Official Publication of the National Lipid Association

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Evaluating Published Clinical Trials and Translating Them into Practice

Also in this issue: Translating Clinical Trial Evidence into Practical Medicine Guidelines for the Guidelines — Impact and Controversies This issue sponsored by the Southeast Lipid Association

Volume 13 Issue 1 Winter 2015 visit www.lipid.org SPRING CLINICAL LIPID UPDATE REGISTER NOW! 2015

FEBRUARY 27–MARCH 1, 2015 DENVER, CO NATIONAL LIPID ASSOCIATION

Hosted by the Paci c and Southwest Chapters

ACHIEVING NEW HEIGHTS IN Keynote Address LIPID MANAGEMENT Working Together to Prevent One Million Heart Attacks and Strokes Janet Wright, MD Clinical Lipid Update Friday, February 27 at 4:00 PM February 27–March 1, 2015 Featured Presentations ApoB in Risk Assessment and the Diagnosis Professional Development Courses and Treatment of the Atherogenic Dyslipoproteinemias February 26–27, 2015 Allan D. Sniderman, MD

Sunday, March 1 at 9:00 AM

Understanding the Molecular Biology of Atherosclerosis: The Future of Prevention and Intervention in Heart Disease Paul N. Hopkins, MD, MSPH

Saturday, February 28 at 10:30 AM NATIONAL LIPID ASSOCIATION

The ApoC-III Story: Hypertriglyceridemia, Atherogenesis, and Therapeutic Inhibition Frank M. Sacks, MD lipid.org/springclu Saturday, February 28 at 1:45 PM In This Issue: Winter 2015 (Volume 13, Issue 1)

Editors 2 From the NLA President JAMES A. UNDERBERG, MD, MS, FACPM, FACP, FNLA* Full Speed Ahead Clinical Assistant Professor of Medicine —Terry A. Jacobson, MD, FACP, FNLA NYU School of Medicine & NYU Center for Prevention of Cardiovascular Disease Director Bellevue Hospital Lipid Clinic 5 From the SELA President Look for the NLA Community logo to discuss New York, NY Researching Progress articles online at www.lipid.org ROBERT A. WILD, MD, PhD, MPH, FNLA* —Lori A. Alexander, MSHS, RD, CCRC, FNLA Clinical Epidemiology and Biostatistics and Clinical Lipidology Professor Oklahoma University Health Sciences Center 6 Letter from the LipidSpin Editors 25 Case Study Oklahoma City, OK Holiday Gifts Applying Clinical Trial Data to Patient —James A. Underberg, MD, MS, FACPM, FACP, Managing Editor Management: A Case Study MELISSA HEYBOER FNLA —Paul Ziajka, MD, PhD, FNLA National Lipid Association Executive Director 7 Clinical Feature 27 Chapter Update CHRISTOPHER R. SEYMOUR, MBA National Lipid Association Translating Clinical Trial Evidence into Contributing to the NLA Mission Practical Medicine —Lori A. Alexander, MSHS, RD, CCRC, FNLA Contributing Editor —Ralph Vicari, MD, FACC, FNLA KEVIN C. MAKI, PhD, CLS, FNLA 29 Member Spotlight Associate Editor for Patient Education 11 Guest Editorial Deborah S. Croy, NP, DNP, RN, VANESSA L. MILNE, MS, NP, CLS Cardiac Vascular Nurse and Family Nurse Practitioner Guidelines for the Guidelines — ANP-BC, AGPCNP-BC, CLS, AACC Bellevue Hospital Lipid Clinic Impact and Controversies New York, NY —Kahlid H. Sheikh, MD, MBA, FACC, FNLA 31 Education, News and Notes

LipidSpin is published quarterly by the National Lipid Association 14 EBM Tools for Practice 33 Events Calendar 6816 Southpoint Parkway, Suite 1000 Clinical Trials of Alternative Medicine: Jacksonville, FL 32216 Phone: 904-998-0854 | Fax: 904-998-0855 Testing Whether Magic Works 34 Foundation Update —Gregory S. Pokrywka, MD, FACP, NCMP, FNLA Copyright ©2015 by the NLA. All rights reserved. 35 References Lipid Luminations Visit us on the web at www.lipid.org. 16 HPS2-THRIVE Commentary 37 Patient Tear Sheet The National Lipid Association makes every effort to —Dave Dixon, PharmD, BCPS, CDE, AACC, FNLA provide accurate information in the LipidSpin at the —Evan Sisson, PharmD, MSHA, CDE, FAADE time of publication; however, circumstances may alter certain details, such as dates or locations of events. Any changes will be denoted as soon as possible. 18 Specialty Corner The NLA invites members and guest authors to provide scientific and medical opinion, which do not Physical Activity and Lipid Disorders: necessarily reflect the policy of the Association. Circa 2014 —Ralph LaForge, MSc, CLS, FNLA Clarification: In the Practical Pearls article titled “Lowering Triglycerides with Omega-3 Fatty Acids” from the Fall 2014 issue, the word “supplements” 22 Practical Pearls should have been used rather than “OTC.” Selection of Dyslipidemia Guidelines in Special Populations *indicates ABCL Diplomate status —Pamela Morris, MD, FACC, FACP, FACPM, FAHA, FNLA

Official Publication of the National Lipid Association 1 From the NLA President: Full Speed Ahead

TERRY A. JACOBSON, MD, FACP, FAHA, FNLA National Lipid Association President Professor of Medicine, Emory University Atlanta, GA Director, Lipid Clinic and Cardiovascular Risk Reduction Program Diplomate, American Board of Clinical Lipidology

It also reaffirms the importance of lower Recommendations. Janet S. Wright, MD, cholesterol goals and targets consistent will be presenting the Keynote Address with the 2012 Cholesterol Treatment “Working Together to Prevent One Million Discuss this article at Trialist’s (CTT) meta-analysis of all statin Heart Attacks and Strokes.” She will be www.lipid.org/lipidspin clinical trials. speaking about the Million Hearts initiative and how we can all work together to Greetings, National Lipid Association As a result of requests by many NLA prevent an additional one million heart members! I hope this holiday season members, the NLA leadership has attacks and strokes. The full program, has been a joyous one. As we look back recently posted a slide set comparing including those talks centered on the on 2014, we can reflect on the many the ACC/AHA Guidelines with the NLA Recommendations and the ACC/AHA accomplishments the NLA has put forth. NLA Recommendations. The new slide guidelines, can be viewed online at And, as we look toward the New Year, we presentation — created in large part by lipid.org/springclu. are encouraged for what’s to come — both Carl Orringer, MD, FNLA, and reviewed by for the NLA as a whole and for the field of an NLA Recommendations Review Panel — The Midwest Lipid Association will clinical lipidology. compares and contrasts the perspectives be hosting the 2015 Annual Scientific provided by the ACC/AHA Guidelines and Sessions June 11–14, 2015, in Chicago. Most recently, I had the opportunity to the NLA Recommendations. You can find This is a great opportunity to submit your attend the American Heart Association’s the slide set by visiting, abstracts to be included in the poster hall. Annual Scientific Sessions in Chicago lipid.org/recommendations. All accepted abstracts will be published in November, where the results of the in the Annual Scientific Sessions edition IMPROVE-IT Trial were presented. I was In addition, you will want to make sure of the Journal of Clinical Lipidology (JCL) very excited to hear the results, and as I to attend the NLA Spring Clinical Lipid and up to five abstracts will be selected hoped, the outcome reaffirms the NLA’s Update (CLU) — sponsored by the to be presented during the oral abstract Part 1 Recommendations for the Patient- Pacific Lipid Association and Southwest presentation session during the annual Centered Management of Dyslipidemia. Lipid Association — Feb. 27– March 1, meeting. The study also refocuses the emphasis 2015, in Denver. One of the sessions back to the importance of reducing all will focus on the controversies in clinical I especially urge all Young Investigators (in atherogenic lipoprotein particles, and lipid management, with presentations on training students, residents, and fellows supports our position that lower is better. the ACC/AHA Guidelines and the NLA or members in practice for less than five

2 LipidSpin years) to submit an abstract. As lead their science published in the JCL. Also, author of an accepted abstract, Young lets get to see and acknowledge those Investigators also will have the chance to NLA members who are providing effective compete for the NLA’s enhanced Young mentorship of Young Investigators and Investigator Award. Cash prizes of $1,000 supporting the development of future and $500 along with additional travel lipidologists. The submission deadline for grants will be awarded to the top three all abstracts is Feb. 23, 2015. For more finalists. The award winners will receive information, or to submit your abstract, recognition at a special ceremony during visit lipid.org/abstracts. the Annual Scientific Sessions. In addition, the first place winner will be selected We hope to see you at our upcoming to present his or her abstract during the meetings and appreciate your continued live abstract session and have the poster support of the NLA and the field of clinical published in the LipidSpin following the lipidology. meeting. Also, all Young Investigator lead authors with accepted abstracts will Happy New Year! n receive complimentary registration to the Scientific Sessions. In addition, 4th and 5th place awardees will receive travel grants to get to and from the meeting. Make sure to inform any resident, fellow, or in-practice member of this great opportunity to get

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Official Publication of the National Lipid Association 3 What is your 2015 New Year’s Resolution?

Expand your knowledge of Clinical Lipidology? Advance your personal standard of practice? Improve clinical decision making skills?

The National Lipid Association’s

Online Course

can help you achieve your resolution and advance your career!

Topics: Features: Advanced Lipidology: Cardiovascular Biomarkers, Complete lectures synchronized Atherosclerosis Imaging, and Evidence Based Practice with slides from the five courses

Evidence Based Medicine, Cardiovascular Risk Complete from anywhere on Assessment, and Practice Guidelines computer, laptop, or iPad/tablet

Vascular Biology and Atherosclerosis Pathogenesis Earn CME/CE credits

Lipoprotein Metabolism, Genetics, and Familial Prepare for certification Lipid Disorders Bonus online resources and Pharmacology: Lipid Lowering Drugs, Drug Interactions, tools to enhance your learning Drug Safety, Randomized Controlled Trials, Evidence and practice Based Treatment, and Combination Therapy

Nutrition and Non-Pharmacologic Therapy For more information, visit lipid.org/mastersonline Obesity, Metabolic Syndrome, and Diabetes Mellitus

CME Credit provided by the National Lipid Association CE credit provided by Postgraduate Institute for Medicine This activity has been approved for AMA PRA Category 1 Credit™ This activity is eligible for ACPE and ANCC credit This activity is eligible for CDR credit See final activity program for specific details.

Full accreditation information available at www.lipid.org/mastersonline. For questions about this educational activity contact the NLA at 904-998-0854. 4 LipidSpin From the SELA President: Researching Progress

LORI A. ALEXANDER, MSHS, RD, CCRC, FNLA Site Manager, St. John’s Center for Clinical Research Ponte Vedra, FL Diplomate, Accreditation Council of Clinical Lipidology

I am honored and excited to serve medicine movement described it as “the as President of the Southeast Lipid conscientious, explicit, and judicious Association (SELA). My passion for lipids use of current best evidence in making heralds back to the formation of the decisions about the care of individual Discuss this article at www.lipid.org/lipidspin Florida Lipid Associates in 1994, led by patients.”1 A practitioner’s own knowledge Paul Ziajka, MD, PhD, FNLA, and some and clinical experience is one aspect; others interested in lipid research and understanding how relevant research treatment. It has been gratifying to see the applies to a specific patient is another. I want to thank our great Executive progression of that passion over the years “Good doctors use both clinical expertise Board of Directors and all of the SELA and the formation of SELA, and then the and the best available external evidence, members who have volunteered to help National Lipid Association (NLA). and neither alone is enough.”1 on committees, participate in projects, or have just offered support and guidance this One of the duties of a chapter president is As a clinical researcher myself, I believe year. In the Chapter Update on page 27, I to host an issue of the LipidSpin, choosing this issue will prove valuable in helping to highlight some of the ideas and initiatives topics and authors. The theme for this translate the evidence-based medicine of we will be pursuing. I look forward to a LipidSpin is “Evaluating Published Clinical clinical trials to good use in caring for our fantastic 2015! n Trials and Translating Them into Practice,” patients. And as a Registered Dietitian, I and SELA members eagerly responded. have been afforded the best opportunity to References are listed on page 35. I want to thank each author for rising to care for and educate my patients — the task and sharing their expertise in the allowing them to be on the “cutting edge” current articles. Many thanks as well to of treatments in clinical trials, but also the expert guidance of Melissa Heyboer teaching them the importance of a healthy with the NLA, and the LipidSpin editors, lifestyle. Many clinical trials are double- James Underberg, MD, MS, FNLA, and blinded, so if there is a placebo group, Robert Wild, MD, MPH, PhD, FNLA. patients learn to appreciate how important diet and exercise can be to their overall One of the founders of the evidence-based health.

