority 1670 demic NHP models. In all animal models, maximum serum populations is lacking. This study reports the results of

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1671 genetic testing and lp(a) levels for 100 patients at GHS with require more aggressive treatment or an alternative way to 1727 1672 an LDL-C .190mg/dL. identify those with the FH genotype. 1728 1673 Methods: All patients had a 7 gene genetic test (LDLR, Objective/Purpose: As part of the GENE-Minority 1729 1674 PCSK-9 apoB, apoE, CETP, LDLRAP1, SREBF2) and study at Grady Health System (GHS) in Atlanta, Georgia, 1730 1675 Lp(a) measured in mg/dL. Patient were prospectively the probability of FH was determined. Within this indigent 1731 1676 included from either the advanced lipid clinic or a system minority population, a large proportion of patients are 1732 1677 list of patients with an LDL-C .190 mg/dL. Patients were unaware of their family history. Thus tools that rely heavily 1733 1678 excluded if they had a secondary cause for elevated LDL-C, on patient-reported family history make the diagnosis of 1734 1679 were pregnant, were incarcerated, or were age ,18 years FH difficult without a genetic test. An alternative approach 1735 1680 old. Coronary Calcium Scoring was also conducted for may be the use of CAC scores as an option to help risk 1736 1681 primary prevention patient and is reported separately. stratify primary prevention patients. The aim of this study 1737 1682 1738 Results: One hundred patients were included in the study. was to characterize the CAC scores of asymptomatic 1683 1739 Ninety-seven black, 2 hispanic, and 1 caucasian. Median patients with baseline LDL-C ,190 mg/dL, and to 1684 1740 baseline LDL-C 229 (IQR 214-250). Forty-three percent of compare the CAC scores of patients with a positive versus 1685 1741 patients have ASCVD. Baseline Dutch Lipid Score was 5 negative genetic test. 1686 1742 (IQR 3-5). Overall, 12 patients had a positive genetic test. Methods: Patients were included if they presented with 1687 1743 Nine percent of patients had an LDL-C raising genetic an LDL-C ,190 mg/dL and had no ASCVD. All patients 1688 1744 defect. Eight patients had an LDLR mutation, 1 an apoB, had a genetic test and CAC scan. The genetic test evaluated 1689 1745 and 3 patients had an apoE mutation. LDL-C in genetically 7 mutations associated with FH. CAC score and percentile, 1690 1746 positive patients was significantly higher than the negative based on patient demographics, were compared across 1691 1747 group at 272 (238-289) vs 227 (211-245), median (IQR). patients with positive versus negative genetic tests. 1692 1748 Fifty patients had an Lp(a) above 50 mg/dL (median 52 1693 Results: Of a total of 54 patients, 98% of whom were 1749 [IQR 19.5-127.5]. Only 1 patient with a positive genetic 1694 African-American, 29 (53.7%) had a calcium score of 0. Of 1750 test had a physical exam finding listed in the Dutch Lipid 1695 the 25 patients with a positive CAC score, the median 1751 Criteria. 1696 adjusted population CAC percentile was 97% [IQR 78-99]. 1752 1697 Conclusions: The incidence of genetically positive FH is Those with a positive CAC score were generally older than 1753 1698 similar in this minority population, compared to other the zero CAC group (mean age, 57 vs 53 years). Of the 6 1754 1699 studied groups. There was no difference in median Dutch patients who had a FH genetic defect, only 2 had a positive 1755 1700 Lipid Score, prior to genetic testing, between those who CAC score (mean age 61 years) while 4 had a score of zero 1756 1701 had a positive genetic test and those who were negative. (mean age 34 years). 1757 1702 There was no difference between the two groups with Conclusions: In this predominate African-American 1758 1703 regards to median lp(a). Existing population based clinical population, a clear association between elevated CAC 1759 1704 tools for a diagnosis of FH, such as the Dutch Lipid scores and the FH phenotype was not demonstrated. Less 1760 1705 Criteria, failed to adequately identify genetically positive than half of the cohort exhibited a positive CAC score and 1761 1706 FH in this minority population. most of the genetically positive patients had a CAC score of 1762 1707 zero. These data show that while CAC is a helpful tool at 1763 1708 331 stratifying risk, it cannot replace genetic testing for patients 1764 . 1709 Coronary Artery Calcium scores in with baseline LDL-C 190 mg/dL. 1765 1710 asymptomatic minority subjects with 1766 1711 phenotypic Familial Hypercholesterolemia* 1767 1712 1768 1713 Allison M. Hester, PharmD, 339 1769 1714 Mary Katherine Cheeley, PharmD, Increasing Diagnostic Yield for Inherited 1770 1715 Adrian Brown, PharmD, Lipidemias: Next-Generation Sequencing of 1771 1716 Terry Jacobson, MD, FNLA, (Atlanta, GA) An Expanded Panel 1772 1717 1773 1718 Lead Author’s Financial Disclosures: None. Gregory Kellogg, MS, CGC, 1774 1719 Study Funding: Funded by an investigator initiated Alex Bisignano, BS, 1775 1720 study grant from Sanofi/Regeneron. Malgorzata Jaremko, PhD, FACMG, FACB, (New York, NY) 1776 1721 Background/Synopsis: There is very little data about 1777 1722 using coronary calcium (CAC) scores to further risk stratify Lead Author’s Financial Disclosures: This author 1778 1723 those who present with the FH phenotype (LDL-C levels is a full-time employee of Phosphorus Diagnostics, the 1779 1724 ,190 mg/d). Coronary artery calcium (CAC) scoring may location where this research was performed. 1780 1725 be one method to identify those at higher CV risk who may Study Funding: None. 1781 1726 1782

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1783 Background/Synopsis: The diagnosis of inherited 343 1839 1784 lipid disorders is complicated by clinical overlap be- Genetic Testing for Hypertriglyceridemia - 1840 1785 tween syndromes, contributions of lifestyle and environ- Pilot Data from a Single Center Lipid Clinic 1841 1786 ment, and a spectrum of genetic risk, ranging from 1842 1787 monogenic Mendelian disease to polygenic risk. Tar- Trevor Dalton Hadley, BS, Xiaoming Jia, 1843 1788 geted genetic testing based only on clinical and biochem- Christie Ballantyne, Mendel Roth, 1844 1789 ical phenotype can therefore be difficult due to these Carter Ma, Vijay Nambi, (Houston, TX) 1845 1790 1846 confounding variables. Multi-gene panel testing has been Lead Author’s Financial Disclosures: None. 1791 demonstrated to be an effective method of increasing 1847 None. Genetic testing from this pilot 1792 diagnostic yield in inherited cancers and other clinical Study Funding: 1848 study was provided without charge by GBinsight. 1793 specialties, and could therefore be useful in inherited 1849 1794 lipidemia testing. Background/Synopsis: Severe elevations of triglyc- 1850 1795 erides can cause pancreatitis and triglyceride (TG) rich 1851 Objective/Purpose: We sought to determine the yield 1796 lipoproteins are likely causal risk factors for atheroscle- 1852 of testing of a multi-gene panel associated with a spectrum 1797 rotic cardiovascular disease (ASCVD) based on epide- 1853 of inherited lipidemias in a consecutive series of patients 1798 miologic and Mendelian randomization studies. 1854 referred for clinical testing. 1799 Moreover, genetic linkage studies have provided novel 1855 1800 Methods: Next-generation-sequencing (NGS) analyzing targets for therapy against hypertriglyceridemia. While 1856 1801 a 21 gene panel was performed on 91 consecutive hypertriglyceridemia is often a polygenic disease, ge- 1857 1802 patients referred for inherited lipidemia testing. netic testing has potential to affect clinical decision 1858 1803 Variants were classified in accordance with ACMG making. 1859 criteria. 1804 Objective/Purpose: The aim of this pilot study is to 1860 1805 Results: Pathogenic/Likely Pathogenic variants were evaluate the clinical utility of genetic testing in a lipid 1861 1806 identified in 18 patients. LDLR variants associated with clinic for patients with hypertriglyceridemia. 1862 familial hypercholesterolemia (FH) were identified in 12/ 1807 In collaboration with GBinsight, we con- 1863 91 (13.2%) patients. Heterozygous ABCG5 variants Methods: 1808 ducted a pilot study of 40 patients who had genetic 1864 (c.1336C.T; p.Arg446Ter and c.1166G.A; p.Ar- 1809 testing. Patients presented to lipid clinic from January 1865 g389His) associated with sitosterolemia were identified 1810 2018 to December 2018 and provided informed consent 1866 in 2 patients, and one patient was compound heterozy- 1811 and saliva samples. Monogenic variants were reported as 1867 gous for an APOB variant (exon 19-20 deletion) associ- 1812 pathogenic/likely pathogenic, variants of unknown sig- 1868 ated with hypobetalipoproteinemia and an ABCG8 1813 nificance, likely benign/benign in accordance to Amer- 1869 variant (c.547delC; p.Gln183fs) associated with sitoster- 1814 ican College of Medical Genetics recommendations. 1870 olemia. Two patients carried the same LPL variant 1815 Polygenic risk scores were also calculated for each 1871 (c.953A.G; p.Asn318Ser) associated with risk for 1816 individual. 1872 1817 hypertriglyceridemia and lipoprotein lipase deficiency, 1873 Results: During the study period, 12 patients with a 1818 and one patient carried the c.1214C.T (p.Thr405Met) 1874 history of hypertriglyceridemia underwent genetic 1819 LIPC variant associated with hepatic lipase deficiency. In 1875 testing. All but 2 of the patients has documented TG . 1820 5/6 patients with non-LDLR variants, the indication for 1876 500mg/dL. Of these, 3 patients had pathogenic variants, 1821 testing was a diagnosis of familial hypercholesterolemia 1877 and all 12 had at least one variant of uncertain 1822 (ICD10: E78.01). 1878 significance projected as likely high-risk. The prevalence 1823 Conclusions: The inheritance pattern of familial lip- 1879 of diabetes was 25%. The mean (standard deviation) for 1824 idemia is a spectrum, ranging from monogenic disease to 1880 relevant clinical data were: highest documented TG 1906 1825 polygenic risk. Three patients were heterozygous carriers 1881 (1992), high-density lipoprotein (HDL) cholesterol 31 1826 for autosomal recessive disease and a fourth was com- 1882 (16), non-HDL cholesterol 204 (112), fasting glucose 1827 pound heterozygous for variants associated with two 1883 117 (61), and BMI 27.0 (4.5). Genotypic data per 1828 different recessive diseases, indicating that carrier status 1884 individual are presented in Table 1. 1829 may contribute to the phenotype in these patients. In two 1885 1830 others, a variant in a gene not related to the primary Conclusions: Genetic testing in patients with 1886 1831 indication for testing was identified, further indicating hypertriglyceridemia has a high yield for pathogenic 1887 1832 that variants in other genes may contribute to the variants and variants of unknown significance projected 1888 1833 phenotype of patients clinically diagnosed with FH. In as likely high risk. Larger studies are needed which 1889 1834 summary, NGS for an expanded panel of lipid disorders include various ethnic groups, especially South 1890 1835 can identify variants that contribute to patient phenotype Asians, as previous recommendations may have under- 1891 1836 and is a cost-effective method of increasing diagnostic estimated the benefit of routine genetic testing in this 1892 1837 yield. population. 1893 1838 1894

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1895 1951 1896 Table 1 1952 1897 Highest 1953 1898 Polygenic recorded TG **Presenting lipid 1954 1899 Patient Race Variant Zygosity Risk Score level (mg/dL) values (mg/dL) 1955 1900 1 Hispanic LPL(c.953A.G(p.Asn318Ser)) > Heterozygous 98 1493 TG 1493 1956 1901 APOA5(c.56C.G(p.Ser19Trp)) Heterozygous HDL-C 28 1957 1902 APOE(E4(p.Cys130Arg)) Heterozygous Non-HDL-C 354 1958 1903 APOE(E2(p.Arg176Cys)) Heterozygous 1959 1904 ZPR1(c.*724C.G) Heterozygous 1960 1905 2 South Asian ABCA1(c.1913G.A(p.Arg638Gln)) Heterozygous 98 1518 TG 1371 1961 1906 HDL-C 11 1962 . 1907 LPL(c.929G A(p.Cys310Tyr)) Homozygous Non-HDL-C 98 1963 1908 3 Caucasian CREB3L3(c.731_732insG(p.Lys244Glufs)) Heterozygous 90 2353 TG 148 1964 LMF1(c.1052G.A (p.Arg351Gln)) Heterozygous HDL-C 50 1909 1965 SVEP1(c.8105A.G (p.Asp2702Gly)) Heterozygous Non-HDL-C 137 1910 ZPR1(c.*724C.G) Heterozygous 1966 1911 4 Caucasian APOA5(c.56C.G(p.Ser19Trp)) Homozygous 94 417 TG 356 1967 1912 ZPR1(c.*724C.G) Homozygous HDL-C 55 1968 1913 Non-HDL-C 208 1969 1914 5 Caucasian APOE(E4(p.Cys130Arg)) Heterozygous 7 1119 TG 658 1970 1915 HDL-C 24 1971 1916 Non-HDL-C 269 1972 1917 6 South Asian ABCA7(c.274G.T(p.Gly92Trp)) Heterozygous 84 1000 TG 160 1973 1918 APOE(E4 (p.Cys130Arg)) Heterozygous HDL-C 50 1974 . 1919 POMC(c.706C G(p.Arg236Gly)) Heterozygous Non-HDL-C 143 1975 PPARG(c.625G.T(p.Ala237Ser)) Heterozygous 1920 1976 7 South Asian LMF1(c.1317C.G(p.Tyr439Ter)) > Homozygous 98 1100 TG 531 1921 LPA(c.4262G.A(p.Arg1421Gln)) Heterozygous HDL-C 15 1977 1922 Non-HDL-C 119 1978 1923 8 South Asian GPIHBP1(c.230G.A(p.Cys77Tyr)) Homozygous 96 4500 TG 3995 1979 1924 HDL-C 26 1980 1925 Non-HDL-C 444 1981 1926 9 Caucasian ABCG8(c.55G.C (p.Asp19His)) Heterozygous 91 520 TG 197 1982 1927 APOA5(c.553G.T(p.Gly185Cys)) Heterozygous HDL-C 46 1983 1928 CD300LG(c.244C.T(p.Arg82Cys)) Heterozygous Non-HDL-C 100 1984 1929 10 Hispanic APOA5(c.56C.G(p.Ser19Trp)) Heterozygous 44 7145 TG 1567 1985 1930 APOE(E4(p.Cys130Arg)) Heterozygous HDL-C 24 1986 LPA(c.5673A.G(p.Ile1891Met)) Heterozygous Non-HDL-C 276 1931 1987 11 Caucasian LPL(c.953A.G(p.Asn318Ser)) > Heterozygous 100 1359 TG 1109 1932 APOA4(c.37G.A(p.Val13Met)) Heterozygous HDL-C 13 1988 1933 APOA5(c.56C.G(p.Ser19Trp)) Heterozygous Non-HDL-C 198 1989 1934 LCAT(c.619G.A(p.Gly207Ser)) Heterozygous 1990 1935 LPA(c.3947+467T.C) Homozygous 1991 1936 ZPR1(c.*724C.G) Heterozygous 1992 1937 12 Caucasian APOE(E2(p.Arg176Cys)) Heterozygous 26 353 TG 160 1993 1938 LPA(c.4262G.A(p.Arg1421Gln)) Heterozygous HDL-C 35 1994 1939 ZPR1(c.*724C.G) Heterozygous Non-HDL-C 99 1995 1940 TG 5 triglyceride, HDL-C 5 high density lipoprotein cholesterol 1996 1941 > Indicates variant classified as pathogenic. All other variants are classified as variants of undetermined significance projected as likely high risk. 1997 1942 * Indicates a translation termination (stop) codon 1998 **Lipid results are preclinic laboratory values from the visit that genetic testing sample was collected 1943 1999 1944 2000 1945 2001 1946 2002 1947 2003 1948 2004 1949 2005 1950 2006

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2007 351 Lead Author’s Financial Disclosures: Andrew 2063 2008 A novel mutation of APOB in two siblings with Castro is an employee of Ambry Genetics. 2064 2009 2065 hypercholesterolemia Study Funding: None. 2010 2066 2011 Abigail Sprunger, OMS II, Luke Hamilton, MS, Background/Synopsis: The American College of 2067 2012 Tyler Hamby, PhD, Don Wilson, MD, (Fort Worth, TX) Medical Genetics and Genomics (ACMG) recommends 2068 2013 clinical genetic testing laboratories to return secondary 2069 2014 Lead Author’s Financial Disclosures: None. findings (SF) with diagnostic exome sequencing in 2070 2015 Study Funding: None. 59 genes associated with medically actionable 2071 2016 Background/Synopsis: Familial hypercholesterolemia conditions. Among these genes are APOB and LDLR, 2072 2017 (FH) is a common genetic disorder cause of premature genes associated with familial hypercholesterolemia 2073 2018 atherosclerosis due to chronically elevated low-density (FH). Through clinical diagnostic exome sequencing, 2074 2019 lipoprotein cholesterol (LDL-C) levels from birth. Individ- individuals and family members with disease-causing 2075 2020 uals with FH experience an increased risk of premature alterations in FH genes can be identified. These in- 2076 2021 cardiovascular disease (CVD), and lack of early identifica- dividuals may or may not have prior known symptoms of 2077 2022 tion and treatment increases the risk of CVD-related FH; however, a causative pathogenic alteration in the 2078 2023 coronary events later in life. LDLR or APOB gene is sufficient for a definite 2079 2024 Objective/Purpose: We report two siblings with FH diagnosis of FH, per Dutch Lipid Clinic Network 2080 2025 caused by a novel mutation in APOB. criteria. 2081 2026 Methods: Electronic medical records were reviewed for Objective/Purpose: We aim to assess the rate of 2082 2027 two patients with FH. pathogenic alterations in APOB or LDLR in individuals 2083 2028 and their family members undergoing diagnostic exome 2084 Results: Two biologically related siblings (male age 9, 2029 sequencing, 2085 female age 11) were found to have LDL-C levels .95th 2030 2086 centile for respective age and gender. Neither sibling had Methods: We retrospectively analyzed SF results of 2031 2087 preexisting medical conditions nor a history of chronic APOB and LDLR and provided clinical information from 2032 2088 medications. Both siblings were found to have the same 15,832 individuals from 7,990 families. 2033 2089 missense variant in the APOB gene, a novel mutation Results: In total, 13 individuals (0.08% of individuals) 2034 2090 causing hypercholesterolemia. Because of parental con- from 10 families (0.13%) were positive for a pathogenic 2035 2091 cerns regarding use of statins, both were treated with a alteration in APOB and 31 individuals (0.20% of in- 2036 2092 cholesterol absorption inhibitor. dividuals) from 24 families (0.30%) were positive for a 2037 2093 Conclusions: Despite the benefits of early identification of pathogenic alteration in LDLR. Overall, 44 individuals 2038 (0.28%) from 34 families were positive for an FH 2094 2039 those at moderate-to-severe risk, several knowledge gaps 2095 impede successful cholesterol screening of children: misun- pathogenic alteration. The average age of testing was 2040 , , 2096 derstanding goals of screening, the best screening method, and 26.2 years (range 1 to 67), with 16 individuals 18 2041 years old (36.4% of positive individuals). 10 (22.7%) 2097 2042 ideal age for screening and for intervention. Current guide- 2098 lines recommend universal cholesterol screening and selective positive individuals were under 9 years old. Among patients 2043 5 2099 screeningstartingat10and2years of age, respectively. tested between ages 9-18 (n 2,349), 0.3%% had a 2044 pathogenic FH alteration. 2100 2045 Although not routinely preformed, identification of a genetic 2101 mutation helps to 1) confirm the diagnosis of FH; and 2) One family had a reported family history of hypercholes- 2046 terolemia (paternal grandmother of proband), but the 2102 2047 serves as an additional risk factor for CVD, aids risk 2103 stratification and clinical-decision making, and helps deter- alteration present in this family was not paternally in- 2048 herited. No individuals had a reported personal history of 2104 2049 mine the timing and intensity of treatment that would provide 2105 the best long-term health benefits. In addition to lipid- hypercholesterolemia. All individuals were heterozygous 2050 for reported pathogenic alterations. 2106 2051 lowering medications, treatment should include global reduc- 2107 2052 tion of all CVD risk factors through health education, and Conclusions: The prevalence of FH-positive individ- 2108 2053 adoption of life-long, heart-healthy living with a goal to uals within our cohort (1/500) is lower than some 2109 , 2054 reduce LDL-C levels to 100mg/dL or at least 50% or more. previously reported estimates of 1/200-1/250, but higher 2110 than that reported in a 1000 Genomes assessment (1/ 2055 354 2111 2056 1000) even without the addition of the genes PCSK9 and 2112 Exome Secondary Findings identifies an LDLRAP1. It is uncertain if the scarcity of clinical 2057 incidental FH prevalence rate of 1 in 500 2113 2058 history of hypercholesterolemia indicates a lack of blood 2114 cholesterol testing, under-reporting by patients, and/or 2059 Andrew Castro, MS, CGC, Kirsten Blanco, BS, 2115 lack of FH-related discussion between provider and 2060 Tami Johnston, MS, CGC, Benjamin Feldmann, MS, CGC, 2116 patient. Regardless, no individuals with a pathogenic 2061 Jill Dolinsky, RN, MS, CGC, 2117 alteration had a reported personal or family history of 2062 Zoe Powis, MS, CGC, (Aliso Viejo, CA) 2118

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2119 hypercholesterolemia, indicating the increased need for Inclusion Criteria Exclusion Criteria 2175 2120 screening and genetic testing for FH. Given that FH ≥1 prescription claim for a statin medication Niacin use 2176 in 2010 2121 mutation carriers have a higher risk of coronary artery ICD-9 codes indicating the presence of any 2177 Age ≥45 years of the following conditions during the 6- 2122 disease at all LDL levels, patients with FH mutations month baseline period: 2178 Known gender, insurance type, and 2123 identified through diagnostic exome sequencing warrant geographic region Pregnancy 2179 2124 follow up by a cardiologist or lipid specialist, including Continuous enrollment with medical and Severe liver disease 2180 pharmacy benefits during the baseline period Acute or chronic pancreatitis 2125 a number of minor children, age. and ≥6 months starting on the index date, or 2181 2126 death within 6 months of the index date Malabsorption syndrome or 2182 gastric/intestinal bypass surgery 2127 ≥1 medical claim with a diagnosis or 2183 procedure code representing ASCVD and/or HIV/AIDS 2128 diabetes 2184 Hypertriglyceridemia End-stage renal disease, hemodialysis, 2129 Elevated TG cohort: TG ≥150 mg/dL at most or peritoneal dialysis 2185 recent laboratory test prior to index date 2130 Myositis, polymyositis, or 2186 262 Comparator cohort: TG <150 mg/dL and rhabdomyolysis 2131 HDL-C >40 mg/dL 2187 Drug or alcohol abuse 2132 The Economic Burden of Hypertriglyceridemia 2188 2133 Among US Adults With Diabetes or 2189 2134 Atherosclerotic Cardiovascular Disease on 2190 2135 Statin Therapy* 2191 2136 Figure 1 Inclusion and Exclusion Criteria of Participants 2192 2137 Brian C. Case, MD, Adam Bress, PharmD, MS, 2193 2138 Paul Kolm, PhD, Sephy Philip, PharmD, Jennifer Herrick, 2194 2139 Craig Granowitz, MD, PhD, Peter Toth, MD, PhD, 2195 Lead Author’s Financial Disclosures: None. 2140 Wenjun Fan, MD, MS, Nathan Wong, PhD, MPH, 2196 2141 Michael Hull, MS, Study Funding: Supported by a research grant from 2197 2142 William Weintraub, MD, (Washington, DC) Amarin Pharma, Inc. 2198 2143 2199 2144 2200 Table 1 Generalized Linear Models with Bootstrapping for Total Health Care Costs (PPPM) in the Follow-up Period for Various 2145 2201 Population Subsets 2146 2202 2147 Study Group: Triglycerides $ 150 mg/dL vs. 2203 2148 Comparison: Triglycerides , 150 mg/dL and HDL-C . 40 mg/dL 2204 2149 Estimated Mean 2205 2150 Population Subset Difference1 LCL (95%) UCL (95%) 2206 2151 Overall 194.79 147.57 241.43 2207 2152 Age, years 2208 2153 45-54 232.63 148.85 331.60 2209 2154 55-64 174.30 99.89 253.19 2210 2155 65+ 176.75 100.97 247.69 2211 2156 Gender 2212 2157 Male 209.54 138.72 286.89 2213 2158 Female 181.76 114.57 237.55 2214 2159 Coverage Type 2215 2160 Commercial 211.40 148.53 272.56 2216 Medicare 136.28 69.56 208.02 2161 2217 Geographic Region 2162 Northeast 177.39 26.36 327.83 2218 2163 Midwest 209.11 76.05 357.89 2219 2164 West 178.72 15.36 343.56 2220 2165 South 194.48 137.36 246.60 2221 2166 Diabetes 2222 2167 Yes 202.64 154.09 257.09 2223 2168 No 166.88 54.20 281.00 2224 2169 ASCVD 2225 2170 Yes 230.42 129.46 325.30 2226 2171 No 179.06 131.21 235.99 2227 2172 1Estimated mean differences were calculated using adjusted GLM models with gamma distribution and log link on the model outcome, total costs in 2228 2173 the follow-up period as per patient per month (PPPM). A total of 1,000 bootstrap iterations were conducted for each analysis to produce bias-corrected 2229 upper and lower 95% confidence intervals (Cameron, A.C., Trivedi, P.K. Microeconomics Using Stata. Stata Press: College Station, 2009). Outcomes were 2174 adjusted for age, gender, insurance coverage, geographic region, diabetes in baseline, and ASCVD in baseline. 2230

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2231 2287 $ 2232 Table 2 Projected number of US adults 45 years taking a statin and with ASCVD or diabetes, adjusted incremental total healthcare 2288 costs, and total annual costs associated with triglycerides $150 mg/dL compared to ,150 mg/dL + HDL-C.40 mg/dL overall and in 2233 2289 subgroups. 2234 2290 2235 Adjusted Incremental Total 2291 Healthcare Costs from OPTUM 2236 Population Sizes (95% CI), in Projected annual 2292 Research Database, USD 2237 Millions from NHANES cost burden due to 2293 2238 Triglycerides Triglycerides $150 mg/dL vs. triglycerides $150 mg/dl 2294 2239 ,150 mg/dL + Triglycerides Triglycerides ,150 mg/dL + vs ,150 mg/dl + HDL-C 2295 2240 Group HDL-C.40 mg/dL $150 mg/dL HDL-C.40 mg/dL .40 mg/dL, Billions of USD 2296 2241 Overall 8.3 (7.1-22.3) 5.1 (4.3-5.9) $2,340 ($1,770-$2,900) $11.9 ($8.5-$15.3) 2297 2242 Age, yrs 2298 2243 45 to ,55 1.0 (0.6-1.3) 0.8 (0.6-1.1) $2,790 ($1,790-$3,980) $2.2 ($1.1-$3.4) 2299 2244 55 to ,65 1.6 (1.2-2.2) 1.5 (1.0-2.1) $2,090 ($1,200-$3,040) $3.1 ($1.3-$4.9) 2300 2245 65+ 5.7 (4.9-6.5) 2.8 (2.3-3.3) $2,120 ($1,210-$2,970) $5.9 ($3.3-$8.6) 2301 2246 Sex 2302 2247 Male 4.4 (3.8-5.0) 2.6 (2.0-3.2) $2,510 ($1,660-$3,440) $6.5 ($3.8-$9.3) 2303 2248 Female 3.9 (3.1-4.7) 2.5 (2.0-3.1) $2,180 ($1,370-$2,850) $5.5 ($3.3-$7.7) 2304 2249 Diabetes 2305 Yes 4.6 (4.0-5.2) 3.9 (3.2-4.5) $2,430 ($1,850-$3,090) $9.5 ($6.6-$12.4) 2250 2306 No 3.7 (2.9-4.5) 1.2 (0.8-1.6) $2,000 ($650-$3,370) $2.4 ($0.6-$4.2) 2251 ASCVD 2307 2252 Yes 5.2 (4.2-6.2) 2.5 (2.0-3.0) $2,770 ($1,550-$3,900) $6.9 ($3.7-$10.2) 2308 2253 No 3.1 (2.7-3.5) 2.6 (2.2-3.1) $2,150 ($1,570-$2,830) $5.6 ($3.7-$7.5) 2309 2254 2310 2255 2311 2256 2312 2257 2313 diabetes or CVD taking statin therapy with ‘normal’ 2258 Background/Synopsis: Hypertriglyceridemia (HTG) 2314 triglycerides (TG) as defined as TG ,150 mg/dL and 2259 is associated with increased cardiovascular disease (CVD) 2315 risk. However, the cost burden of HTG-related CVD in high-density lipoprotein cholesterol (HDL-C) .40 mg/dL 2260 $ 2316 2261 high-risk US adults is not well characterized. compared to those with HTG as defined as 150 mg/dL 2317 2262 Objective/Purpose: We estimated the HTG-related regardless of HDL-C. Population sizes were estimated from 2318 the 2011-2014 National Health and Nutrition Examination 2263 healthcare cost burden among US adults with CVD or 2319 Surveys. Adjusted mean total annual healthcare costs in 2264 diabetes taking statin therapy. 2320 2015 US dollars were estimated using the Optum Research 2265 Methods: We estimated population sizes and annual 2321 Database. The annual total healthcare cost burden was 2266 healthcare costs among US adults age $ 45 years with 2322 estimated by multiplying the population size by the mean 2267 2323 annual total incremental healthcare costs overall and within 2268 2324 2269 subgroups. 2325 2270 Results: There were 5.1 (95% CI, 4.3-5.9) million and 2326 Table 3 Adjusted incremental total healthcare cost from $ 2271 8.3 (95% CI, 7.1-22.3) million US adults age 45 years 2327 Optum Research Database based on insurance type and also $ 2272 with diabetes and or CVD with TG 150 mg/dl (HTG) 2328 region within the United States. , . 2273 and TG 150 mg/dl + HDL-C 40mg/dl (‘normal’), 2329 2274 Adjusted Incremental Total Healthcare respectively. The mean adjusted incremental total one-year 2330 $ 2275 Costs from OPTUM Research Database, USD healthcare costs in adults with TG 150 mg/dl compared 2331 , . 2276 Triglycerides $150 mg/dL vs. Triglycerides to those with TG 150 md/dl + HDL-C 40mg/dl was 2332 2277 ,150 mg/dL + HDL-C.40 mg/dL $2,340 (95% CI, $1,770-$2,900). This leads to a projected 2333 annual cost burden associated HTG in patients with 2278 Coverage Type 2334 2279 diabetes or CVD of $11.9 billion (95% CI, $8.5B- 2335 2280 Commercial $2,540 ($1,780 - $3,270) $15.3B). The annual cost burden is higher for adults 2336 Medicare $1,640 ($830 – $2,500) 2281 over the age of 65 years old, with 2.8 million (95% CI, 2337 Region 2282 2.3M-3.3M) US adults with HTG, leading to a projected 2338 Northeast $2,130 ($320 - $3,930) annual cost burden associated with HTG of $5.9 billion 2283 Midwest $2,510 ($910 - $4,290) 2339 (95% CI, $3.3B-$8.6B). The mean adjusted incremental 2284 West $2,140 ($180 - $4,120) 2340 2285 South $2,330 ($1,650 - $2,960) total one-year healthcare cost in adults with HTG and 2341 diabetes is $2,430 (95% CI, $1,850-$3,090), which leads 2286 5 2342 CI Confidence interval to a total projected annual cost burden $9.5 billion. The

