Risk Factors and Trends in Incidence of Heart Failure Following Acute Myocardial Infarction

Home , Heart failure, Myocardial infarction

Jennifer Wellings, MD, John B. Kostis,MD*, Davit Sargsyan, MS, Javier Cabrera, PhD, and William J. Kostis, PhD, MD for the Myocardial Infarction Data Acquisition System (MIDAS 31) Study Group

Patients who develop heart failure (HF) after an acute myocardial infarction (AMI) are at higher risk of adverse fatal and nonfatal outcomes. Published studies on the incidence and associations of HF after infarction have been contradictory, with some reporting increasing and others decreasing incidence. Between 2000 and 2015, 109,717 patients admitted for a first AMI in New Jersey were discharged alive. In the 15 years from 2000 to 2015, the rates of admission for HF in AMI patients who were discharged alive decreased by 60%, from 3.48% to 1.4%, at 1-year follow-up. At 5 years of follow-up, the decline was more pronounced, from 7.21% to 1.4%, an 80% decline. All-cause death, and the combined end point of admission for HF or death, showed decreasing trends. Cox regression indicated a decrease in the risk of admission for HF over time (hazard ratio [HR] 0.955, 95% confidence interval [CI] 0.949 to 0.961). Younger age, male gender, and commercial insurance were associated with lower HRs for HF (p <0.001), whereas history of hypertension, diabetes, kidney, or lung disease were associated with higher HRs (p <0.001). There was no significant difference in the rate of HF between subendocardial and transmural AMI (adjusted OR was 0.96, CI 0.90 to 1.03, p = 0.241). Revascularization was associated with a marked decrease in HF admissions (adjusted OR 0.22, 95% CI 0.19 to 0.25, p <0.001 for percutaneous coronary intervention and OR 0.44, 95% CI 0.38 to 0.51, p <0.001 for CABG). In conclusion, the rate of admission for HF after discharge for a first myocardial infarction as well as all-cause death decreased markedly from 2000 to 2015. © 2018 Elsevier Inc. All rights reserved. (Am J Cardiol 2018;122:1–5)

Acute myocardial infarction (AMI) remains one of the with longitudinal follow-up for up to 30 years. MIDAS con- leading causes of death in the United States.1,2 Treatment ad- tains discharge data, including the reason for admission, and vancements have resulted in a decrease in mortality following up to 8 additional diagnoses derived from the New Jersey State- AMI, but heart failure (HF) remains a significant wide Hospital Uniform Billing System. MIDAS data are merged complication.3–5 Patients with HF after AMI are at higher risk with the New Jersey death registration files for date of death of adverse outcomes including recurrent AMI, longer hos- and cause of death. Death information is validated using the pitalization, stroke, ventricular arrhythmias, cardiac arrest, and National Death Index for deaths outside the state. In this ret- death.6–9 Published studies on the incidence and associa- rospective study with a 5-year follow-up, we used a subset of tions of HF after infarction have been contradictory with some MIDAS records for patient admissions with a first AMI, where reporting increasing and others decreasing incidence. The the AMI was the reason for admission who did not have an purpose of the present report is to investigate the rate of de- AMI admission within 5 years before the index AMI. veloping HF in first-time AMI patients admitted to New Jersey Diagnoses were encoded using International Classifica- hospitals, to evaluate co-morbid conditions associated with tion of Disease 9th Revision (ICD-9) billing codes. Patients the development of HF, and to examine time trends of these older than 18 years who were admitted between the years 2000 rates from 2000 to 2015. to 2015 with codes of transmural AMI (anterior, ICD-9 410.0x, 410.1x; inferior, ICD-9 410.2x, 410.4x; lateral, ICD-9 410.3x, Methods 410.5x; posterior, ICD9 410.6x), subendocardial (ICD-9 The Myocardial Infarction Data Acquisition System 410.7x), and other/unspecified (ICD-9 410.8x, 410.9x) were (MIDAS) is a statewide database that includes all cardiovas- included in the data set. Covariates were patient demograph- cular disease admissions to nonfederal hospitals in New Jersey ics and co-morbidities: age (by decade), gender, first AMI discharge year, hypertension (401.xx to 405.xx), diabetes (250.xx), chronic liver disease (571.xx), chronic kidney disease Rutgers Robert Wood Johnson Medical School, Cardiovascular Insti- (CKD, 585.xx), chronic obstructive pulmonary disease (COPD, tute, New Brunswick, New Jersey. Manuscript received January 8, 2018; 490.xx to 496.xx), and disorder of lipid metabolism (272.x). revised manuscript received and accepted March 13, 2018. See page 4 for disclosure information. This subset of records for 109,717 patients was used to es- This study was funded, in part, by the Robert Wood Johnson Founda- timate the rate of admission for HF (ICD-9 codes 428.0, tion (Princeton, NJ). 428.20, 428.21, 428.23, 428.30, 428.31, 438.33, 428.40, *Corresponding author: Tel: (732) 235-7685; fax: (732) 235-7039. 428.41, and 428.43) at 30 days, 90 days, 180 days, 1 year, E-mail address: [email protected] (J.B. Kostis). and 5 years. Patients with cancer (ICD-9 codes 140.xx to