Official Publication of the National Lipid Association 5 Letter From the LipidSpin Editors: Holiday Gifts

JAMES A. UNDERBERG, MD, MS, FACPM, FACP, FNLA Clinical Assistant Professor of Medicine NYU School of Medicine & NYU Center for Prevention of Cardiovascular Disease Director Bellevue Hospital Lipid Clinic New York, NY Diplomate, American Board of Clinical Lipidology

cholesterol, apolipoprotein B, and/or and it also suggests that using non-statin LDL particle number to lower goals is medications, such as ezetimibe, is an key to the prevention of atherosclerotic important part of this management. cardiovascular disease. Discuss this article at Recent data from new medications www.lipid.org/lipidspin Just recently, data published in the in development, particularly PCSK9 American Journal of Managed Care inhibitors, also suggests that even at low I write this with the holiday season having suggests that “increasing medication attained LDL-C levels in high risk patients just passed us. As I sit back and reflect on adherence was associated with improved additional cardiovascular risk reduction the past year, it occurs to me that we have LDL-C levels.”1 While IMPROVE-IT focused may be achieved. This is an exciting time much to be thankful for! This past year we on a population of high risk patients at to practice clinical lipidology! The future embraced the extensive statin safety report the very low end of the LDL cholesterol is bright with hope and for even greater from the National Lipid Association. This spectrum, when placed next to the expectations for our patients. New and was followed in September by the release accumulated data preceeding IMPROVE-IT, improved interventions are right around of our Recommendations for the Patient- it would be hard not to extrapolate the the corner; and our approach fits perfectly Centered Management of Dyslipidemia. inference to high risk patients not at goal, with the aggressive utilization of current who by definition potentially can gain and future pharmacologic interventions. Finally, just this past November in even greater benefit from larger absolute Combining these options with our Chicago at the American Heart Association reductions in LDL-C, Non-HDL-C, ApoB, continued focus on lifestyle interventions meeting, the long-awaited results of and LDLp. and aggressive patient and physician the IMPROVE-IT study were released. education programs is our gift that keeps While purists might argue this was not For those of us who care for patients with on giving — right now and in years to a titrate-to-goal study, the results only inherited disorders of LDL metabolism come. strengthen the concept that atherogenic such as Familial Hypercholesterolemia lipoproteins play a central causal role (FH), this further reinforces NLA’s Happy New Year to you and yours! n in the development of atherosclerosis Recommendations to reduce LDL-C to < and by extension targeting Non-HDL 100 mg/dL in high risk patients with FH, References are listed on page 35.

6 LipidSpin Clinical Feature: Translating Clinical Trial Evidence into Practical Medicine

RALPH VICARI, MD, FACC, FNLA Vice President, Foundation of the National Lipid Association Founder, MIMA Century Research Associate Professor of Cardiovascular Medicine Department of Medical Education University of Central Florida College of Medicine Melbourne, FL Diplomate, American Board of Clinical Lipidology

Over the course of my 36-year career, guidelines are derived from a generation of the practice of medicine has changed formidable clinical research. For instance, dramatically. When I was an intern as of 2014, who would not consider at Georgetown University Hospital, using aspirin, beta blockers, and statins Discuss this article at we treated heart attacks with oxygen, for patients with a recent myocardial www.lipid.org/lipidspin morphine, and sometimes not much infarction? From the Second International more than prayers. Barely anyone at that Study of Infarct Survival (ISIS-2)3 to the time could conceive of doing a cardiac Beta-Blocker Heart Attack Trial (BHAT)4 catheterization on an acute myocardial and on to 4S, to mention a few, we have infarction. The progress we all enjoy in established clinical guidelines that benefit For example, in 1995, the 4S trial medicine is based on two major factors: patient outcomes. randomized 4,444 male patients with the rapid evolution of medical technology, coronary artery disease to receive an and scientific evidence gleaned from Having been a clinical trialist and clinician average dose of 33 mg of simvastatin clinical trials, particularly those trials as well, I often ask myself if the patient versus placebo. The average pre-study powered adequately enough to reduce before me whom I am asked to manage low-density lipoprotein cholesterol (LDL- cardiovascular morbidity and mortality.1 would have been included in one or more C) level was 188 mg/dl. So, going back to of the outcome studies based on the 1995, how should we have best managed Outcome-based clinical research in specific recruitment criteria. a female coronary patient with an LDL-C cardiovascular medicine has given birth to level of 140? At that time, we were forced innumerable treatments that have been Often, because of patient diversity, specific to make a decision that was not guided proven to reduce morbidity and, in some clinical trial data is not directly applicable. directly by patient-specific outcome data. cases, total mortality. The Scandinavian We are obliged to make clinical decisions Clinical judgment infused by clinical trial Simvastatin Survival Study (4S)2 was the for the patients’ maximum benefit based data guided our decision to use lipid- “grandfather study in lipidology” that was on experience and/or extrapolation of lowering therapy in this atypical patient. shown to decrease overall mortality. It is scientific outcome results. It is only with Clinical trial data often lags behind, or this type of research that has driven us clear knowledge of specific trial inclusion never will exactly answer how best to to utilize pharmaceuticals and technology and exclusion criteria, and endpoint treat the vast majority of patients we treat. to ultimately benefit our patients. Our results that we make clear evidence-based Fortunately, many statin trials since 1995 best clinical pathways and treatment decisions. added diverse patients as compared to the

Official Publication of the National Lipid Association 7 4S population, which make our decisions easier. In addition, safety data from many sources about statins in clinical trials and in practice makes us very comfortable with their use.5

We continually search to further reduce risk by combining statins with other medications both in practice and in randomized clinical trials. There have been four recent studies combining statins with other pharmaceutical agents to treat metabolic dyslipidemia.6-9 Two of the studies combined statins with fibrates and two combined statins with long-acting niacin.6,7 Intuitively, as lipidologists, we would like to believe that treatable risk exists for hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C), and yet all of these RCT studies seemingly refute this belief. No study and no clinical trials are perfect both in 153mg/dl, respectively. It is well known disease who has an HDL of 30 mg/dl and design and/or implementation. In the that FIELD investigators were allowed to has triglycerides of 300 mg/dl? following, I will dissect the recent studies titrate statin doses in accordance with that combine statins and fibrates/niacin their clinical judgment based on unblinded In the Helsinki Heart Study (HHS), there for purposes of attempting to help the LDL-C levels. Unfortunately, 17 percent was a dramatic benefit seen in patients on practicing clinician make rational decisions of the placebo group in this trial were a fibrate who had triglyceride levels greater about the use of combination therapy in uptitrated on their statin therapy; whereas than 204 mg/dl and an LDL/HDL ratio of patients with metabolic dyslipidemia. only 9 percent of the fenofibrate group >5.10 In the subpopulation of FIELD with received additive statin treatment. How true metabolic dyslipidemia, the outcomes The Fenofibrate Intervention and Event much this influenced the negative trial were very favorable, with a significant Lowering in Diabetes (FIELD) study6 outcome is unclear. reduction in cardiovascular morbidity and randomized nearly 10,000 diabetic patients mortality. The pertinent clinical issue is: to receive fenofibrate versus placebo, The outcomes of FIELD were somewhat Can we rely on subpopulation data to make usually in combination with statins. Of the disappointing for many of us. It showed patient decisions? The statistical answer randomized patients in the FIELD study, no statistically significant reduction in to this question is no; yet the majority of 80 percent had the metabolic syndrome, the primary endpoint of cardiovascular patients randomized to FIELD would not but only 38 percent had metabolic morbidity and mortality. Overall mortality have been placed on combination therapy dyslipidemia, defined as a triglyceride was higher in the fenofibrate group, but in my practice! Sometimes we are forced level > 150 mg/dl, with a HDL-C level this was not statistically significant. The to rely on subpopulation results. < 40mg/dl in males and < 50mg/dl in major benefit of fenofibrate in FIELD females. Inclusion criteria for participation was on diabetic microvascular disease As clinicians, we are confronted with in the FIELD study were a total cholesterol progression. This was seen in the retinal a quandary based on study design and level from 116 mg/dl to 251mg/dl, a total subpopulation group as well as in those overall outcomes in a diabetic population. cholesterol to HDL-C ratio (Chol/HDLc) > with peripheral vascular disease and Here is where we must, in my view, avoid 4, and a triglyceride level > 89mg/dl. The microalbuminuria. A clinical question that generalization and treat the patient at mean LDL-C level prior to randomization arises, based on the design flaws in FIELD, hand, even without direct outcome data was 119mg/dl. The mean HDL-C and is what we should do with a statin-treated to perfectly support our best judgment. triglyceride levels were 42mg/dl and diabetic patient with coronary artery Would I treat a diabetic with coronary

8 LipidSpin disease who has an HDL of 30mg/ reduced with combination statin-fibrate placebo group was asked to take 250 mg of dl and triglycerides of 300 mg/dl with treatment. And finally, a continuing theme crystalline niacin to help maintain the blind fenofibrate when on statin therapy? For is that in the ACCORD trial for participants due to flushing. me, the answer is yes. And for those who with triglycerides >204 mg/dL and who would not treat this patient because the also had an HDL-C<39 mg/dL, there was During the course of the AIM-HIGH study, FIELD trial did not reach clear statistical a 31-percent decrease in the primary investigators were allowed to manipulate differences in its primary outcome, a combined endpoint. statin doses to maintain LDL-C levels less valid approach would be to consider the than 80. There was considerably more benefits of treatment on the outcome statin-added therapy on trial in the placebo of microvascular disease alone. Many group. This could have influenced the trial diabetics develop complications from “However, with any outcome. The study (n = 3,414) was not retinopathy, nephropathy, or peripheral large and a 25-percent dropout and down vascular disease, and this often results in individual patient, titration rate in the active treatment group blindness, dialysis, or amputation. While occurred. morbidity and mortality are the strongest certainty from existing outcomes to base clinical judgment; we trial data does not The results of AIM-HIGH showed no also must have regard for a patient’s pain significant difference in cardiovascular and suffering. Often, these components of always directly apply morbidity or mortality at a mean follow-up patient care and judgment are not readily time of 36 months in the niacin-treated appreciated as critical components of to that individual.” patients. There was a tendency to more evidence-based medicine. adverse events in the treatment group and a disturbing increase in stroke rate. The Action to Control Cardiovascular Risk Based on these findings the AIM-HIGH in Diabetes (ACCORD) lipid trial7 was The take-home message here is that, if data and safety monitoring board (DSMB) sponsored by the National Institutes of we had chosen a higher-risk population discontinued the trial prematurely, with Health’s Heart, Lung and Blood Institute to study in the first place, outcomes may only 50 percent of predicted outcomes (NHLBI) to answer the question of have been different. Also, in my view, events recorded. whether adding a fenofibrate to a statin in only a therapeutic nihilist would disregard diabetic patients influences cardiovascular the beneficial effects of fenofibrate on For most clinicians and trialists,7,8 the outcomes. The diabetic population in the progression of microvascular disease AIM-HIGH study results came as a ACCORD was at more risk for CVD than in diabetics based on combined FIELD/ surprise. We have all seen progression of those entered into the FIELD study. ACCORD results! coronary and vascular disease in patients Similar results were found however. After with optimal LDL-C levels and significant nearly five years of combined therapy, How about the recent niacin outcome metabolic dyslipidemia. These results left no significant differences in the primary studies — from trial data to practical use us with high hopes of positive results from outcome of myocardial infarction, ischemic in clinical practice? The Atherothrombosis the other niacin-statin mega trial Heart stroke, and cardiovascular death were Intervention in Metabolic Syndrome with Protection Study 2 — Treatment of HDL found in the comparator arms. Mean entry Low HDL/High Triglyceride and Impact to Reduce the Incidence of Vascular Events lipid levels of LDL-C in the ACCORD trial on Global Health Outcomes (AIM-HIGH) (HPS2-THRIVE) trial.9 were 100 mg/dl, triglycerides of 162 mg/dl, study8 was a prospective randomized and HDL-C of 38 mg/dl. These entry lipid clinical trial adding niacin ER therapy HPS-2 THRIVE randomized more than values are not characteristic of the highest- to high-risk statin-treated patients. 25,000 high-risk vascular patients risk group of diabetics with profound Participants had mean entry LDL-C levels of worldwide to compare niacin extended metabolic dyslipidemia. Microvascular 71mg/dl, mean baseline triglyceride levels release (ER) plus laropiprant, an outcomes, nevertheless, were favorably of 161 mg/dl, and mean HDL levels of 35 antiflushing agent, added to optimal affected. Retinopathy progression was 6.5 mg/dl. Also, 1,500-2,000 mg of extended- statin therapy versus placebo. There were percent of the fenofibrate group and 10.2 release niacin was added to simvastatin no specific HDL-C inclusion criteria in percent in the placebo group (P = .003). based on pre-randomization tolerance and this study. Baseline mean lipid values in Progression of microalbuminuria also was compared to no addition (placebo). The the HPS-2 THRIVE on simvastatin, with