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2343 adjusted incremental total healthcare costs were higher in Objective/Purpose: To examine the prevalence of TG 2399 2344 adults with HTG and ASCVD, $2,770 (95% CI, $1,550- $135 mg/dL in the overall US adult population, in those 2400 2345 $3,900), compared to adults with HTG but without who are statin-treated, and according to presence of 2401 2346 ASCVD, $2,150 (95% CI, $1,570-$2,830). This increase ASCVD and/or diabetes. 2402 2347 2403 in total healthcare costs leads to an annual cost burden of Methods: We studied 9593 US adults aged 20 years and 2348 2404 $6.9 billion (95% CI, 3.7B-10.2B) for adults with both older (projected to 219.9 million) in the US National Health 2349 2405 HTG and ASCVD. and Nutrition Examination Survey (NHANES; 2007-2014) 2350 2406 Conclusions: The financial burden related toHTG in who had available morning fasting TG. We determined the 2351 2407 patients with residual CV risk beyond LDL-C lowering is proportions of individuals with TG $135 mg/dL according 2352 2408 substantial and interventions used to prevent or reduce this to statin use, LDL-C levels, diabetes, ASCVD, and/or age. 2353 2409 residual CV risk may result in cost savings as well as Results: Overall, the proportion of adults with TG $135 2354 reducing the clinical burden in the United States. 2410 2355 mg/dL was 32% (71M individuals; Table). Among statin- 2411 $ 2356 treated adults, the proportion with TG 135 mg/dL was 2412 2357 39% (15M) and ranged from 35% to 48% for those who 2413 , 2358 also had LDL-C controlled to 100 mg/dL, diabetes, and/ 2414 276 2359 or ASCVD (Table). 2415 2360 Prevalence of US Adults With Triglycerides Conclusions: Based on our analysis, more than 30% 2416 $ 2361 135 mg/dL: NHANES 2007-2014 (71M) of all US adults have TG $135 mg/dL, including 2417 39% (15M) of those being treated with statins. Better 2362 Sephy Philip, RPh, PharmD, Wenjun Fan, MD, MS, 2418 2363 efforts are needed to identify and address ASCVD risk in 2419 Craig Granowitz, MD, PhD, statin-treated individuals with TG $135 mg/dL, including 2364 Peter Toth, MD, PhD, Nathan Wong, PhD, (Bedminster, NJ) 2420 2365 lifestyle modification adherence measures, and the use of 2421 2366 Lead Author’s Financial Disclosures: Employ- evidence-based pharmacologic therapies shown to reduce 2422 2367 ment, ownership interests (Amarin Pharma Inc.). ASCVD risk. 2423 2368 Study Funding: Amarin Pharma Inc. 2424 2369 Background/Synopsis: Hypertriglyceridemia is asso- 2425 2370 2426 ciated with increased atherosclerotic cardiovascular disease 285 2371 2427 (ASCVD) risk and remains prevalent in US adults due to Comparison of Atherosclerotic Plaque 2372 the increasing prevalence of obesity, insulin resistance, and 2428 2373 Characteristics among Normal and High 2429 other risk factors. Moderately elevated triglycerides (TG) Triglycerides (TGs) Patients 2374 are also associated with increased ASCVD risk, even in 2430 2375 statin-treated patients with well-managed low-density lipo- Lavanya Cherukuri, MD, Chandana Shekar, MD, 2431 2376 protein cholesterol. The recently completed REDUCE-IT April Kinninger, MD, Divya Birudaraju, MD, 2432 2377 cardiovascular outcomes trial included statin-treated pa- Sajad Hamal, MD, Ferdinand Flores, MD, 2433 2378 tients with high ASCVD risk and baseline TG 135 to 499 John Tayek, MD, Sion Roy, MD, Matthew Budoff, MD, 2434 2379 mg/dL. John Nelson, MD, Amit Johanis, (Torrance, CA) 2435 2380 2436 2381 2437 2382 2438 2383 2439 5 5 2384 Table Weighted Prevalence of TG 135 mg/dL Among Adults 20 Years in NHANES 2007-2014 2440 2385 Patients With TG 5135 Total Number of 2441 2386 Prevalence, % mg/dL, millions* Patients, millions* 2442 2387 2443 Overall 32.1 70.5 219.9 2388 Statin treated 39.0 15.2 38.9 2444 2389 Statin treated and LDL-C ,100 mg/dL 35.0 7.6 21.7 2445 2390 Statin treated and diabetes 47.6 5.9 12.4 2446 2391 Statin treated and ASCVD 38.7 4.1 10.6 2447 2392 Statin treated and diabetes or ASCVD 43.0 8.1 18.7 2448 2393 Statin treated and diabetes or ASCVD and 545 yrs 43.0 7.6 17.7 2449 2394 Statin treated and diabetes or ASCVD 39.3 4.9 12.5 2450 2395 and 545 yrs and LDL-C ,100 mg/dL 2451 2396 *Projected number of US adults. 2452 2397 2453 2398 2454

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2455 2511 2456 Table 1 Baseline characteristics among patients 2512 2457 Baseline Demographics High TGs group (n548) Normal TGs group (n548) p-value 2513 2458 2514 Age (years)* 57.2 6 8.8 57.46 6 9.25 0.902 2459 Male Gender (%) 31 31 1.00 2515 2460 BMI (kg/m2)* 32.7 6 6.0 32.69 6 7.52 0.986 2516 2461 Diabetes (%) 32 32 1.00 2517 2462 Hypertension (%) 36 34 0.646 2518 2463 Current Smoker (%) 1 6 0.0497 2519 2464 Family History of CAD (%) 15 22 0.1421 2520 2465 HDL Cholesterol (mg/dL) 37.9 6 9.1 49.3 6 17.6 0.00 2521 2466 LDL Cholesterol (mg/dL) 95.4 6 42.2 71.4 6 28.9 0.004 2522 6 6 , 2467 Triglycerides (mg/dL) 270.6 82.9 106.1 36.8 .0001 2523 2468 2524 2469 2525 2470 Table 2 Quantitative plaque scores (median 6 SD) 2526 2471 Normalized Quantitative Plaque Scores High TGs group (n548) Normal TGs group (n548) p-value 2527 2472 2528 2473 Normalized Total Dense Calicified Volume 46.2 6 145.4 23.5 6 327.6 0.44 2529 6 6 2474 Normalized Total Fibrous Fatty Volume 25.2 56.5 18.3 78.8 0.32 2530 6 6 2475 Normalized Total Fibrous Volume 93.9 175.5 132.3 290.4 0.79 2531 Normalized Total Low Attenuation Volume 13.8 6 57.1 1.9 6 45.4 0.02 2476 2532 TNCP Volume 132.2 6 267.4 175.9 6 384.6 0.94 2477 Total Plaque Volume 195 6 373.1 250.9 6 639.5 0.99 2533 2478 2534 2479 2535 2480 Lead Author’s Financial Disclosures: None. Conclusions: Individuals enrolled in the EVAPORATE 2536 2481 Study Funding: None. trial, with higher TGs had more low attenuation plaque 2537 2482 2538 Background/Synopsis: Hyperlipidemia is a major risk when compared to the individuals with normal TGs. As low 2483 2539 factor for cardiovascular disease (CVD). We compared attenuation plaque is more vulnerable to plaque rupture, 2484 2540 patients with high triglycerides (TGs) enrolled in a double- prompt treatment to lower triglycerides are of vital 2485 2541 blinded, randomized trial EVAPORATE (Effect of Vascepa importance. 2486 2542 on Improving Coronary Atherosclerosis in people with 2487 2543 High Triglycerides Taking Statin Therapy), with those with 2488 296 2544 normal TGs. 2489 Meta-analysis of Effects of Triglyceride 2545 2490 Objective/Purpose: We intended to assess the differ- Modifiers on Cardiovascular Outcomes* 2546 2491 ences in atherosclerotic plaque burden and characteristics 2547 2492 between these two groups. Hammad Rahman, MD, Safi Khan, MD, 2548 2493 Methods: We identified 48 patients with TGs .200mg/dl Swapna Talluri, MD, Muhammad Asif, MD, 2549 2494 undergoing Coronary Computed Tomography Angiography Tehseen Hammad, MBBS, 2550 2495 (CCTA) (31 male) enrolled in the EVAPORATE trial. We Edo Kaluski, MD, FACC, (Sayre, PA) 2551 2496 matched this cohort 1:1 by age, gender, body mass index 2552 Lead Author’s Financial Disclosures: None. 2497 and diabetes with individuals averaging TGs ,150 mg/dl, 2553 2498 (31 male) (Table 1). Using semi-automated plaque analysis Study Funding: None. 2554 2499 software, we quantified coronary plaque (total, calcified, Background/Synopsis: The impact of triglyceride 2555 2500 non-calcified including fibrous, fibrous-fatty and low atten- (TG) lowering therapy on cardiovascular (CV) outcomes 2556 2501 uation plaque) volume on their CCTAs. Median levels remains unclear. 2557 2502 between the cohorts normalized coronary plaque and lipids Objective/Purpose: To investigate the effects of TG 2558 2503 (HDL and TGs) were tested via the Wilcoxon Rank Sum modifiers on CV disease. 2559 2504 test, whereas mean LDL, age and BMI were analyzed by Methods: 30 randomized trials having $200 patients 2560 2505 independent t tests. Risk factor differences (DM, HTN, with $6-month follow-up period were selected using 2561 2506 smoking, family history of CAD) between the cohorts were PubMed/Medline, EMBASE and the CENTRAL (Incep- 2562 2507 assessed with Chi-square. tion- 30 May 2018) comparing TG modifiers [fibrates, 2563 2508 Results: Patients with high TGs had more low attenuation niacin or omega-3 fatty acids (Ʊ-3)] with the control group. 2564 2509 plaque (LAP) volume when compared to the patients with Outcomes were major adverse cardiovascular events 2565 2510 normal TGs [13.8 +/- 57.1 mm3 v/s 1.9 +/- 45.4 mm3 (p (MACE) [composite of myocardial infarction (MI), stroke, 2566 value 0.02)]. (Table 2). CV mortality and coronary revascularization (CR)], its

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2567 components and all-cause mortality. These were reported as other rare APOE mutations usually associated with other 2623 2568 relative risk (RR) with 95 % confidence interval (CI) using conditions, including diabetes mellitus and/or familial 2624 2569 random effects model. combined hyperlipidemia. The disease may be associated 2625 2570 Results: In analysis of 140,529 patients with mean with premature cardiovascular disease, as well as tuber- 2626 2571 follow-up of 46 6 19.8 months, TG-modifiers significantly oeruptive and palmar xanthomas. 2627 2572 reduced MACE (RR: 0.92; 95 % CI, 0.89-0.96; P,0.001), Objective/Purpose: Our goal was to fully evaluate a 2628 2573 CV mortality (RR: 0.94; 95 % CI, 0.89-0.98; P50.008), MI patient presenting with severe hypertriglyceridemia, 2629 2574 (RR: 0.86; 95% CI, 0.80-0.92; P,0.001) and CR (RR: pancreatitis, diabetes, and plantar xanthomas. 2630 2575 2631 0.94; 95% CI, 0.91-0.98; P50.005) but had neutral effect Methods: A careful history, physical examination, lipid 2576 2632 on stroke (RR: 1.02; 95% CI, 0.93-1.12; P50.64) and all- and lipoprotein testing, standard clinical chemistry, and 2577 2633 cause mortality (RR: 0.99; 95% CI, 0.95-1.04; P50.78). lipase and amylase measurements were performed. 2578 2634 Subgroup analysis revealed significantly lower MACE, CV Computed tomography scans of the abdomen and pelvis 2579 2635 mortality and MI rates limited to studies without back- were used to confirm the diagnosis of pancreatitis. APOE 2580 2636 ground statin therapy. Significant reduction of MACE and genotyping was carried out at Boston Heart Diagnostics in 2581 2637 MI was derived mostly from fibrates while CV mortality Framingham, MA, and next generation DNA sequencing 2582 2638 was limited to Ʊ-3 use. Moment of meta regression ana- was performed at the LPL, APOC2, APOA5, LMF1, 2583 2639 lyses demonstrated significantly decreased MI and CR GPIHBP1, GCKR, CREB3L3, GPD1, APOE, and 2584 2640 associated with absolute reduction (mmol/L) of LDL-C; APOC3 gene loci as well as other genes associated with 2585 2641 however no beneficial effect was noted by absolute reduc- lipid disorders, including LDLR, APOB, and PCSK9, on 2586 2642 tion of triglycerides or absolute increase of HDL-C. the Illumina MiSeq platform at the Robarts Research 2587 2643 Conclusions: TG modifiers significantly reduced Institute at the University of Western Ontario, Canada. 2588 2644 MACE, CV mortality and MI in the absence of concurrent 2589 Results: A 56-year-old obese Caucasian woman pre- 2645 statin therapy. 2590 sented with pancreatitis, marked hypertriglyceridemia, and 2646 2591 uncontrolled diabetes mellitus. She has a history of mild 2647 2592 carotid disease, abdominal aorta non-obstructive athero- 2648 2593 sclerotic disease, and subclavian and coronary artery 2649 2594 calcifications. She was noted to have right Achilles tendon 2650 2595 xanthomas and multiple large chronic non-tender non- 2651 2596 pruritic bilateral plantar xanthomas on the soles of her 2652 2597 feet with no palmar or tuberoeruptive xanthomas. Her non- 2653 . 2598 fasting lipids in mg/dL were: triglycerides (TG) 1575 and 2654 . 2599 total cholesterol (TC) 650. Fasting lipid and apolipopro- 2655 2600 tein (apo) levels in mg/dL were: TG 1273, TC 493, direct 2656 2601 low-density lipoprotein cholesterol (LDL-C) 210, high- 2657 2602 density lipoprotein cholesterol (HDL-C) 36, apoB 224, and 2658 2603 lipoprotein (a) 8. She was managed with intravenous fluids 2659 2604 and insulin, and was subsequently placed on fish oil, 2660 2605 fenofibrate, atorvastatin, ezetimibe, and pioglitazone, along 2661 2606 with a low-fat, low-sugar diet. Her follow-up fasting lipid 2662 2607 values in mg/dL were: TG 509, TC 216, direct LDL-C 66, 2663 2608 HDL-C 48, and apoB 134. She had the APOE E3/3 2664 2609 Figure 1 Forest plot comparing Triglyceride (TG) modifiers for genotype, and was heterozygous for the APOE missense 2665 2610 major adverse cardiovascular outcomes (MACE). 2666 2611 308 2667 2612 Severe Combined Hyperlipidemia, 2668 2613 Heterozygous APOE p.V254E, Pancreatitis, 2669 2614 Diabetes Mellitus, and Plantar Xanthomas* 2670 2615 2671 2616 Brian Cheung, MD, Barry Tedder, MD, FACC, 2672 2617 Ernst Schaefer, MD, FNLA, 2673 2618 Robert Hegele, MD, (Jonesboro, AR) 2674 2619 2675 2620 Lead Author’s Financial Disclosures: None. 2676 2621 Study Funding: Dyslipidemia Foundation. 2677 2622 Background/Synopsis: Severe combined hyperlipid- 2678 emia is a condition caused by the APOE E2/2 genotype or Plantar Xanthomas on Left Foot:

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2679 lipolysis, leading to severe hypertriglyceridemia and high- 2735 2680 risk of pancreatitis. Data on postprandial dietary fatty acid 2736 2681 (FA) metabolism are however limited in this population. 2737 2682 Objective/Purpose: To compare postprandial meta- 2738 2683 bolism among FCS patients, healthy controls and subjects 2739 2684 with multifactorial chylomicronemia (MCM). 2740 2685 2741 Methods: Twenty-one patients with FCS (11 women/10 2686 2742 men) aged 55 [43-60] (median [IQR]) with a body mass 2687 2743 index (BMI) of 23.4 [21.6-25.5] kg/m2) underwent a low- 2688 2744 fat (13g) liquid meal test labeled with 3H-palmitate and 2689 2745 were compared to 32 healthy controls (18 women/14 men) 2690 2746 aged 47 [33-55] with a BMI of 25.9 [24.9-27.6] kg/m2 and 2691 2747 to 12 MCM subjects (4 women/8 men) aged 58 [50-62] 2692 2748 with a BMI of 32.5 [29.2-34.2] who underwent a high-fat 2693 2749 (100g) liquid meal test with either 3H- or 13C-palmitate 2694 Plantar Xanthomas on Right Foot: 2750 labeling. A subset of participants simultaneously underwent 2695 2751 intravenous infusion of d5-glycerol (9 FCS, 21 controls, 11 2696 2752 MCM) or d2-palmitate (7 FCS, 19 controls, 10 MCM) to 2697 2753 measure plasma glycerol and nonesterified FA appearance 2698 2754 rates and dietary FA spillover. 2699 2755 2700 Results: Fasting plasma glucose levels and postprandial 2756 2701 glucose area under the curve (AUC) were higher in FCS 2757 , 2702 than in controls (P 0.05), but similar to MCM whereas 2758 2703 plasma fasting insulin levels and postprandial insulin AUC 2759 2704 in FCS were similar to levels in controls, but lower than in 2760 , 2705 MCM (P 0.05). Fasting plasma TG levels were higher in 2761 2706 FCS (23.50 [12.71-29.95]) than in controls (0.67 [0.50- 2762 , 2707 1.11] ) and MCM (2.42 [1.69-4.62] (P 0.05). Plasma TG 2763 2708 AUC was 22 and 7-fold higher in FCS than in controls and 2764 , 2709 MCM, respectively (P 0.05). Chylomicron tracer activity 2765 2710 AUC was also much higher in FCS (% ingested dose.360- 2766 Achilles Tendon Xanthomas on Right Foot: 5 , 2711 min 62 [40-115]) than in controls (17 [11-32], P 0.05) 2767 5 2712 mutation p.V254E, with a normal polygenic triglyceride and MCM (22 [5-76], P NS). Plasma glycerol appear- 2768 2713 risk score. ance rate AUC, a marker of total TG lipolysis, was almost 3 2769 2714 Conclusions: This case illustrates the interplay of and 4-fold lower in FCS than in controls and MCM, 2770 , 2715 obesity, diabetes, and a rare APOE mutation (p.V245E) in respectively (P 0.05) while plasma palmitate appearance 2771 2716 causing severe combined hyperlipidemia, pancreatitis, and rate was similar in all groups. Dietary FA spillover rate was 2772 2717 extensive plantar xanthomas. This patient responded well to almost 4-fold higher in FCS than in controls (4.3 [1.5-7.5] 2773 , 2718 lifestyle and medication therapy. vs. 1.0 [0.8-1.3] % ingested dose.360min) (P 0.05) but 2774 2719 similar to MCM (5.0 [1.5-7.4]). 2775 FCS is characterized by increased dietary 2720 338 Conclusions: 2776 FA spillover despite profound impairment in LPL-mediated 2721 Familial Chylomicronemia Syndrome is 2777 chylomicron lipolysis, suggestive of impaired adipose 2722 associated with increased dietary fatty acid 2778 tissue dietary FA storage. More studies are needed to 2723 spillover in the circulation despite lower total 2779 determine the mechanisms of this pathophysiological 2724 postprandial triglycerides 2780 2725 feature of FCS. 2781 2726 Andre C. Carpentier, MD, Frederique Frisch, MSc, 2782 355 2727 Diane Brisson, PhD, 2783 2728 Daniel Gaudet, MD, PhD, (Sherbrooke, QC) Correlation between chylomicronemia 2784 2729 diagnosis scores and post-heparin lipoprotein 2785 2730 Lead Author’s Financial Disclosures: None. lipase activity 2786 2731 Study Funding: IRSC grant (AC MOP 341582). 2787 Etienne Khoury, PhD, 2732 2788 Background/Synopsis: Familial Chylomicronemia Daniel Gaudet, MD, PhD, 2733 2789 Syndrome (FCS) is a rare monogenic autosomal recessive Diane Brisson, PhD, (Saguenay, QC) 2734 disorder characterized by severe reduction of lipoprotein 2790 lipase (LPL)-mediated triglyceride (TG)-rich lipoprotein Lead Author’s Financial Disclosures: None.

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2791 Study Funding: None. with LPL deficiency (LPLD, omim: 238600) or familial 2847 2792 2848 Background/Synopsis: Chylomicronemia (CM) is chylomicronemia syndrome (FCS), a rare autosomal reces- 2793 2849 associated with plasma accumulation of chylomicrons and sive disease, sustainably present TG levels above 1,000 mg/ 2794 2850 is characterized by severe hypertriglyceridemia (triglycer- dl (chylomicronemia) due to genetically acquired very low 2795 2851 ide (TG) . 1000 mg/dl). CM phenotype is due to LPL activity. Most patients with chylomicronemia do not 2796 2852 functional or genetic defects in lipoprotein lipase (LPL) have FCS however and present secondary or multifactorial 2797 2853 mediated TG-rich lipoproteins lipolysis. Familial chylomi- chylomicronemia (MCM). Although FCS and MCM are 2798 2854 cronemia syndrome (FCS) is a rare autosomal recessive both characterized by chylomicronemia, they importantly 2799 2855 form of CM caused by null loss-of-function variants in LPL differ in term of risk, comorbidities and disease manage- 2800 2856 or LPL-related genes. Post-heparin LPL activity is impor- ment. Compared to FCS, patients with MCM have higher 2801 2857 tantly reduced in FCS (, 20% of normal). Most individuals and highly fluctuating LPL activity. Measuring LPL 2802 2858 with CM are not affected by FCS however and present activity is not clinically simple since it is based on 2803 2859 multifactorial CM (MCM), in which plasma LPL activity complex, expensive and time- consuming post-heparin 2804 2860 levels are higher and more variable than in FCS. FCS and methods. Plasma glycerol appearance rate (as assessed by 2805 2861 MCM importantly differ in terms of risk of disease, using d5-glycerol labeled tracer) and free glycerol plasma 2806 2862 comorbidities and clinical management. Different scoring concentrations are markers of TG hydrolysis and are both 2807 2863 systems were proposed to help clinicians to accurately significantly lower in FCS than in MCM. 2808 2864 distinguish FCS and MCM. Objective/Purpose: This study aimed to estimate the 2809 relation between post-heparin plasma LPL activity and 2865 2810 Objective/Purpose: The aim of this study was to 2866 assess the relation between plasma post-heparin LPL plasma free glycerol levels in subjects with 2811 chylomicronemia. 2867 2812 activity and two CM diagnosis scoring systems: an Euro- 2868 Methods: This study was performed in a sample of 25 2813 pean score and a Canadian score which includes surrogate 2869 subjects with chylomicronemia. Post-heparin plasma LPL 2814 markers of TG hydrolysis. 2870 activity was measured using 2 different colorimetric assays 2815 Methods: Post-heparin plasma LPL activity was 2871 and glycerol with an enzymatic method. Analyses were 2816 measured using colorimetric assay among a sample of 29 2872 performed by using Spearman’s rank correlation tests. 2817 subjects with chylomicronemia (21 FCS and 8 MCM). 2873 2818 Spearman’s rank correlation and Mann-Withney U test Results: Post-heparin LPL activity (median and inter- 2874 2819 were used. quartile range) was significantly lower in FCS (0% [0-6.6]) 2875 , 2820 Results: There was a significant (p,0.001) difference in than in MCM (89.4% [80.6-103.4]) (p 0.001). There was 2876 2821 post-heparin LPL activity (median and interquartile ranges) a significant correlation between post-heparin LPL activity 2877 2822 between FCS (0% [0-6.6]) and MCM (83.2% [69.1-92.3]). and free glycerol levels, whatever the method used 2878 5 5 5 5 2823 Both the European (rs5-0.55, p50.002) and the Canadian (rs 0.67, p 0.03; rs 0.41 p 0.05). Adding plasma 2879 2824 (rs5-0.64, p,0.001) scoring systems showed good corre- apolipoprotein (apo) B levels, anthropometrics and other 2880 2825 lations with post-heparin LPL activity. covariates to the model further increase the relation, as 2881 suggested by the correlation observed between LPL activity 2826 Conclusions: Although these results were obtained 2882 and apoB (rs50.56, p50.01) or the body mass index 2827 among a small sample, they suggest that both the European 2883 (rs50.47, p50.03). 2828 and the Canadian diagnosis scoring systems fairly correlate 2884 2829 with post-heparin plasma LPL activity and may contribute Conclusions: These results suggest that free glycerol, the 2885 2830 to adequately distinguish between FCS and MCM. end-product of TG hydrolysis, used alone or in association 2886 2831 with other covariates, could represent a useful, low cost and 2887 2832 easily available surrogate of post-heparin LPL activity 2888 2833 359 measurement and may clinically contribute to differentiate 2889 2834 Free glycerol correlate with post-heparin FCS from MCM. 2890 2835 lipoprotein lipase activity and contribute to 2891 2836 differentiate familial vs. multifactorial 2892 2837 chylomicronemia 364 2893 2838 Lipase Maturation Factor 1 Contributes to ER 2894 2839 Diane Brisson, PhD, Redox Homeostasis† 2895 2840 Etienne Khoury, PhD, 2896 2841 Daniel Gaudet, MD, PhD, (Saguenay, Quebec) Saskia Neher, PhD, (Chapel Hill, NC) 2897 2842 2898 2843 Lead Author’s Financial Disclosures: None. Lead Author’s Financial Disclosures: None. 2899 2844 Study Funding: None. Study Funding: American Heart Association and Na- 2900 2845 Background/Synopsis: Lipoprotein lipase (LPL) is a tional Lipid Association. 2901 2846 key enzyme of triglyceride (TG) hydrolysis in TG-rich Background/Synopsis: Lipoprotein lipase (LPL) is a 2902 lipoproteins, namely chylomicrons and VLDLs. Patients secreted lipase that clears triglycerides from circulating

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2903 lipoproteins. Correct LPL folding and subsequent exit from Methods: 72 subjects of the prospective, double-blind 2959 2904 the endoplasmic reticulum (ER) require lipase maturation randomized multicenter EVAPORATE (Effect of Vascepa 2960 2905 factor 1 (LMF1). LMF1 is an ER-resident transmembrane on Improving Coronary Atherosclerosis in people with 2961 2906 protein, but the mechanism by which it promotes LPL High Triglycerides Taking Statin Therapy) trial underwent 2962 2907 folding is unknown. baseline Coronary Computed Tomography Angiography 2963 2908 Objective/Purpose: We aim to uncover how LMF1 (CCTA). CCTA was evaluated using a modified 17-segment 2964 2909 promotes LPL folding and secretion. American Heart Association coronary tree model. Coronary 2965 2910 2966 Methods: We used proteomics, molecular biology and Artery Calcium (CAC) Score, Total Plaque Severity (TPS: 2911 2967 microscopy to determine how LMF1 functions. total amount of plaque in segment), Total Non-Calcified 2912 2968 Results: We identified LMF1-binding partners necessary Plaque Score (TNPS) and Segment Involvement Score 2913 (SIS: total number of segments with plaque) were inter- 2969 2914 for LPL secretion and found partners including oxidore- 2970 ductases and lectin chaperones. These results suggest that preted by expert readers. Triglycerides, LDL-C and HDL-C 2915 were analyzed for association with semi-quantitative plaque 2971 2916 LMF1 enables the formation of LPL’s five disulfide bonds. 2972 In agreement with this hypothesis, we found that, in LMF1- scores using multivariable regression analysis, after adjust- 2917 ing for confounding variables. 2973 2918 deficient cells, LPL is aggregated due to the formation of 2974 Results: The average age and body mass index were 56.3 2919 incorrect intermolecular disulfide bonds. We also found that 2975 + 8.6 years and 33.4 + 6.8 kg/m2, respectively. 41 (56.9%) 2920 loss of LMF1 results in a more oxidized ER. Additionally, 2976 of the participants were male. In a population of patients 2921 we found that LMF1 does more than simply folding lipases. 2977 with elevated triglycerides, low HDL-C was independently 2922 We identified novel LMF1 clients including fibronectin and 2978 associated with increased CAC (p50.024), and trends for 2923 the low-density lipoprotein receptor (LDLR). Both contain 2979 both low HDL-C and non-calcified plaque (p50.06) as well 2924 multiple, non-sequential disulfide bonds. 2980 as higher triglycerides and non-calcified plaque (p50.072) 2925 Conclusions: We conclude that LMF1 contributes to 2981 were noted. 2926 redox homeostasis in the ER and is needed for secretion of 2982 2927 some ER client proteins that require reduction of non- Conclusions: Patients with low HDL-C levels had higher 2983 2928 native disulfides during their folding. CAC scores after adjustment for age, gender, BMI, 2984 2929 diabetes, hypertension, current smoking and family history 2985 of CAD. As higher CAC scores are associated with greater 2930 Imaging in Atherosclerosis 2986 2931 risk of coronary events, these findings show that low HDL- 2987 C is an independent risk factor for coronary artery disease 2932 265 2988 in persons with high triglycerides. 2933 Relationship between Lipid Levels and 2989 2934 Coronary Atherosclerotic Plaque Scores by 2990 2935 Coronary Computed Tomography Angiography 2991 2936 (CTA) in Subjects with Elevated Triglycerides Table 1 Baseline Characteristics in Patients with High 2992 2937 Triglycerides 2993 2938 Alice Lee, April Kinninger, MPH, Subjects at Baseline 2994 2939 Eranthi Jayawardena, BS, Chandana Shekar, MD, (n572) 2995 2940 Lavanya Cherukuri, MD, Christopher Dailing, BS, 2996 Baseline Demographics 2941 Sajad Hamal, MS, Ferdinand Flores, BS, 2997 2942 Matthew Budoff, MD, John Nelson, MD, (Torrance, CA) Age (years)* 56.3 6 8.6 2998 2943 Male Gender (%) 41 (56.9) 2999 2 6 2944 Lead Author’s Financial Disclosures: None. BMI (kg/ m )* 33.4 6.8 3000 2945 Study Funding: Amarin Pharma, Inc. Diabetes (%) 52 (74.3) 3001 Hypertension (%) 52 (73.2) 2946 Background/Synopsis: We studied a population of 3002 Current Smoker (%) 2 (2.8) patients undergoing coronary CT angiography for assess- 2947 Family History of CAD (%) 28 (40.6) 3003 2948 ment of plaque progression in a double blind randomized Lipid Levels (mg/dL)* 3004 2949 trial – EVAPORATE. We evaluated factors that were HDL Cholesterol 38.6 6 10.6 3005 2950 associated with increased plaque burden in patients with LDL Cholesterol 97.4 6 44.1 3006 2951 elevated triglycerides at baseline. We did find an associa- Triglycerides 261.4 6 72.6 3007 2952 tion between low HDL cholesterol levels and increased Semi-quantitative Plaque Scores* 3008 2953 atherosclerosis. Therefore, HDL cholesterol levels should TNPS 4.6 6 3.9 3009 2954 be considered when assessing coronary artery disease risk Total CAC Score 370.4 6 585.4 3010 6 2955 in persons with elevated triglycerides. TPS 6.6 5.1 3011 2956 Objective/Purpose: To investigate the association be- HDL 5 high density lipoprotein, LDL 5 low density lipoprotein, 3012 2957 TNPS 5 total non-calcified plaque score, CAC 5 coronary artery 3013 tween low density lipoprotein cholesterol (LDL-C), high 5 2958 calcium, TPS total plaque severity 3014 density lipoprotein cholesterol (HDL-C) and triglycerides *Indicates any data reported as mean 6 SD and coronary plaque prevalence.

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3015 271 Conclusions: The ELC is acquired and appears most 3071 3016 For Whom The Lobe Folded.....When? commonly in the 4th decade. Once present, the crease 3072 3017 remains and becomes more prominent with time. This 3073 3018 Robert Charles Lichtenberg, MD, study does not attempt to assess the association with 3074 3019 Jyothsna Bandaru, MD, (Berwyn, IL) coronary atherosclerosis or the cause but rather answers 3075 3020 3076 Lead Author’s Financial Disclosures: None. the clinical question: 3021 For Whom The Lobe Folded.....When? 3077 3022 Study Funding: None. 3078 3023 Background/Synopsis: The diagonal ear lobe crease 3079 3024 (ELC), first describe by Frank in 1973 (1) has been 3080 3025 suggested to be an easily detectable sign of atherosclerosis 283 3081 3026 by several studies (2-5). As recent as 2015 the diagonal Association between Lipids and Coronary 3082 3027 bilateral ELC was independently associated with cardio- Atherosclerotic Plaque Characteristics 3083 3028 vascular events comprising not only coronary but also 3084 Lavanya Cherukuri, MD, Chandana Shekar, MD, 3029 cerebrovascular and vascular disease. Others have said it is 3085 April Kinninger, MPH, Divya Birudaraju, MD, 3030 simply a sign of aging (6). A post-mortem analysis of 376 3086 Eranthi Jayawardena, Sajad Hamal, MS, 3031 patients with an average age of 70 years demonstrated a 3087 Ferdinand Flores, BSN, John Tayek, MD, Sion Roy, MD, 3032 strong association with coronary atherosclerosis(7). What is 3088 Matthew Budoff, MD, John Nelson, MD, (Torrance, CA) 3033 not known is for those whom the lobe folded...... when? 3089 3034 Objective/Purpose: This study investigated the onset Lead Author’s Financial Disclosures: None. 3090 3035 of the ELC in patients being followed in a community Study Funding: None. 3091 3036 3092 based Cardiology clinic who have at least one ELC. High Triglycerides (TGs) and 3037 Background/Synopsis: 3093 Methods: Patients seen in a single cardiologist office with low High-Density Lipoprotein Cholesterol (HDL-C) are 3038 3094 Coronary Artery Disease who had single or bilateral ELC associated with increased insulin resistance, hypertension, 3039 3095 were asked to provide photographs going back to at least and obesity. HDL-C, in turn, has a cardioprotective effect 3040 3096 age 10 years, with one photo/ decade that showed their ears because of its role in reverse cholesterol transport, endo- 3041 3097 well enough to determine the presence of a diagonal ELC. thelial cell function, and its antioxidant activity. Therefore, 3042 3098 Between 2004 and 2017, 205 submitted at least one patients with low HDL-C and high TGs are at higher risk 3043 3099 photograph but only 68 patients submitted adequate for coronary artery disease (CAD) and adverse cardiac 3044 3100 photographs to be able to detect the ELC and its decade events. 3045 of onset. These 68 patients form the basis of this report. 3101 3046 Objective/Purpose: We investigated the relationship 3102 Results: The 68 patients included 58 male (85%) with an 3047 between atherosclerotic plaque burden and lipids levels in 3103 age range of 37-74. The table below reports the number per 3048 patients with hypertriglyceridemia and low HDL-C. 3104 decade at which time at least one ELC was detected. 3049 Methods: 70 individuals (37 men) with hypertriglycer- 3105 3050 Decade 1st 2nd 3rd 4th 5th 6th idemia (TGs .200mg/dl), enrolled in the EVAPORATE 3106 3051 Number with first ELC 0 0 4 46 14 4 (Effect of Vascepa on Improving Coronary Atherosclerosis 3107 3052 Percent of Total 6% 68% 20% 6% in people with High Triglycerides Taking Statin Therapy) 3108 3053 The photo depicts a typical diagonal ELC and gives an trial and undergoing Cardiac Computed Tomography Angi- 3109 3054 example of submitted photographs. ography (CCTA) at our center were identified (Table 1). 3110 3055 Using semi-automated plaque analysis software, we 3111 3056 measured coronary plaque (total, calcified, non-calcified 3112 3057 including fibrous, fibrous-fatty and low attenuation plaque) 3113 3058 volume on the CCTA. Univariate regression analysis was 3114 3059 used to measure the linear relationship between log-trans- 3115 3060 formed normalized plaque type and burden and lipid metrics. 3116 3061 Results: Increasing HDL levels were linearly associated 3117 3062 with decreasing normalized fibrous, total non-calcified, and 3118 3063 total plaque volumes. A 1mg/dl increase in HDL resulted in 3119 3064 a 4% decrease in normalized fibrous plaque and a 3% 3120 3065 decrease in total non-calcified, and total plaque volumes. 3121 3066 Increasing Non-HDL levels were also linearly associated 3122 3067 with decreasing normalized fibrous plaque volumes. A 3123 3068 1mg/dl increase in non-HDL resulted in a 1% decrease in 3124 3069 normalized fibrous plaque volume. No significant associa- 3125 3070 Top: Serial photos per decade from single patient Bottom: tion was found between triglycerides and coronary plaque. 3126 Example of Ear lob crease (Tables 2 and 3).

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3127 in preventing coronary artery disease. Further studies to 3183 Table 1 Demographics of the individuals enrolled 3128 investigate the association of these lipids and lipid lowering 3184 3129 Baseline Characteristics Mean 6 SD (n570) therapies on coronary plaque progression are also 3185 3130 3186 Age (years)* 56.31 6 8.3 warranted. 3131 Male Gender (%) 37.00 3187 3132 BMI (kg/m2)* 33.7 6 6.6 3188 3133 Diabetes (%) 49.00 Lipid Management Best Practices 3189 3134 Hypertension (%) 52.00 3190 3135 Current Smoker (%) 1.00 3191 3136 Family History of CAD (%) 19.00 258 3192 3137 HDL Cholesterol (mg/dL) 38.5 6 9.4 3193 6 The Role of Niacin in the Management of 3138 LDL Cholesterol (mg/dL) 95.6 43.8 † 3194 6 Dyslipidemia 3139 Triglycerides (mg/dL) 262.4 74.2 3195 Non-HDL Cholesterol (mg/dL) 142.46 43.6 3140 Joseph M. Keenan, MD, (Jordan, MN) 3196 3141 3197 3142 Lead Author’s Financial Disclosures: None. 3198 Table 2 Normalized Quantitative Plaque Volume 3143 Study Funding: Innovite Corporation, Lonza Corpora- 3199 3144 Type of Plaque Mean 6 SD (mm3) tion, Upsher-Smith corporation, NIH (NHLBI), Quaker 3200 3145 Normalized Total Dense Calcified Plaque 106.1 6 135.0 Oats Corporation. 3201 3146 Normalized Total Fibrous Fatty Plaque 36.8 6 52.1 Background/Synopsis: This presentation will briefly 3202 3147 Normalized Total Fibrous Plaque 154.1 6 195.5 review Niacin (NA) research literature and specifically 3203 3148 Normalized Total Low Attenuation Plaque 23.0 6 48.3 review 4 RCTs (JMK is PI) using wax-matrix extended- 3204 3149 Normalized Total Non Calcified Plaque 213.9 6 271.8 release NA(WMER) to underscore the importance of the 3205 3150 Normalized Total Plaque 320 6 369.6 NA as both a primary agent and ‘‘add on’’ agent in the 3206 3151 global management of CVD. 3207 3152 Objective/Purpose: The latest ‘‘Cholesterol Manage- 3208 3153 3209 Conclusions: As low HDL-C and high non-HDL are ment Guidelines’’ endorsed by 12 national organizations 3154 3210 associated with non-calcified plaque, screening and optimal literally ‘‘dumped’’ NA as a lipid agent, stating it has 3155 3211 medical therapy targeted towards these lipids are important only a limited role in hypertriglyceridemia. This appears 3156 3212 3157 3213 3158 3214 3159 Table 3 Univariate regression analysis 3215 3160 Plaque Type *Log Adjusted Lipid b sd p value 3216 3161 3217 Normalized Total Dense Calified Volume HDL Cholesterol (0.035) 0.02 0.159 3162 3218 LDL Cholesterol (0.001) 0.01 0.823 3163 Triglycerides (0.002) 0.00 0.570 3219 3164 Non-HDL Cholesterol (0.003) 0.01 0.537 3220 3165 Normalized Total Fibrous Fatty Volume HDL Cholesterol (0.031) 0.02 0.107 3221 3166 LDL Cholesterol (0.002) 0.00 0.712 3222 3167 Triglycerides (0.001) 0.00 0.595 3223 3168 Non-HDL Cholesterol (0.002) 0.00 0.570 3224 3169 Normalized Total Fibrous Volume HDL Cholesterol (0.036) 0.02 0.023 3225 3170 LDL Cholesterol (0.006) 0.00 0.096 3226 3171 Triglycerides (0.002) 0.00 0.384 3227 3172 Non-HDL Cholesterol (0.007) 0.00 0.045 3228 Normalized Total Low Attenuation Volume HDL Cholesterol (0.022) 0.02 0.348 3173 3229 LDL Cholesterol (0.003) 0.00 0.53 3174 Triglycerides (0.001) 0.00 0.705 3230 3175 Non-HDL Cholesterol (0.002) 0.01 0.649 3231 3176 Normalized TNCP Volume HDL Cholesterol (0.032) 0.02 0.039 3232 3177 LDL Cholesterol (0.004) 0.00 0.229 3233 3178 Triglycerides (0.002) 0.00 0.418 3234 3179 Non-HDL Cholesterol (0.005) 0.00 0.133 3235 3180 Normalized Total Plaque Volume HDL Cholesterol (0.036) 0.02 0.025 3236 3181 LDL Cholesterol (0.004) 0.00 0.201 3237 3182 Triglycerides (0.002) 0.00 0.457 3238 Non-HDL Cholesterol (0.006) 0.00 0.106

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3239 to be a significant oversight in the ‘‘Guideline’s’’ Study Funding: Research reported in this publication 3295 3240 recommendations of best practices’’. was supported by the National Heart, Lung, and Blood 3296 3241 Methods: NA was the first single agent to demonstrate Institute of the National Institutes of Health under Award 3297 3242 significant reduction in CVD events and mortality. It has Number K12HL137942. 3298 3243 3299 been shown in multiple studies, both alone and in combi- Background/Synopsis: Individuals with familial hy- 3244 3300 nation (including statins) to be effective in reducing CVD percholesterolemia (FH) are often undiagnosed and under- 3245 3301 events and mortality. NA has the broadest range of lipid/ treated. Cholesterol guidelines recommended aggressive 3246 3302 CVD benefits of any agent available. treatment, but often this is not implemented in practice. 3247 3303 Results: It lowers LDL-C (specifically small, dense Although some strategies to promote the uptake of 3248 3304 LDL-c) up to 26%, raises HDL-C (specifically Apo-A1) guideline-recommended care for non-familial hypercholes- 3249 3305 up to 22%, reduces TG up to 15%, and is the only agent terolemia exist, these strategies for FH are lacking. 3250 3306 that reduces Lp(a) up to 22%. In addition, NA has non- 3251 Objective/Purpose: The purpose of this study is to 3307 lipid benefits that have been shown to reduce reactive 3252 uncover barriers and facilitators to care that individuals 3308 oxygen species that are associated with the oxidation of 3253 with FH experience and organizational stakeholders face 3309 LDL-C, and reduces vascular chemo-attractant particles 3254 when treating individuals with FH. 3310 and Monocyte adhesion protein associated with early 3255 Methods: Semi-structured interviews were conducted 3311 atherosclerosis. The early knock on NA therapy was high 3256 with individuals with FH, defined as having a problem 3312 rate of intolerance (flushing) which has been largely 3257 list diagnosis (ICD 10: E78.01) or a pathogenic or likely 3313 eliminated by WMER (WMER RCTs average 3-4% drop 3258 pathogenic FH variant, and organizational stakeholders 3314 out). More recently, 2 large clinical trials (AIM-HIGH, 3259 involved in the care of individuals with FH. Questions 3315 HPS-2THRIVE) reported disappointing results using 3260 were tailored to each stakeholder group interviewed 3316 polygel NA in combination with a statin and they 3261 regarding barriers and facilitators to caring for FH. Audio 3317 reported a negative conclusion on the NA/statin combi- 3262 recordings of the interviews were transcribed verbatim, 3318 nation. Review of these studies revealed significant 3263 assessed for accuracy, and independently coded by two 3319 design flaws, and cast serious doubt on many of their 3264 reviewers. 3320 conclusions. Another large combination NA/statin RCT 3265 Results: A total of 25 individuals with FH were 3321 done since these flawed studies yielded largely positive 3266 interviewed. Two-thirds were female (18/25) and all were 3322 results. In addition to the broad lipid and non-lipid 3267 white. A majority were . or 5 55 years of age (15/25) and 3323 benefits NA is the least expensive lipid lowering agent 3268 about half (11/25) had a college degree or higher education. 3324 available (about $10/month for WMER, $60/month 3269 Many described only recently learning that their high 3325 generic ezetimibe). 3270 cholesterol was a specific condition called FH. Most 3326 3271 Conclusions: The guidelines focus on LDL-C goals individuals described barriers related to medications, health 3327 3272 clearly makes statins the first choice for most dyslipide- insurance, or the healthcare system; however, a few 3328 3273 mias. However, with 18+% of persons ‘‘statin intolerant’’ reported no barriers to caring for their FH. Other barriers 3329 3274 and an additional percentage of persons having significant experienced by some were related to various personal 3330 3275 residual CVD risk despite statin therapy, NA remains an demands, including medical or financial and caring for 3331 3276 appropriate and cost effective ‘‘add on’’ agent. Further- family members. Individuals mentioned that care teams and 3332 3277 more, for the ‘‘Guidelines’’ to be relevant and useful to the access to resources were important in facilitating their care. 3333 3278 global epidemic of CVD they should offer alternative Nine organizational stakeholders (pharmacists, cardiolo- 3334 3279 recommendations/options for nations or individuals that gists, genetic counselors, primary care provider, and health 3335 3280 can’t afford $37,000 QALY (statins) or $330,000 QALY plan employees) were interviewed; of those, 67% (6/9) 3336 3281 (PCSK9-1). NA is a logical first choice for Metabolic were male and had an average of 7 years in their current 3337 3282 Syndrome and other mixed dyslipidemias with mild LDL-C position. About half (5/9) were directly involved in the care 3338 3283 elevation. of individuals with FH, while the others were indirectly 3339 3284 involved. The majority stated that FH education among 3340 3285 clinicians was lacking, and FH management could be 3341 3286 improved if there was a standard of care across healthcare 3342 3287 277 systems. Another related theme throughout the interviews 3343 3288 Uncovering barriers and facilitators to caring was a desire for FH experts, such as cardiologists and 3344 3289 for familial hypercholesterolemia* pharmacists, to deliver professional development on 3345 3290 optimal care for those with potential and diagnosed FH. 3346 Laney K. Jones, PharmD, MPH, Olivia Schlottmann, BS, 3291 3347 Alanna Rahm, PhD, Terry Seaton, PharmD, Conclusions: Individuals and organizational stake- 3292 3348 Christina Gregor, BS, holders have experienced barriers and facilitators to caring 3293 3349 Amy Sturm, MS, Marc Williams, MD, (Danville, PA) for FH. These barriers and facilitators will be used to 3294 develop implementation strategies to improve the uptake of 3350 Lead Author’s Financial Disclosures: None. guideline-based recommendations in the care of FH.

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3351 295 costs and QALY when added to standard background 3407 3352 An updated cost-effectiveness analysis of therapy (maximally tolerated statin with/without ezeti- 3408 3353 evolocumab therapy for reducing mibe). Incremental costs ranged from $22,228 to $3,411, 3409 3354 cardiovascular events in very high-risk depending on the baseline rate, and QALY gained ranged 3410 3355 patients with atherosclerotic cardiovascular from 0.39 to 0.44. ICER ranged from $56,655 to $7,667 per 3411 3356 disease according to the 2018 ACC/AHA QALY gained; therefore, for any baseline rate in VHR 3412 3357 guideline patients with ASCVD, ICER were below generally 3413 3358 accepted willingness-to-pay thresholds. Moreover, ICER 3414 3359 Gregg C. Fonarow, MD, Ben van Hout, PhD, were below $50,000 per QALY gained for any baseline rate 3415 3360 Guillermo Villa, PhD, $6.9 per 100 patient-years. If background therapy included 3416 3361 Jorge Arellano, MSc, MPhil, maximally tolerated statin with ezetimibe, ICER would 3417 3362 Peter Lindgren, PhD, (Los Angeles, CA) range from $59,331 to $10,584. 3418 3363 3419 Lead Author’s Financial Disclosures: Reports Conclusions: At its current list price, the addition of 3364 evolocumab to standard background therapy demonstrates 3420 3365 consulting for Abbott, Amgen, Bayer, Janssen and 3421 Novartis. high value across a range of CV event rates in VHR patients 3366 with ASCVD. 3422 3367 Study Funding: Amgen. 3423 3368 Background/Synopsis: Based on FOURIER results, 320 3424 3369 Fonarow et al. (2017) evaluated the cost-effectiveness of 3425 Evaluating a population health approach to 3370 evolocumab when added to standard background therapy 3426 statin use: pharmacist driven interventions in 3371 (maximally tolerated statin with/without ezetimibe) in 3427 patients with type 2 diabetes mellitus* 3372 patients with atherosclerotic cardiovascular disease 3428 3373 (ASCVD). In October 2018, a 60% list price reduction Kyle A. Troksa, PharmD, 3429 3374 for evolocumab was announced, aimed at improving value Sarah Billups, PharmD, 3430 3375 and lowering patient copays. Shortly thereafter, the 2018 Joseph Saseen, PharmD, (Aurora, CO) 3431 3376 American College of Cardiology/American Heart Associ- 3432 3377 ation Multisociety Guideline on the Management of Blood Lead Author’s Financial Disclosures: None. 3433 3378 Cholesterol (2018 ACC/AHA guideline) recommended Study Funding: None. 3434 3379 proprotein convertase subtilisin-kexin type (PCSK9) in- Background/Synopsis: In the context of value-based 3435 3380 hibitors in very high-risk (VHR) patients with ASCVD healthcare, a common population health initiative is 3436 3381 whose low-density lipoprotein cholesterol levels remain initiation of statin therapy in patients with type 2 diabetes 3437 3382 $70 mg/dL despite standard background therapy, among mellitus (T2DM). Many studies have shown that pharma- 3438 3383 other patient populations. cist managed services increase statin initiation rates; how- 3439 3384 Objective/Purpose: To present an updated cost-effec- ever, limited data have compared the effectiveness of 3440 3385 tiveness analysis of evolocumab added to standard back- different population health approaches targeting initiation 3441 3386 ground therapy in VHR patients with ASCVD defined of statin therapy. 3442 3387 according to the 2018 ACC/AHA guideline, using the new Objective/Purpose: The purpose of this analysis is to 3443 3388 evolocumab list price. compare statin initiation rates with a population health 3444 3389 3445 Methods: This updated analysis, based on the original initiative among 4 University of Colorado primary care 3390 3446 model by Fonarow et al. (2017), incorporates new data for 2 clinics with embedded clinical pharmacists to 5 clinics with 3391 3447 key parameters: (1) an evolocumab annual list price of non-embedded clinical pharmacists. Primary outcome is the 3392 3448 $5,850 and (2) a baseline cardiovascular (CV) event rate rate of prescribing a statin among patients with T2DM who 3393 3449 (myocardial infarction, ischemic stroke, and CV death) are not on statin therapy after statin therapy was recom- 3394 3450 reflecting the 2018 ACC/AHA guideline definition of VHR. mended by the clinical pharmacist. 3395 The updated baseline rate was modeled by adjusting the 3451 3396 Methods: This retrospective cohort analysis evaluated a 3452 real-world baseline rate from the original analysis, which population health program that identified primary preven- 3397 modeled a mixture of VHR and non-VHR patients with 3453 3398 tion patients with T2DM, age 40-75 years, with LDL-C of 3454 ASCVD, by the rate ratio of VHR to non-VHR patients 70-189 mg/dL with no active statin prescription through 3399 observed in FOURIER. Model outcomes included CV 3455 3400 electronic health record (EHR) registries. One cohort had 3456 events, costs, quality-adjusted life-years (QALY), and embedded clinical pharmacists (interprofessional model 3401 incremental cost-effectiveness ratios (ICER). 3457 3402 within the primary care clinic) while the other had 3458 Results: In FOURIER, VHR patients had approximately 3403 centrally-located clinical pharmacists. Each evaluated pa- 3459 two-fold the baseline rate of non-VHR patients, yielding 3404 tients to determine if statin therapy was indicated. When 3460 plausible baseline rates ranging from 6.4 to 12.3 per 100 3405 indicated, statin therapy was recommended to providers 3461 patient-years for VHR patients with ASCVD in the real 3406 using two approaches: (A) written EHR recommendation 3462 world. Evolocumab was associated with both increased within 7 days prior to an upcoming office visit or (B)

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3463 provision of a list of pre-reviewed patients for whom the Objective/Purpose: To describe US geographic varia- 3519 3464 clinical pharmacist recommended statins. Providers could tions in utilization of lipid lowering therapy (LLT), LDL-C 3520 3465 indicate approval and the pharmacist then performed levels, and the proportion of patients with patients with 3521 3466 telephone outreach to initiate therapy. Pharmacists recom- persistent LDL-C elevations among LLT-treated patients 3522 3467 mended statin therapy in 870 patients between March 1, with atherosclerotic cardiovascular disease (ASCVD). 3523 3468 3524 2018 and November 10, 2018. Based on the a priori sample Methods: This retrospective cohort study used a nation- 3469 3525 size calculation, 136 patients were randomly selected from ally representative healthcare claims database linked to data 3470 3526 each cohort. Data were analyzed using a Chi-square test, from a large national lab-data aggregator to characterize 3471 , 3527 with p-values 0.05 identified as statistically significant. LDL-C levels and LLT use among approximately 23 3472 3528 Results: Statin initiation was 41.9% and 36.8% in the million patients. Patients were indexed to their most recent 3473 3529 embedded and non-embedded cohorts, respectively LDL-C test date during the index-period (01/01/2016 to 06/ 3474 3530 (p50.38). In the embedded cohort, all recommendations 30/2018). The LDL-C levels and current LLT use among 3475 3531 were made using approach A (EHR note prior to office ASCVD patients were assessed at the state level. Direct 3476 3532 visit); whereas, in the non-embedded cohort, 77 recom- standardized rates for patients with elevated LDL-C 3477 3533 mendations were made with approach A and 59 were made ($70mg/dL) despite treatment with LLT (prescription 3478 3534 with approach B (prospective patient panel), with resultant claim within 90 days pre-index) were reported adjusting 3479 3535 statin initiation rates of 41.6% and 30.5% respectively for age and gender estimates from the latest census data 3480 3536 (p50.19). available (2017 Current Population Survey). 3481 3537 Conclusions: This clinical pharmacist population health 3482 Results: There were 4,259,270 ASCVD patients (mean 3538 initiative increased the rate of statin prescribing in eligible 5 5 5 3483 age 69years, males 52.2%, mean LDL-C 93.2 mg/dL) 3539 patents with T2DM. Both embedded and non-embedded 3484 in our study population, with 46.7% patients having atleast 3540 clinical pharmacists models were successful. Population 3485 oneclaim of LLT (90 days pre-index). At the national level 3541 health approaches that target eligible patients for statin 3486 and after standardizing, overall 70.9% patients were found 3542 therapy prior to their next office visit may be more effective $ 3487 to have an elevated LDL-C at 70mg/dL, and 33.9% at 3543 than prospectively evaluating an entire patient panel. $ 3488 100mg/dL respectively; despite receiving LLT. At the 3544 3489 national level, variations in standardized rates of patients 3545 3490 with elevated LDL-C specific to age and gender were also 3546 observed (Table 2). Substantial geographic variation was 3491 327 3547 3492 observed - both in terms of receipt of current LLT and the 3548 Geographic Variation In LDL-C Levels And $ 3493 proportion of patients with elevated LDL-C ( 70mg/dL) 3549 Lipid Lowering Therapy Use In Patients With while under treatment. The proportion of ASCVD patients 3494 Atherosclerotic Cardiovascular Disease 3550 3495 receiving any LLT (90 days pre-index) ranged from 55.9% 3551 in Massachusetts to 67.9% in Vermont. The overall 3496 Seth J. Baum, MD, Sasikiran Nunna, PhD, 3552 standardized rate of patients with elevated LDL-C 3497 Pallavi Rane, PhD, Kiran Philip, MD, 3553 ($70mg/dL) despite LLT treatment ranged from 58.0% 3498 Mohdhar Habib, PhD, 3554 in Colorado to 75.8% in Maine. 3499 Xin Wang, PhD, Rolin Wade, RPh, MS, (Boca Raton, FL) 3555 3500 3556 3501 Lead Author’s Financial Disclosures: S.J. Baum 3557 3502 serves as President of the American Society of Preventive 3558 Cardiology, President of Northridge Heart Associates, Table 1 LDL-C levels among LLT treated patients, US 2016- 3503 2018 3559 3504 President and CMO of Excel Medical Clinical Trials, and 3560 3505 is a Clinical Affiliate Professor in the Department of LDL-C ASCVD Patients (%) 3561 3506 Integrated Medical Sciences at the of Florida Atlantic ,70mg/dL 34.4% 3562 3507 University; serves on scientific advisory boards for Akcea 70-99mg/dL 39.5% 3563 3508 Therapeutics, Amgen Inc., Regeneron, and Sanofi; is a 100-129mg/dL 17.4% 3564 3509 consultant for Akcea Therapeutics, Amgen Inc., Cleveland 130-189mg/dL 7.9% 3565 3510 HeartLab, Inc., Gerson Lehrman Group, Inc., Guidepoint $190mg/dL 0.8% 3566 3511 Global, LLC, Novo Nordisk A/S, Regeneron, and Sanofi; 3567 3512 and is a speaker for Akcea Therapeutics, Amgen Inc., 3568 3513 Aralez Pharmaceuticals Inc., Boehringer Ingelheim, and Table 2 Standardized rates of patients with 3569 LDL-C $70mg/dL despite current LLT 3514 Novo Nordisk A/S. 3570 3515 Study Funding: This study was funded by Amgen Inc. Age (years) Males Females 3571 3516 3572 Background/Synopsis: Hyperlipidemia is a highly 18-44 71.2% 74.2% 3517 prevalent chronic condition in the US, with research 45-64 68.1% 77.1% 3573 3518 showing that only 1 out of every 3 adults with elevated 65+ 57.3% 69.3% 3574 LDL-C has their condition under control.