Official Publication of the National Lipid Association 9 or without Ezetimibe, were an LDL-C 2. The majority of statin patients 6. I believe it is reasonable to use of 63 mg/dl, HDL-C of 44 mg/dl, and I have put on fibrates or niacin fibrates in high-risk diabetics, triglycerides of 125 mg/dl. There were in the past 30 years have lipid particularly those with metabolic 10,000 Chinese patients randomized to profiles before treatment that dyslipidemia, to reduce HPS-2 THRIVE. are much worse than mean HDL microvascular disease. and triglyceride levels in all of The DSMB of HPS-2 STRIVE stopped the aforementioned studies. The practice of medicine should always the study prematurely because of a lack I am not taking any of these be based on best evidence when there is of benefit on the primary cardiovascular patients off therapy unless they proven outcome data relevant to patients morbidity/mortality endpoint and an experience side effects. How meeting the inclusion and exclusion increase in adverse events. The majority do I rationalize this? There are criteria of the trials. However, with any of these adverse events were related four prior fibrate trials (HHS,10 individual patient, certainty from existing to “minor hyperglycemic problems.” Veterans’ Affairs — High-Density trial data does not always directly apply Specifically, the skin reaction rate was Lipoprotein Intervention Trial to that individual. This is where the art from four to five times as high and the rate [VA-HIT],12 FIELD, and ACCORD), of medicine and clinical experience are of musculoskeletal events was nearly twice one prescription omega-3 study necessary to make therapeutic decisions. as high in the treatment (added niacin (Japan eicosapentaenoic acid Lipid The hard endpoints of most CVD clinical ER) group. The rate of serious myopathy Intervention Study [JELIS]),13 trials are not all that should guide us in our was sixfold higher in the treatment group. and two niacin trials (Coronary treatment strategies. Pain and suffering Gastrointestinal side effects, overall Drug Project [CDP]14 and AIM- are important in patient care, but are bleeding and infection rates also were HIGH) that show benefits in those not common endpoints in cardiovascular increased in the study patients on niacin/ patients in the lowest HDL and trials. As a trialist and clinician, I believe laropiprant. A disproportionate number of highest triglyceride groups. the marriage of scientific knowledge and adverse events occurred in the Chinese practical experience should guide our best cohort. 3. In those high-risk patients with decisions for patient care. n significant metabolic dyslipidemia So, as trialist and clinicians scratch their (triglycerides>200mg/dl, HDL Disclosure statement: Dr.Vicari has no disclosures to report. heads about these results, what should <35mg/dl in males, <45mg/dl we do practically for our high-risk patients in females), I am still prescribing References are listed on page 35. with metabolic dyslipidemia and well- both fibrates and niacin in controlled LDL-C levels on statin therapy? combination with statins. I am particularly careful to monitor the My own clinical judgment is as follows: use of niacin ER, especially during (Note that most of my patients on statin the titration phase. I monitor my therapy with metabolic dyslipidemia have patients’ fasting glucoses with demonstrated vascular disease and are, each titration of niacin if they are therefore, at high or highest NCEP risk.)11 diabetic and every other titration if they are non-diabetic. 1. Particularly in patients with I am diligent in educating the mild metabolic dyslipidemia on 4. niacin ER-treated patients about statin therapy, diet, exercise, and side effects. With this caution, weight loss are almost always I am able to get more than 70 effective at normalizing the percent of patients on 1,000 mg lipid panel. Getting patients to or more. consume less carbohydrate and fat calories and to participate in a 5. I use fish oil (1,000 mg/day) in programmed exercise regimen is all patients with vascular disease, extremely effective. regardless of their lipid profile.

10 LipidSpin Guest Editorial: Guidelines for the Guidelines — Impact and Controversies

KHALID H. SHEIKH, MD, MBA, FACC, FNLA Director of Cardiology, Cape Canaveral Hospital Assistant Professor, University of Central Florida College of Medicine Cocoa Beach, FL Diplomate, American Board of Clinical Lipidology

This issue of LipidSpin is dedicated to of which suffered from shortcomings in “Evaluating Published Clinical Trials the development process. In response, and Translating Them into Practice.” the Institute of Medicine (IOM) Clinical trials are the basis for advancing assembled an expert committee to provide our knowledge of effective therapies in recommendations to ensure that practice Discuss this article at medicine. Well-conducted clinical trials, guidelines would truly represent an www.lipid.org/lipidspin particularly those with results that can be unbiased and evidence-based compilation replicated, traditionally have been used to of knowledge and standards of therapy. develop practice guidelines. A year in the making, in 2011, the IOM since their release, the IOM standards for committee’s report, “Clinical Practice practice guidelines have been met with Practice guidelines have far-reaching Guidelines We Can Trust,” was released.1 praise, criticism, and controversy. implications. They provide medical practitioners with guidance on the Review of IOM Standards standard of care derived from evidence- “The new guidelines After an exhaustive process of research, based medicine. They also have economic review, and even public comment, the impact, as they can promote and validate are silent with IOM committee outlined eight standards certain therapies and destroy others. They for clinical practice guideline development. have administrative impacts, because respect to patients (Table 1) The new standards addressed a they can form the basis of establishing older than 75 and variety of problems that were identified by payment, authorization, and regulatory the IOM committee. However, two major policies by administrative agencies and those younger than issues were given special emphasis. health insurance plans. They have legal implications, because they can form the than 40.” One was the sheer number of guidelines basis for medical standards of care used available to clinicians. Many had conflicting in peer review and medical malpractice recommendations and a process of issues. The IOM claims that its new standards development that was not transparent. A will minimize the chances that important charge of the committee was to ensure Over the past 15 years, a plethora of health decisions are based on information that future guidelines are developed in a practice guidelines have emerged, many that may be biased or erroneous. However, trustworthy, evidence-based process.

Official Publication of the National Lipid Association 11 The second concern was addressing Eight Standards for Clinical Practice Guidelines Published by the IOM conflicts of interest. The committee found that many guidelines have been developed Establishing transparency with fairly egregious conflicts of interest, Management of conflict of interest such as instances when drug companies Guideline development group composition substantially fund guideline development. Clinical practice guidelines/systematic review intersection A more subtle, but potentially equally Establishing evidence foundations for and rating strength of recommendations important, conflict of interest was Articulation of recommendations recognized in which clinical experts External review involved in developing practice guidelines Updating had inherent biases because of their affiliation with industry. Table 1. Institute of Medicine. Practice Guidelines We Can Trust. National Academies Press, Washington, DC; 2011 http://iom.edu/Reports/2011/Clinical-Practice-Guidelines-We-Can- Trust.aspx (accessed September 1, 2014). Validations of IOM Standards The assertions of the IOM committee regarding the problems it identified in Criticisms of IOM Standards Impact of IOM Standards on Lipid clinical practice guidelines have been The IOM standards have been criticized Guidelines supported by objective and independent as being impractical and inflexible. To After much delay and anticipation, last reviews. A recent report reviewed be labeled trustworthy, the IOM states, year the American College of Cardiology/ 130 randomly chosen clinical practice a practice guideline must meet all eight American Heart Association (ACC/AHA) 2 guidelines. Only 44 percent met the standards. If most clinical practice released the report of their expert panel median number of IOM standards. guidelines already are not meeting IOM task force, which was intended to be an Another report found that, in a review of standards, then how practical are the updated set of guidelines for cholesterol 149 practice guidelines, only 46 percent IOM standards? We know we cannot management in the U.S.5 They were incorporated a grading or classification have high-level evidence for everything expected to provide a comprehensive 3 system for their recommendations. we do in medicine. Do we leave clinicians review on both the science and clinical unsupported in instances where high- evidence linking atherosclerosis to Both of these studies found that more quality evidence does not exist? disordered lipid metabolism and by than half of the guidelines reviewed did A second criticism of the IOM report incorporating recent clinical trials not reveal conflict-of-interest statements. is the underlining belief system that of lipid intervention; they also were Of those that did, more than 70 percent working with industry to develop and expected to provide the most up-to-date disclosed that the writing committee commercialize new therapies is somehow recommendations for clinicians to evaluate chairperson(s) had conflicts of interest. inherently bad and should be managed and optimize cardiovascular risk as it Guidelines from non-U.S. groups and or eliminated. The problem with this relates to lipids. For most clinicians, the medical specialty societies were the philosophy is that it fails to recognize the ACC/AHA report fell far short of these least likely to include conflict-of-interest expertise and value from industry-academia expectations, and ended up being another information or meet the other IOM collaboration. set of specialty society guidelines. standards. Lastly, the IOM report fails to substantially The ACC/AHA report acknowledged that These reports also found that the mean meet its own standards.4 Subjected to it was influenced by the IOM’s 2011 age of guidelines was more than five years. scrutiny, the IOM document completely report on the development of trustworthy Thus, practice guidelines are not updated passed only two of its own standards, clinical guidelines. The expert panel’s with sufficient frequency to reflect changes partially passed two and failed four. recommendations were derived primarily in clinical knowledge. Furthermore, Therefore, one could question whether from randomized controlled trials guidelines were more likely to emphasize the new IOM standards were, in fact, (RCTs). The virtual exclusion of evidence benefits of treatment rather than potential trustworthy. other than that from RCTs restricted harms. the scope of the new guidelines. No

12 LipidSpin recommendations were formulated when As a result, the NLA has put forth its sufficient evidence was not available. new Recommendations for Patient- Thus, the new guidelines left clinicians “When it comes to Centered Management of Dyslipidemia.8 in the position of having to use their own practice guidelines, a The evidence base considered in clinical judgment to arrive at many clinical the development of new consensus decisions instead of having science-based reasonable question recommendations emphasized results and expert guidance to inform these from RCTs but also included subgroup clinical choices. to pose to the IOM is assessments and pooled analysis for multiple trials, epidemiologic, genetic, In addition to criticisms of its method- whether, in our quest metabolic, and mechanistic investigations. ology, the ACC/AHA report has been The panel acknowledged that the primary soundly criticized for many of its clinical for trustworthy, we results from RCTs represent the strongest recommendations, or lack thereof. One have compromised evidence from which to draw conclusions major criticism is that, with respect to about the benefits and risks of treatment lipid-lowering therapies, only statins were effectiveness.” strategies. However, RCT evidence has considered. Furthermore, the concept of limitations and often is incomplete or low-density lipoprotein (LDL) goals for of uncertain relevance to patients with treatment was completely ignored. By not (CRP), calcium score, ApoB, and carotid characteristics that may differ in important making LDL the centerpiece of the new intimal medial thickness, generally have ways from those who participated in RCTs. guidelines, they largely disregarded the been dismissed. traditional lipid hypothesis. When it comes to practice guidelines, a If the ACC/AHA document was intended reasonable question to pose to the IOM is More controversy arose from the new to adhere to the IOM standards regarding whether, in our quest for trustworthy, we Pooled Cohort Risk assessment as a conflict of interest, it failed to do so.7 Of have compromised effectiveness. n replacement for the Framingham risk the 13 authors in the main treatment calculator.6 The ACC/AHA risk algorithm guideline panel who were not NHLBI Disclosure statement: Dr. Sheikh received honorarium has been purported to overestimate 10- staffers, seven had financial relationships as a member of the speakers bureau from Amarin and Boehringer Ingelheim. year risk. As a result, an estimated 30 with pharmaceutical companies that million to 40 million lower-risk Americans manufacture statins. Of the 10 expert References are listed on page 35. will be eligible for drug therapy. reviewers for the panel, three had financial relationships with pharmaceutical The new guidelines place increased companies that manufacture statins. emphasis on lifestyle modifications. Of the 11 people on the risk prediction However, an interesting aspect of the panel, five had financial relationships new guidelines is that lifestyle is highly with pharmaceutical companies that promoted without randomized clinical trial manufactures statins. evidence. Thus, it seems that RCTs are only applied to drug therapy. Response to IOM Standards The National Lipid Association (NLA) The new guidelines are silent with respect has failed to endorse the new ACC/ to patients older than 75 and those AHA guidelines. Likewise, the American younger than 40. They do not comment Association of Clinical Endocrinologists on genetic dyslipidemias, metabolic (AACE) not only declined to endorse syndrome, or primary prevention. They the guidelines but also recommended do not adequately address potential harm that its members continue to use AACE associated with statin use. Nontraditional guidelines, which generally agree with risk factors, such as C-reactive protein Adult Treatment Panel 3 (ATP 3).