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3575 Conclusions: The current study highlights the persistent competence on average 20% and 26% respectively 3631 3576 high burden of elevated LDL-C, pervasive underuse of LLT (N51794). Follow-up surveys indicate that the download- 3632 3577 in patients with ASCVD and substantial geographic able animations, posters, and AR tool have aided physician- 3633 3578 variations in the US. The study also highlights the need patient communication. These tools have easily translated 3634 3579 of better lipid management in such patients to reduce their into practice with 80% of responding physicians indicating 3635 3580 cardiovascular risk. the VR/AR improved recall and 83% reporting change to 3636 3581 their practice based on the innovate education (N5204), 3637 3582 leading to a potential benefit for 7,841 CVD patients. This is 3638 349 3583 a 22% gain in reported practice change compared to similar 3639 3584 Technological advancements in CME increase programs MLG conducted without VR/AR the year prior. 3640 knowledge gains and the translation of 3585 Conclusions: The inclusion of innovative technological 3641 education to practice within cardiovascular 3586 tools has provided valued education and resources for 3642 care. 3587 HCPs and patients alike. This innovation positively affects 3643 3588 the management of patients with hypercholesterolemia. 3644 3589 Matthew Frese, MBA, Brooke Hefele, Lauren Welch, MA, 3645 3590 Christina Gallo, Andrew Grzybowski, (New York, NY) 3646 3591 Lead Author’s Financial Disclosures: None. Lipid Management in Special Populations 3647 3592 3648 Study Funding: This activity was supported by an 3593 3649 educational grant from Sanofi and Regeneron. 3594 261 3650 Background/Synopsis: Over the past three years, Med 3595 Severe hypercholesterolemia secondary to 3651 Learning Group (MLG) has incorporated virtual reality and 3596 drug-induced cholestatic liver injury 3652 3597 augmented reality (VR and AR) tools into its educational 3653 3598 platform to further engage learners, enhance comprehen- Diana Vinh Venci, PharmD, Kelly Bartsch, PharmD, 3654 3599 sion, improve recall, and support practice change. These Erica Davidson, PharmD, 3655 3600 tools are also downloadable and re-scripted to help engage Abigail Rabatin, PharmD, 3656 3601 patients. This innovation makes the information ’sticky’ by Michael Milks, MD, (Columbus, OH) 3657 3602 providing clear clinical insights in a concise manner while 3658 Lead Author’s Financial Disclosures: None. 3603 also giving participants clinical practice tools to improve 3659 3604 the care of their patients. Study Funding: None. 3660 3605 In 2018, MLG conducted a variety of educational oppor- Background/Synopsis: Hypercholesterolemia may 3661 3606 tunities inclusive of VR and AR animations on the manifest in cases of cholestatic liver disease or injury. 3662 3607 pathophysiology of hypercholesterolemia and the mecha- Cholestasis may arise from various underlying causes and 3663 3608 nism of action of the latest recommended therapies to may be marked by severely elevated serum LDL-C on 3664 3609 ultimately reduce the risk of CVD. Outcomes from these standard laboratory measures. In cholestasis, apparent 3665 3610 programs demonstrate how this advanced continuing med- LDL-C elevation may be due to production of Lipopro- 3666 3611 ical education (CME) results in greater knowledge gains, tein-X (Lp-X) rather than true excess of LDL or other 3667 3612 practice improvements, and patient engagement. atherogenic lipoproteins. Lp-X has similar density to LDL, 3668 3613 Objective/Purpose: Innovative VR and AR, when resulting in its false identification as LDL on most assays. 3669 3614 appropriately incorporated into CME, can improve cardi- However, Lp-X does not contain apolipoprotein B (apoB) 3670 3615 ologists’ understanding of pathophysiology as well as and is not considered atherogenic. 3671 3616 current and emerging therapies in hypercholesterolemia Objective/Purpose: This case report reviews the pre- 3672 3617 care in order to reduce the risk of CVD. sentation and management of a patient with severe hyper- 3673 3618 Methods: MLG incorporated VR into 2018 CVD educa- cholesterolemia secondary to drug-induced cholestatic liver 3674 3619 tional experiences, and offered participants VR and AR injury and evaluation of suspected Lp-X elevation. 3675 3620 tools to view from their smart device for continuous Methods: A retrospective review was performed of the 3676 3621 learning and to share with their patients to enhance patient patient’s pertinent history and objective testing preceding 3677 3622 engagement. Pre/posttests, electronic surveys, and phone acute hepatic injury and course of care thereafter. 3678 3623 interviews were conducted to assess the value of these A 61 year-old woman with asthma and hypertension was 3679 3624 technologies in not only enhancing HCP knowledge but newly diagnosed with pulmonary aspergillosis. Treatment 3680 3625 also supporting practice change and improving the patient was initiated with a 4-month course of itraconazole, 3681 3626 experience. sulfamethoxazole/trimethoprim, and prednisone. After 3 3682 3627 Results: Over 2,300 participants have viewed MLG’s months of therapy, she presented with marked elevations in 3683 3628 activities. Interspersing VR animations into education hepatic function tests and was admitted for drug induced 3684 3629 helped HCPs visualize how therapies work in a unique liver injury (DILI) in a cholestatic pattern, likely secondary 3685 3630 manner that improved recall and comprehension. From to itraconazole and sulfamethoxazole/trimethoprim; both 3686 pretest to posttest, learners improved knowledge and medications were held. She was re-admitted 2 months later

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3687 for evaluation of hyponatremia to 113-119 mg/dl, found to Survey responses were analyzed to determine common 3743 3688 be pseudohyponatremia secondary to severe hypercholes- barriers to lipid management. 3744 3689 terolemia with total cholesterol .2100 mg/dL, LDL Methods: A multi-section questionnaire was dissemi- 3745 3690 cholesterol .1200 mg/dL (above upper limits of assay). nated to individuals living in central Maine. Targeted 3746 3691 For DILI, ursodiol was initiated and prednisone was distribution efforts at local cultural and educational centers, 3747 3692 continued. Atorvastatin 40 mg and ezetimibe 10 mg daily healthcare organizations, and media outlets were imple- 3748 3693 were initiated for hypercholesterolemia. mented to maximize the representation of Franco-Ameri- 3749 3694 Results: This patient was followed in hepatology and cans. Univariate frequencies and bivariate correlations were 3750 3695 lipid clinics for management of hepatic injury and hyper- conducted to assess model components and determine 3751 3696 cholesterolemia. Serum cholesterol improved with progres- relationships between clinical indicators, health beliefs, 3752 3697 sive resolution of DILI. Patient’s baseline ASCVD 10-year and barriers to care. 3753 3698 3754 risk was 4%, on-treatment LDL was 54 mg/dL, apoB 95 Results: Approximately 83% (n 5 170) of survey 3699 3755 mg/dL, and she had no other ASCVD risk factors or evident respondents were Franco-American or French-Canadian. 3700 3756 subclinical atherosclerotic disease on available imaging. In the total respondent cohort, 70% were female, and 51% 3701 3757 Thus, ezetimibe was discontinued and coronary artery were 65 years of age or older. Approximately 43% of 3702 3758 calcium scoring was recommended to guide the decision individuals reported having high cholesterol, while nearly 3703 3759 whether to discontinue atorvastatin, per the patient’s 70% indicated a family history of cardiovascular disease. 3704 3760 preference. Less than 9% of respondents expressed a personal FH 3705 3761 Conclusions: This patient’s lipid panel trend follows the diagnosis, and 10% reported experiencing a heart attack or 3706 3762 course and resolution of hepatic injury. Initial severe stroke. We observed that affective barriers to lipid man- 3707 3763 cholesterol elevation was inconsistent with historic baseline agement, (e.g. knowing when to seek help (28%), trust in 3708 3764 and incongruent with measured apoB level. The authors medicine (25%), worry about diagnosis (20%), and fear of 3709 3765 propose that the apparent LDL-C elevation on assay was judgment (13%)) were more frequently reported than 3710 3766 secondary to Lp-X elevation that resolved in parallel to instrumental barriers (e.g. health care costs (18%), time 3711 3767 resolution of hepatic injury. conflicts (15%), and lack of health insurance (12%). 3712 3768 Moreover, we found the combined additive scales of each 3713 3769 barrier category to be significantly correlated with an 3714 269 3770 external health locus of control (p , 0.05). 3715 Abstract Title: Perceived Barriers to Lipid 3771 3716 Management for Suspected Familial Conclusions: Our findings affirm the importance for 3772 3717 Hypercholesterolemia Franco-American clinicians to consider common barriers to lipid manage- 3773 3718 Founder Populations* ment perceived by their patients, including their ability to 3774 3719 proactively seek care, concern over potential diagnoses, and 3775 3720 Reed Mszar, BS, Sara Buscher, fear of resulting judgement. Sustained efforts to increase 3776 3721 Heidi Taylor, PhD, awareness of FH and its treatment strategies, particularly in 3777 3722 Dervilla McCann, MD, MPH, (New Haven, CO) founder populations, can help mitigate the consequences of 3778 3723 these barriers and empower patients to engage in early 3779 Lead Author’s Financial Disclosures: None. 3724 health-promoting behaviors. 3780 3725 Study Funding: None. 3781 3726 Background/Synopsis: Familial hypercholesterolemia 273 3782 3727 (FH) is a common genetic disorder characterized by Familial Chylomicronemia Syndrome: 3783 3728 elevated cholesterol levels and is associated with an Distinguishing the Rare Among the Common 3784 3729 increased risk for developing premature coronary heart in Adults for Appropriate Management† 3785 3730 disease (CHD). Though FH affects all racial and ethnic 3786 3731 groups, the condition is more prevalent among certain Masako Ueda, MD, Frances Burke, MS, RD, 3787 3732 subpopulations, including French-Canadians and Franco- Denis Sviridov, MD, PhD, Maria Escobar, BS, Laura 3788 3733 Americans. Less than 10% of the estimated 1.3 million Walters, BS, Dusanka Lalic, BS, Tracey Sikora, BS, 3789 3734 individuals living with FH in the United States have been Harley Greene, AB, Stephanie DerOhannessian, MS, 3790 3735 diagnosed. These trends not only support the need to Adam McIntyre, BSc, Emil deGoma, MD, 3791 3736 evaluate barriers to effective lipid management, but also Alan Remaley, MD, PhD, Robert Hegele, MD, 3792 3737 to better understand health-related behaviors for at-risk Daniel Rader, MD, 3793 3738 individuals. Richard Dunbar, MD, MSTR, (Philadelphia, PA) 3794 3739 Objective/Purpose: Our study applied components of 3795 None. 3740 the Health Belief Model to the Franco-American FH Lead Author’s Financial Disclosures: 3796 3741 founder population in central Maine. This widely utilized Study Funding: None. 3797 3742 theoretical framework was originally designed to predict Background/Synopsis: Hypertriglyceridemia (HTG) 3798 health-related behaviors and examine disease perceptions. is common, but familial chylomicronemia syndrome (FCS)

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3799 is a very rare cause of severe HTG, associated with volanesorsen, which lowered her TG from 3,447 to 201 3855 3800 pancreatitis, which can be fatal. It is due to impaired mg/dL (w94% reduction) within 90 days which persisted 3856 3801 lipoprotein lipase (LPL) function, commonly caused by bi- for several months. The result seemed to indicate that 3857 3802 allelic LPL loss-of-function mutations. Mutations in the inhibiting the production of APOC3 by ASO could 3858 3803 genes encoding apolipoprotein C-II, apolipoprotein A-V, effectively enhance the residual LPL lipolytic activity and 3859 3804 lipase maturation factor 1, and glycosylphosphatidylinosi- lower TG. 3860 3805 tol-anchored high-density lipoprotein-binding protein are Conclusions: Our case demonstrates the importance of 3861 3806 also causes of FCS. identifying FCS even in adults with HTG for prescribing the 3862 3807 Although FCS generally presents in childhood with acute most appropriate therapy. In particular, the favorable result 3863 3808 pancreatitis and HTG, it should also be considered as a of the clinical trial was promising that novel biologics may 3864 3809 diagnosis in adults with severe HTG. Unlike polygenic become an optional therapy in certain patients with FCS 3865 3810 HTG, dietary fat-restriction is the mainstay of treatment in beyond dietary management in the future. 3866 3811 FCS which is critical in preventing pancreatitis since 3867 3812 traditional medications are ineffective. 3868 3813 Objective/Purpose: We present three siblings, 279 3869 3814 including fraternal twins, whose definitive diagnosis of Case Presentation: A family history of early 3870 3815 FCS in their 50’s prompted changes in dietary recommen- myocardial infarction in a family with 3871 3816 dations that stabilized their clinical picture. We also report elevated lipoprotein(a) 3872 3817 a favorable finding from a clinical trial with a novel 3873 3818 biologic in which the female twin partook. Michael Parker Ayers, MD, 3874 3819 Daniel Soffer, MD, 3875 Methods: The siblings participated in an institutionally 3820 Douglas Jacoby, MD, (Philadelphia, PA) 3876 approved study, investigating the genetic etiology of 3821 3877 dyslipidemia at the University of Pennsylvania, and they 3822 Lead Author’s Financial Disclosures: None. 3878 consented to research genetic testing and allowed us to 3823 Study Funding: None. 3879 obtain their medical information. 3824 Background/Synopsis: Patient XY is 52 year-old 3880 3825 Results: FCS diagnosis in the siblings was confirmed by woman with dyslipidemia and a family history of fatal 3881 . 3826 finding of a homozygous LPL variant, c.617T C, p.V206A, myocardial infarction in her father at 45 years of age. Her 3882 3827 corroborated by reduced LPL activities, and altered molec- four daughters, ranging from 21 to 25 years-old, underwent 3883 3828 ular dynamics that indicated dysfunctional LPL. cardiovascular risk assessment at our lipid clinic. The 3884 3829 The three siblings had suffered from multiple pancreatitis daughters have relatively benign traditional lipid profiles, 3885 3830 episodes, and the twins required multiple hospitalizations with low-density-lipoprotein cholesterol (LDL-C) levels 3886 3831 prior to their visit to our clinic. Their dietary history ranging from 85 to 112 mg/dL (calculated by Friedewald 3887 3832 revealed the use of a low-carbohydrate diet, which was formula). Their advanced lipid testing, however, reveals 3888 3833 inappropriate for FCS, worsened their TG control. A very significant lipoprotein-(a) (Lp(a)) elevations, ranging from 3889 3834 low-fat diet was promptly prescribed and their TG levels 70 to 236 mg/dL (30 mg/dL 5 upper limit of normal 3890 3835 stabilized with a reduction in pancreatitis episodes. [ULN]; 90th to 99.8th percentile). Their carotid intimal 3891 3836 The female twin qualified to enroll in a clinical study for media thickness (IMT) ranged from 0.49 mm to 0.57 mm, 3892 3837 the treatment of HTG, receiving multiple doses of an values in the highest two quartiles. In each daughter, the 3893 3838 experimental APOC3 antisense oligonucleotide (ASO), degree of Lp(a) elevation roughly corresponded to the 3894 3839 extent of carotid intimal medial thickness. 3895 3840 Carotid IMT is an established surrogate marker for 3896 3841 atherosclerosis and a strong independent predictor of 3897 3842 cardiovascular events. Lipoprotein(a) is a cholesterol-rich 3898 3843 lipid particle derived from LDL with apolipoprotein(a) 3899 3844 crosslinked to apopliprotein B (apoB). Clinical epidemio- 3900 3845 logic and genome wide association studies confirm that 3901 3846 Lp(a) is a heritable marker of atherogenicity and arterial 3902 3847 thrombosis. Despite multiple proposed pathogenic mecha- 3903 3848 nisms linking Lp(a) to atherosclerosis and arterial throm- 3904 3849 bosis, it is unknown whether directly targeting (a) 3905 3850 attenuates risk. Statins, traditionally the foundation of 3906 3851 pharmacotherapy for atherosclerosis cardiovascular disease 3907 3852 reduction, do not reduce Lp(a) levels in prospective trial, 3908 3853 and can even cause Lp(a) elevations. Proprotein convertase 3909 3854 subtilisin/kexin type 9 inhibitors (PCSK9i) and niacin 3910 reduce Lp(a) levels by modest amounts, though the APOC3 Graph:

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3911 3967 3912 Table of Results Advanced Lipid Testing and Sub-clinical Atherosclerosis Testing Results 3968 3913 LDL-C j HDL j Tri LDL-P Apo-B 3969 3914 (mg/dL) (mmol/L) (mmol/L) Lp(a) mg/dL Carotid IMT (mm) 3970 3915 Mother in 2006 120 j 79 j 69 1533 149j 0.71 (.75th percentile) without plaques 3971 3916 Mother in 2018 112 j 79 j 69 70 3972 3917 Daughter A 120 j 79 j 69 71 96 0.49 (.50th percentile) without plaques 3973 3918 Daughter B 101 j 97 j 67 943 83 236 0.57 (.75th percentile) without plaques 3974 3919 Daughter C 85 j 111 j 69 885 71 149 0.47 (.50th percentile) without plaques 3975 3920 Daughter D 114 j 87 j 70 70 0.45 (.50th percentile) without plaques 3976 3921 3977 3922 3978 3923 mechanisms are still unknown. A phase III trial is under- socioeconomic backgrounds. Thus, our study evaluated 3979 3924 way with the antisense drug, AKCEA-APO(a)-Lrx, that the demographics of an urban population with respect to the 3980 3925 specifically targets Lp(a) levels. timeliness and appropriateness of initiating statin therapy in 3981 3926 Objective/Purpose: Not applicable. patients with initial LDL greater than 190mg/dL. 3982 3927 Methods: Not applicable. Objective/Purpose: To determine whether demo- 3983 3928 Results: See attached table. graphics such as race and gender impacted intensity of 3984 3929 statin used and time to statin initiation in patients with 3985 Conclusions: Multiple organizations have called for 3930 initial LDL greater than 190mg/dL. 3986 universal and directed screening of Lp(a) levels. The 2018 3931 3987 Cholesterol Guidelines recommend acknowledging high Methods: We performed a single center, retrospective 3932 3988 Lp(a) levels as a risk-enhancing feature for stratification in observational study in a predominantly urban population. 3933 3989 moderate ASCVD risk patients in whom the indication for Patients with initial LDL levels greater than 190mg/dL 3934 3990 use of statins may be uncertain. The European Athero- presenting at The University of Illinois-Chicago Hospital 3935 3991 sclerosis Society (EAS) issued a consensus statement and Clinics between Jan 1, 2013 and Dec 31, 2014 were 3936 3992 calling for screening moderate-high ASCVD risk patients. included. These patients were then evaluated for intensity 3937 3993 Identification of family members of patients with prema- and timing of statin therapy after initial lipid profile and 3938 3994 ture ASCVD and high Lp(a) may help identify an stratified according to race and gender. Data was recorded 3939 3995 important risk factor and ultimately, target of therapy for 12 months after the initial lipid profile. 3940 3996 early in life. The family described above represents the Results: 499 patients were included in the study. Mean 3941 3997 complexity of early identification of ASCVD risk without age was 50.3 years, 61.9% identified as female, and 59.7% 3942 3998 a clear recommendation for treatment. We believe that were black. 61.7% of patients had a diagnosis of hyper- 3943 3999 additional study is needed to clarify the role of primary tension, 32.2% with diabetes, and 30.8% had significant 3944 4000 prevention in patients with high Lp(a) and a family smoking histories. Mean initial LDL level was 231mg/dL. 3945 4001 history of premature ASCVD, but low calculated ASCVD With regards to intensity of statin started, 38.2% of patients 3946 4002 risk. were not started on any statin therapy while 16.2% of 3947 patients were started on a high intensity statin (p50.038) 4003 3948 over 12 months. There was no significant difference 4004 3949 between either race or gender with regards to intensity of 4005 3950 291 4006 Intensity and Timing of Statin Initiation in statin started. 3951 In terms of time to statin start, 38.2% were not started on 4007 3952 Patients with initial LDL Greater Than 190 4008 mg/dL in an Urban Medical Center: A any statin while 29.8% were immediately started on statin 3953 therapy (p50.04). Of those started on statin therapy 4009 3954 Retrospective Observational Single Center 4010 University Experience* immediately, only 11.4% were started on a high intensity 3955 statin (p50.039). Again, no significant difference was seen 4011 3956 4012 Sanket R. Gokhale, MD, Noreen Nazir, MD, (Chicago, IL) between either race or gender. 3957 4013 Conclusions: Although a significant difference between 3958 4014 Lead Author’s Financial Disclosures: None. race or gender with regards to the intensity or timeliness of 3959 4015 Study Funding: None. statin initiation was not observed, the undertreatment of 3960 4016 Background/Synopsis: Severely elevated serum LDL severely elevated LDL across all study participants is 3961 4017 level (.190mg/dL) is an independent risk factor in the significant. Given the high prevalence of other comorbid 3962 4018 development of premature complications of artherosclerotic conditions amongst this vulnerable patient population, it is 3963 4019 cardiovascular disease (ASCVD) and current guidelines crucial that primary care physicians are educated on the 3964 4020 recommend immediate initiation of high intensity statin importance of primary prevention of premature ASCVD 3965 4021 therapy. Unfortunately, limitations in care continue to exist, complications and the aggressive treatment of severely 3966 4022 especially amongst patients from disadvantaged elevated serum LDL levels.

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4023 302 304 4079 4024 Clinical Management of Elevated Abstract Title: Patient Characteristics and 4080 4025 Lipoprotein(a) in A Large Cohort of Familial Prescribing Patterns for Patients Approved 4081 4026 Hypercholesterolemia Patients and Denied PCSK9 Inhibitors in Real-World 4082 4027 Practice 4083 4028 Daniel Rader, MD, 4084 4029 Douglas Jacoby, MD, Alexander Blake Smith, MD, Drew Johnson, MD, 4085 4030 Daniel Soffer, MD, (Philadelphia, PA) Kumar Sarkar, MD, 4086 4031 Alissa Connelly, BSN, RN, 4087 4032 Lead Author’s Financial Disclosures: None. Dean Karalis, MD, FACC, FNLA, (Philadelphia, PA) 4088 4033 Study Funding: None. 4089 4034 Background/Synopsis: Familial hypercholesterolemia Lead Author’s Financial Disclosures: None. 4090 4035 (FH) patients may exhibit both elevated low-density Study Funding: None. 4091 4036 lipoprotein (LDL-c) and elevated lipoprotein(a) [Lp(a)] Background/Synopsis: Proprotein convertase subtili- 4092 4037 through genetic inheritance. Several studies suggest sin/kexin type 9 inhibitors (PCSK9i) are approved for 4093 4038 elevated Lp(a) as a clinical risk factor significantly and patients with familial hypercholesterolemia (FH) or clinical 4094 4039 independently associated with cardiovascular disease risk atherosclerotic cardiovascular disease (ASCVD) who 4095 4040 in patients with FH. However, targeted modification of require additional lipid lowering beyond dietary measures 4096 4041 Lp(a) in FH patients in real-world settings remains poorly and statin use. Despite their efficacy and positive outcome 4097 4042 described. studies, providers have found significant barriers to pre- 4098 4043 Objective/Purpose: To determine the cardiovascular scribing them in real-world practice. 4099 4044 disease burden and treatment patterns respective of Lp(a) in Objective/Purpose: To identify patient characteristics 4100 4045 a large FH cohort at a tertiary academic center. and changes in lipid lowering therapy (LLT) in patients 4101 4046 Methods: A retrospective query was conducted in The approved compared to those not approved for a PCSK9i 4102 4047 University of Pennsylvania Health System (UPHS) using prescription in a real-world setting. 4103 4048 the FH ICD-10 code, E78.01. Plasma Lp(a) concentrations Methods: The study was a retrospective review of 4104 4049 were evaluated in these patients with results in the electronic medical records from a large cardiology practice 4105 4050 electronic health record. Elevated Lp(a) was defined as in Pennsylvania over a 36-month period. Patient demo- 4106 4051 concentrations $50 mg/dL. graphics, clinical information, insurance approval, and 4107 4052 4108 Results: The query returned 1417 FH patients [703 seen in changes in LLT were collected for patients prescribed a 4053 4109 the Penn Lipid Clinic, 714 seen elsewhere in UPHS)] of PCSK9i. We compared the data collected for those 4054 4110 whom 27% (389 of 1417) had an Lp(a) result. Of these approved to those not approved for a PCSK9i via standard 4055 4111 patients, 87% of patients (338 of 389) had seen a provider in t-test and chi-square testing. Approval rates were compared 4056 4112 the Penn Lipid Clinic, and 50% of patients (194 of 389) had based on age, gender, statin use, diagnosis and insurance 4057 4113 elevated Lp(a) with a median of 139 mg/dL (interquartile type. P-values for binomial categories (diagnosis and 4058 4114 range, 84-225 mg/dL). Factors associated with elevated insurance type) were compared directly. P-values , 0.05 4059 4115 Lp(a) included the non-white race (odds ratio 1.37, confi- were considered statistically significant. 4060 4116 dence interval 0.82 to 2.30), the male gender (1.16, 0.77 to Results: Data was collected on 120 patients, of which 4061 4117 1.75), prescription of niacin (1.91, 1.20 to 3.06), prescription 67.5% were approved for a PCSK9i. Of the 39 patients not 4062 4118 of a proprotein convertase subtilisin/kexin type 9 (PCSK9) approved, only 5 (12.8%) had any changes to their LLT (1 4063 4119 inhibitor (2.09, 1.40 to 3.13), and prevalent cardiovascular had the statin dose increased, 3 had a low dose statin 4064 4120 disease (1.42, 0.95 to 2.13). Among patients with a Lp(a) added and in 1 ezetimibe was added). Of the 81 approved, 4065 4121 result, median age at initiation of lipid-lowering therapy was 13 (16.0%) had changes to their statin therapy (7 had their 4066 4122 50 years old and median age at FH diagnosis was 55 old statin discontinued and 6 had the dose lowered), 2 stopped 4067 4123 years; among patients without a Lp(a) result, median age at ezetimibe, and 1 stopped their bile acid sequestrant. Of 4068 4124 initiation of lipid-lowering therapy was 55 years old and those approved 27.3% discontinued their PSCK9i in 4069 4125 median age at FH diagnosis was 57 years old. follow up. 4070 4126 4071 Conclusions: In a large cohort of FH patients, particu- Conclusions: Approximately one-third of patients are 4127 4072 larly those not seen in a lipid clinic, a large majority have being denied a PCSK9i despite appropriate clinical in- 4128 4073 not been evaluated for Lp(a). Among those patients with at dications and high LDL-C levels on a maximally tolerated 4129 4074 least one Lp(a) result, half demonstrate elevated Lp(a) statin regimen. There is a high discontinuation rate among 4130 4075 which associates with a higher cardiovascular disease those approved for a PCSK9i. Among those not approved, 4131 4076 burden. The 2018 Cholesterol Guidelines suggest that few had additional changes to their LLT including adding 4132 4077 high Lp(a) levels are a risk-enhancing feature that may ezetimibe. There is a need for payors to improve access to 4133 4078 support the need for intensification of cholesterol-lowering appropriate patients for a PCSK9i and for providers to 4134 pharmacotherapy. improve compliance with a PCSK9i once approved and to

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4135 4191 Table 1 Results: Nine patients who received evolocumab under- 4136 went neuropsychological assessment with RBANS prior to 4192 4137 Patient Characteristics Approved (%) Denied (%) P-value initiation of therapy and follow-up testing after initiation of 4193 4138 4194 Number of Patients 81 39 therapy. The mean age of the cohort was 58 (+/-9) and 44% 4139 Age (Years) 66.2 61.9 0.028 were male. Average education was 15 years. Seven patients 4195 4140 LDL-C Prior to PCSK9i 141.0 162.4 0.046 had known coronary artery disease. The mean change from 4196 4141 Rx (mg/dL) baseline (standard deviation, p-value) over an average of 4197 4142 Male Gender 31 (38.3) 18 (46.2) 0.41 452 days (+/-157) in the raw score for the immediate 4198 4143 Current Statin Use 24 (29.6) 9 (23.1) 0.45 memory, visuospatial/constructional, language, attention, 4199 4144 Past Trial of 52 (64.2) 29 (74.4) 0.27 delayed memory and total scale were -1.78 (13.26, p 5 4200 4145 High-Intensity 0.7), 6.56 (13.79, p 5 0.19), -4.11 (12.58, p 5 0.36), -1.67 4201 Statin 4146 (7.37, p 5 0.51), 2.67 (8.31, p 5 0.36), and 0.44 (6.11, p 5 4202 Trial of $ 2 Statins 56 (69.1) 30 (76.9) 0.38 4147 0.83) respectively. 4203 4148 Ezetimibe Use 46 (56.8) 22 (56.4) 0.97 4204 Diagnosis- ASCVD 68 (84.0) 30 (76.9) 0.35 Conclusions: There was no significant change in cogni- 4149 4205 Diagnosis- FH 13 (16.0) 9 (23.1) tive function in multiple domains observed in patients 4150 4206 Insurance Type- 50 (61.7) 25 (64.1) 0.80 receiving evolocumab over an average of 15 months. 4151 Commercial 4207 4152 Insurance Type- 31 (38.3) 14 (35.9) 4208 4153 Medicare 4209 4154 319 4210 4155 Homozygous Familial Hypercholesterolemia in 4211 use other available LDL-C lowering drugs in patients 4156 the United States: Data from the CASCADE-FH 4212 denied a PCSK9i to lower LDL-C to goal. † 4157 Registry 4213 4158 4214 4159 Marina Cuchel, MD, PhD, Joshua Knowles, Iris Kindt, 4215 Peter Shrader, Lisa Hudgins, P. Duell, Michael Shapiro, 4160 306 4216 Daniel Rader, Sarah de Ferranti, John Larry, 4161 Cognitive Function in Patients on 4217 Linda Hemphill, Irwin Benuck, Rolf Andersen, Seth Baum, 4162 Evolocumab* 4218 Katherine Wilemon, Matthew Roe, John Guyton, 4163 4219 John Kane, Christie Ballantyne, MacRae Linton, 4164 Qian Ye, MD, Meghana Halkar, MD, Max Trenerry, PhD, 4220 4165 Erica Kludtke, RN, Stephen Kopecky, MD, (Rochester, MN) Patrick Moriarty, Samuel Gidding, (Philadelphia, PA) 4221 4166 4222 Lead Author’s Financial Disclosures: None. Lead Author’s Financial Disclosures: Research 4167 4223 Study Funding: None. Grant; Significant; RegenxBio, Regeneron, Akcea, NIH. 4168 Study Funding: Amgen. 4224 4169 Background/Synopsis: There was inconclusive evi- 4225 Homozygous Familial hyper- 4170 dence on neurocognitive side effects of proprotein con- Background/Synopsis: 4226 cholesterolemia (HoFH) is a rare genetic condition (prev- 4171 vertase subtilisin-kexin type 9 (PCSK9) inhibitors from 4227 alence 1 in 250,000) characterized by extremely elevated 4172 early clinical trials with lack of proper methodology to 4228 LDL-C levels from birth, CVD that may manifest clinically 4173 assess cognitive function. A recent study that prospectively 4229 in childhood, and often aortic stenosis. Treatment response 4174 evaluated cognitive function in patients who received 4230 is generally inadequate and multiple lipid lowering treat- 4175 PCSK9 inhibitor therapy or placebo using the Cambridge 4231 ments are necessary. The CVD burden and treatment 4176 Neuropsychological Test Automated Battery found no 4232 intensity among patients with HoFH in the US is poorly 4177 significant between-group difference. 4233 characterized. 4178 Objective/Purpose: Our study aims to evaluate cogni- 4234 4179 tive function in patients receiving evolocumab at our Objective/Purpose: To describe patients diagnosed 4235 4180 institution using a personalized validated neuropsycholog- with HoFH participating in the FH Foundation’s 4236 4181 ical tool that assesses multiple domains administered by a CASCADE FH (CAscade SCreening for Awareness and 4237 4182 single psychologist experienced in this technique. DEtection of Familial Hypercholesterolemia) patient 4238 4183 Methods: In patients who were started on evolocumab registry. 4239 4184 between Jan 2015 to Dec 2017 at Mayo Clinic in Rochester Methods: We conducted an observational analysis of the 4240 4185 MN, we prospectively assessed cognitive function using the baseline data from 40 HoFH patients enrolled in the 4241 4186 Repeatable Battery for the Assessment of Neuropsycho- CASCADE FH Registry through 17 US lipid clinics 4242 4187 logical Status (RBANS) at baseline prior to therapy between April 2014 and January 2018. 4243 4188 initiation and 10-20 months after starting therapy. RBANS Results: Out of 4549 FH patients present in the 4244 4189 consists of 10 subtests which give 5 scores for the 5 CASCADE FH Registry, 40 patients (18 males and 22 4245 4190 domains tested: immediate memory, visuospatial/construc- females) were identified as having HoFH on the basis of 4246 tional, language, attention, and delayed memory. genetic diagnosis (n529, 72.5%) or LDL-C levels above

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4247 500 mg/dl and positive family history. Median (Q1, Q3) age extracted for patients with a repeat lipid profile performed 4303 4248 at diagnosis was 4 years (2, 12) and at time of enrolment in closest to 12 months from baseline along with documented 4304 4249 the registry was 24 (10, 42). LDL-C levels prior to the use of lipid-lowering therapies. The Dutch Lipid Clinic 4305 4250 initiation of lipid lowering treatment were 694+/-167 mg/ Network Criteria was used to determine the probability of 4306 4251 dl. At time of enrollment in the registry, 62.5% of HoFH FH. The Wilcoxon Signed-Ranked Test was used to 4307 4252 had prior documentation of CAD, 40% had prior PCI or compare the change in median LDL-C from baseline to 4308 4253 CABG, 12.5% prior valve replacement and 10% had 12 months. 4309 4254 received liver transplant. Thirty-four (85%) patients were Results: A total of 278 individual patients with baseline 4310 4255 receiving lipid lowering therapy: 80% statins (60% high LDL-C $250 mg/dL were identified and 159 met entry 4311 4256 intensity), 60% ezetimibe, 17.5% lomitapide, 7.5% each criteria. The majority (59%) were classified as having 4312 4257 niacin, resins and PCSK9 inhibitors. Seventeen subjects probable/definite FH. The mean age was 52 years, 53% 4313 4258 (42.5%) received LDL apheresis. 45% of the patients were were black, and 66% female. The median baseline LDL-C 4314 4259 treated with two different therapies, 25% with three and 5 was 270 mg/dL (IQR 257-292). Established ASCVD was 4315 4260 % with four. Mean LDL-C levels during treatment present in 35.8% of patients and 25% had premature 4316 4261 remained elevated at 310+/-224 mg/dl (range 37 to 769). ASCVD. Common comorbidities included hypertension 4317 4262 Conclusions: Diagnosis of HoFH was made relatively (62.9%), obesity (42.7%), and diabetes (32.7%). Nearly 4318 4263 early in this cohort of patients followed at US centers. three-fourths (74.2%) were not on statin therapy at baseline 4319 4264 However, CVD (both atherosclerotic and valvular) in these and non-statin use was rare. In a subgroup of 96 patients 4320 4265 patients was highly prevalent, treatment was sub-optimal with a follow-up lipid panel, the LDL-C decreased by a 4321 4266 and LDL-C levels remained elevated, underscoring the mean of 37% to 170 mg/dL (p,0.001); however, 76% still 4322 4267 difficult of treating this condition and the need for had LDL-C levels $130 mg/dL. Statin use at follow-up was 4323 4268 nationwide recognition for the optimization of the thera- 77% with 38.5% receiving a high-intensity statin and 4324 4269 peutic approach. 36.4% receiving a moderate-intensity statin. Non-statin 4325 4270 use was infrequent (15.6%). 4326 4271 4327 Conclusions: The management of FH at an academic 4272 328 4328 medical center was poor among those with an initial LDL- 4273 Characterization of Familial 4329 C $250 mg/dL. A significant number of patients were 4274 Hypercholesterolemia Management at an 4330 eligible for therapy intensification. Next steps will include 4275 Academic Medical Center* 4331 provider education and implementation of clinical decision 4276 4332 support tools. 4277 Danielle Hess, BS, Stephanie Seto, BS, 4333 4278 Pramit Nadpara, PhD, 4334 4279 Evan Sisson, PharmD, MSHA, 4335 4280 Dave Dixon, PharmD, (Richmond, VA) 4336 4281 4337 Lead Author’s Financial Disclosures: None. 4282 4338 4283 Study Funding: None. 4339 4284 Background/Synopsis: Familial hypercholesterolemia 4340 4285 (FH) is an underrecognized inherited disorder and major 4341 4286 cause of premature atherosclerotic cardiovascular disease 4342 4287 (ASCVD). While several studies have evaluated patients 4343 4288 meeting the FH phenotype, low-density lipoprotein choles- 4344 $ 4289 terol (LDL-C) 190 mg/dL, few have characterized the 4345 $ 4290 management of patients with higher LDL-C levels ( 250 4346 4291 mg/dL) who are more likely to have FH. 4347 4292 Objective/Purpose: To characterize the management 332 4348 4293 of FH at an academic medical center as part of a quality 4349 How Can We Reduce Cardiovascular Disease 4294 improvement initiative. 4350 Risks in Black Women? 4295 Methods: Electronic health records were utilized to 4351 4296 identify outpatients with earliest (baseline) documented Aneesha Thobani, MD, Puja Mehta, MD, 4352 4297 LDL-C of $ 250 mg/dL between 2006 and 2016. We Senait Asier, MD, Lian Li Karleigh Murphy 4353 4298 excluded patients , 21 years old, documented secondary Gina Lundberg, MD, (Atlanta, GA) 4354 4299 cause(s) of dyslipidemia, or insufficient data due to an 4355 4300 absence of clinical notes. Baseline characteristics included Lead Author’s Financial Disclosures: None. 4356 4301 age, race/ethnicity, sex, ASCVD history, family history of Study Funding: None. 4357 4302 ASCVD or elevated LDL-C, comorbidities, and use of Background/Synopsis: Synopsis: According to AHA 4358 lipid-lowering therapies. Follow-up lipid profiles were data from 2015, 47.7% of Black females have

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4359 4415 4360 Table 1 CVD Risk factors in screened Black women stratified by age. 4416 4361 P- value P- value P- value 4417 4362 (Ages 20-40 (Ages 40-60 (Ages 20-40 4418 4363 Age 20-40 Age 40-60 Age 60+ vs. 40-60 vs. 60+ vs. 60+ 4419 4364 (n5190) (n5394) (n5205) groups) groups) groups) 4420 4365 Body Mass Index 30.8 6 8.46 32.3 6 7.01 31.03 6 6.1 -NS -NS -NS 4421 4366 Systolic Blood Pressure (mmHg) 122.83 6 15.32 133.64 6 19.21 142.43 6 18.86 ,0.001 ,0.001 ,0.001 4422 4367 Diastolic Blood Pressure (mmHg) 81.21 6 11.61 84 6 12.41 79.55 6 11.04 -NS ,0.001 -NS 4423 4368 Total Cholesterol (mg/dL) 175.05 6 32.85 193.97 6 38.89 196.91 6 39.16 ,0.001 -NS ,0.001 4424 4369 Triglycerides (mg/dL) 122.42 6 82.15 135.77 6 84.15 138.36 6 89.27 0.018 -NS 0.067 4425 4370 Low Density Lipoprotein (mg/dL) 92.6 6 30.56 110.69 6 41.62 106.16 6 33.96 ,0.001 -NS ,0.001 4426 6 6 6 4371 High Density Lipoprotein (mg/dL) 58.09 16.39 59.01 16.43 62.73 17.18 -NS 0.021 0.01 4427 4372 4428 4373 cardiovascular disease (CVD) compared to 35.1% of across the lifespan. The ongoing rise in SBP throughout the 4429 4374 White, 33.0% of Hispanic, and 27.0% of Asian females. ages with the rise in TC, LDL-C and TG in women over 40 4430 4375 It is crucial to identify CVD risk factors in Black females undoubtedly adds to the numbers of Black women being 4431 4376 early and implement targeted education and preventive diagnosed with hypertension, metabolic syndrome and 4432 4377 care. As part of the Emory Women’s Heart Center 10,000 diabetes, and leads to a higher burden of CVD in Black 4433 4378 Women Hypertension Screening Project, we screened women. 4434 4379 Black females for CVD risk factors. 4435 4380 4436 Objective/Purpose: To assess CVD risk factors in 335 4381 Black Women and identify trends with increasing age to 4437 Evaluation of the Safety Profile of Proprotein 4382 determine which age groups to target for education for risk 4438 Convertase Subtilisin/Kexin Type 9 (PCSK9) 4383 reduction. 4439 4384 Inhibitors in Patients with Chronic Kidney 4440 Methods: 789 Black women were screened for blood 4385 Disease* 4441 pressure and CVD risk factors from 2015-2018 as part of 4386 4442 community based health screening. Personal medical in- Nubriel Hernandez, PharmD, 4387 4443 formation was collected along with blood pressure, body Roda Plakogiannis, BS, PharmD, 4388 4444 mass index (BMI) and point of care cholesterol levels were Naeem Baalbaki, PharmD Candidate, (New York, NY) 4389 4445 measured using Alere Cholestech LDX analyzer. Descrip- 4390 4446 tive statistics, T-tests, and chi square analysis were Lead Author’s Financial Disclosures: None. 4391 4447 performed. Study Funding: None. 4392 4448 Evidence has shown that pa- 4393 Results: Mean age was 50.38 +/-13.82. For the group Background/Synopsis: 4449 tients with chronic kidney disease (CKD) have difficulty in 4394 overall, the BMI was 31.61 +/-7.20, systolic blood pressure 4450 obtaining optimal lipid levels with statin therapy, thereby 4395 (SBP) 133.32 +/-19.51 mmHg, diastolic blood pressure 4451 increasing the risk for cardiovascular disease. This patient 4396 (DBP) 82.17 +/-12 mmHg, total cholesterol (TC) 190.14 4452 population often presents with increases in the total choles- 4397 +/-38.52 mg/dL, triglycerides (TG) 133.12 +/- 85.10 mg/ 4453 terol (TC), low density lipoproteins (LDL), non-high-density 4398 dL, low-density lipoprotein cholesterol (LDL-C) 105.14 +/- 4454 lipoproteins (non-HDL), triglycerides (TG) and decreases in 4399 37.94 mg/dL and high-density lipoprotein cholesterol 4455 high density lipoproteins (HDL). There is currently limited 4400 (HDL-C) 59.74 +/- 16.69 mg/dL. Data was further stratified 4456 data on PCSK9 inhibitor use in CKD patients because of 4401 by age groups for sub-analysis (Table 1). There was an 4457 , , exclusion criteria and limited patient populations from 4402 increase in TC (p 0.001), LDL-C (p 0.001), and TG 4458 5 previous trials. PCSK9 inhibitors used as monotherapy or 4403 (p 0.018) when comparing the 20 to 40 and 40 to 60 age 4459 in combination with statin therapy have demonstrated 4404 groups. Also there was an age associated escalation in SBP 4460 , significant LDL-C lowering. The results of this study will 4405 (p 0.001) seen all three age groups. 4461 add to the limited literature to date regarding the safety 4406 Conclusions: CVD education programs need to be 4462 profile of PCSK9 inhibitors in the CKD population. 4407 tailored toward Black women at different age ranges. 1- 4463 4408 Hypertension education should started before age 20 and Objective/Purpose: The objective of this study is to 4464 4409 continue throughout the lifespan. 2-Education geared evaluate the safety of PCSK9 inhibitors in patients with 4465 4410 toward young Black women on diet, fats, exercise, healthy chronic kidney disease (CKD). 4466 4411 lifestyles and sodium restriction may diminish the rise in Methods: This is a retrospective chart review of patients at 4467 4412 lipids and SBP seen between ages 20 to 40 and 40 to 60. 3- NYU Langone Health (NYULH), a 1,069-bed tertiary hospital 4468 4413 Targeting young Black females to maintain a healthy BMI in New York City. All patients within NYULH with chronic 4469 4414 prior to childbearing years is reinforced as Black women kidney disease (CKD) receiving a PCSK9 inhibitor from 4470 are entering their 20’s with a BMI .30 and this continues January 2016 to June 2018 were reviewed. Patients’

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4471 demographics, comorbidities, laboratory data and details of their use in many patients. Patients with dermatomyositis 4527 4472 lipid lowering therapy (medications, doses, frequencies, and often have skeletal muscle weakness, making the use of 4528 4473 duration) were collected based on the retrospective review of statins challenging. The management of patients with this 4529 4474 electronic health records (EHR). Patients were included in this diagnosis has not been clearly defined. This case series 4530 4475 study if they were greater than 18 years of age with a describes five patients with dermatomyositis, seen at The 4531 4476 diagnosis of CKD stages III-V. Patients were excluded if they Ohio State University Wexner Medical Center Cardiovas- 4532 4477 had an intolerance to PCSK9 inhibitors prior to the 180-day cular Risk Reduction and Lipid Clinic between 2014 and 4533 4478 follow-up period. The primary outcome of this study is the 2018, their treatment, and subsequent relevant outcomes. 4534 4479 change in kidney function as measured through blood urea Objective/Purpose: To review the management of 4535 4480 nitrogen (BUN), serum creatinine (SCr), and estimated dyslipidemias in patients with baseline musculoskeletal 4536 4481 glomerular filtration rate (eGFR) over a follow-up of 6 dysfunction secondary to dermatomyositis. 4537 4482 4538 months post-PCSK9 inhibitor initiation. Secondary measures Methods: We performed a retrospective chart review of 4483 4539 of assessment will include changes in lipid values from patients at an academic medical center lipid clinic with a 4484 4540 obtained lipid panels, creatinine kinase (CK) levels, and any diagnosis of dermatomyositis and indication for statin 4485 4541 documented adverse drug events. therapy. Patients were required to be seen for at least one 4486 4542 Results: Over 180 patients were identified to have follow up visit to verify tolerance. 4487 reported CKD and a history of PCSK9 inhibitor use. 4543 4488 Results: Five adult patients were included in our analysis, 4544 However, only 18 patients met the inclusion criteria. At all with biopsy confirmed (intermediate or definite) derma- 4489 baseline, 15 patients had CKD stage 3, one patient had 4545 4490 tomyositis prior to establishing with the lipid clinic. 4546 CKD Stage 4 and two patients had borderline CKD stage 2- Indications for statin therapy included coronary artery 4491 3. Approximately, 50% of the patients had an increase in 4547 4492 bypass grafting, recurrent myocardial infarction, non- 4548 SCr (8/18), an increase in BUN (10/18) and a decrease in obstructive coronary artery disease on left heart catheter- 4493 GFR (9/18) at the 6-month follow-up. A rise or decline in 4549 4494 ization, possible familial hypercholesterolemia, and an 4550 SCr, BUN and/or GFR of 50% or greater was not noted in elevated 10 year risk .20%; all also carried additional 4495 any of the patients evaluated. Additionally, patients did not 4551 4496 risk factors. At the initial visit, only one patient was on 4552 report any intolerance to PCSK9 inhibitors within the 6- statin therapy, which was stopped shortly after at the 4497 month follow-up period. Within this patient population, 4553 4498 request of her neuromuscular physician, and three of the 4554 lipid-lowering efficacy of PCSK9 inhibitor therapy re- remaining patients had failed statin therapy in the past due 4499 mained similar to previously demonstrated data. 4555 4500 to SAMS. Therapies were chosen in conjunction with the 4556 Conclusions: Based on the limited evidence, the use of 4501 patient’s dermatomyositis physician (rheumatology, neuro- 4557 PCSK9 inhibitors after 6 months of treatment, appears to be 4502 muscular) and based on patient tolerance and response. 4558 safe in the CKD population, however monitoring of renal 4503 Three patients were approved for trial of statin therapy 4559 function is still warranted in these patients. Larger studies 4504 while managing physicians preferred avoidance of statins in 4560 with longer follow-up periods are required to determine if 4505 the remaining two patients. Four patients were approved for 4561 there is a clinical difference in safety amongst the use of 4506 use of non-statin therapies, specifically ezetimibe and 4562 PCSK9 inhibitors in patients with CKD stage 3 or greater. 4507 alirocumab. At the time of their most recent clinic visits, 4563 4508 all patients were tolerating their lipid lowering regimen and 4564 four of the patients had reached guideline specified LDL 4509 337 4565 4510 targets, with the fifth patient deferring further statin 4566 Management of Dyslipidemia in Patients with titration until resolution of a dermatomyositis flare (current 4511 Dermatomyositis: A Case Series 4567 4512 LDL reduction 33%). 4568 4513 Kelly Bartsch, PharmD, BCPS, CLS, Conclusions: Though dermatomyositis patients have 4569 4514 Erica Davidson, PharmD, BCACP, C, baseline myopathy, they often warrant lipid lowering 4570 4515 Abigail Rabatin, PharmD, BCACP, therapy. Experience with our center’s small cohort demon- 4571 4516 Diana Vinh, PharmD, BCPS, CL, strates that tolerable and effective regimens, including 4572 4517 Margueritte Hevezi, PharmD, CLS, CDE, statins, can be found for this patient population. 4573 4518 Michael Milks, MD, 4574 4519 4575 John Larry, MD, 340 4520 4576 Laxmi Mehta, MD, FACC, (Columbus, OH) Gender Differences in Response to PCSK9 4521 4577 Inhibitor Therapy 4522 Lead Author’s Financial Disclosures: None. 4578 4523 Study Funding: None. Paul Ziajka, MD, PhD, FNLA, (Winter Park, FL) 4579 4524 Background/Synopsis: Statins remain the preferred 4580 4525 initial therapy for most patients with hyperlipidemia and Lead Author’s Financial Disclosures: Speakers 4581 4526 elevated cardiovascular risk. However, they may also cause bureau Amgen, Sanofi, Regeneron. 4582 statin associated muscle symptoms (SAMS) that can limit Study Funding: None.

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4583 Background/Synopsis: The introduction of PCSK9 transplant allograft vasculopathy (CAV) and shows mortal- 4639 4584 inhibitors in 2015 added a potent therapeutic option for ity benefit at ten years. 4640 4585 lipid lowering therapy. Both FDA approved agents, alir- Objective/Purpose: We sought to determine the pattern 4641 4586 ocumab and evolocumab, have well documented LDL-C of statin use in the OHT population in a single transplant 4642 4587 lowering effects as well cardiovascular event reduction center with specific attention to intensity of statin therapy 4643 4588 data. and assessed its association with transplant outcomes. 4644 4589 4645 Objective/Purpose: Previous studies have demon- Methods: Retrospective data points from 211 OHT patients 4590 4646 strated a trend for a more robust LDL-C reduction in men at a single center were collected from the electronic medical 4591 4647 versus women with both alirocumab and evolocumab record. For all patients, statin use was recorded as low, 4592 4648 therapy. Anecdotal reports also suggest that women have moderate, and high intensity based on the 2013 ACC/AHA 4593 4649 a higher rate of significant hypo-responsiveness to PCSK9 guidelines. Patient’s yearly catheterization reports were 4594 4650 inhibitor therapy than men. This study (1) examines the reviewed for diagnosis of CAV. Time from OHT to CAV 4595 4651 gender specific effects of alirocumab and evolocumab on diagnosis was calculated from the date of the diagnosing 4596 4652 LDL-C lowering and (2) examines the gender specific catheterization and the mortality data was determined from 4597 4653 effects on the variability of response to PCSK9 inhibitor medical records. In addition, systolic blood pressure, lipid 4598 4654 therapy. levels, and HbA1c were recorded. Comparison between CAV 4599 4655 and no-CAV groups was made using Fisher exact, chi-square 4600 Methods: A retrospective chart review was conducted at 4656 or t-test and significant predictors of CAV was determined 4601 the Florida Lipid Institute in Orlando. Pre- and post- PCSK9 4657 using a Cox proportional Hazards model. 4602 inhibitor therapy LDL-C levels were collected in patients 4658 4603 started on the initial dose of alirocumab (75 mg sq every two Results: Among 211 OHT patients, average time to 4659 4604 weeks) and evolocumab (140 mg sq every two weeks). follow-up was 5.8 years (0.5-26). There were 19 deaths 4660 4605 Results: Data was collected from 150 patients on PCSK9 (9%) and 101 (48%) developed CAV. Statin intensity data 4661 4606 inhibitor therapy - 67 on alirocumab and 83 on evolocu- was available in 195 patients- 40% (77) were on high- 4662 4607 mab. There were no gender differences in the alirocumab intensity, 42% (81) on moderate-intensity, 12% (22) on low- 4663 4608 group for LDL-C lowering : 51% +/- 16% for men and 54% intensity statin respectively and 6% (11) were not on a statin. 4664 4609 +/-16% for women (p50.48). In the alirocumab group the Compared to the non-CAV group, CAV patients had higher 4665 , 4610 LDL-C lowering response ranged from 5% to 90% but systolic BP and HbA1C (p 0.05) but no difference in lipid 4666 4611 there were no gender differences in the variability of values or statin intensity. No difference in statin intensity or 4667 4612 response (p50.94). In the evolocumab group men had a lipid values were also noted among patients who died. In a 4668 4613 statistically significant better LDL-C lowering response Cox Proportional Hazards model to predict time to occur- 4669 4614 (68% +/- 14%) compared to women (61% +/-12%) rence of CAV, statin intensity (1.4; CI-1.05-1.8), history of 4670 4615 (p50.01). In the evolocumab group the LDL-C lowering kidney transplant (0.4; 0.78-0.97) and CMV viremia (1.72; 4671 4616 response ranged from 33% to 92% but there were no gender CI-1.02-2.9) were significant predictors in a model that also 4672 4617 differences in the variability of response (p50.99). included lipid values, BP, HbA1C and h/o diabetes. 4673 4618 Conclusions: Alirocumab had no gender differences in Conclusions: The majority of OHT patients are on statin 4674 4619 LDL-C lowering response or the variability of LDL-C therapy including moderate to high-intensity statin. The 4675 4620 lowering response (i.e. men and women had a similar intensity of statin therapy is associated with time to 4676 4621 distribution of hypo- and hyper-responders). Evolocumab occurrence of CAV. Since we collected data on statin 4677 4622 had a more robust LDL-C lowering in men than in women intensity at the time of diagnosis of CAV, this may be 4678 4623 but the variability of LDL-C lowering had no gender reflective of changes made after diagnosis of CAV. Lipid 4679 4624 difference (i.e. men and women had a similar distribution values are not related to intensity of CAV and therefore 4680 4625 of hypo- and hyper-responders). should not be used to assess need for escalation of therapy. 4681 4626 4682 4627 346 360 4683 4628 Significance of Lipid Management in Cardiac Race/Ethnic differences in dyslipidemia 4684 4629 Transplant Population patterns in Youth 4685 4630 4686 4631 Indu Poornima, MBBS, Nidhi Bansal, MD, MPH, 4687 4632 Juliette Power, MD, Mark Doyle, PhD, (Pittsburgh, PA) Kristen Tejtel, MD, PhD, MPH, (Houston, TX) 4688 4633 4689 4634 Lead Author’s Financial Disclosures: None. Lead Author’s Financial Disclosures: None. 4690 4635 Study Funding: None. Study Funding: None. 4691 4636 Background/Synopsis: Statin therapy offers long-term Background/Synopsis: Recent estimates form Na- 4692 4637 morbidity and mortality benefits after orthotopic heart tional Health and Nutrition Examination Survey 4693 4638 transplant (OHT), regardless of lipid levels. Treatment (NHANES) indicate that 7.8% of children aged 8-17 years 4694 with statins significantly reduces the incidence of cardiac have elevated levels of Total Cholesterol (.200 mg/dL)