Official Publication of the National Lipid Association 13 EBM Tools for Practice: Clinical Trials of Alternative Medicine: Testing Whether Magic Works

GREGORY S. POKRYWKA, MD, FACP, NCMP, FNLA Assistant Professor of General Internal Medicine Johns Hopkins University School of Medicine Director, Baltimore Lipid Center Baltimore, MD Diplomate, American Board Clinical Lipidology

practitioners and societies, and even Alt- why “the type of inferential statistics Med-friendly government officials,2 such used in medicine have intrinsic flaws to prescientific and long-discredited practices which CAM interventions appear to be Discuss this article at as homeopathy, acupuncture (“a theatrical particularly vulnerable.” When even a www.lipid.org/lipidspin placebo”), reiki, and others are infiltrating well-designed clinical trial is performed, our medical schools and hospitals, without the predictive power of the results is I have in mind a prospective clinical trial scientific proof of their efficacy and safety. dependent on the prior plausibility of in which I study a common children’s These practices often come under the the phenomenon being studied. How to phenomenon, detailing the differences guise of integrative medicine, an attempt establish this prior plausibility? Conformity between genders, location, ethnicity, to “treat the whole patient” by integrating to scientific laws and principles is one biometrics, dental data, monetary value, traditional medicine with Alt-Med. criterion – the Tooth Fairy, homeopathy etc. It’s a common phenomenon that (in which the “treatment” is so diluted most parents have photos of and have Good clinicians attempt to treat the that it contains not even one molecule experienced ourselves. I’m sure we whole patient in the first place. However, of the original substance!), “energy could generate a lot of highly statistically many physicians, being rushed by the medicine,” reiki, Bach Flower Therapy, significant data and make many useful many pressures engendered by electronic acupuncture (there is no identifiable “chi” insights. medical records and volume-based nor “meridian”), and many others all fail reimbursement, have ceded to the Alt- to meet this criteria. Another criterion is I’m talking about what our children find Med practitioners the beneficial effects of “falsifiability”: Science aims to produce left under their pillows by the Tooth Fairy. talking to the patient and a more extended falsifiable hypotheses; pseudoscience often One problem — the Tooth Fairy doesn’t “laying on of hands” experience. As far as cannot. Another criterion is “Ockham’s really exist. combining traditional medicine with Alt- razor,” according to which if two models Med, as a famous phrase goes,3 “Mixing describe the observations equally well, This phenomenon, Tooth Fairy Science,1 apple pie with cow pie doesn’t make the the simpler one is more likely to be happens daily throughout America, at many cow pie taste better, it makes the apple pie true, e.g. the placebo effect in Alt-Med of our hospitals and institutions of higher taste worse.” interventions. Applying Bayes’ theorem, learning. Under pressure from alternative that is the probability of an inference’s medicine (Alt-Med or Complementary Two recent articles are pertinent. Maurizio being true is dependent on prior and Alternative Medicine [CAM]) Pandolfi and Giulia Carreras4 discuss plausibility — Bayes’ theorem provides a

14 LipidSpin readers is the Trial to Assess Chelation Key Points: Therapy (TACT), the $30 million multi-  “Alternative Medicine” practices (e.g. homeopathy, acupuncture, reiki, center trial funded by tax dollars and and many others) are infiltrating our medical schools and hospitals without the National Center for Complementary scientific proof of their prior plausibility and efficacy. and Alternative Medicine (NCCAM)  Applying Bayes’ theorem, that is the probability of an inference’s being true to determine the safety and efficacy of is dependent on prior plausibility, it is inopportune to interpret P values at ethylenediaminetetraacetic acid (EDTA) face value, especially when they are calculated from results obtained testing hypotheses with low prior probability/plausibility. chelation therapy for individuals with coronary artery disease (CAD) and prior  Science-based medicine (SBM) is distinguished from EBM by the recognition myocardial infarction (MI). The trial that, before doing a clinical trial on a medical treatment, there must be a reasonably high prior plausibility that the treatment will work. was conducted despite a lack of prior plausibility, possible mechanism of action  Unless new treatments are consistent with the laws of science, their and preclinical trial data, as well as assessment in clinical trials is unrevealing, predicts little, and is even unethical. multiple failed smaller trials. Many study sites were dubious alternative medicine clinics, and the treatment itself poses risks principled way of combining new evidence trials’ support for the tested hypothesis. to patients.9 When finally reported, results with prior beliefs — it is inopportune to It is important to note that “biologically were negative except for one subgroup interpret P values at face value, especially plausible” does not mean “knowing the (diabetics), and all results have come under when they are calculated from results exact mechanism.” It means that the much deserved and damning criticism.10 obtained by testing hypotheses with low mechanism should not be so scientifically prior probability/plausibility. Clinicians implausible as to be reasonably considered An esteemed lipidology colleague, when tend to be easily swept up in P values, impossible and not violate well-established engaged in debate over these issues, often neglecting how heavily dependent laws of biology, chemistry, and physics (as accused those of us practicing SBM of they are on prior probability/plausibility reiki, homeopathy, and acupuncture do, for being biased and closed minded in our of hypotheses being tested. (This is very example). assessment of prior plausibility for Alt-Med low for Alt-Med modalities such as those treatments. He’s certainly correct. SBM is mentioned above.) It is critical to realize “Extraordinary claims require extraordinary biased in favor of science because science that the P value tends to exaggerate evidence,” as philosopher David Hume works. Science also does not pretend support for the hypothesis tested, once said.6 Many clinical trials are to know everything. Who knows what especially if the scientific plausibility of the imperfect and bias-prone and should not pharmacologic treatments await discovery hypothesis is low. Any difference can be be weighted as superior evidence of truth out there? But unless new treatments are shown to be statistically significant if the in circumstances where prior plausibility consistent with the laws of science, their numbers are large enough. What counts is low. In RCT’s testing modalities with assessment in clinical trials is unrevealing, is clinically meaningful clinical differences low plausibility, confounding bias effects predicts little, and is even unethical. found to be statistically significant. are very much magnified, producing a high false-positive rate.7 Despite their lack “Keep your minds open and stay thirsty my David Gorski and Stephen Novella5 lament of biological plausibility and pre-clinical friends, but don’t let your brains fall out!” that the usual process of evidence-based studies, Alt-Med clinical trials are, in fact, — The Most Interesting Scientist in the medicine (EBM), wherein treatments often driven by popularity with the public World. n proceed to randomized clinical trials after and funding sources. The authors have biological plausibility is determined and distinguished science-based medicine Disclosure statement: Dr. Pokrywka received compelling evidence from preclinical (SBM) from EBM by the recognition that, consulting fees from Amarin and AstraZeneca. He received speaker honoraria from Amarin, AstraZeneca, studies has been amassed, has been before doing a clinical trial on a medical Daiichi Sankyo Inc., Kowa Pharmaceuticals, upended in the case of Alt-Med treatments, treatment, there must be a reasonably high LipoScience Inc., Health Diagnostics Labs, Genzyme, for which clinical trials are conducted prior plausibility that the treatment will Metagenics, and Genentech. prematurely. Some of these trials will have work.8 “positive P values” but, as explained above, References are listed on page 35. the low prior plausibility undermines the An example perhaps familiar to many

Official Publication of the National Lipid Association 15 Lipid Luminations: HPS2-THRIVE Commentary

DAVE DIXON, PharmD, BCPS, CDE, AACC, FNLA Assistant Professor, VCU School of Pharmacy Richmond, VA Diplomate, Accreditation Council of Clinical Lipidology

EVAN SISSON, PharmD, MSHA, CDE, FAADE Associate Professor, VCU School of Pharmacy Richmond, VA

the incidence of flushing. After a median The overall lack of benefit with niacin- follow-up of 3.9 years, niacin-laropiprant laropiprant is difficult to reconcile with did not reduce the primary outcome of earlier niacin trial data. Although niacin first major vascular event but did increase was the primary target drug, the observed Discuss this article at the risk of niacin-related serious adverse effects may have been influenced by the www.lipid.org/lipidspin events. addition of laropiprant. Similarly, patients receiving ezetimibe plus simvastatin The Heart Protection Study 2 — Treatment Some have suggested that increasing achieved lower low-density lipoprotein of HDL to Reduce the Incidence of high-density lipoprotein cholesterol cholesterol (LDL-C) levels than those Vascular Events (HPS2-THRIVE) trial was (HDL-C) with niacin is ineffective at taking simvastatin alone (53 mg/dL vs. 56 a randomized, double-blind, multicenter reducing cardiovascular risk based on the mg/dL, respectively), potentially masking clinical trial.1 Enrolled subjects were results from HPS2-THRIVE; however, the any additional benefits from niacin. between ages 50 and 80 and had a history stated purpose and study design do not of vascular disease. After a four-week fully support this conclusion.2 The study A more likely explanation for the lack of run-in phase with simvastatin 40mg daily did not establish specific entry criteria benefit is related to the ethnicity of the (ezetimibe was added if total cholesterol for lipoprotein levels or target patients population (57.4 percent from Europe remained >135 mg/dL), subjects with low HDL-C. HPS2-THRIVE primarily and 42.6 percent from China). The first were randomized to extended-release included patients with an HDL-C >43 mg/ impact of combining these two groups was niacin-laropiprant or matching placebo. dL (49.2 percent) and only 19.1 percent of observed during the run-in phase. During Laropiprant, a prostaglandin D2 inhibitor, the study population had a baseline HDL-C this period, fewer anticipated differences may improve niacin tolerability by reducing <35 mg/dL. in lipid levels (12 percent LDL-C reduction

16 LipidSpin from baseline in Europe, 7 percent in to prostaglandin-mediated vasodilation, level that would not traditionally warrant China) prompted the steering committee the observed study incidence represents additional intervention. Consequently, to increase study enrollment from a major strike against laropiprant. As these results may validate the benefit 20,000 to 25,000. Although the overall expected, patients receiving niacin were of aggressive cholesterol management, incidence of major vascular events was more likely to experience worsening especially in patients who are male, not significantly different between groups, insulin resistance. The increased incidence smoked, or are from Europe. Although the patients from Europe receiving niacin of glucose-related hospitalization in sample size of this study is impressive, had fewer events compared with placebo patients with pre-existing diabetes was characteristics of the study population (11.3 percent versus 12.4 percent), but no not observed in other studies. Although from which the data were derived must be difference existed for patients from China a subgroup analysis by ethnicity was not considered before applying the findings to (15.8 percent versus 15.5 percent). provided, it is possible that this increase individual patients in clinical practice. n was influenced by the Chinese population The incidence of niacin-associated serious and related to increased niacin sensitivity Disclosure statement: Dr. Dixon received speaker honorarium from Sanofi. Dr. Sisson received speaker adverse effects also was influenced by or health-system custom for care of honorarium from AADE. the population demographics. Patients in patients with glucose excursions. References are listed on page 35. China receiving niacin-laropiprant were 10 times as likely to experience myopathy The authors concluded that the addition of compared with those in Europe. Although niacin-laropiprant “to statin-based LDL-C patients with active peptic ulcer disease lowering therapy did not significantly were excluded, those with a history of reduce the risk of major vascular events.” peptic ulcer disease were allowed to A key omission from this conclusion is that enroll. Because the mechanism of niacin- the patients achieved a mean non-HDL-C related gastrointestinal bleeding is due of 84 mg/dL prior to randomization, a

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Official Publication of the National Lipid Association 17 Specialty Corner: Physical Activity and Lipid Disorders: Circa 2014

RALPH LAFORGE, MSC, CLS, FNLA Managing Director, Duke Lipid Clinic Preceptorship Program Durham, NC Diplomate, Accreditation Council of Clinical Lipidology

diminished total cholesterol or low-density LDL-C Response lipoprotein cholesterol (LDL-C). Still, Although exercise programs have the best regardless of how you rationalize physical chance of reducing LDL-C when there is activity, we don’t “burn” off cholesterol. associated body-weight reduction, they Discuss this article at With that said, and for numerous metabolic also can favorably alter lipoproteins in the www.lipid.org/lipidspin and genetic reasons, an individual’s lipid absence of body-weight changes when and lipoprotein profile is nearly always appropriate exercise training volumes are improved with sufficient weekly physical used. Most studies evaluating the total Blood Lipid Response to Physical activity. When all of the many exercise cholesterol and/or LDL-C response to Activity and Exercise Training training-lipoprotein trials are taken into exercise training have found very little A prevailing myth among patients consideration, the overall recommendation to only moderate decreases in LDL-C. and many healthcare providers is for the quantity and quality of physical Many studies used inadequate exercise the notion that physical exercise activity necessary for lipid and lipoprotein volumes and/or energy expenditure or “burns” or oxidizes cholesterol or improvement is provided by the 2014 failed to control for confounding variables cholesterol-rich particles similar to the guidelines on exercise and dyslipidemia by such as training-induced changes in utilization of fatty acids and glucose. the American College of Sports Medicine:1 plasma volume, dietary habits, or seasonal This doesn’t happen. Cholesterol is a Aerobic exercise, five or more days a variation in cholesterol and lipoproteins. sterol, a lipid molecule biosynthesized by week, 30 to 60 minutes per day, at 40 On average, sufficient volume exercise all animal cells because, among other to 75 percent of aerobic capacity. training by itself will reduce LDL-C by 4 to purposes, it is an essential structural 7 percent but the response can be quite component of animal cell membranes that Although this guideline is somewhat variable.2,3 The percent reduction depends is required to maintain both membrane nonspecific, it is helpful to know that this on baseline lipid values, the total energy structural integrity and fluidity. In other amount of physical activity is consistent expenditure of the exercise program plus a words, it is not an oxidizable substrate with recommendations for long-term host of other variables (Figure).3,4 fuel supporting exercise energy. Thus, weight control, i.e. 200 to 300 minutes/ unlike adipose tissue or even carbohydrate week of moderate physical activity or ≥ Very few controlled exercise trials utilization during prolonged exercise, there 2,000 kcal/week of activity. This physical have been conducted on patients with is at best a minimal relationship between activity volume may be accumulated with dyslipidemia, with most evaluating total exercise energy expenditure and repeated exercise bouts of ≥ 10 minutes. those with normal or modestly elevated