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4695 4751 4696 Table 1 Race/Ethnic differences in dyslipidemia in youth 4752 4697 Caucasian Black Asian Hispanic Other/Unknown X2 p-value 4753 4698 4754 N (%) 9120 (72.3%) 2280 (18.1%) 481 (3.8%) 141 (1.1%) 588 (4.7%) 4699 High TC 13.6% 12.1% 21.4% 8.5% 14.8% ,0.001 4755 4700 Low HDL C 32.6% 21.4% 24.1% 44.1% 30.4% ,0.001 4756 4701 High LDL C 10.8% 10% 18.4% 6.5% 13.9% ,0.001 4757 4702 High TG 32.6% 12.5% 35.3% 29.8% 27.5% ,0.001 4758 4703 High TC: Total Cholesterol $ 200, Low HDL C: High-density Lipoprotein Cholesterol # 40, High LDL C: Low-density Lipoprotein Cholesterol $ 130, 4759 4704 High TG: Triglycerides $ 130 4760 4705 4761 4706 and 7.4% of adolescents age 12-19 years have elevated Lead Author’s Financial Disclosures: None. 4762 4707 . 4763 Low-density Lipoprotein cholesterol ( 130 mg/dL). Study Funding: None. 4708 Racial/Ethnic differences have been noted in prevalence 4764 Background/Synopsis: Having low levels of total 4709 of dyslipidemia in adults. 4765 cholesterol (TC) and low-density lipoprotein cholesterol 4710 Objective/Purpose: The goal of our study was to 4766 4711 (LDL-C) are considered desirable due to evidence linking 4767 describe the racial/ethnic differences in hyperlipidemia high levels to increased risk for cardiovascular disease. 4712 among youth referred to a tertiary care facility. 4768 4713 However, marked reductions may indicate the presence of 4769 Methods: We queried the Electronic medical record at 4714 devastating heritable disorders, such as abetalipoproteine- 4770 our institution for all patients seen in pediatric cardiology 4715 mia, hypobetalipoproteinemia, and chylomicron retention 4771 clinic between 2011 and 2018 and obtained their race/ 4716 disease due to bi-allelic mutations in MTTP, APOB, and 4772 ethnicity, age, gender, height, weight, BMI, and lipid 4717 SAR1B, respectively. These disorders are associated with 4773 profile. SPSS was used to do statistical analysis. Chi- 4718 extremely low TC, LDL-C, and undetectable apolipopro- 4774 Square test was used to test differences between the groups. 4719 tein B due to defective assembly and secretion of chylo- 4775 4720 Results: Lipid profiles for 12610 unique subjects were microns from the intestine and very low-density 4776 4721 obtained between 2011 and 2018. The mean age of subjects lipoproteins from the liver. 4777 4722 was 10.4 years (range 3 months-21 years). 54% of subjects Fat malabsorption, often beginning in infancy, is common 4778 4723 were male. The race/ethnic profile is shown in table 1 (see in abetalipoproteinemia and can lead to failure to thrive 4779 4724 attachment). with steatorrhea due to fat-intolerance to breast milk or 4780 4725 Asian American youth are most likely to have high Total formula. Abnormal lipoprotein levels, acanthocytosis and 4781 4726 cholesterol, Low density lipoprotein cholesterol and Tri- hepatic steatosis are other notable features. Devastating 4782 4727 glycerides than other reported races. The Hispanic Amer- manifestations include retinal disease, bone and neuro- 4783 4728 ican youth are most likely to have low High density logical abnormalities, and coagulopathy due to defi- 4784 4729 lipoprotein cholesterol and the Black youth are least likely ciencies of vitamins A, D, E, and K, respectively, that 4785 4730 to have abnormal Triglycerides when compared to other require lipoproteins for transport. There is no treatment 4786 4731 racial/ethnic groups. for abetalipoproteinemia aside from large doses of fat- 4787 4732 Conclusions: Racial/ethnic differences exist in choles- soluble vitamins. Thus, early diagnosis and dietary man- 4788 4733 terol profile in youth. Consideration of race/ethnic differ- agement can dramatically improve the patient’s overall 4789 4734 ences may benefit development of optimal screening condition. 4790 4735 strategies and treatment of youth with dyslipidemia. Further Objective/Purpose: We present a young patient with 4791 4736 research is needed to determine how racial/ethnic differ- abetalipoproteinemia whose growth and development have 4792 4737 ences in dyslipidemia in youth may affect the development been positively impacted by appropriate nutritional inter- 4793 4738 of cardiovascular disease rates in future. vention beginning in infancy. 4794 4739 Methods: The patient and her family participated in an 4795 4740 institutionally approved study, investigating the genetic 4796 4741 Nutrition, Nutrigenomics, Nutraceuticals and etiology of dyslipidemia at the University of Pennsylvania. 4797 4742 Exercise Therapies Growth history was obtained from her parent, nutritionist, 4798 4743 and medical records. 4799 4744 272 Results: The patient was clinically diagnosed with 4800 4745 Importance of Nutritional Intervention for abetalipoproteinemia at 5 months. This diagnosis was 4801 4746 Infants with Abetalipoproteinemia confirmed by the presence of maternally inherited (Int 4802 4747 13+5 G.A -E13 skip), and paternally inherited (insA, 4803 4748 Masako Ueda, MD, Frances Burke, MS, RD, p.N140K-141X (p.N140Kfs*1) MTTP mutations. 4804 4749 Michelle Maeda, MS, RD, Adam McIntyre, MSc, She was seen by a metabolic nutritionist at 7 months because 4805 4750 Robert Hegele, MD, of severe milk-intolerance and poor growth. Commercially 4806 Mary Malloy, MD, Daniel Rader, MD, (Philadelphia, PA) available infant formulas were not tolerated, requiring the

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4807 4863 4808 Table Infant Formula Comparison: based on current data 100 g powder 4864 4809 Special Formula Monogen* Tolerex Alimentum* Neocate Infant* 4865 4810 4866 Calories 444 375 525 483 4811 Protein % 12 11.6 8 11 11 4867 4812 Carbohydrate % 75 62.2 91 39 43 4868 4813 Fat % 11 26.1 2 50 46 4869 4814 LCT g/percent 5.5 g 2.1 g/16% 1 g/1.8% 19.2 g/67% 16.5 g/67% 4870 4815 MCT g/percent 0 10.8 g/84% 0% 9.6 g/33% 8 g/33% 4871 4816 Linolenic Omega-3 600 mg 170 mg 0 446 mg 419 mg 4872 4817 Linoleic Omega-6 2351 mg 900 mg 560 mg 4199 mg 3565 mg 4873 4818 DHA/ARA - 60 mg/60 mg 0 51 mg/103 mg 81.6 mg/81.6 mg 4874 4819 The modular special formula has a relatively low-fat percentage, but with a higher amount of linolenic fatty acids with 600 mg. It provided 21 calories 4875 4820 per ounce. 4876 4821 *Monogen, Alimentum, and Neocate Infant have been reformulated to add DHA/ARA 4877 LCT: Long-chain triglycerides 4822 MCT: Medium-chain triglycerides 4878 4823 DHA: Docosahexaenoic acid 4879 4824 ARA: Arachidonic acid 4880 4825 4881 4826 preparation of a special modular formula containing ProVi- Objective/Purpose: The objective of our studies was 4882 4827 Min, Polycose, corn oil, and flaxseed to provide essential to investigate the physiologic effect, particularly cardio- 4883 4828 fatty acids that were critical for infant growth and develop- protective impact, of PA in animal models and human 4884 4829 ment along with vitamin supplementation. subjects. 4885 4830 The patient had remarkable catch-up growth on the new Methods: Three animal studies were performed to 4886 4831 formula, and both her weight and height increased from investigate the effect of dietary PA on lipid/glucose 4887 , 4832 10%tile to 50%tile within a month. Although she has metabolism, atherosclerotic development, and satiety. 4888 4833 been diagnosed with hepatic steatosis and mild sensory Furthermore, we are currently performing a randomized, 4889 4834 abnormalities, her general health has been good and her double-blinded, crossover, placebo-controlled clinical trial 4890 4835 development has been age-appropriate. She has been play- on supplementation with PA concentrate oil (Clinical- 4891 4836 ing basketball without difficulties. Trials.gov Identifier: NCT03372733) to investigate its 4892 4837 Conclusions: The case clearly shows the importance of effect on cardiometabolic biomarkers. 4893 4838 appropriate nutritional intervention in infancy to minimize Results: In type II diabetic mouse models that were 4894 4839 the devastating manifestations of abetalipoproteinemia. orally administered PA for 4 week, PA improved insulin 4895 4840 resistance and lipid profile through regulating lipogenic and 4896 4841 inflammatory genes. In diet-induced atherosclerotic LDLR- 4897 4842 4898 292 KO mice that were fed Western diet supplemented with PA 4843 concentrate for 12 weeks, dietary PA, but not oleic-rich 4899 The Role of the Novel Lipokine Palmitoleic 4844 olive oil, reduced atherosclerosis. These favorable changes 4900 Acid in Cardiovascular Health: from Bench to 4845 were was associated with improvement of lipid and glucose 4901 Bedside* 4846 metabolism, and favorable changes in regulatory genes 4902 4847 involved in lipid metabolism and inflammation. Further- 4903 4848 Zhi-Hong Yang, PhD, Milton Pryor, BS, 4904 Maureen Sampson, BS, Alexander Sorokin, MD, PhD, more, oral administration of PA also caused dose-depen- 4849 4905 Marcelo Amar, MD, dently increased satiety in SD rats compared with C16:0 or 4850 4906 Alan Remaley, MD, PhD, (Bethesda, MD) C18:1, possibly due to an increase production of satiety 4851 hormones. 4907 4852 4908 Lead Author’s Financial Disclosures: None. Conclusions: In summary, the American Heart Asso- 4853 4909 Study Funding: None. ciation and Dietary Guidelines for Americans have long 4854 4910 Cardiovascular disease (CVD) advised the replacement of saturated fatty acids with 4855 Background/Synopsis: 4911 is a major healthcare problem worldwide and is known to unsaturated fatty acids including MUFAs, but a more 4856 4912 be greatly affected by diet. Consumption of monounsatu- detailed understanding on the effect of various types of 4857 4913 rated fatty acids (MUFA) has favorable effects on CVD dietary MUFAs on CVD risk is needed. Our pre-clinical 4858 4914 risk. Compared with oleic acid (C18:1 n-9) that is the most trials suggest that enrichment of dietary PA may have 4859 4915 common dietary MUFA, there is limited information on the beneficial and perhaps unique effects on CVD risk 4860 4916 cardiovascular effects of other dietary MUFAs, such as factors, and thus could lead to new dietary recommen- 4861 4917 palmitoleic acid (PA; C16:1 n-7) that has been recently dations and improvements in the formulation of MUFA 4862 4918 identified as a novel lipokine coordinating homeostasis. supplements.

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4919 317 studies. However, our unexpected adverse outcomes 4975 4920 Effects of Conjugated Linoleic Acid (CLA) on should be interpreted with caution given the heteroge- 4976 4921 HDL-C and Triglyceride levels in Subjects with neity in study design and quality of the available 4977 4922 and without the Metabolic Syndrome: A evidence, suggesting the need for properly designed 4978 4923 Systematic Review and Meta-analysis large randomized trials. 4979 4924 4980 4925 Rossana Maria Calderon Moreno, MD, 4981 4926 Ricardo Correa Marquez, MD, 4982 4927 Anna Oberg, MD PhD, 358 4983 4928 Stefania Papatheodorou, MD, PhD, (New York, NY) Lipid Effects of Dietary Education as a 4984 4929 Function of Age and Gender 4985 4930 Lead Author’s Financial Disclosures: None. 4986 4931 Study Funding: None. Debra Ann Friedrich, DNP, FNP-BC, CLS, FNLA, 4987 4932 Background/Synopsis: CLA supplementation has Paul Ziajka, MD, PhD, 4988 4933 been widely used by the general population as a weight Bernice Boivin, RDN, 4989 4934 reduction agent. In-vitro and animal studies have reported Nancy Smith, MS, RDN, LDN, CD, (Bradenton, FL) 4990 4935 beneficial metabolic effects including cholesterol and 4991 Lead Author’s Financial Disclosures: None. 4936 triglyceride lowering effects, as well as anti-atherogenic 4992 4937 actions potentially via PPARƴ-activation. However, find- Study Funding: None. 4993 4938 ings in humans have been mixed, with some studies even Background/Synopsis: Evidence demonstrates that 4994 4939 reporting harmful effects. multiple Medical Nutritional Therapy (MNT) sessions by 4995 4940 Objective/Purpose: The aim of the present systematic a registered dietician are clinically effective and cost 4996 4941 review and meta-analysis is to evaluate the available beneficial in patients with dyslipidemia and cardiometa- 4997 4942 evidence of the effects of CLA on relevant aspects of the bolic risk factors. However, data related to the lipid 4998 4943 lipoprotein profile in terms of metabolic syndrome, such as response stratified by age and gender is not clearly defined 4999 4944 HDL-C and triglyceride levels. and will be the focus of the study. 5000 4945 Methods: We conducted a systematic literature Objective/Purpose: The purpose of the study was to 5001 4946 search to identify studies up to December 2017. Only retrospectively examine the lipid response of dietary edu- 5002 4947 randomized controlled trials (RCTs) of t10-c12 CLA cation provided by a registered or licensed Dietician in or 5003 4948 isomer or mix 50:50 CLA t10-c12 and c9-t11 compared upon a referral from a lipid clinic stratified by age and 5004 4949 to placebo on healthy subjects or with components of the gender. 5005 4950 metabolic syndrome were selected. The quality of indi- Methods: Retrospective data was collected to examine 5006 4951 vidual studies was assessed using the Cochrane’s Risk of both gender differences and age (, 40 young adults) versus 5007 4952 Bias tool. When appropriate, results were pooled to (.70 geriatrics) on the normalization components of the 5008 4953 obtain weighted mean differences (WMDs) with 95% lipid panel in patients after receiving dietary education. 5009 4954 CI. Small study effects were assessed in funnel plots, Pre-education baseline lipids and follow-up post-education 5010 4955 and heterogeneity was further explored in subgroup lipids were reviewed. 5011 4956 analysis Results: There were no statistically significant changes 5012 4957 5013 Results: A total of 17 RCTs were included in the in patient weight for the entire population or in any age 4958 5014 qualitative review, which identified between study dif- or gender subset for either dietary education focusing on 4959 5015 ferences in type of participants, length and dose of LDL-C or triglyceride reduction. For the entire LDL-C 4960 5016 intervention, and study quality. Meta-analysis of 13 population (all ages and genders) LDL-C was reduced 4961 5017 studies showed that CLA was associated with a small 13.8% (p,.000001). For the entire triglyceride popula- 4962 5018 reduction in HDL-C levels (-2.06 mg/dL 95%CI -3.74, tion (all ages and genders) triglycerides were reduced 4963 5019 -0.39, p50.016) and an increase in triglyceride levels 26.2% (p5.001). There were no statistically significant 4964 5020 (7.54 mg/dL, 95% CI 1.20, 13.88, p50.020). Subgroup difference with respect to LDL-C or triglyceride 4965 5021 analysis indicated that the differences were largely lowering based on gender. LDL-C lowering based on 4966 5022 driven by interventions with higher CLA doses (. 4g/ age showed a non-statistically significant trend with the 4967 5023 day). Sensitivity analysis removing studies with high risk elderly achieving a greater reduction than younger age 4968 5024 of bias still showed a statistically significant decrease in groups. 4969 5025 HDL-C levels while the effects on triglycerides was no Conclusions: All patients achieved LDL-C lowering 4970 5026 longer seen. after referral to a registered dietician. However, patients 4971 5027 over the age of 76 showed the greatest reduction in LDL-C 4972 Conclusions: Our systematic review and meta-analysis 5028 with dietary education. Medical Nutritional Therapy 4973 concluded that there is no beneficial effects of CLA on 5029 should be considered first line in our elderly patients not 4974 HDL-C and triglycerides levels, in contrast with 5030 the previously mentioned findings from mechanistic at LDL-C goal.

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5031 361 Speaker for Amgen, Amarin, Regeneron, Boehringer 5087 5032 Lifestyle intervention improve the weight and Ingelheim, Boston Heart Diagnostics. 5088 5033 exercise patterns of geriatric depressed Study Funding: Boston Heart Diagnostics. 5089 5034 5090 patients Background/Synopsis: The Reduction of Cardiovas- 5035 5091 cular Events with Icosapent Ethyl-Intervention Trial 5036 Francisco Eduardo Ramirez, MD, (Weimar, CA) 5092 (REDUCE-IT) demonstrated that 4 grams of prescription 5037 5093 eicosapentaenoic acid (EPA) significantly reduced cardio- 5038 Lead Author’s Financial Disclosures: None. 5094 vascular disease (CVD) events including CVD deaths when 5039 Study Funding: None. 5095 added to statin therapy in subjects with LDL-c .40-100 5040 Background/Synopsis: Depressed individuals may 5096 mg/dL, and triglycerides 150-499 mg/dL, and with either 5041 lack motivation to take care of their health. 5097 known CVD aged .45 years, or diabetes mellitus aged 5042 5098 Objective/Purpose: We explore the effect that a med- .50 years plus at least one additional risk stratum criterion. 5043 ical residential lifestyle intervention have on these patients 5099 5044 Objective/Purpose: This study determined the preva- 5100 regarding weight and exercise patterns. . 5045 lence of four risk stratum criteria (age 55 years for males or 5101 Methods: The retrospective intervention took place in . , , 5046 65 years for females, HDL-c 40mg/dL in males or 50 5102 Weimar, CA of 18 days. Patients were evaluated by a board . 5047 mg/dL in females, hsCRP 3.0 mg/L, or stage 3 chronic 5103 certified physicians, some came with the diagnosis of kidney disease) in individuals with type 2 diabetes who met 5048 depression, some were diagnosed with depression at the 5104 5049 the REDUCE-IT criteria for LDL-c and triglycerides. We also 5105 program. This comprehensive lifestyle intervention pro- tested the hypotheses that serum levels of EPA and the ratio of 5050 gram included a whole foods plant-based diet, exercise, 5106 5051 EPA to arachidonic acid (EPA/AA) progressively decreased 5107 water, sunlight, temperance/moderation, fresh air, rest/ according to the number of risk stratum criteria met. 5052 sleep, and emotional, relational support. A baseline mea- 5108 Methods: We used de-identified data from the laboratory 5053 surement of weight and various markers was done 5109 information system of Boston Heart Diagnostics to calculate 5054 including miles walked was captured, at the end the of 5110 the prevalence of REDUCE-IT-Like criteria and serum EPA 5055 the program the same evaluation was repeated. 5111 5056 and EPA/AA levels from blood specimens received during a 5112 Results: In 12 years of patients data, n5107 patients 5057 5-year period from August 2014 through September 2018. 5113 were geriatric and had the diagnosis of major depression at 5058 Results: Among patients with type 2 diabetes aged .50 5114 baseline, from those 107, n596 had the before and end data 5059 years who met the REDUCE-IT criteria for LDL-c and 5115 complete and were used for this study. 5060 triglycerides (n511,646), 96.87% met at least one risk 5116 Average age was 66.7 SD 8.6. At the beginning their weight 5061 stratum criterion (76.42% for age, 70.73% for HDL-c, 5117 in pounds listed as mean, St Dev, mode, median was (164.3, 5062 35.56% for hsCRP, 20.56% for stage 3 kidney disease). 5118 38.5, 158, 157.7). Using the baseline values of Body Mass 5063 This included 72.53% who met two risk criteria, 19.18% 5119 Index, 23% were overweight and 23% were obese. At the 5064 who met three risk criteria, and 4.94% who met four risk 5120 end, the mean, St Dev, mode and median values were 5065 criteria. The median serum levels for patients with 1, 2, 3, 5121 (159.6, 36.2, 146, 155). Regarding their exercise patterns at 5066 and 4 risk stratum criteria were, respectively, 26.6, 23.4, 5122 baseline the mean, St Dev, mode, median, minimum, 5067 20.9, 20.5 mcg/dL for EPA, and 0.086, 0.080, 0.074, 0.071 5123 maximum miles that they were walking per day was (.5, 5068 for EPA/AA ratio (p,0.0001 for trends). 5124 .9, 0, 0, 0, 4), their end walking values listed in the same 5069 5125 order were (3, 1.9, 4, 3, 0.25, 9). Conclusions: This study shows that there is a substantial 5070 burden of residual risk and opportunity for CVD risk 5126 Conclusions: This short-term lifestyle intervention pro- 5071 reduction among patients aged .50 years with type 2 5127 gram of change in diet, exercise and other health compo- 5072 diabetes who meet the REDUCE-IT criteria for LDL-c, and 5128 nents was able help patients improve their wait and increase 5073 triglycerides, since 96.87% met at least 1 risk stratum 5129 their physical activity. The long-term effects of this lifestyle 5074 criterion. The median serum EPA level and EPA/AA ratio 5130 intervention needs to be studied. 5075 progressively decreased with additional risk stratum criteria 5131 5076 suggesting potential greater benefits of EPA supplementa- 5132 5077 Omega-3 Fatty Acids tion with each additional risk criterion present. 5133 5078 5134 5079 299 5135 Prevalence of Diabetes Mellitus with REDUCE- 5080 318 5136 5081 IT-Like Indications: Ramifications for 5137 Residual Risk and Potential Risk Reduction Comparison of EPA and DHA-Rich Fish Oils on 5082 NMR Lipoprotein Metabolism in Adults 5138 5083 5139 John R. Nelson, MD, 5084 5140 Lihong He, PhD, Michael Dansinger, MD, (Fresno, CA) Marcelo Amar, MD, Zhihong Yang, PhD, 5085 Maureen Sampson, Alexander Sorokin, MD, 5141 5086 Lead Author’s Financial Disclosures: Advisory Michael Stagliano, NP, 5142 Board: Amgen, Amarin. Stock: Amgen, Amarin, Pfizer. Alan Remaley, MD, PhD, (Bethesda, MD)

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5143 Lead Author’s Financial Disclosures: None. preserve normal cholesterol distribution as compared to 5199 5144 5200 Study Funding: None. arachidonic acid (AA), an omega-6 fatty acid (FA). 5145 5201 Background/Synopsis: Dietary Omega-3 PUFAs have Objective/Purpose: To compare the effects of EPA and 5146 AA on membrane structure and cholesterol crystalline 5202 5147 potential cardiovascular benefits, but whether its two main 5203 components, namely EPA and DHA differ in some of their domain formation under conditions of hyperglycemia and 5148 oxidative stress. 5204 5149 biological effects on lipoprotein metabolism has not been 5205 Methods: Membrane vesicles were prepared from dili- 5150 well investigated. It has been described that DHA may raise 5206 noleoylphosphatidylcholine (DLPC) at a cholesterol-to- 5151 LDL-C, whereas EPA has a neutral effect or may slightly 5207 phospholipid mole ratio of 0.6:1 and treated with pharma- 5152 lower LDL-C. 5208 cologic levels of EPA and AA at a 1:30 FA to phospholipid 5153 Objective/Purpose: To further elucidate lipoprotein 5209 mole ratio under conditions of hyperglycemia (200 mg/dL). 5154 changes conferred by EPA and DHA. 5210 Changes in membrane lipid organization and width were 5155 Methods: We studied 43 healthy subjects (24 M, 19 F, 5211 measured using small angle X-ray diffraction approaches 5156 age 18-60) consuming less than 1.5 g per day of EPA/DHA 5212 and correlated with lipid hydroperoxide formation. Choles- 5157 in any form, in a randomized crossover, double-blinded 5213 terol domains were identified in experimental samples by 5158 study. Each subject received 3 g/d (4 gel capsules, 3 times/ 5214 the presence of diffraction peaks corresponding to a unit 5159 day) of either EPA-enriched fish oil (225 mg of EPA and 5215 cell periodicity or width of 34 A. 5160 100 mg of DHA, ratio 2:3) or DHA-enriched fish oil (274 5216 Results: Membranes containing EPA had a membrane 5161 mg of DHA and 74 mg of EPA, ratio 0.27) for 6-weeks,  5217 5162 with a wash out period of 8 weeks between arms. Each structure characterized by normal width of 55 Aand 5218 5163 subject was considered its own control, and all 30 subject cholesterol distribution under conditions of hyperglycemia. 5219 5164 analyzed completed both arms of the study. By contrast, AA containing samples yielded diffraction 5220 patterns consistent with a biphasic membrane structure 5165 Results: Both DHA and EPA-enriched supplements were 5221 containing prominent cholesterol crystalline domains and 5166 well tolerated. Compared to baseline EPA and DHA- 5222 phospholipid-enriched membrane bilayer domains with unit 5167 enriched supplementation respectively lead to changes in 5223 cell periodicities of 34 Aand54A , respectively. The width 5168 ApoA-I (-3.9% vs -3.7%), Apo-B (7% vs 5%), Triglycer- 5224 of 34 A corresponds to free cholesterol in an immiscible 5169 ides (-14% vs -13%), HDL-p (p5particle number) (-8% vs 5225 bilayer structure within the membrane. Unlike AA, EPA also 5170 -9%), VLDL-p (-26% vs -23%) and VLDL-z (z5particle 5226 inhibited lipid peroxide formation compared to vehicle. 5171 size) (-17% vs -18%), all p,0.05. In addition, DHA had a 5227 5172 significant increase in large LDL particles over EPA (6% Conclusions: EPA preserved normal membrane structure 5228 5173 DHA vs 2% EPA, p,0.05), as well as a significant increase and cholesterol distribution while reducing lipid oxidation 5229 5174 in HDL-z (1% EPA vs 2.4% DHA, p,0.05). under conditions of hyperglycemia in a manner that was not 5230 reproduced with AA. These data indicate physico-chemical 5175 Conclusions: Taken together, we observed that DHA and 5231 differences between these long chain FAs and support a 5176 EPA demonstrate significant similarities in their effects on 5232 potential benefit for EPA in reducing atherosclerotic 5177 lipids and lipoproteins, but DHA seems to result in larger 5233 cholesterol domain formation and associated pathology at 5178 HDL and LDL size particles that may confer additional 5234 pharmacologic levels. 5179 protective benefits. 5235 5180 5236 5181 341 5237 5182 336 Acute Effects of Curcuminoids, EPA 5238 5183 Eicosapentaenoic Acid, Unlike Arachidonic (Omega - 3), Astaxanthin and GLA On 5239 5184 Acid, Maintains Normal Membrane Structure Cardiovascular Health 5240 5185 and Cholesterol Distribution Under Conditions 5241 5186 of Hyperglycemia Divya Birudaraju, MD, Lavanya Cherukuri, MD, 5242 5187 April Kinninger, MPH, Ryan Pozon, MD, 5243 5188 Samuel Sherratt, CR, BS, R. Mason, PhD, (Beverly, MA) Chandana Shekar, MD, Kashif Shaikh, MD, 5244 5189 Sajad Hamal, MS, Ferdinand Flores, BSN, 5245 5190 Lead Author’s Financial Disclosures: None. Sion Roy, MD, Matthew Budoff, MD, (Torrance, CA) 5246 5191 Study Funding: This study was conducted with financial 5247 5192 support from Amarin Pharma, Inc. Lead Author’s Financial Disclosures: None. 5248 5193 Background/Synopsis: Highly purified, prescription Study Funding: None. 5249 5194 eicosapentaenoic acid (EPA) reduced cardiovascular events Background/Synopsis: We completed a prospective, 5250 5195 in the REDUCE-IT study population, including in patients randomized clinical trial to assess the efficacy of Curcu- 5251 5196 with diabetes. During hyperglycemia, there is abnormal minoids, EPA (Omega-3), Astaxanthin and GLA (CEAG) 5252 5197 membrane cholesterol aggregation which has been linked for improving cardiovascular health (blood pressure, 5253 5198 to oxidative stress and plaque instability. Due to its inflammation and endothelial reactivity) over a 4-week 5254 chemical structure, EPA at a pharmacologic dose may intervention period in individuals with Pre-Hypertension.

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5255 Objective/Purpose: We also assess the role of CEAG 5.0mmHg(P5 0.007), as compared to a slight decrease of 5311 5256 [Quell Gel] administration supplements in improving vascular 1.0 mm Hg in the female placebo group. (Table 3). 5312 5257 health in Pre-hypertensive individuals and in those at risk for Conclusions: Systolic BP were robustly reduced by 5313 5258 becoming hypertensive and other markers of cardiovascular CEAG in all subjects, but specifically noted in females over 5314 5259 function and cardiovascular disease risk factors. 4 weeks. In pre-hypertensive and metabolic syndrome 5315 5260 5316 Methods: We performed a double-blinded, placebo patients, lowering inflammation has been shown to substan- 5261 5317 controlled, randomized clinical trial to investigate the blood tially reduce the risk of developing cardiovascular diseases. 5262 5318 pressure effects of CEAG [ Quell Gel] tablets of 80 individuals Such observations highlight the importance and growing need 5263 5319 (30 men and 50 women). The mean age of participants were for accessible and effective anti-inflammatory interventions. 5264 5320 48.8 +/- 16.0 years. Participants were enrolled and randomized 5265 5321 to CEAG or placebo over 4 weeks. The demographics of both 5266 Other 5322 groups are shown in Table 1. Paired and Independent T tests 5267 5323 were used to analyze the mean differences between and within 5268 264 5324 groups. Repeated Measures ANOVA with Pairwise compari- 5269 Awarness of Risk factors decrease CVD* 5325 sons using Tukey’s test was used to analyze the effect of 5270 5326 CEAG on BP changes among genders in both groups. 5271 Erum Sohail Jiva, ARNP, (Ocala, FL) 5327 Results: The primary endpoint of the study was reduction 5272 Lead Author’s Financial Disclosures: None. 5328 5273 in BP at 4 weeks. There was significant reduction in mean 5329 Study Funding: None. 5274 SBP at 4 weeks in CEAG group compared to baseline 5330 5 5275 [mean+/-SD 4.7 +/- 6.8 (p 0.002)]. (Table 2). The effect was Background/Synopsis: Adequate awareness of risk 5331 5276 greater among females where reduction in mean systolic BP factors and lifestyle modification may help to reduce rate of 5332 5277 (SBP) at 4 weeks in the twenty-four female CEAG group was cardiovascular disease (CVD) who are at high risk and 5333 decrease the long-term complications in those who already 5278 Table 1 Baseline Characteristics among Participants. 5334 5279 have CVD. There is limited data on implementation of 5335 5280 Placebo Active series of educational sessions in community wellness center 5336 5281 n540 n538 or churches to increase access to health care and increase 5337 awareness regarding preventive care. Lack of time during 5282 Age, yrs. (mean 1/2 SD) 45.3 6 17.2 52.2 6 14.0 5338 5283 Female, n (%) 26 (65) 24 (63.2) primary care visit and lack of access due to cultural factors 5339 5284 Hispanics, n (%) 25 (62.5) 25 (62.5) hinders preventive care. 5340 5285 Never Smoked, n (%) 31 (77.5) 28 (73.6) Objective/Purpose: We aimed to conduct multiple 5341 2 5286 Body Mass Index, (kg/m ) 30.2 6 5.9 29.8 6 5.3 educational sessions to increase awareness regarding modi- 5342 1 2 5287 (mean / SD) fiable risk factors in small community church so that we 5343 5288 can decrease rate of CVD. 5344 5289 5345 5290 Table 2 BP reduction stratified by placebo and active treatment (* data present by mean 6 SD and P value comes from paired and 5346 5291 Independent t test) 5347 5292 Difference Difference 5348 5293 Blood within Group Between Groups 5349 5294 Pressure Group Baseline 4 weeks mean 6 SD mean 6 SD P-value* 5350 5295 SBP Active 129.6 6 5.8 124.9 6 8.7 4.6 6 7.1 4.7 6 6.8 5351 5296 Placebo 127.4 6 6.3 127.5 6 7.2 0.1 6 5.9 0.002 5352 5297 DBP Active 70.8 6 4.3 73.5 6 5.9 2.9 6 6.8 1.7 6 7.1 5353 5298 Placebo 72.6 6 5.0 73.7 6 6.3 1.2 6 7.4 0.287 5354 5299 5355 5300 5356 5301 Table 3 Repeated Measures of ANOVA on differences between active and placebo stratified by gender. 5357 5302 5358 Group Active Placebo P-value* 5303 5359 5304 Women Baseline SBP 128.3 6 5.6 129.0 6 6.6 0.695 5360 5305 4 weeks SBP 123.3 6 8.7 128.0 6 6.8 0.007 5361 6 6 5306 Baseline DBP 71.7 5.1 71.8 4.6 0.920 5362 6 6 5307 4 weeks DBP 72.9 5.9 73.8 5.9 0.602 5363 Men Baseline SBP 132.6 6 5.4 129.0 6 5.5 0.077 5308 5364 4 weeks SBP 129.3 6 6.6 127.0 6 6.9 0.084 5309 Baseline DBP 73.2 6 3.6 76.6 6 5.1 0.160 5365 5310 4 Weeks DBP 76.4 6 5.5 72.5 6 5.3 0.354 5366

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5367 Methods: This was a community-based Quasi-experi- 5423 5368 Health Disease Questionnaire: 5424 mental study conducted in small community church among Project Pre-Education Heart Disease Questionnaire 5369 randomly selected adults (.18 years). Data on socio- 5425 5370 demographic characteristics and risk factors collected. Questions True False 5426 5371 Also, knowledge about risk factors of CVD types, their Please respond True/False to the following 5427 5372 risk factors and warning signs for CVD events (stroke and questions below: 5428 5373 heart attack) were acquired using a Heart Disease ques- Polyunsaturated fats are healthier for the heart 5429 5374 tionnaire before and after educational sessions. The ques- then saturated fats. 5430 5375 tionnaire was found to have good internal consistency, Women are less likely to get heart disease after 5431 5376 determined through calculation of Cronbach’s alpha scores menopause than before 5432 5377 of 0.697, amd 0.533 for the pre-and post tests, respectively. Having had chicken pox increases the risk of 5433 5378 getting heart disease 5434 Results: There was a statistically significant increase in 5379 Eating a lot of red meat increases heart disease 5435 patient CVD knowledge mean scores of 1.813 points, from 5380 risk 5436 a pre-test score of 5.703 (SD5 2.514) to a post-test score of Most people can tell whether or not they have 5381 5437 7. 444 (SD 51.108) following the educational intervention high blood pressure 5382 5438 (t (33) 5 5.740, p ,.001). The educational intervention Trans-fats are healthier for the heart then most 5383 5439 was found to be equally effective for both male and other kinds of fats 5384 5440 females, with mean score of 1.965 for females and 1. The most important cause of heart attack is 5385 5441 1.765 for male (t (33)5 .582, p 5.525). Along with change stress 5386 5442 in knowledge, change in participant’s attitude and behavior Walking and gardening are considered types of 5387 exercise that can lower heart disease risk 5443 is noticed. The majority (83%) of participants claimed the 5388 Most of the cholesterol in an egg is in the white 5444 5389 part of the egg. 5445 Table 1.1 Project Demographic & Clinical Characteristic 5390 Smokers are more likely to die of lung cancer 5446 Information 5391 than heart disease. 5447 Taking an aspirin each day decreases the risk of 5392 Please answer the following question 5448 getting heart disease. 5393 Patient Demographic Information: 5449 Age ______Dietary fiber lowers blood cholesterol. 5394 Heart disease is the leading cause of death in the 5450 5395 Gender ______5451 Race ______United States. 5396 5452 Marital Status ______The healthiest exercise for the heart involves 5397 Highest level of education ______rapid breathing for a sustained period of time. 5453 5398 Form of health insurance ______Turning pale or gray is a symptom of having a 5454 5399 Common reason to see Primary Care Provider heart attack. 5455 5400 ______A healthy person’s pulse should return to normal 5456 5401 Height ______within 15 minutes after exercise. 5457 5402 Weight ______Sudden trouble seeing in one eye is a common 5458 symptom of having a heart attack. 5403 Smoking status ______5459 Cardiopulmonary resuscitation (CPR) helps to 5404 Alcohol use ______5460 How many times a week you exercise clear clogged blood vessels. 5405 HDL refers to ‘‘good’’ cholesterol, and LDL refers 5461 5406 ______5462 How many times a week you eat fast food to ‘‘bad’’ cholesterol. 5407 5463 ______Atrial defibrillation is a procedure where hardened 5408 Family history of heart disease arteries are opened to increase blood flow. 5464 5409 ______Feeling weak, lightheaded, or faint is a common 5465 5410 symptom of having a heart attack. 5466 5411 Taller people are more at risk for getting heart 5467 5412 Table 1.2 Participants Medical Status: CVD Risk Factors disease. 5468 5413 ‘‘High’’ blood pressure is defined as 110/80 5469 Frequency Results (systolic/diastolic) or higher. 5414 5470 Risk Factor (%) (n536) (n533) Most women are more likely to die from breast 5415 5471 Hyperlipidemia 48% 45% cancer than heart disease. 5416 Margarine with liquid safflower oil is healthier 5472 5417 Diabetes 50% 55% 5473 Hypertension 45% 42% than margarine with hydrogenated soy oil. 5418 5474 Obesity 60% 67% People who have diabetes are at higher risk of 5419 Smoking 10% 7% getting heart disease. 5475 5420 History of CVD 38% 35% Men and women experience many of the same 5476 5421 Chronic use of medications 52% 55% symptoms of a heart attack 5477 5422 for any of the above conditions (continued on next page) 5478

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5479 (continued) 330 5535 5480 5536 Questions True False Update on dyslipidemia patterns in Chilean 5481 adult population: Findings from the 2016- 5537 Eating a high fiber diet increases the risk of 5482 2017 National Health Survey 5538 5483 getting heart disease 5539 Heart disease is better defined as a short-term 5484 Paulina Mendoza, MD, 5540 illness than a chronic, long-term illness. 5485 5541 Many vegetables are high in cholesterol Guadalupe Echeverria, MSc, (Santiago, Chile) 5486 5542 5487 Bergman et al., (2011). Development of a comprehensive heart disease Lead Author’s Financial Disclosures: None. 5543 knowledge questionnaire. Journal of Health Education, 42 (2), 74-87. 5488 Study Funding: None. 5544 5489 talk show in particular was helpful in facilitating their Background/Synopsis: Cardiovascular diseases (CVD) 5545 5490 understanding of CVD risk factors, and 67.3% of partici- are the leading cause of death worldwide. Their most common 5546 5491 pants claimed that hands on sessions like yoga classes and pathological basis is atherosclerosis, which has a multifacto- 5547 5492 cooking challenge provided good insight and helpful in rial etiology including dyslipidemia as one of the main risk 5548 5493 making lifestyle changes to reduce risk of CVD. factors. Thus, nationwide prevalence assessment of dyslipide- 5549 5494 Conclusions: There exists a significant gap in population mia is a fundamental strategy for public health policymaking 5550 5495 awareness about risk factor modification can decreases rate of in both primary and secondary CVD prevention. 5551 5496 CVD. Treating cause of the cause is challenging due to lack of Objective/Purpose: To determine the prevalence of 5552 5497 access to preventive care. Conducting educational sessions in different dyslipidemic patterns in Chilean adult population. 5553 5498 community wellness center or churches can increase awareness Methods: The 2016-2017 National Health Survey (2016- 5554 5499 regarding prevention and decrease rate of CVD in community. 2017 NHS) is a cross-sectional household survey performed 5555 5500 Key words: Cardiovascular Disease, Risk factors, Prevention in non-institutionalized adults aged $18 years. Complex 5556 5501 design random selection was used in a nationally represen- 5557 5502 Project Evaluation Form: tative sample, which included administrative regions and 5558 5503 Evaluation form urban/rural locations. In a randomly selected subsample of 5559 5504 For the following questions, please circle the response that this survey, fasting total cholesterol, HDL cholesterol, and 5560 5505 matches the extent to which you agree or disagree with the triglycerides were directly measured, whereas LDL choles- 5561 5506 following statements. terol and non HDL cholesterol were calculated. 5562 5507 5563 1. The educational sessions were very informative Results: The subsample included 3,399 subjects with 5508 5564 valid measurements of blood lipids. National weighted 5509 Comments 5565 Don’t agree Somewhat agree Agree Strongly agree prevalences of high total cholesterol (.200 mg/dl), high 5510 5566 LDL cholesterol (.130 mg/dl), high non HDL choles- 5511 5567 2. The objectives of session were cleared terol (.160 mg/dl), hypertriglyceridemia (.150 mg/dl) 5512 5568 Comments and low HDL cholesterol (,40 mg/dl in males and ,50 5513 Don’t Somewhat 5569 Agree Strongly agree mg/dl in females) were 27.4%, 18.8%, 21.6% 34.7%, and 5514 agree agree 5570 47.2%, respectively. Dyslipidemias were more prevalent 5515 5571 in older age groups and at lower socioeconomic levels. 5516 5572 3. All sessions were clear in language and easily understandable 38.8% of Chilean adults had at least two lipid abnor- 5517 5573 malities (high LDL cholesterol, high triglycerides, or low 5518 Don’t Somewhat Comments 5574 Agree Strongly agree HDL cholesterol) and 13% (1.2 million subjects) ex- 5519 agree agree 5575 hibited alterations in all three lipid measurements. Thus, 5520 5576 achievement of recommended levels of these lipids -as 5521 5577 4. Timing of each session was appropriate indicated above- reached only 32.0% of the overall 5522 5578 Don’t Somewhat Comments population. 5523 Agree Strongly agree 5579 5524 agree agree Conclusions: Some form of lipid abnormality affects 5580 5525 two out of three adults in Chile. Low HDL cholesterol, 5581 high non HDL cholesterol and triglycerides, and mixed 5526 5. Educational material provided was helpful 5582 5527 dyslipidemias were very frequent even at higher preva- 5583 Don’t Somewhat Comments lences than LDL hypercholesterolemia. This pattern of 5528 Agree Strongly agree 5584 5529 agree agree atherogenic dyslipidemia is consistent with a high prev- 5585 5530 alence of sedentarism, overweight, obesity and metabolic 5586 5531 Suggestions for future sessions syndrome in Chile. Rather than focusing exclusively on 5587 5532 ______coverage for LDL cholesterol lowering drug therapy, these 5588 5533 ______findings call for action highlighting the need of population 5589 5534 ______wide as well as more comprehensive lipid-based preven- 5590 ______tive strategies.

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5591 333 342 5647 5592 Serving the Underserved: Are We Overlooking Virtual Patient Simulation Improves Clinical 5648 5593 HoFH Patients? Decision-Making in Dyslipidemia: Success of 5649 5594 Online CME 5650 5595 Linda C. Hemphill, MD, FNLA, 5651 5596 Anne Goldberg, MD, FNLA, FACP, Jelena Spyropoulos, PhD, Piyali Shin, (New York, NY) 5652 5597 G. Hovingh, MD, PhD, MBA, 5653 5598 Jerome Cohen, MD, FNLA, FACC, Lead Author’s Financial Disclosures: None. 5654 5599 Dean Karalis, MD, FACC, FNLA, (Boston, MA) Study Funding: The funding for the educational activity 5655 5600 was provided by an independent educational grant from 5656 5601 Lead Author’s Financial Disclosures: Amgen Sanofi US and Regeneron Pharmaceuticals and Amgen. 5657 5602 (consulting fee), Regeneron (consulting fee), IONIS Background/Synopsis: Patients with dyslipidemia are 5658 5603 (research funding), Regeneron/Sanofi (research at high risk for cardiovascular (CV) events. However, many 5659 5604 funding). patients are not optimally managed, leaving them vulner- 5660 5605 Study Funding: Supported in part by Aegerion, Inc. and able to CV events. 5661 5606 REGENXBIO Inc. Objective/Purpose: This study was conducted to 5662 5607 Background/Synopsis: The National Lipid Associa- determine if an online continuing medical education 5663 5608 tion (NLA) Health Quality & Research Committee (CME) intervention could improve the performance of 5664 5609 identified the need to conduct a survey to better under- cardiologists and primary care physicians (PCPs) in man- 5665 5610 stand the diagnosis and treatment of patients with familial aging patients with dyslipidemia. 5666 5611 hypercholesterolemia (HoFH) among primary care pro- Methods: The CME intervention comprised two cases 5667 5612 fessionals. It is estimated that up to 300,000 Americans presented in a virtual patient simulation (VPS) platform 5668 5613 have HoFH and are usually seen first by primary care that allows learners to order lab tests, make diagnoses, and 5669 5614 providers. These patients develop atherosclerotic vascular prescribe treatments in a manner matching the scope and 5670 5615 disease at an early age and most remain undiagnosed and depth of actual practice. Learners’ clinical decisions were 5671 5616 undertreated. analyzed using a sophisticated decision engine. Tailored 5672 5617 Objective/Purpose: To evaluate the knowledge of clinical guidance (CG), based on current evidence and 5673 5618 primary care providers in the diagnosis and treatment of expert recommendation, was provided following each de- 5674 5619 HoFH. cision and learners were then given the opportunity to 5675 5620 Methods: An electronic survey was sent out in June modify their decisions. Decisions were collected post-CG 5676 5621 and July of 2018 to 14,904 medical professionals and compared with each user’s baseline (pre-CG) decisions 5677 5622 licensed in the United States who treat patients with using a 2-tailed paired t-test to determine P values. 5678 5623 5679 elevated LDL-C levels. 504 healthcare providers Results: Significant absolute improvements were 5624 5680 completed the survey. observed after clinical guidance: 5625 5681 Results: Most respondents were physicians (85%) and 5626 Case 1 (n5 248 cardiologists; n5596 PCPs): 5682 the majority (88%) did not consider themselves lipid 5627 5683 specialists. Most respondents (69%) treat patients with - Diagnose dyslipidemia: 27% improvement among car- 5628 5684 LDL-C . 400 mg/dL, and 53% identified such patients as diologists (16% pre-CG vs 42% post-CG; P,.001) and 5629 5685 having HoFH. 82% of the respondents would use a risk 29% improvement among PCPs (16% pre-CG vs 45% 5630 5686 calculator to assess cardiovascular risk in such a patient. post-CG; P,.001) 5631 5687 Regarding treatment, 80% would treat with a high-intensity - Order eGFR testing: 10% improvement among cardiol- 5632 5688 statin, 60% would add a PCSK9 inhibitor, and only 13% ogists (41% pre-CG vs 51% post-CG; P5.01) and 11% 5633 5689 would consider LDL apheresis. Approximately 2/3 of improvement among PCPs (35% pre-CG vs 46% post- 5634 5690 respondents do not have access to an LDL apheresis center. CG; P,.001) 5635 5691 Over half of respondents (63%) would refer to a lipid - Appropriately order ezetimibe: 17% improvement 5636 5692 specialist; 14% as their 1st choice, 22% as their 2nd choice among cardiologists (16% pre-CG vs 33% post-CG; 5637 5693 and 27% as their last choice. 37% do not have access to a P5.01) and 21% improvement among PCPs (9% pre- 5638 5694 lipid specialist. Most respondents would start lipid lowering CG vs 30% post-CG; P,.001) 5639 5695 medications in a patient with HoFH after the age of 18. 5640 Case 2 (n5141 cardiologists; n5 509 PCPs): 5696 Only 24% would treat male and 20% female HoFH patients 5641 5697 at a younger age. - Diagnose CAD: 33% improvement among cardiolo- 5642 gists (3% pre-CG vs 39% post-CG; P5.004) and 48% 5698 5643 Conclusions: Many primary care providers do not 5699 adequately treat HoFH and do not have access to a lipid improvement among PCPs (9% pre-CG vs 57% post- 5644 , 5700 specialist. There is a need to provide more education to CG; P .001) 5645 - Order patient education and counseling: 14% improve- 5701 5646 primary care providers and to ensure them greater access to 5702 lipid specialists. ment among cardiologists (42% pre-CG vs 56% post-

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5703 CG; P5.002) and 21%% improvement among PCPs 5759 5704 (45% pre-CG vs 66% post-CG; P,.001) 5760 5705 - Order follow-up appointment: 43% improvement 5761 5706 among cardiologists (15% pre-CG vs 58% post-CG; 5762 5707 P5.003) and 44% improvement among PCPs (11% 5763 5708 pre-CG vs 55% post-CG; P,.001) 5764 5709 - Assess adherence to lifestyle and medications: 42% 5765 5710 improvement among cardiologists (15% pre-CG vs 5766 5711 57% post-CG; P5.004) and 43% improvement among 5767 5712 PCPs (12% pre-CG vs 55% post-CG; P,.001) 5768 5713 - Initiate PCSK9 inhibitor therapy: 35% improvement 5769 5714 5770 among cardiologists (31% pre-CG vs 66% post-CG; Figure 1 Forest plot comparing Omega-3 fatty acids with the 5715 P5.01) and 35% improvement among PCPs (23% pre- control for major adverse cardiovascular events (MACE) 5771 5716 CG vs 58% post-CG; P,.001) 5772 5717 - Order dietary changes: 15% improvement among car- revascularization (CR)]. The secondary outcomes were 5773 5718 diologists (44% pre-CG vs 59% post-CG: P5.003) and components of the MACE and all-cause mortality. The 5774 5719 11% improvement among PCPs (48% pre-CG vs 59% outcomes were estimated as relative risk (RR) with 95 % 5775 5720 post-CG; P,.001) confidence interval (CI) using a random effects model. 5776 5721 Results: In analysis of 23,383 patients with IHD (mean 5777 5722 Conclusions: This study demonstrates that VPS that age of 5767 years and mean follow-up of 31617 months), 5778 5723 immerses and engages the specialists in an authentic and use of n-3 FAs did not result in significant reduction of 5779 5724 practical learning experience can improve evidence-based MACE (RR: 0.93; 95% CI, 0.84-1.04; P50.22) as 5780 5725 clinical decisions of specialists related to the management of compared to the control group (Figure. 1). In contrast, n- 5781 5726 dyslipidemia. The study also uncovered educational gaps 3 FAs significantly lowered CV mortality (RR: 0.79; 95% 5782 5727 related to diagnosis, treatment and patient-centered care CI, 0.65-0.96; P50.02) in patients with IHD. There was no 5783 5728 strategies, suggesting that additional education on these topics significant reduction in terms of MI (RR: 0.87; 95% CI, 5784 5729 can improve clinical care of patients with dyslipidemia. 0.67-1.12; P50.27), all-cause mortality (RR: 0.97; 95% CI, 5785 5730 0.80-1.18; P50.75), stroke (RR: 0.72; 95% CI, 0.10-4.95; 5786 5731 P50.74), and CR (RR: 0.99; 95% CI, 0.92-1.06; P50.69) 5787 5732 Pathophysiology of Atherosclerosis with the n-3 FA use. 5788 5733 Conclusions: Use of n-3 FAs led to improved CV 5789 5734 310 mortality in patients with IHD, however, it failed to reduce 5790 5735 Effects of Marine Omega-3 Fatty Acids on the overall MACE. 5791 5736 Cardiovascular Outcomes in Patients with 5792 5737 Ischemic Heart Disease: A Meta-Analysis* 5793 5738 357 5794 5739 Hammad Ur Rahman, MD, 18-Day Residential Lifestyle Program 5795 5740 Tehseen Hammad, MBBS, Improves Lipids 5796 5741 Edo Kaluski, MD, FACC, (Sayre, PA) 5797 5742 Francisco Eduardo Ramirez, MD, Neil Nedley, MD, 5798 Lead Author’s Financial Disclosures: None. 5743 John Hartman, BS, Kendra LeBrun, BS, (Weimar, CA) 5799 5744 Study Funding: None. 5800 Lead Author’s Financial Disclosures: None. 5745 Background/Synopsis: Previous meta-analyses had 5801 5746 not addressed the impact of marine omega-3 fatty acids Study Funding: None. 5802 5747 (n-3 FAs) specifically in the ischemic heart disease (IHD) Background/Synopsis: Elevated lipid levels are asso- 5803 5748 patients. The role of n-3 FAs in the IHD population remains ciated with cardiovascular diseases such as atherosclerosis 5804 5749 uncertain. and myocardial infarction. 5805 5750 Objective/Purpose: To investigate the effects of n-3 Objective/Purpose: We explore the effect of intensive 5806 5751 FAs on cardiovascular (CV) outcomes in the IHD patients. lifestyle interventions on lipids. 5807 5752 Methods: Total of 8 randomized trials having $ 200 Methods: The intervention took place in Weimar CA. 5808 5753 patients with at least $ 1-year follow-up period were Restrospective data from 11 years of patients that finished 5809 5754 selected using PubMed/Medline, EMBASE and the CEN- the intervention was used. The 18 day medical holistic 5810 5755 TRAL (Inception- 30 November 2018) evaluating n-3 FAs intervention administered during the program changed 5811 5756 supplementation in patients with IHD (excluded trials with patient lifestyle habits in the areas of sleep, physical 5812 5757 fish advice alone). The primary outcome was major adverse activity, plant-based diet, hydration, sun exposure, self- 5813 5758 cardiovascular events (MACE) [composite of myocardial control, addictions, respiration, mental health, spirituality 5814 infarction (MI), stroke, CV mortality and coronary and relationships among others applied by health

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5815 professionals including board certified physicians. An year followed by extended, monthly evolocumab + SOC for 5871 5816 education component was included to train the patients to all. Here we report lipid effects and safety of evolocumab, 5872 5817 continue with the change long term. including anti-drug antibodies (ADA), over the 5-year 5873 5818 A retrospective paired-samples t-test was conducted to study. Updated final efficacy and safety data, including 5874 5819 compare serum glucose, total cholesterol, HDL, and LDL neurocognitive and muscle events, and new-onset diabetes, 5875 5820 levels before and after the residential intervention program. await final patient visits (June 2018) and will be available 5876 5821 All values are reported as mg/dl. for presentation at AHA. 5877 5822 Results: Baseline total cholesterol dropped from group Results: Of 1324 patients randomized to enter the 5878 5823 mean 213.3 (SD: 45.77) to 187.0 (SD: 37.79) mg/dL t (396)5 OSLER-1 SOC-controlled period for 1 year, 1255 (mean 5879 5824 18.4 p,0.001; Serum fasting glucose dropped from mean age 57 years; 53% female) continued into the evolocumab 5880 5825 104.9 (SD: 35.53) to 99.21 (SD: 29.76) mg/dL; t (396)53.5 + SOC period starting at year 2. Evolocumab reduced 5881 5826 p,0.001. Serum HDL cholesterol changed from 49.53 (SD: median LDL-C at years 1, 2, 3, 4, and 5 by 61% (N5818), 5882 5827 15.67) to 47.56 (SD: 13.96) mg/dL; t (396)55.1 p,0.001. 59% (N51122), 59% (n51059), 59% (n51012), and 58% 5883 5828 Serum LDL cholesterol decreased from mean 128.3 (SD: (n5870), respectively. Adverse events (AE) were reported 5884 5829 40.03) to 107.3 (SD: 31.32) mg/dL; t (396)517.2 p,0.001. in 79%, 74,%, 71%, 67%, and 65% of patients and serious 5885 5830 Chol/HDL ratio was reduced from an average of 4.751 (SD: AEs were reported in 7%, 7%, 8%, 7%, and 7% of patients 5886 5831 2.000) to 4.221 (SD: 1.318); t (396)57.1 p,0.001. each year (years 1 through 5). AEs leading to drug 5887 5832 5888 Conclusions: The intervention was effective reflected in discontinuation occurred in 2.8%, 0.8%, 1.3%, 1.0% and 5833 5889 the results of the 5 categories measured. The biggest t- 0.2% of patients each year (years 1-5). Two SOC and 2 5834 5890 values were found in total serum cholesterol levels (t 5 evolocumab patients transiently tested positive for binding 5835 5891 18.411) and LDL levels (t 5 17.260). Long term study is ADAs in Year 1, with no subsequent or new binding or 5836 5892 being plan to see if the changes continue. neutralizing ADAs detected to date. 5837 5893 Conclusions: In OSLER-1, the longest duration study of 5838 5894 a PCSK9 inhibitor to date, evolocumab consistently 5839 5895 reduced LDL-C with no increase in AEs over time and 5840 Pharmacological Control of Lipids and 5896 no neutralizing antibodies. 5841 Lipoproteins 5897 5842 297 5898 5843 Final Report of the OSLER-1 Study: Long-Term 314 5899 5844 Evolocumab for the Treatment of Alirocumab Reduces Total Nonfatal 5900 5845 Hypercholesterolemia Cardiovascular and Fatal Events in the 5901 5846 ODYSSEY OUTCOMES Trial† 5902 5847 Michael Koren, MD, Marc Sabatine, MD, 5903 5848 Robert Giugliano, MD, Gisle Langslet, MD, Robert Pordy, MD, Harvey White, DSc, 5904 5849 Stephen Wiviott, MD, Andrea Ruzza, MD, Yuhui Ma, PhD, Gregory Schwartz, MD, PhD, Marco Alings, MD, PhD, 5905 5850 Andrew Hamer, MD, Deepak Bhatt, Vera Bittner, MD, MSPH, 5906 5851 Scott Wasserman, MD, Chern Eng Chiang, MD, PhD, Rafael Diaz, MD, 5907 5852 Frederick Raal, MBBCh, MMED, PhD, (Jacksonville, FL) Jay Edelberg, MD, PhD, Shaun Goodman, MD, MSc, 5908 5853 Corinne Hanotin, MD, Robert Harrington, MD, 5909 Lead Author’s Financial Disclosures: employment 5854 J. Wouter Jukema, MD, PhD, Takeshi Kimura, MD, 5910 (significant): Jacksonville Center for Clinical Research, a 5855 Robert Gabor Kiss, MD, PhD, Guillaume Lecorps, MSc, 5911 company that has received research funds and consulting 5856 Kenneth Mahaffey, MD, Angele Moryusef, MD, 5912 fees from Amgen, Pfizer, Regeneron, Sanofi, and The 5857 Michael Szarek, PhD, Matthew T. Roe, MD, MHS, 5913 Medicines Company. 5858 Pierluigi Tricoci, MD, PhD, Denis Xavier, MD, MSc, 5914 5859 Study Funding: Amgen. Andreas Zeiher, MD, Gabriel Steg, MD, (Tarrytown, NY) 5915 5860 Background/Synopsis: Evolocumab and other mono- 5916 5861 clonal antibodies against PCSK9 reduced major adverse Lead Author’s Financial Disclosures: Employ- 5917 5862 CV outcomes in clinical trials of patients with CV disease ment, Regeneron Pharmaceuticals, Inc; Ownership interest: 5918 5863 treated up to a median of 2.8 years. Regeneron Pharmaceuticals, Inc. 5919 5864 Objective/Purpose: OSLER-1 evaluated long-term Study Funding: Sanofi & Regeneron Pharmaceuticals, 5920 5865 evolocumab treatment in a diverse population of hypercho- Inc. 5921 5866 lesterolemic patients now exposed for up to 5 years (year 1 Background/Synopsis: In ODYSSEY OUTCOMES, 5922 5867 standard of care [SOC] controlled, years 2-5 open label). first occurrence of coronary heart disease (CHD) death, 5923 5868 Methods: OSLER-1 enrolled patients who completed 1 myocardial infarction (MI), fatal/nonfatal ischemic stroke, 5924 5869 of 5 double-blind, controlled studies of evolocumab, and or hospitalization for unstable angina (UA) was reduced 5925 5870 randomized patients 2:1 to open-label evolocumab 420 mg from 1052 for placebo to 903 for alirocumab (hazard ratio 5926 monthly + SOC; n5882) versus SOC alone (n5442) for 1 [HR] 0.85; p50.0003). However, this does not reflect the