18 LipidSpin triglycerides and/or LDL-C. An often quoted meta-analysis of 13 studies by George Kelley and co-workers found a non-significant decrease of less than 1 percent in LDL-C, independent of changes in body weight.5 The problem with this finding, as is often the case in interpreting meta-analysis findings, is that there was a wide range in training modalities (e.g. running, swimming, stationary cycling, dance), often at energy expenditures not reliably reported and an average training stimulus of ~40 minutes per session, 3.9 times a week, at mostly moderate- intensity exercise levels. This weekly volume of exercise, approximately 1,600- 1,800 kcal/week, is insufficient by current recommendations (≥ 2,000 kcal/week) to demonstrate meaningful reductions in (e.g., lipoprotein and hepatic lipase, increased HDL-C by 6 percent. Among LDL-C and, of course, at that volume of apolipoprotein (apo) CII, III) explaining exercise variables, exercise duration physical activity most adults are likely to up to 50 percent of the variation in HDL- was found to be the most important lose some body weight, and experience a C.9,10 For this reason, healthcare providers determinant of increase in HDL-C on reduction in adiposity. should be cautious in predicting the HDL-C multivariate analysis.13 There have been response in clients, because there is a mixed findings among studies investigating The use of nuclear magnetic resonance considerable variation in the magnitude the relationship between exercise intensity imaging technology (NMR) to assess of changes in HDL-C. There also are and increases in HDL-C, with some studies the low-density lipoprotein particle individuals with genetic variants of very reporting the necessity for more vigorous concentration (LDL-P) response to exercise low HDL-C (hypoalphalipoproteinemia: exercise intensities.14 training has demonstrated efficacy.6-8 HDL levels <30 mg/dL) and, in general, Moderate volumes and intensities (e.g., they will respond minimally to even high Resistance training also may generate walking ~12 miles per week at 40 to 55 volumes of exercise training. On average, increases in HDL-C. There are reports percent of aerobic capacity) significantly exercise training by itself can increase that from six to nine weeks of resistance reduced LDL-P when total cholesterol and HDL-C by 3 to 25 percent, depending on training (eight to 10 exercises) three Friedewald-predicted LDL-C remained baseline lipid values, triglyceride response, times a week can significantly increase essentially unchanged.8 Such patients on and total exercise volume (i.e., added HDL-C — from 4 to 9 percent — in a return clinic visit would be considered weekly energy expenditure) but, as a men and women.15,16 At least one study unresponsive to exercise therapy when rule, the HDL-C response to training is demonstrated greater HDL-C increases a conventional lipid profile was used quite moderate.3 The increase in HDL is with higher-intensity resistance training to score the patient’s progress. Thus, likely linked to triglyceride reduction (via (80 to 90 percent at one-repitition advanced lipoprotein measures, such the action of cholesterol ester transfer maximum) compared to moderate-intensity as the determination of LDL-P by NMR protein).11 Most exercise trials support training.16 However, not all studies technology, may improve the ability to between 700 and nearly 2,000 kcal of demonstrate significant increases.17 track exercise-associated responses. exercise per week to significantly alter HDL-C.12 Kodama performed a large meta- Non-HDL Response HDL-C Response analysis of 25 randomized controlled trials As important as non-HDL-C is to managing The high-density lipoprotein cholesterol of exercise alone, without diet or drug atherosclerotic risk, there is very little (HDL-C) response to exercise training therapy, and found that aerobic exercise research that has exclusively evaluated the is under considerable genetic influence, at an intensity of ~5.3 MET’s (65 percent response to exercise training. However, with underlying genetic polymorphisms of max aerobic capacity) significantly at least one meta-analysis retrospectively

Official Publication of the National Lipid Association 19 looked at non-HDL responsivity and found on plasma triacylglycerol (TAG) triglycerides and decreased HDL-C, as well a decrease of approximately 6 mg/dL in concentration, i.e., beyond that as other cardiometabolic risk factors.22 A response to aerobic exercise training attributed to acute exercise; modest amount of exercise training can programs between 10 and 104 weeks.18 hence, exercise should be prevent the deteriorating lipid profile that This meta-analysis included male as well as performed on a regular and is seen with inactivity.23 This is particularly pre- and postmenopausal females. uninterrupted basis to maintain true for LDL and HDL size, LDL-P, and The majority of subjects included in the lower TG. total HDL cholesterol. In fact, it appears studies were white, however, blacks, that only seven to 10 miles of walking a Hispanics, Japanese, and Asians were also represented. The greatest non-HDL response apparently is observed when dietary and exercise interventions are combined.

Triglyceride Response Compared to other lipids, such as LDL- C, elevated baseline triglycerides (TG) (e.g. >150 mg/dL) are generally more responsive to exercise training of sufficient volume. Triglyceride mobilization and utilization appear to be in direct proportion to exercise energy expenditure. Unlike LDL-C, triglycerides generally decrease immediately after a session of high-volume endurance exercise (e.g., greater than 45 minutes of sustained effort), and remain lower for up to 48 hours after the session. Several facts stand out after reviewing Figure 1. scores of exercise-triglyceride metabolism trials:19 Overall, exercise training programs week will prevent inactivity-associated • Exercise-induced TG-lowering is also have been shown to decrease deterioration in these lipid parameters.23 acute, in that it manifests after fasting triglycerides by 4 to 37 percent just a single bout of exercise (approximate mean change of 24 Exercise and Postprandial Lipemia 20 and is not the result of repeated percent). Overall, exercise is most Postprandial lipemia is essentially the exercise sessions (i.e., training), effective in lowering triglycerides when blood lipid, particularly triglyceride (and and it is short-lived, in that it is baseline levels are elevated (i.e., >150 mg/ associated triglyceride-rich particles), readily reversed when exercise is dL), activity is moderate to intensive, and response to a meal, particularly a fatty 21 withdrawn. total caloric intake is reduced. The same meal. Depending on how much fat or • Numerous studies have confirmed exercise-generated response holds true sugar is consumed in a meal, a person with the initial hypothesis that the for exercise training and very low density normal fasting triglycerides will increase magnitude of the decrease in lipoprotein (VLDL) because VLDL’s carry their triglycerides by 100 to 200+ mg/ plasma TG concentration after a most of the triglyceride in plasma — the dL for two to six hours after a high fat single exercise session and after VLDL triglyceride and plasma triglyceride meal.24 Those with visceral obesity, the 19 training is the same (i.e., 15 to 50 levels are almost the same. metabolic syndrome or type 2 diabetes can percent). have much larger increases in post-meal • These observations suggest that Inactivity and Lipids triglycerides. The problem of prolonged, chronic exercise does not have Being sedentary, particularly daily sitting elevated postprandial triglyceride states is an equally sustainable effect time, has been associated with elevated that, for the amount of time triglycerides

20 LipidSpin are elevated much above 250-300 mg/dL, that each session (e.g., 30+ minutes) Disclosure Statement: Mr. LaForge received speaker honorarium from AstraZeneca. there is diminished arterial function, lower includes an abundance of contraction HDL-C and exposure of the arterial wall repetitions versus, for example, just three References are listed on page 35. to atherogenic lipoprotein particles (e.g., sets of 10 to 12 repetitions of four or five intermediate-density lipoprotein (IDL) and exercises. A recent review of 13 published VLDL remnant particles). Over the past 15 RT and lipid response trials reinforced years, there has been abundant research the requirement of higher repetition supporting the finding that sufficient RT doses for a sufficient stimulus lipid exercise timed anywhere from several and lipoprotein response.29 The review hours to 12 hours before a fat-rich meal concluded that it consistently has been will reduce postprandial lipemia by 20 to shown that the increased volume of 40 percent.25 This also was observed in movement via increased numbers of sets men with baseline hypertriglyceridemia, and/or repetitions has a greater impact who experienced a 30 to 39 percent on the lipid and lipoprotein parameters reduction in postprandial triglycerides than increased RT intensity (e.g. high- with prior moderate and vigorous exercise, weight, low-repetition training) a view also respectively.26 The relative suppression supported by other recent studies.30 of triglycerides can last up to 36 hours after a significant bout of exercise, e.g., >400 kcal. Some investigators report “...nearly all studies that women may be more responsive than men to reducing postprandial TG have demonstrated with exercise.27 This somewhat blunted triglyceride response to high-fat or high- some improvement in glycemic meals is one of the benefits of engaging in aerobic physical activity the lipid profile.” every day. There also are reports that higher-intensity exercise may be more effective than moderate intensity exercise Final Word at reducing postprandial TG, even when Although there is wide individual variation both are matched for the same total energy in the lipid and lipoprotein response expenditure.28 Having patients exercise to a given amount of exercise training, at least every other day is an excellent nearly all studies have demonstrated way to keep triglycerides and associated some improvement in the lipid profile. triglyceride-rich atherogenic particles The greatest exercise-induced changes reasonably suppressed. in lipoproteins occur when there are significant reductions in adiposity. Lastly, Resistance Training and Lipid it is important to note that there are Disorders numerous variables that control the Resitance training (RT) has shown some lipid response to exercise training, not promise as a means to improve the blood the least of which are baseline lipid lipid profile, but the effect is modest at values, net energy cost (in kcal) of the best. It is not recommended as the primary exercise program, gender, and a host of form of exercise therapy for people with genetic influences (e.g., Apo CII and III dyslipidemia but RT certainly can play a genotypes, to name but a few). The precise supportive role. The lipid and lipoprotein mechanisms responsible for these changes response to RT largely depends on the remain to be elucidated but very likely energy expenditure of the resistance include those denoted in Figure 1. n training session, which essentially means

Official Publication of the National Lipid Association 21 Practical Pearls: Selection of Dyslipidemia Guidelines in Special Populations

PAMELA B. MORRIS, MD, FACC, FACP, FACPM, FAHA, FNLA Director, Preventive Cardiology Co-director, Women’s Heart Care Charleston, SC Diplomate, American Board of Clinical Lipidology

cholesterol guidelines.2 High- or very high-risk patient groups Awareness of additional published guidelines for Quantitive risk scoring is not necessary for initial risk statin non-benefit groups assessment in patients with the following conditions:* Discuss this article at will help clinicians make • Diabetes mellitus, type 1 or 2 www.lipid.org/lipidspin individualized decisions • Chronic kidney disease, stage ≥3B with patients. • LDL-C ≥190 mg/Dl: severe hypercholesterolemia phenotype, which includes FH Atherogenic lipoproteins play a critical role Case Presentation: • ASCVD in the initiation and progression of vascular The patient is a 52-year- ASCVD, atheroslerotic cardiovascular disease; FH, familial atherosclerosis, and decades of research old white woman with hypercholesteremia; LDL-C, low-density lipoprotein cholesterol. have clearly demonstrated the benefits Stage IV polycystic *Patients in these categories are all at high or very high risk for an ASCVD event and should be treated accordingly. of lipid-lowering therapy for prevention kidney disease who is of atherosclerotic cardiovascular disease seen for cardiovascular Table 1. NLA Recommendations (ASCVD) events. However, despite the risk assessment and publication of guidelines for management recommendations for ASCVD prevention. symptoms is a diagnosis of mitral valve of dyslipidemia by numerous professional She follows a heart-healthy diet and has a prolapse associated with occasional societies, there still are inadequate body mass index (BMI) of 17.69 kg/m2. palpitations. She is, otherwise, completely numbers of patients receiving evidence- She participates in spin class three days asymptomatic. She is not dialysis- based therapy. One factor contributing a week and walks five miles two days dependent. to this gap in care is confusion among a week. She has known hypertension, healthcare providers regarding selection which is well controlled on amlodipine A physical exam was unremarkable. and implementation of appropriate 10 mg daily. She smoked cigarettes for Laboratory analysis revealed creatinine guidelines, particularly for special patient three to four years when she was in high 2.4 mg/dl, eGFR 23 ml/min/1.73 m2, populations.1 In addition, not all at-risk school. She has no history of diabetes. total cholesterol 228 mg/dl, high-density patients clearly match one of the defined She was told several months ago that she lipoprotein cholesterol (HDL-C) 56 mg/dl, statin-benefit groups as identified by the has mild hyperlipidemia and seeks further low-density lipoprotein cholesterol (LDL-C) 2013 American College of Cardiology/ recommendations for management. Her 141 mg/dl, and triglycerides 155 mg/dl. American Heart Association (ACC/AHA) only history of cardiovascular disease or Liver function studies are normal.

22 LipidSpin Rate of coronary death or non-fatal MI (by age and eGFR) Rate (95% CI) of coronary death or non-fatal MI (per 1000 patient-years) Overall Male Female Age >40 years (eGFR G1-G4) 14.0 (14.6–15.3) 17.4 (16.9–17.9) 12.7 (12.3–13.1) eGFR G3a-G4 19.0 (18.8–19.8) 23.4 (22.6–24.2) 16.4 (15.8–17.0) eGFR G1-G2 9.7 (9.3–10.0) 12.0 (11.4–12.6) 6.7 (6.3, 7.2) Age >50 years (eGFR G1-G4) 17.3 (17.0–17.7) 20.2 (19.6–20.8) 14.8 (14.3–15.3) eGFR G3a-G4 19.9 (19.4–20.4) 24.3 (23.4–25.2) 16.9 (16.3–17.5) eGFR G1-G2 12.9 (12.4–13.4) 15.2 (14.5–16.0) 9.7 (9.0–10.5) Age >40–50 years (eGFR G1-G4) 3.2 (2.9–3.6) 4.7 (4.2–5.4) 1.6 (1.2–2.0) eGFR G3a-G4 4.7 (3.7–6.0) 5.9 (4.3–8.1) 3.6 (2.5–5.3) eGFR G1-G2 3.0 (2.6–3.3) 4.6 (4.0–5.3) 1.2 (0.9–1.6)

Table 2. KDIGO5

To determine preventive therapy for Treatment of Blood Cholesterol to Reduce that only a few large, randomized ASCVD risk reduction in this patient Atherosclerotic Risk in Adults includes controlled trials and post-hoc analyses with chronic kidney disease (CKD), an evidence statement that patients with of the subgroup of CKD patients from an appropriate assessment of risk and manifest clinical ASCVD and CKD Stages statin trials in the general population selection of treatment guidelines must I-IV benefit from high-intensity statin are available to inform the guidelines. be considered. The new ACC/AHA CV therapy. The panel examined a sub-analysis Specific statins and statin or ezetimibe Risk Calculator has not been validated of patients with ASCVD and moderate doses are recommended for each stage in patients with CKD and this algorithm CKD (eGFR <60 ml/min/1.73 m2) from of CKD and dose titration to a specific cannot be accurately used to predict this the Treating to New Targets study.6 LDL-C goal is not recommended. (Table 3) patient’s 10-year or lifetime risk of ASCVD Atorvastatin 80 mg significantly reduced Neither ACC/AHA nor KDIGO guidelines events.3 The recently published National the incidence of major cardiovascular recommend initiation of statin therapy or Lipid Association (NLA) Recommendations events compared to atorvastatin 10 mg in combination treatment with statin and for Patient-Centered Management of patients with moderate CKD (HR=0.68; ezetimibe in dialysis-dependent patients on Dyslipidemia identifies patients with CKD Recommended doses (mg/d) of statins in adults with CKD Stages 3B and 4 as high- or very high- risk and indicate that quantitative risk eGFR G3a-G5, including patients on scoring is not necessary for initial risk Statin eGFR G1-G2 dialysis or with a kidney transplant assessment. (Table 1)4 Similarly, according to the 2013 Clinical Practice Guideline Lovastatin GP nd for Lipid Management in CKD, published Fluvastatin GP 801 by the Kidney Disease: Improving Global Atorvastatin GP 202 Outcomes (KDIGO) panel, the relationship Rosuvastatin GP 103 between LDL-C and ASCVD events is Simvastatin/Ezetmibe GP 20/104 weaker in CKD patients than in individuals Pravastatin GP 40 with normal renal function.5 This may be Simvastatin GP 40 related to the atherogenic dyslipidemia Pitavastatin GP 2 often present in CKD, characterized by Table 3. KDIGO5 near-normal levels of LDL-C, elevated LDL particle number, reduced HDL-C, and 95 percent CI 0.55 to 0.84, p=0.0003). the basis of results from the AURORA (A elevated triglycerides. Therefore, therapy The ACC/AHA guidelines do not make Study to Evaluate the Use of Rosuvastatin is not guided by the LDL-C level but rather specific recommendations for primary in Subjects on Regular Hemodialysis: An by the absolute risk of coronary events prevention in patients with moderate CKD. Assessment of Survival and Cardiovascular based on the patient age and stage of CKD Events), Deutsche Diabetes Dialyse Studie or eGFR. (Table 2) The KDIGO panel provides recommenda- (4-D), and Sorafenib HCC Assessment tions for patients at all stages of CKD. Randomized (SHARP) trials.7-9 However, The 2013 ACC/AHA Guideline on the However, the experts acknowledge patients already on lipid-lowering therapy

Official Publication of the National Lipid Association 23 Stage V are considered She would, therefore, require at least Intensity of Statin therapy* to be a matter of clinical moderate-intensity statin to achieve these High-intensity daily Moderate-intensity daily judgment. goals, which is consistent with KDIGO dosage LDL-C 50% dosage LDL-C 30% to <50% ≥ recommendations. (Table 4) Atorvastatin 40–80 mg Atorvastatin 10–20 mg The current patient with Rosuvastatin 20–40 mg Fluvastatin 40 mg bid Stage IV CKD has a high Clinicians are faced daily with at-risk Fluvastatin XL 80 mg rate of coronary death patients and patients in special populations Lovastatin 40 mg Pitavastatin 2–4 mg or nonfatal myocardial who do not clearly fall into one of the Pravastatin 40–80 mg infarction as assessed four statin-benefit groups identified by Rosuvastatin 5–10 mg in Table 2 (16.9 per the ACC/AHA cholesterol guidelines. The Simvastatin 20–40 mg 1,000 patient years, NLA Recommendations and guidelines for bid, twice per day; LDL-C, low-density lipoprotein cholesterol. 95 percent CI 16.3 to special populations are of great help in *Individual responses to statin therapy should be expected to vary in clinical practice. Moderate- or high-intensity statin therapy is 17.5). KDIGO guidelines more personalized ASCVD risk reduction preferred unless not tolerated. recommend therapy with for the diverse patients that providers must either fluvastatin 80 care for each day. n Table 4: NLA Recommendations (Table 12) mg, atorvastatin 20 mg, at the time of progression to dialysis may rosuvastatin 10 mg, simvastatin/ezetimibe 20/10 mg, pravastatin 40 mg, simvastatin Disclosure statement: Dr. Morris has received speaker continue treatment. In agreement, the NLA and/or advisory board honoraria from AstraZeneca, Recommendations state that the evidence 40 mg, or pitavastatin 2 mg daily. (Table 3) LipoScience, Aegerion, and Genzyme. The NLA Recommendations specify goals in this patient population is limited and References are listed on page 36. inconsistent. Thus, therapy and goals for of non-HDL-C <130 mg/dl and LDL-C atherogenic lipoprotein levels in CKD <100 mg/dl for this high-risk patient.

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Why participate in the NLA-SAP? 1 Approved for Maintenance of Certification points by: • Earn up to 150 CME/CE credits © 2013, By National Lipid Association, Jacksonville, Florida. All Rights Reserved.

• Earn points toward ABIM Maintenance of Certi cation The ve-volume series provides more than 500 board-review • Prepare to become certi ed in Clinical Lipidology style questions with robust, evidence-based critiques. • Increase your knowledge in Lipidology • Identify areas of strengths and opportunities for further study • Complete the program anywhere- no travel costs and no time away from patients and family

Activities available in print format or as online activity – includes access to mobile app designed for iPad and Andriod tablets

24 LipidSpin Case Study: Applying Clinical Trial Data to Patient Management: A Case Study

PAUL ZIAJKA, MD, PhD, FNLA Director, Florida Lipid Institute Winter Park, FL Director, American Board of Clinical Lipidology

Case: lipoprotein cholesterol (LDL-C) of 126 The patient was a 62-year-old Caucasian mg/dL, triglycerides of 156 mg/dL, and a woman when she was first seen at the high-density lipoprotein cholesterol (HDL- Florida Lipid Institute in 2010. She C) of 48 mg/dL — non-HDL was 157 mg/ had hypertension that was treated dL. Her high-sensitivity C-reactive protein Discuss this article at with losartan/HCTZ. She had no other (hs-CRP) was elevated at 3.6 mg/L, and www.lipid.org/lipidspin significant past medical history. She her fasting blood sugar was 112 mg/dL. All had a family history of hypertension and other values on her complete blood count diabetes and one brother who developed (CBC), comprehensive metabolic panel, cardiovascular cause. It was designed for angina at the age of 48. Her review of urine analysis (UA), and TSH were within a treatment duration of five years but systems was negative — specifically, she normal limits. was terminated at a median observation had no complaints of chest pain, transient period of only 1.9 years by the data ischemic episodes, or claudication. Her She was specifically referred by her safety monitoring committee because only medication was the losartan/HCTZ internist with the question, “Should this of an overwhelming benefit seen in the and she had no known drug allergies. She woman be on a statin?” rosuvastatin group. At termination, the had never been on lipid-modifying therapy. active treatment group had a hazard ratio JUPITER Study: of 0.56 for the aggregate endpoint, 0.46 On physical exam, the patient’s height The Justification for the Use of Statins in for MI, 0.52 for stroke, and 0.80 for death was 5-foot-4, her weight was 180 pounds, Primary Prevention (JUPITER) study was from any cause. When the study ended, her waist circumference was 38 inches, published in 2008.1 The study enrolled the rosuvastatin arm had an average LDL-C and her blood pressure on treatment was 17,802 apparently healthy men over 50 reduction of 50 percent and an hs-CRP 130/86. Her temperature, respiratory years old and women over 60 years old reduction of 37 percent. rate, and pulse were normal. Her cardiac, who had an LDL less than 130 mg/Dl, pulmonary, abdominal, neurological, and an hs-CRP >2.0 mg/L. They were The study received some criticism2 dermatological, and vascular exams were randomized 1:1 to rosuvastatin 20 mg or following publication focused primarily on all normal. placebo once daily. The study’s primary the early termination and the definition of outcome was a reduction in an aggregate “apparently healthy.” Critics pointed out A fasting lipid panel obtained by her endpoint of myocardial infarction (MI), that, in JUPITER’s “apparently healthy” referring physician showed total stroke, revascularization, hospitalization population, 25 percent had hypertension cholesterol of 205 mg/dL, a low-density for unstable angina, and death from any (systolic BP>145), 50 percent were

Official Publication of the National Lipid Association 25 overweight, 25 percent were obese, 41 ATP criteria for the diagnosis of metabolic percent met the clinical criteria for the syndrome, a diagnosis found in a significant metabolic syndrome, and less than 17 portion of the JUPITER study population. percent were taking a daily aspirin. In the spirit of the patient-centered approach emphasized by the new NLA Recommendations,3 I met with the patients “She was specifically and her husband to discuss treatment options. She decided, based in large part referred by her on the JUPITER study results, to start internist with the rosuvastatin 20 mg once daily. She also was referred to the clinic’s dietitian for question, ‘Should weight and CVD risk reduction dietary this woman be on a interventions. Case Follow-Up: statin?’” The patient most recently was seen at the Florida Lipid Institute in August. She remains free from cardiovascular disease. In 2010, based on the results from Her most recent lipid profile — on TLC JUPITER, the U.S. Food and Drug plus rosuvastatin 20 mg once daily — Administration (FDA) approved showed TC = 136 mg/dL, LDL = 60 mg/ rosuvastatin for the “primary prevention dL, triglycerides = 80 mg/dL, HDL = of cardiovascular disease in individuals 60 mg/dL, and nonHDLC 76 mg/dL. Her without clinically evident coronary heart hs-CRP is <1.0. After meeting with the disease but with an increased risk of dietitian a total of four times since her cardiovascular disease based on age >50 initial presentation, AT’s weight is down years old in men and >60 years old in 20 pounds, her waist circumference is 34 women, hsCRP> 2 mg/L and the presence inches, her fasting blood sugar is 88, and of at least one additional cardiovascular she no longer meets any of the criteria risk factor.” (Crestor Package labeling) defining the metabolic syndrome.

Back to the Case: Her care was patient-centered and I was After I first saw the patient, I repeated the delighted to work with an informed, lipid panel and hs-CRP. Her repeat labs compliant patient. n showed TC = 203 mg/dL, LDL-C = 124 mg/dL, triglycerides 160 mg/dL, HDL-C = Disclosure statement: Dr. Ziajka received speaker honoraria from Kowa Pharmaceuticals, Abbott 47 mg/dL, non-HDLC 156 mg/dL, and an Laboratories, Merck and Co., Atherotech Inc., Hunter hs-CRP = 3.8. Heart Lab and AstraZeneca. He’s received a research grant from Genzyme and consulting fees from Hunter Heart Lab. a. According to ATP guidelines, her LDL goal References are listed on page 36. was <130 and, based on that criteria, she clearly did not warrant statin therapy. But the patient could easily have been a “poster child” for the JUPITER study population, meeting all of the criteria identified in the FDA’s expanded indication for rosuvastatin. She also met all of the

26 LipidSpin Chapter Update: Contributing to the NLA Mission

LORI A. ALEXANDER, MSHS, RD, CCRC, FNLA Site Manager, St. John’s Center for Clinical Research Ponte Vedra, FL Diplomate, Accreditation Council of Clinical Lipidology