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5927 5983 5928 Table 1: 5984 5929 HR (95% CI) P-value 5985 5930 5986 Death and total nonfatal CV events (n55425) 5931 Alirocumab : placebo HR for nonfatal events (n52186 vs. n52513) 0.87 (0.8220.93) ,0.0001 5987 5932 Alirocumab : placebo HR for fatal events (n5334 vs. n5392) 0.83 (0.7120.97) 0.02 5988 5933 Association between nonfatal and fatal events 2.04 (1.7822.29) – ,0.0001 5989 5934 Frailty variance 0.94 (95% CI 0.9020.97) – ,0.0001 5990 5935 Death and total nonfatal CV events restricted to MI, stroke, or UA (n52999) 5991 5936 Alirocumab : placebo HR for nonfatal events (n51034 vs. n51239) 0.84 (0.7720.91) ,0.0001 5992 5937 Alirocumab : placebo HR for fatal events (n5334 vs. n5392) 0.82 (0.6820.99) 0.04 5993 5938 Association between nonfatal and fatal events 3.29 (2.8623.72) – ,0.0001 5994 2 , 5939 Frailty variance 0.87 (95% CI 0.84 0.91) – 0.0001 5995 5 5940 Analysis of first event: death or nonfatal CV event (n 3064) 5996 Alirocumab : placebo HR for first event (n51437 vs. 1627) 0.88 (0.8220.94) 0.0002 5941 5997 5942 CI, confidence interval; CV, cardiovascular; HR, hazard ratio; UA unstable angina. 5998 5943 5999 5944 6000 5945 full impact of treatment, as many patients had multiple 321 6001 5946 events and non-CHD death and other nonfatal cardiovas- Efficacy and Safety of Triplet Therapy With 6002 5947 cular (CV) events were excluded. Bempedoic Acid, Ezetimibe, and Atorvastatin 6003 5948 Objective/Purpose: Here we describe effects of alir- in Patients with Hypercholesterolemia 6004 5949 ocumab on total (first and subsequent) nonfatal CV events 6005 5950 and all-cause death by a model that accounts for the Diane MacDougall, MS, Lulu Ren Sterling, PhD, 6006 5951 relationship between nonfatal and fatal events. John Rubino, MD, Jeffrey Hanselman, MS, 6007 5952 Stephen Nicholls, MD, PhD, (Ann Arbor, MI) 6008 Methods: Patients with acute coronary syndrome (ACS) 5953 6009 and LDL cholesterol $70 mg/dL, non-HDL cholesterol 5954 Lead Author’s Financial Disclosures: Esperion 6010 $100 mg/dL, or apolipoprotein B $80 mg/dL on 5955 employee. 6011 maximum tolerated dose of atorvastatin or rosuvastatin 5956 Study Funding: This clinical trial was funded by 6012 were randomized 1:1 to treatment with alirocumab or 5957 Esperion Therapeutics Inc. 6013 placebo. The present analysis included all-cause death and 5958 Background/Synopsis: Patients with hypercholester- 6014 total nonfatal CV events (MI, stroke, hospitalization for 5959 olemia often fail to achieve sufficient cholesterol reduction, 6015 UA or heart failure, or ischemia-driven coronary revascu- 5960 despite the use of guideline-recommended lipid-lowering 6016 larization). A sensitivity analysis restricted nonfatal events 5961 therapies at maximally tolerated doses. Bempedoic acid, an 6017 to MI, stroke, or UA. Total nonfatal and fatal event hazard 5962 oral, first-in-class ATP-citrate lyase inhibitor, reduces low- 6018 functions were jointly estimated, linked by a shared frailty 5963 density lipoprotein cholesterol (LDL-C) when administered 6019 accounting for patient risk heterogeneity and correlated 5964 alone or in combination with statins or ezetimibe. 6020 within-patient nonfatal events. The model also determines 5965 6021 if nonfatal events are associated with an increased risk for Objective/Purpose: To evaluate the extent of LDL-C 5966 6022 death. Treatment effects were summarized by HRs and lowering achieved during triplet therapy with bempedoic 5967 6023 compared against the customary analysis of first nonfatal acid, ezetimibe, and atorvastatin. 5968 6024 CV event or death. Methods: This phase 2, randomized, double-blind, pla- 5969 6025 Results: There were 5425 total deaths or nonfatal CV cebo-controlled study enrolled adults with fasting LDL-C 5970 of 130 to 189 mg/dL following washout of lipid-lowering 6026 5971 events, 77% greater than first events (3064). Alirocumab 6027 produced similar relative reductions in first and total drugs and nutritional supplements. After completing a 6- 5972 week screening/washout period, eligible patients were 6028 5973 events when compared with placebo. Importantly, 6029 there were 385 fewer total events with alirocumab versus randomized 2:1 to treatment with triplet therapy (bempe- 5974 doic acid 180 mg, ezetimibe 10 mg, and atorvastatin 20 mg) 6030 5975 190 fewer first events. Nonfatal CV events were 6031 associated with a higher risk of death, and the frailty or placebo once daily for 6 weeks. The primary endpoint 5976 was the percent change from baseline in LDL-C at week 6. 6032 5977 variance indicated substantial inter-patient heterogeneity 6033 Sixty-three patients were enrolled at 14 sites in 5978 in risk. Results: 6034 the United States: 43 patients were randomized to triplet 5979 Conclusions: In patients with ACS, the total number of 6035 therapy and 20 patients to placebo. Mean baseline LDL-C 5980 deaths and nonfatal CV events prevented with alirocumab 6036 5981 was twice the number of first events prevented. Total event concentrations were 154 and 156 mg/dL in patients 6037 5982 reduction may be a useful metric to gauge the efficacy of receiving triplet therapy and placebo, respectively. At 6038 alirocumab after ACS. week 6, triplet therapy lowered LDL-C by 63.6% compared

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6039 with a 3.1% lowering in the placebo group. LDL-C drugs and nutritional supplements were discontinued if 6095 6040 lowering with triplet therapy was significantly greater applicable, a 3-month lipid stabilization period wherein 6096 6041 than placebo (difference, -60.5% [95% confidence interval: patients initiated background therapy with subcutaneous 6097 6042 -68.0% to -53.0%]; p,0.001). Significant reductions with evolocumab 420 mg/3.5 mL administered via the Push- 6098 6043 triplet therapy vs placebo (p,0.001 for all comparisons) tronex(R) system once monthly, and a 2-month double- 6099 6044 were observed for non-high-density lipoprotein cholesterol blind treatment period. Patients were required to have LDL- 6100 6045 (-60.0% vs -1.3%), total cholesterol (-47.1% vs -1.1%), C $160 mg/dL prior to initiating evolocumab and LDL-C 6101 6046 apolipoprotein B (-53.5% vs 0.6%), high-sensitivity C- $70 mg/dL prior to randomization. Eligible patients were 6102 6047 reactive protein (median, -47.7% vs -2.7%), and triglycer- randomized 1:1 to treatment with bempedoic acid 180 mg 6103 6048 ides (-27.4% vs 8.9%). No appreciable treatment effect on or placebo once daily added to background evolocumab for 6104 6049 high-density lipoprotein cholesterol was observed. In the 2 months. The primary endpoint was the percent change 6105 6050 triplet therapy group, 90.2% of patients achieved an LDL-C from baseline in LDL-C at month 2. 6106 6051 ,70 mg/dL and 95.1% of patients had a reduction in LDL- Results: A total of 59 patients were randomized: 28 to 6107 6052 Cof.50% at week 6 No patients in the placebo group met bempedoic acid and 31 to placebo. Mean LDL-C at the end 6108 6053 either treatment goal. The majority of treatment-emergent of the evolocumab-only lipid stabilization period was 103 6109 6054 adverse events were mild to moderate in severity; adverse mg/dL, and was similar in patients randomized to bempedoic 6110 6055 event rates were comparable in the 2 treatment groups. No acid or placebo. Two-month treatment with bempedoic acid 6111 6056 patients experienced clinically relevant aminotransferase or lowered LDL-C by 27.5%, whereas LDL-C in the placebo 6112 6057 creatine kinase elevations. group increased by 2.8% (placebo-corrected difference, 6113 6058 Conclusions: Oral, once-daily, combination therapy with -30.3%; p,0.001). With reference to the secondary end- 6114 6059 bempedoic acid 180 mg, ezetimibe 10 mg, and atorvastatin points, reduction in LDL-C of a similar magnitude was 6115 6060 20 mg lowered LDL-C by 64% and was well tolerated, with observed at month 1 of the treatment period. Patients in the 6116 6061 an adverse event profile similar to that of the placebo group. bempedoic acid treatment group also experienced significant 6117 6062 Most patients (.90%) who received triplet therapy expe- reductions compared with placebo in apolipoprotein B 6118 6063 rienced .50% LDL-C lowering from baseline and (-21.8% vs 2.7%; p,0.001), non-high-density lipoprotein 6119 6064 achieved LDL-C ,70 mg/dL. cholesterol (-23.0% vs 1.3%; p,0.001), total cholesterol 6120 6065 (-17.0% vs 0.6%; p,0.001), and high-sensitivity C-reactive 6121 6066 protein (-34.4% vs -1.6%; p50.029). Changes in lipopro- 6122 6067 tein(a), high-density lipoprotein cholesterol, and triglycer- 6123 6068 323 ides were similar between treatment groups. Rates of 6124 6069 Lipid Lowering With Bempedoic Acid Added to treatment-emergent adverse events were similar in the 6125 6070 Proprotein Convertase Subtilisin/Kexin Type 9 bempedoic acid and placebo treatment groups. 6126 6071 6127 Inhibitor Therapy: A Randomized Controlled Conclusions: Bempedoic acid provided significant addi- 6072 6128 Trial tional lipid lowering throughout a 2-month treatment period 6073 6129 when added to background PCSK9 inhibitor therapy, with a 6074 James McKenney, PharmD, Diane MacDougall, MS, 6130 safety profile similar to that of placebo. 6075 Lulu Ren Sterling, PhD, 6131 6076 Stephanie Kelly, BS, John Rubino, MD, (Richmond, VA) 6132 6077 6133 Lead Author’s Financial Disclosures: None. 344 6078 6134 Study Funding: This clinical trial was funded by Real-world health care costs incurred by early 6079 adopters of PCSK9 inhibitor therapy* 6135 6080 Esperion Therapeutics Inc. 6136 6081 Background/Synopsis: Combination therapy is often Michael Wesley Milks, MD, ChienWei Chiang, PhD, 6137 6082 required to reach optimal lipid levels in patients with Wendy Xu, PhD, John Larry, MD, Laxmi Mehta, MD, 6138 6083 elevated low-density lipoprotein cholesterol (LDL-C) Lang Li, PhD, Sheldon Retchin, MD, 6139 6084 despite lipid-lowering monotherapy. Bempedoic acid, an MSPH, (Columbus, OH) 6140 6085 oral, once daily, first-in-class inhibitor of ATP-citrate lyase, 6141 6086 has been shown to provide additional LDL-C lowering Lead Author’s Financial Disclosures: None. 6142 6087 when added to background treatment with a statin or Study Funding: The project described was supported by 6143 6088 ezetimibe. Award Number Grant UL1TR002733 from the National 6144 6089 Objective/Purpose: To assess the efficacy and safety Center For Advancing Translational Sciences. The content 6145 6090 of bempedoic acid added to stable proprotein convertase is solely the responsibility of the authors and does not 6146 6091 subtilisin/kexin type 9 (PCSK9) inhibitor background necessarily represent the official views of the National 6147 6092 therapy in patients with elevated LDL-C. Center For Advancing Translational Sciences or the Na- 6148 6093 Methods: This phase 2, randomized, double-blind, pla- tional Institutes of Health. 6149 6094 cebo-controlled study consisted of 3 phases: a 1.5-month Background/Synopsis: Proprotein convertase subtili- 6150 screening/washout period during which all lipid-modifying sin/kexin type 9 inhibitors (PCSK9i) reduce atherogenic

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6151 low density lipoprotein cholesterol (LDL-C) by an addi- treated individuals are needed to provide more precise 6207 6152 tional 60% beyond standard lipid-lowering therapies and estimates of cost-effectiveness. 6208 6153 result in a significant decrease in atherosclerotic cardiovas- Objective/Purpose: The goal of this study was to 6209 6154 cular disease (ASCVD) events. However, the initial annual define the real-world economic impact of PCSK9i among 6210 6155 cost of PCSK9i therapy in the United States exceeded early adopters. 6211 6156 6212 $14,000, which has raised cost-effectiveness concerns. Methods: The Truven Health MarketScan Commerical 6157 6213 Published data from simulated models have estimated Claims and Encounters Database was queried for individ- 6158 6214 annual cost-effective prices to be $4,500-$10,000 to uals continuously enrolled in a commercial health insur- 6159 6215 achieve a conventional quality-adjusted life-year threshold. ance plan for 12 months prior to and 12 months after 6160 6216 However, real-world health care costs incurred by PCSK9i- PCSK9i initiation in 2015 or 2016. Presence (ASCVD+) or 6161 6217 absence (ASCVD-) of prior ASCVD events for each 6162 6218 participant was determined: ASCVD+ was defined as any 6163 6219 claim for unstable angina (ICD-10 code I20.xx), myocar- 6164 6220 dial infarction (I21.xx), or stroke (I63.xx), in the 12 months 6165 6221 preceding the PCSK9i initiation period. Claims for phar- 6166 6222 maceutical, inpatient, and outpatient health care were 6167 6223 compared among 3 groups of individuals: 1) ASCVD- 6168 6224 with use of PCSK9i, 2) ASCVD+ with use of PCSK9i, and 6169 6225 3) a comparison group (n51,000) of ASCVD+ individuals 6170 6226 who did not initiate PCSK9i. 6171 6227 6172 Results: A total of 1,944 early PCSK9i adopters met 6228 5 5 6173 inclusion criteria (ASCVD+, n 973; ASCVD-, n 971). 6229 6174 Initiation of PCSK9i was associated with an average 6230 6175 increase of $10,733 in total pharmaceutical (lipid lowering 6231 6176 drug and otherwise) costs (Fig. 1A). Outpatient and 6232 6177 inpatient costs (Figs. 1B, 1C) increased modestly (11% 6233 6178 and 29%, respectively) among ASCVD- who initiated 6234 6179 PCSK9i and markedly (104% and 292%, respectively) 6235 6180 among ASCVD+ who did not initiate PCSK9i. Outpatient 6236 6181 and inpatient costs decreased (-10% and -42%, respec- 6237 5 6182 tively; combined mean reduction $6,744) among 6238 6183 ASCVD+ who initiated PCSK9i. 6239 6184 Conclusions: Among early adopters of PCSK9i therapy, 6240 6185 outpatient and inpatient costs decreased among ASCVD+ 6241 6186 but not ASCVD- individuals. Outpatient and inpatient costs 6242 6187 were much higher in ASCVD+ individuals who did not 6243 6188 start PCSK9i. These real-world results suggest that in- 6244 6189 dividuals with prior ASCVD events may benefit from 6245 6190 greater cost-effectiveness of PCSK9i. A recognized limita- 6246 6191 tion is that the association between PCSK9i initiation and 6247 6192 costs may be subject to confounding factors. Further study 6248 6193 may elucidate the mechanism of this difference, such as 6249 6194 fewer ASCVD testing or revascularization procedures 6250 6195 among PCSK9i-treated individuals. 6251 6196 6252 6197 6253 6198 345 6254 6199 Determinants of response and tolerability of 6255 6200 PCSK9 inhibitor therapy 6256 6201 6257 6202 Anthony S. Wierzbicki, MD, DPhil, FRCPath, 6258 6203 Timothy Reynolds, MD FRCPath, 6259 6204 Figure 1 (A, B, and C): Total pharmaceutical (A, top panel), Hanini Vijayenthiran, MB BS, Zofia McMahon, MSc SRN, 6260 6205 outpatient (B, middle panel), and inpatient (C, bottom panel) costs Radha Ramachandran, MRCP FRCPath, 6261 6206 in the 12 months prior to (‘‘pre’’) vs. 12 months following Adie Viljoen, MB BS FRCPath, 6262 (‘‘post’’) the early adopter PCSK9i initiation period. Martin Crook, MD FRCP FRCPath, (London, England)

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6263 Lead Author’s Financial Disclosures: None. 353 6319 6264 6320 Study Funding: Unrestricted educational grant from Distribution of Apolipoprotein(a)-Containing 6265 6321 Amgen to Professor T.J. Reynolds and investigators for Species in Human Plasma Assessed by Fast 6266 6322 audits of lipid clinic prescribing. Protein Liquid Chromatography 6267 6323 PCSK9 inhibitor therapy is 6268 Background/Synopsis: Michael Boffa, PhD, Julia St . John, MSc, 6324 recommended for patients with genetic hyperlipidemias, 6269 Amer Youssef, PhD, 6325 established cardiovascular disease and those unable to 6270 Marlys Koschinsky, PhD, (London, England) 6326 6271 tolerate current routine lipid-lowering therapies. Studies 6327 6272 suggest that some patients cannot tolerate PCSK9 therapy Lead Author’s Financial Disclosures: Research 6328 6273 but the characteristics of these patients are unclear. 6329 Objective/Purpose: This audit of PCSK9 prescribing 6274 contract with Ionis. 6330 6275 in a university hospital and 2 district general hospitals 6331 Study Funding: Canadian Institutes for Health Research, 6276 investigated the factors related to efficacy and tolerability 6332 natural Sciences and Engineering Research Council of Canada. 6277 of PCSK9 inhibitor therapy. 6333 6278 Methods: Data on patients attending lipid clinic services Background/Synopsis: Lipoprotein(a) (Lp(a)) consists 6334 6279 and prescribed PCSK9 was obtained following all prescrip- of apolipoprotein(a) (apo(a)) covalently linked to apolipo- 6335 6280 tions for this therapy followed up for up to 1 year. Other data proteinB100 (apoB100) in a lipoprotein particle with similar 6336 6281 gathered included demographics, co-morbidities, other drug lipid composition to LDL. Fundamental questions regarding 6337 6282 therapies, pre- and post-treatment lipids, liver alanine trans- the biogenesis and metabolism of Lp(a) remain unresolved, 6338 6283 aminase function (ALT), creatine kinase (CK) and glycated particularly the site of Lp(a) assembly and the nature of the 6339 6284 haemoglobin (HbA1c). Concomitant drug therapies were apoB100-containing species involved. 6340 6285 classified by principal indication e.g. anti-thrombotic, anti- Objective/Purpose: We aim to address reports of small 6341 6286 hypertensive, anti-depressant, analgesic, immunosuppressant, amounts of apo(a) in plasma, kinetic data suggesting 6342 6287 thyroid hormone or vitamin D supplementation. Data were dissociation of apo(a) from Lp(a) with possible reassocia- 6343 6288 analysed by multiple linear and logistic regression. tion with triglyceride-rich lipoproteins (TRLs), and the 6344 6289 Results: Data was available for 132 patients, average age appearance of Lp(a) in TRL-containing fractions in hyper- 6345 6290 61 (SD13) years, 54% male, 70% with familial hyper- triglyceridemic subjects. 6346 6291 cholesterolaemia, 71% intolerant to 2+statins, 40% with Methods: We subjected fasting plasma from two in- 6347 6292 coronary heart disease and 16% with contra-indications to dividuals with high or low Lp(a) levels to fast protein liquid 6348 6293 statin therapy. Diabetes was present in 12% and current chromatography (FPLC) over a Superose 6 column to 6349 6294 smoking in 9%. Any statin therapy had been introduced in separate lipoprotein classes by size under native conditions. 6350 6295 47% and ezetimibe in 46% by time of PCSK9 prescription. Results: We found, using an apo(a)-specific ELISA, that 6351 6296 Anti-depressants were prescribed in 5%, diabetes drugs in Lp(a)elutedinabroadpeak,centered approximately on the 6352 6297 13%, analgesics in 16% and vitamin D in 7%. Baseline LDL-containing peak but also extending into the VLDL-size 6353 6298 lipid values were cholesterol 303mg/dl; triglycerides range; the latter characteristic was particularly evident for the 6354 6299 212mg/dL; HDL-C 60mg/dl, LDL-C 206mg/dL and Lp(a) subject with high Lp(a) levels. No apo(a) was detectable in 6355 6300 184nmol/L with ALT 26(13)iu/L, CK 128(83)iu/L and later fractions where free apo(a) would be expected to elute. 6356 6301 HbA1c 42(13)mmol/mol. After PCSK9 therapy with evo- Addition of -aminocaproic3 acid ( -ACA,3 a lysine analog) had 6357 6302 lucumab (81%) or alirocumab (19%) achieved LDL-C was no impact on the elution profile of apo(a), indicating a lack of 6358 6303 117mg/dl (44% reduction; P,,0.001) and Lp(a) 113nmol/ non-covalent apo(a) complexes with apoB100-containing 6359 6304 L (39% reduction; p50.003) and HbA1c 42(14)mmol/mol. particles. We also supplemented the plasma with purified, 6360 6305 11% of patients discontinued PCSK9 therapy usually due to recombinant 17-kringle apo(a) (17K). The majority of this 6361 6306 flu-like symptoms and myalgia and mostly after the first material eluted in a pattern identical to Lp(a) itself, suggesting 6362 6307 injection. PCSK9I efficacy was not related to initial that the added apo(a) became associated with predominantly 6363 6308 diagnosis or NICE category for initiation, baseline lipids LDL-size particles. Western blot analysis of column fractions 6364 6309 or other biochemistry, concomitant diagnoses or therapies. revealed that at least some of the added apo(a) was non- 6365 6310 Among patients discontinuing PCSK9 therapy only the covalently associated with these particles. Interestingly, we 6366 6311 presence of concomitant analgesics (including for neuralgic achieved the same results as for 17K when we used an apo(a) 6367 6312 and chronic pain) predicted outcome (b5 2.23; p50.01). variant lacking the strong lysine-binding sites in kringle KIV 6368 6313 Conclusions: PCSK9 inhibitors in clinical practice show types 7 and 8 (17KDLBS7,8), indicating that these interac- 6369 6314 efficacy in line with clinical trial data and independent of tions do not depend on these lysine binding sites, which are 6370 6315 baseline characteristics and indications. Discontinuation was otherwise key for Lp(a) assembly. A small peak of apo(a) in 6371 6316 seen in 11% of patients similar to that found in trials in statin- fractions spanning a size range smaller than HDL was 6372 6317 intolerant patients. The only predictor of likely discontinuation detected by ELISA, although this material was not observable 6373 6318 was the prescription of analgesia for neuralgic or chronic pain. on western blots. As before, addition of ε-ACA did not 6374

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6375 materially affect the elution profiles of either apo(a) variant. It 6431 6376 did, however, appear to dissociate non-covalent complexes of Table 2 Baseline Characteristics among Participants 6432 6377 17KDLBS7, 8 with particles in the VLDL-size range. Placebo Active 6433 6378 Conclusions: Our findings are consistent with the n532 n530 6434 6379 6435 essential absence of uncomplexed apo(a) in plasma as 2 6 6 6380 Age, yrs. (mean +/ SD) 61.9 7.77 58.66 9.10 6436 well as with the non-covalent association of Lp(a) with Female, n (%) 23 (71.88) 17 (56.67) 6381 6437 TRLs being mediated by the apo(a) component. Ethnicity 6382 White, n (%) 5 (15.63) 6 (20) 6438 6383 6439 Visceral Obesity, Metabolic Syndrome and African-American, n (%) 5 (15.63) 4 (13.33) 6384 Hispanic, n (%) 16 (50) 16 (53.33) 6440 6385 Atherosclerosis Asian, n (%) 6 (18.75) 4 (13.33) 6441 6386 284 Body Mass Index, (kg/m2) 32.67 6 6.66 33.67 6 9.11 6442 2 6387 Effects (Critical Role) of Nitrite and Nitrate (mean +/ SD) 6443 SBP, mmHg (mean +/2 SD) 142.7 6 10.7 143.1 6 10.6 6388 determinants in Saliva and Plasma Correlating 6444 DBP, mmHg (mean +/2 SD) 79.7 6 10.6 81.7 6 11.2 6389 Cardio Metabolic factors 6445 6390 6446 6391 Divya Birudaraju, MD, Lavanya Cherukuri, MD, 6447 6392 April Kinninger, MPH, Kashif Shaikh, MD, 6448 6393 Chandana Shekar, MD, Sajad Hamal, MS, double-blinded study for 12 weeks, with an interim visit at 6449 6394 Ferdinand Flores, BSN, Sion Roy, MD, William Sotka, MA, 2 weeks( Table 2) Inorganic NO3 tablets (Berkeley Life 6450 6395 Shawn Green, PhD, Matthew Budoff, MD, (Torrance, CA) Tablet) consisted of nitrate-rich beetroot extract, thiamine 6451 6396 nitrate, and potassium nitrate in the presence of ascorbic 6452 6397 Lead Author’s Financial Disclosures: None. acid, to facilitate NO formation. 6453 6398 Study Funding: None. Results: At 12 weeks, the bio conversion of NO3 to NO2/ 6454 6399 Background/Synopsis: Endothelial nitric oxide (NO) NO after 2 hrs. post-ingestion of inorganic NO3 supple- 6455 6400 bioavailability is a diagnostic marker and has been a major ment showed salivary strip levels of median +SD of 110.0+ 6456 6401 topic of research, which has clinical implications for 163.28 after receiving placebo tablets, as compared to 6457 6402 monitoring cardiovascular disease(CVD) and metabolic 435.0+297.93 (p,0.0001) among the 30 participants that 6458 6403 syndrome that includes obesity, hypertension, hyperlipid- received the inorganic NO3 supplement. As predicted, 6459 6404 emia and impaired glucose tolerance. plasma nitrate levels increased significantly more in the 6460 6405 Objective/Purpose: We hypothesized to assess the NO3 supplement group vs the placebo group {190 +170.37 6461 6406 efficacy of inorganic nitrate-containing tablets (NO3) to vs. 41.60+68.8 respectively (p,0.003)}.(Table 1) 6462 6407 elevate NO bioavailability. Conclusions: Inorganic NO3 supplementation demon- 6463 6408 Methods: 62 individuals (22 men and 40 women; the strated significant increase in NO. Inorganic NO3 supple- 6464 6409 mean age of 60.4+9.0 years) with mean baseline systolic mentation has the potential to be used to complement 6465 6410 and diastolic Blood pressure (BP).120 and 80 mg Hg antihypertensive and hyperlipidemic therapies, including 6466 6411 respectively who were randomized to receive daily an 314 plant-based dietary approaches, for improvement in 6467 6412 mg NO3 or NO3-free (placebo) tablets in a randomized vascular function. 6468 6413 6469 6414 6470 6415 6471 6416 Table 1 Significant correlation of plasma and salivary nitrate and nitrite/ Salivary strip Test (Berkeley Test Strip) _adjusted Values in 6472 6417 active and placebo groups : 6473 6418 Group Baseline 2 hours P-value* 2 weeks P-value* 12 weeks P-value* 6474 6419 6475 6420 Placebo Plasma Nitrate 49.166 27.22 37.61 6 95.16 0.47 42.26 6 99.28 0.65 41.60 6 68.88 0.450 6476 6 6 , 6 , 6 , 6421 Plasma Nitrite 0.11 0.13 0.09 0.12 0.0001 0.12 0.22 0.0001 0.05 0.13 0.0001 6477 6 6 6 6 6422 Salivary Nitrate 31.3455 275.3043 122.744 960.13 0.013 146.56 446.92 0.06 68.70 1503.39 0.881 6478 Salivary Nitrite 150 6 277.98 119.43 6 651.37 0.744 160.59 6 841.32 0.30 143.39 6 362.90 0.865 6423 6479 Salivary Strip 20.00 6 64.51 110.00 6 131.24 ,0.0001 110.00 6 245.48 0.0006 110.0 6 163.28 0.001 6424 Active Plasma Nitrate 39.75 6 26.52 167.67 6 107.27 0.016 232.54 6 139.11 0.00 190.06 6 170.37 0.003 6480 6425 Plasma Nitrite 0.07 6 0.22 0.20 6 0.36 ,0.0001 0.14 6 0.26 ,0.0001 0.16 6 0.42 ,0.0001 6481 6426 Salivary Nitrate 27.75 6 284.01 2,177.62 6 4.352.13 ,0.0001 1,878.47 6 6,218.14 ,0.0001 1,516.65 6 3,625.42 ,0.0001 6482 6427 Salivary Nitrite 19.09 6 670.04 1,315.93 6 1,801.33 0.0001 913 6 2260.06 ,0.001 970.24 6 1452.94 ,0.0001 6483 6428 Salivary Strip 20.00 6 53.36 435.00 6 332.24 ,0.0001 435.00 6 335.17 ,0.0001 435.0 6 297.93 ,0.0001 6484 6429 *data present by median 6 SD and P value comes from Wilcoxon Signed Rank test 6485 6430 6486

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