It was an honor and privilege for the higher rates of modifiable risk factors Southeast Lipid Association (SELA) to such as hyperlipidemia, obesity, diabetes, host the National Lipid Association (NLA) hypertension, and smoking. Dr. Croy Scientific Sessions in Orlando, Fla. this has reached out to Virginia’s Federally past May 2014. Excellent topics and Qualified Health Centers to see how Discuss this article at presenters offered practical knowledge SELA members can collaborate with www.lipid.org/lipidspin for integrating the latest clinical research them to provide and encourage education guidelines into practice. I was pleased to and advocacy. She has also contacted chair the Abstracts Committee, and was the Virginia Community Health Care common diets, which should be a core impressed with all the submissions. Marisa Association about planning a SELA skill of anyone managing patients with Schoen, BA, was recognized with the educational conference, possibly in March dyslipidemia. The publication is to be titled First Place Young Investigator Award. Her 2015. This is a wonderful way to involve “Nutritional Intervention and Dyslipidemia: poster was titled “Statins and Cognitive interested SELA members in spreading Review of the Contents and Lipid Effects Function: A Systematic Review.” All of the the word about the importance of lipid of Common Diets.” The creation of scientific posters abstracts were published management. For more information, see illustrated color figures representing in the June 2014 Journal of Clinical the Member Spotlight section of this common diets are planned for a number Lipidology. I hope you will encourage all LipidSpin (Page 29), which features her of ongoing and future NLA initiatives. This Young Investigators to begin thinking contributions! project is best integrated with others at about submitting their abstracts for this the NLA who have an interest in nutrition year’s NLA Scientific Sessions held in Another SELA initiative being proposed, interventions to further the overall goals of Chicago in June 2015. prompted by Dr. Harold Bays’ ideas the organization. and leadership, is a project geared One of the projects SELA is pursuing is toward improving patient care. This is I also want to share the initiatives of the being led by SELA Secretary Deborah another opportunity to engage the many Florida (FLA) Committee, led by President Croy, DNP, RN, ANP-BC, AGPCNP-BC, extraordinary talents of volunteer SELA Sandra Kreul, ARNP. Each year the CLS, AACC. Dr. Croy recognized the members to craft an educational review, committee selects a topic and develops a need for improving lipid management with plans for publication in a peer- presentation for its members to use in the in underserved areas, especially in the reviewed journal. Many clinicians are community, for speaking and educating. southern region of the U.S. Patients in deficient in their knowledge of nutrition This year Dr. Paul Zaijka has put together the south across the stroke belt have intervention and the lipid effects of a talk on “The Evolution of Cholesterol

Official Publication of the National Lipid Association 27 Management Guidelines” for members to and Atherosclerosis,” and providing them use in talks throughout their communities. with valuable and current information on Other projects of the FLA Committee managing their patients’ lipid issues. include furthering relationships with other organizations, such as the Florida SELA is a very active, creative, and Chapter of ACC and the Florida Dietetic energetic organization that is always Association. FLA Committee member looking to involve more of its members. If and SELA Board Member Dr. Greg Cohn you have a particular interest or passion is participating in an Internal Medicine and want to become involved, email Residency Program at Florida Atlantic [email protected] at the NLA and let University in Boca Raton, Fla. Residents us know! We’ll take it from there. n rotate among three hospitals, and spend one day each month at Dr. Cohn’s Disclosure statement: Ms. Alexander has no office focusing on cardiovascular disease disclosures to report. prevention. He emphasizes the difference between lipids and lipoproteins, utilization of advanced lipid testing, and diseases such as PCOS. He will be lecturing to the residents on “Lipids, Lipoproteins

REGISTER NOW NATIONAL LIPID ASSOCIATION SCIENTIFIC SESSIONS Palmer House Hotel Chicago, IL Hosted by the Midwest Lipid Association Scientific Sessions June 11–14, 2015 Professional Development Courses June 10–11, 2015

CME Credit Provided by National Lipid Association lipid.org/sessions This activity has been approved for AMA PRA Category 1 Credit™. Full accreditation information is available at www.lipid.org/sessions

28 LipidSpin Member Spotlight: Deborah S. Croy, DNP, RN, ANP-BC, AGPCNP-BC, CLS, AACC

DEBORAH S. CROY, DNP, RN, ANP-BC, AGPCNP-BC, CLS, AACC Nurse Practitioner, Bland County Medical Clinic Bastian, VA

“Security is mostly a superstition. It does called Abbs Valley in the Virginia coalfields not exist in nature, nor do the children and remained in the rural Virginia area to of men as whole experience it. Avoiding treat and advocate for the underserved danger is no safer in the long run than populations. She received her Masters in Discuss this article at outright exposure. Life is either a daring Nursing from Duke University and most www.lipid.org/lipidspin adventure or nothing.” – Helen Keller recently earned her Doctor of Nursing Practice degree from Johns Hopkins School This quote is a favorite of Deborah S. of Nursing. She noted that this was a far Croy, DNP. She says, “If one female cry from the first school she attended as of income, makes treatment for them who was blind and deaf could make a child that had an outhouse and used a more challenging. In addition, many of Dr. such a contribution to humanity, if we potbelly coal stove for heat! Croy’s patients have been diagnosed with who have no or limited disabilities apply bipolar disorder and depression, and are on ourselves, think of what we can do.” This Dr. Croy is an Adult Nurse Practitioner medications known to increase their risk of is Dr. Croy’s philosophy when it comes employed in a Federally Qualified dyslipidemia. to treating underserved patients in rural Community Health Center where she Virginia and West Virginia. treats patients with dyslipidemia and Despite these various setbacks, Dr. Croy metabolic disorders on a daily basis. Many and her coworkers have become advocates Dr. Croy has known since the age of 8 of her patients are either uninsured or for her underserved patients. Past SELA that she wants to treat and help find a underinsured and, without their clinic, President, Ralph LaForge, urged Dr. Croy cure for heart disease. As a young girl, she would go without medical care. The Health to become involved with the National Lipid witnessed her coal mining father become Center has a contract so it can obtain labs Association (NLA). Not long after she also disabled due to cardiovascular disease and at cost. This allows patients to receive became a certified Clinical Lipid Specialist. suffer multiple myocardial infarctions. basic labs, including their lipid profiles, She says, “I found in the NLA there are At that time, she vowed to dedicate her at an affordable cost. The patients in many like-minded practitioners and was life to finding a cure for heart disease so the rural population that Dr. Croy sees invited to take a leadership role and join that other young children would not lose have a higher than national incidence of the SELA board.” quality time with their parents. Dr. Croy diabetes and dyslipidemia. This, coupled grew up in an unincorporated community with the fact that many suffer from a lack Dr. Croy is also very involved with the

Official Publication of the National Lipid Association 29 A view of Dr. Croy’s hometown, Pocahontas, Va.

American College of Cardiology, serving on three committees and is their incoming Cardiac Care Associate liaison for the state of Virginia. She uses her roles in both organizations to act as a voice for the underserved population and to create awareness. She says that “many people do not know that they can get free medication for the indigents through pharmaceutical programs.” Her goal for the field of lipidology would be to see more collaboration and funding for the study of rural, underserved patients and those with different ethnicities. She would also like to see the development of medications Deborah Croy with her staff at Bland County Medical Clinic. with fewer adverse drug reactions so her patients can continue to take them.

Despite the everyday challenges she faces in her rural area, Dr. Croy says her favorite part of her job is having the opportunity to get to know her patients and their families. She is able to form a relationship with them and, in return, they treat her as part of the family. Outside of work and volunteering, Dr. Croy loves traveling, photography, and dancing. She also enjoys taking nature walks looking for Native American artifacts. n

30 LipidSpin Education and Meeting News and Notes

NLA Achieves Accreditation with policies of the ACCME and also positions attending the annual meeting will have all- Commendation from ACCME itself as a leader in its field. This designation day access to a private lounge with free wi- The National Lipid Association (NLA) was is only awarded to approximately 20 percent fi, soft drinks, and snacks – not to mention surveyed this year by the Accreditation of ACCME accredited providers. Support bragging rights! Your chapter needs your Council for Continuing Medical Education was provided to the NLA staff during the help! If you want your chapter to win, make (ACCME) and awarded Accreditation ACCME survey process by Dr. Robert Wild, sure to reach out to your colleagues who with Commendation for the next six Chair-CME Committee, and Dr. Peter Jones, are not NLA members yet and tell them years as a provider of continuing medical Chief Science Officer. why they should join the NLA. To request education for physicians. The NLA’s new membership and marketing materials, email accreditation term expires Nov. 30, 2020. New Slide Set Available Comparing Membership Manager, Britney Caldwell ACCME accreditation seeks to assure the ACC/AHA Guidelines vs. NLA at [email protected]. Visit lipid.org/ medical community and the public that Recommendations competition2015 for more information NLA provides physicians with relevant, View and download the new slide and current winning chapter. effective, practice-based continuing medical presentation that compares and contrasts education that supports U.S. healthcare the perspectives provided by the ACC/AHA Register Now for the NLA’s Spring quality improvement. The ACCME Guidelines and the NLA Recommendations Clinical Lipid Update in Denver employs a rigorous, multilevel process for for the Patient-Centered Management There’s still time to register evaluating institutions’ continuing medical of Dyslipidemia. Many NLA members for the National Lipid education programs according to the high requested a slide set that compares these Association’s Spring Clinical accreditation standards adopted by all seven viewpoints, and Carl Orringer, MD, FNLA, Lipid Update. The 2015 ACCME member organizations. These took the initiative to develop them. It was Spring CLU will take place organizations of medicine in the U.S. are reviewed by an NLA Recommendations in Denver Feb. 27–March the American Board of Medical Specialties, panel for accuracy, content, and balance 1, 2015, at the Grand Hyatt Denver. the American Hospital Association, and includes the latest discussion of the Based on this year’s theme, “Achieving the American Medical Association, the recent IMPROVE-IT Trial results. This new New Heights in Lipid Management,” you Association for Hospital Medical Education, slide set is one of many tools on the NLA will learn about the latest controversies the Association of American Medical Recommendations available on the website in lipid management, the impact of public Colleges, the Council of Medical Specialty at lipid.org/recommendations. policy in health care, evolving strategies for Societies, and the Federation of State prediction and treatment, and emerging Medical Boards of the US, Inc. Membership Competition targets for atherosclerosis prevention. If Does your chapter have you miss pre-registration, onsite registration The ACCME’s decision was based on a what it takes to be a VIP? is also available. Visit lipid.org/springclu survey of the NLA’s written self-study report Join your fellow colleagues for more information. Use promo code of CME processes and procedures, evidence in the Member Recruitment DSCLU15 for a $50 discount toward of performance in practice through CME Competition for 2015 to see meeting registration. activity files, and an interview with NLA which chapter has what it takes to win a staff and volunteers. Accreditation with VIP Lounge at the 2015 Annual Scientific Submit your Abstracts for the NLA Commendation is a significant achievement Sessions in Chicago. If your chapter recruits Annual Scientific Sessions in Chicago in CME and is awarded to providers that the most new members by May 15, 2015, The National Lipid Association is currently demonstrate compliance in all criteria and every member of that chapter who is accepting abstracts for the Annual Scientific

Official Publication of the National Lipid Association 31 Sessions in Chicago June 11–14, 2015. This detailing the process and deadlines. Board Upcoming ISA 2015 Meeting is your opportunity to submit your science members with expiring terms have been The 17th International Symposium on for inclusion in the NLA’s 2015 Poster Hall. contacted directly to notify them if they are Atherosclerosis (ISA) is scheduled for May The NLA Poster Hall will cover a vast array eligible to serve another term. A complete 23-26, 2015, in Amsterdam, Netherlands. of topics in 16 categories including clinical nomination application includes at least The scientific program is designed in a novel applications of biomarkers, epidemiology two letters of recommendation, a CV, and format, organized in four major themes: of cardiovascular disease, management an updated financial disclosure. Nominees Dyslipidemia, Pathogenesis, Prevention, of statin intolerance, and imaging in may submit additional supporting material and Epidemiology of atherosclerosis. The atherosclerosis. All accepted abstracts for the Nominating Committee to consider. abstract submission deadline has been will also be published in the 2015 Annual Please check the NLA website for additional extended to Feb. 1, 2015. For more Scientific Sessions edition of the Journal of information. information, visit isa-2015.com. Clinical Lipidology. Visit lipid.org/abstracts to submit online and for more information. Call for Honors and Awards Masters in Lipidology Course Available Nominations Online Soon Pay Your Dues for 2015 The NLA Honors and Awards nomination The Masters in Lipidology Course, The 2015 NLA dues statements and window is now open. The deadline to traditionally offered as an ancillary course membership cards have been mailed. In nominate is Friday, March 6, 2015. prior to NLA meetings, will be released addition to paying your 2015 dues, this The NLA has established several types as an online course in early 2015! is a great opportunity to donate to the of recognition: Fellow of the NLA, NLA This comprehensive program provides Foundation of the NLA. Donate online or Distinguished Achievement Award, and physicians, physician assistants, pharmacists, add your end of year contribution when NLA Honorary Lifetime Membership nurse practitioners, nurses, dietitians, and you pay your 2015 NLA dues. To pay your Award. To view the awards criteria and other healthcare professionals with an dues online, visit lipid.org/dues. For more requirements or to submit a nomination, interest in lipid management, with complete information or questions regarding dues, visit lipid.org/awards. lectures synchronized with slides from contact Membership Manager Britney the live course. The Masters in Lipidology Caldwell at [email protected]. NLA Releases Annual Summary of online course provides an intensive Clinical Lipidology 2015 curriculum covering lipoprotein metabolism, Mentors Needed for Mentor/Mentee Have you received your copy of the genetics, vascular biology, atherosclerosis, Program Annual Summary of Clinical Lipidology biomarkers, imaging, Cardiometabolic Did you know that the NLA has established with the latest issue of the Journal of disorders, lifestyle interventions, and a mentoring program to help develop the Clinical Lipidology? This annual summary is pharmacologic therapies. The curriculum next generation of clinical, academic, intended to be a ‘‘living document,’’ with is designed for healthcare professionals and administrative leaders in the field of future annual updates that will be based on who desire to practice at an advanced level lipidology by pairing early career members emerging science, clinical considerations, within the field. with established members? We hope you and new NLA position and consensus will take the time to get involved in this statements. The goal is to provide clinicians Available via computer, laptop, or iPad/ wonderful initiative. More details about an ongoing resource that translates the tablet, the program provides participants the Mentor/Mentee program and latest advances in medical science toward with the flexibility to complete modules application are available on the evaluation and treatment of patients from virtually anywhere. Participants receive lipid.org/education/fellows. with dyslipidemia. To learn more, visit access to online resources and lipid.org/nla/national-lipid-association- tools to enhance learning and practice. NLA and Chapter Board Nominations releases-annual-summary-clinical- For full Accreditation information, visit Nominations for At-Large and Officer lipidology-2015. lipid.org/mastersonline. positions will open up in the end of January. An email will go out to all NLA members

32 LipidSpin NLA Events Calendar

2015 National Lipid Association Lipid Academy SPRING CLINICAL LIPID UPDATE Clinical Lipid Update—Spring February 26–27, 2015 2015 Hosted by the Pacific and Southwest Chapters Denver, CO February 27–March 1, 2015 June 10–11, 2015 Grand Hyatt Denver Chicago, IL Denver, CO September 17–18, 2015 FEBRUARY 27–MARCH 1, 2015 lipid.org/springclu DENVER, CO Pittsburgh, PA NATIONAL LIPID ASSOCIATION

2015 National Lipid Association Scientific Sessions Hosted by the Midwest Lipid Association June 11–14, 2015 Palmer House Hotel NATIONAL LIPID ASSOCIATION SCIENTIFIC SESSIONS Chicago, IL June 11–14, 2015 Masters in Lipidology Palmer House Hotel lipid.org/sessions Chicago, IL February 26–27, 2015 Denver, CO

2015 National Lipid Association June 10–11, 2015 Clinical Lipid Update—Fall Chicago, IL Hosted by the Northeast and Southeast Chapters September 17–18, 2015 September 18–20, 2015 Pittsburgh, PA Omni William Penn Hotel Pittsburgh, PA lipid.org/fallclu

JOB LISTING

Lipidologist Needed to Take Over Practice in Tallahassee, Fla. There is an excellent opportunity for an internist, family physician, which will allow for the addition of three endocrinologists. Dr. Smith cardiologist, or endocrinologist to take over a referral practice of wishes to retire in 2015 but will remain on as a consultant to the lipidology. The applicant must be a diplomate of the American Board of new director for a period of time. The work environment is pleasant, Clinical Lipidology. The Tallahassee Memorial Lipid Center has been in academic, and rewarding. The salary, which is based on RVUs, is operation for more than five years and has approximately 100 referring negotiable and the present conversion factor is quite good. physicians, for a total of more than 500 annual referrals. J. Orson Smith, MD, FACC, is the current director, working with Nancy Smith, Telephone: (850) 431-5474 RD, CDE, CLS. They were joined in December 2014 by Elizabeth Ford, Fax: (850) 431-4711 ARNP-BC. The Lipid Center is in the same building as the Tallahassee Address: 1981 Capital Circle NE, Tallahassee, FL 32308 Memorial Diabetes Center and the Tallahassee Memorial Bariatric Website: TMH.org/LIPIDCenter Center. Current plans are to eventually move into a larger building, Email: [email protected]

Official Publication of the National Lipid Association 33 Foundation Update

ANNE C. GOLDBERG, MD, FNLA President, Foundation of the National Lipid Association Associate Professor of Medicine Washington University School of Medicine St. Louis, MO Diplomate, American Board of Clinical Lipidology

the campaign via media interviews and causes and prevention of heart disease. publications and the FNLA’s social media In addition to his work in lipids, Dr. accounts. The final results of the poll will Hunninghake served as the director of provide a snapshot of cholesterol awareness the Heart Disease Prevention Clinic at the Discuss this article at levels across the country and will be University of Minnesota. He contributed to www.lipid.org/lipidspin revealed in a full paper to be released in numerous clinical trials of important lipid- December 2015. This collaboration is lowering medications as well as outcomes I hope everyone had a wonderful Holiday focused on helping to address the unmet trials involving lipid lowering. Season and a Happy New Year! To kick needs of cardiovascular health and the off the New Year, the Foundation of the role cholesterol plays. It is our hope to The Foundation has had a significant focus National Lipid Association (FNLA) is hard at provide resources to help patients better geared toward patient awareness and work with new projects and partnerships. understand and take control of their heart education concerning disorders such as health. FH, and this award has been created in Most recently, the FNLA collaborated with order to continue that focus and to further Sanofi US and Regeneron Pharmaceuticals In addition, the Foundation will be encourage clinicians in their research and Inc. in their launching of an unbranded sponsoring a special abstract award at the study of familial hypercholesterolemia. cholesterol awareness campaign, 2015 NLA Annual Scientific Sessions in The winner will be determined by the “Cholesterol Counts” on Dec. 15, 2014. Chicago from June 11–14, 2015. In honor Foundation of the NLA Board of Directors The campaign consists of polling patients of Donald B. Hunninghake, MD, a pioneer once the abstract committee has approved on their base knowledge of cholesterol, in lipid research, the Foundation is offering the abstracts in this category. The award — lipid disorders, and their own risk The Foundation of the National Lipid $1,500 and a $1,000 travel grant — will associated with LDL-C. The poll is being Association Donald Hunninghake Familial be presented to the winner at the Honors disseminated through an unbranded Hypercholesterolemia Abstract Award for and Awards Ceremony at the NLA 2015 website, CholesterolCounts.com, and the best submitted abstract specifically in Annual Scientific Sessions. Please check through a market research firm — Harris, a the area of familial hypercholesterolemia lipid.org/abstracts for more information Nielsen company. (FH) research. on submitting an abstract in this category for consideration of this award. The Ralph M. Vicari, MD, FACC, FNLA, will act Dr. Hunninghake — a graduate of the Foundation is looking forward to seeing as the Foundation’s program spokesman University of Kansas Medical School — exciting research in this very important in this effort. The FNLA will help market had an illustrious career dedicated to the area. n

34 LipidSpin References

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When the author attempted to question the TACT lead author 11. Ginsberg HN. Diabetic dyslipidemia: basic mechanisms underlying (at Am Soc Prev Cardiology meetings) about these problems with the common hypertriglyceridemia and low HDL cholesterol levels. the study he wasn’t even allowed to finish his questions before Diabetes. 1996 Jul;45 Suppl 3:S27-30. Guest Editorial dismissive answers were given. To my knowledge the many concerns about this trial have not been answered in print. 12. Bays H, Toth P, Kris-Etherton P, et al. Obesity, adiposity and 1. Institute of Medicine. Practice Guidelines We Can Trust. dyslipidemia: A consensus statement from the National Lipid Additional Resources National Academies Press, Washington, DC; 2011 http://iom. Association. Journal of Clinical Lipidology. 2013;7:304-383. edu/Reports/2011/Clinical-Practice-Guidelines-We-Can-Trust.aspx http://www.sciencebasedmedicine.org/ Exploring issues and con- 13. Kodama, S., S. Tanaka, K. Saito, M. et.al. (2011). 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Official Publication of the National Lipid Association 35 middle-aged overweight men. Lipids in Health and Disease 2013, 5 Kidney Disease: Improving Global Outcomes (KDIGO) Lipid Work 12:131 Group. KDIGO clinical practice guideline for lipid management in chronic kidney disease. Kidney Int Suppl. 2013;3:259-305. 15. Costa RR, Alberton C, Tagliari M, et al. Effects of resistance training on the lipid profile in obese women. J Sports Med Phys Fitness. Mar 6 Shepherd J, Kastelein JJP, Vera Bittner, et al. for the Treating to 2011;51(1):169-77. New Targets Investigators. Intensive lipid lowering with atorvastatin in patients with coronary heart disease and chronic kidney 16. Sheikholeslami VD, Ahmadi S, et al. Changes in cardiovascular risk disease: TNT (Treating to New Targets) Study. J Am Coll Cardiol. factors and inflammatory markers of young, healthy, men after six 2008;51:1,448-1,454. weeks of moderate or high intensity resistance training. J Sports Med Phys Fitness. Dec 2011;51(4):695-700. 7 Fellström BC, Jardine AG, Schmieder RE, et al. for the AURORA Study Group. Rosuvastatin and cardiovascular events in patients 17. Wooten JS, Phillips MD, Mitchell JB, et al. Resistance exercise undergoing hemodialysis. N Engl J Med. 2009;360:1,395-1,407. and lipoproteins in postmenopausal women. Int J Sports Med. Jan 2011;32(1):7-13. 8 Wanner C, Krane V, März W, et al. for the German Diabetes and Dialysis Study Investigators. Atorvastatin in Patients with Type 2 18. Kelley GA, Kelley KS, Tran ZV. Walking and Non-HDL-C in adults: Diabetes Mellitus Undergoing Hemodialysis. N Engl J Med. 2005; a meta-analysis of randomized controlled trials. Prev. Cardiol. 353:238-248. 2005;8:102-107. 9 Baigent C, Landray MJ, Reith C, et al. for the SHARP Investigators. 19. Magkos F. Very low-density lipoprotein metabolism in response to The effects of lowering LDL cholesterol with simvastatin plus exercise: Mechanisms of hypotriacylglycerolemia. Progress in Lipid ezetimibe in patients with chronic kidney disease (Study of Heart Research. 2009;48:171-190. and Renal Protection): a randomised placebo-controlled trial. The 20. Trejo-Gutierrez JF and Fletcher G. Impact of exercise on blood lipids Lancet. 2011;377(9784):2,181-2,192. and lipoproteins. Journal of Clinical Lipidology. 2007;1:175-181.

21. Durstine JL, Grandjean PW, Cox CA, and Thompson PD. Lipids, Case Study lipoproteins and exercise. Journal of Cardiopulmonary Rehabilitation. 2002;22:385-398. 1. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein; 22. Staiano A, Harrington D, Katzmarzyk P, et al. Sitting time NEJM. 2008;359:2,195-2,207. and cardiometabolic risk in U.S. adults: associations by sex, race, socioeconomic status and activity level. Br J Sports Med. 2. Kappagoda CS and Amsterdam EA. Another look at the results of the 2014;48:213-219. JUPITER Trial; AJC. 2009;104:1,603-1,605.

23. Slentz CA, Houmard JA, Johnson JL, et al. Inactivity, exercise 3. National Lipid Association recommendations for patient-centered training and detraining, and plasma lipoproteins. Journal of Applied management of dyslipidemia: Part 1 – executive summary Terry A. Physiology. 2007;103:432-442. Jacobson, Matthew K. Ito, Kevin C. Maki, Carl E. Orringer, Harold E. Bays, Peter H. Jones, James M. McKenney, Scott M. Grundy, Edward 24. Cohen JC, Noakes TD, Benade AJ. Serum triglyceride responses A. Gill, Robert A. Wild, Don P. Wilson, W. Virgil Brown DOI: http:// to fatty meals: effects of meal fat content. Am J Clin Nutr. 1988 dx.doi.org/10.1016/j.jacl.2014.07.007 Journal of Clinical Lipidology, May;47(5):825-7. Vol. 8, Issue 5 473-488 25. Malkova D, Gill J. Effects of exercise on postprandial metabolism. Future Lipidology. 2006;1:743-755.

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Practical Pearls

1 Morris PB, Ballantyne CM, Birtcher KK, et al. Review of clinical practice guidelines for the management of LDL-related risk. J Am Coll Cardiol. 2014;64:196-206.

2 Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/ AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2,889- 2,934.

3 Goff DC Jr., Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2,935- 2,959.

4 Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for patient-centered management of dyslipidemias: Part 1 – executive summary. J Clin Lipidol. 2014;8:473-488. Cynthia G. Rodriguez, DNP, ARNP, FNP-BC, CLS, FNLA

FOR YOUR PATIENTS Genetic Testing and Cholesterol

Discuss the need for genetic testing with your healthcare provider. It is not necessary for most. If you have a genetic test, the result may help determine the best treatment and if any of your family members should be tested.

Genetic Testing What does it tell you? What does it affect?

Apolipoprotein E (apoE) Genotype Your risk of having a disorder • The way your body makes called “dysbetalipoproteinemia” and stores cholesterol and triglycerides.

• People with this disorder are at risk for heart disease.

Familial Hypercholesterolemia (FH) If you have genetic mutations, • The way your body makes and such as in the LDL Receptor, processes cholesterol. PCSK9 or ApoB genes, that cause FH • People with FH are at risk for heart disease.

Familial Chylomicronemia Syndrome If you have genetic mutations, • The way your body forms and (FCS) such as in the Apo C II and LPL processes triglycerides. genes, that cause FCS. • People with FCS are at risk for pancreatitis.

SLCO1B1 Genotype (Statin Myopathy) Your risk of having muscle • Your ability to take Statins. side effects from a group of cholesterol lowering medications called Statins.

References Cleveland Heart Lab. http://www.clevelandheartlab.com/ Health Diagnostic Laboratory Inc. http://www.hdlabinc.com/

Health Care Providers—access this tear sheet at www.learnyourlipids.com 6816 Southpoint Pkwy Suite 1000 Jacksonville, Florida 32216