165.xx, 170.xx to 176.xx, and 180.xx to 239.xx) were ex- Table 2 cluded from the analysis. Rates of admission for heart failure Statistical analyses were performed using R version 3.4.1 Myocardial infarction 30-Day 90-Day 180-Day 1-Year 5-Years software. Odds ratios (ORs) for HF admission, all-cause death, discharge year and the combined end point of HF admission or all-cause death after the first AMI discharge were estimated using general- 2000 0.90 1.90 2.84 3.48 7.21 2001 0.71 1.55 2.22 2.84 7.01 ized linear models with logit link function (logistic regression). 2002 0.82 1.62 2.42 3.13 6.55 The models estimated the OR at 30 days, 90 days, 180 days, 2003 0.97 1.80 2.27 2.92 6.03 1 year, and 5 years, adjusted for age, gender, ethnicity, first 2004 0.87 1.70 2.31 3.07 6.07 AMI discharge year, type of insurance, and history of hy- 2005 0.89 1.50 2.12 2.77 5.77 pertension, diabetes, chronic liver disease, CKD, COPD, and 2006 0.78 1.57 2.09 2.95 5.61 disorder of lipid metabolism. Additionally, the Cox propor- 2007 0.80 1.61 2.05 2.79 5.84 tional hazard model was used to estimate hazard ratios of 2008 0.98 1.78 2.51 3.09 5.74 readmissions for HF associated with the previously men- 2009 0.78 1.38 1.92 2.55 5.35 tioned risk factors. 2010 0.92 1.53 1.99 2.52 4.50 2011 1.04 1.79 2.23 2.84 5.70 2012 0.67 1.19 1.79 2.42 4.11 Results 2013 0.59 1.30 1.60 2.23 3.60 From 2000 to 2015, 109,717 patients were admitted with 2014 0.50 0.99 1.39 1.87 2.29 a first AMI in New Jersey. The mean age of patients dis- 2015 0.67 1.10 1.30 1.40 1.40 charged alive after a first AMI admission was 63.3 (SE 14.4). Thirty-four percent of the patients were women; about half of the patients (53.8%) had commercial insurance (including Blue Cross and HMO), and 37.3% had Medicare (Table 1). difference in the rate of HF between subendocardial and trans- At 1-year follow-up, the rate of admission for HF in pa- mural AMI (adjusted OR was 0.96, confidence interval [CI] = tients discharged alive after a first AMI decreased by 60% 0.90 to 1.03, p 0.241). Revascularization was associated with from 3.48% in 2000 to 1.4% in 2015. The rates of admis- a marked decrease in HF admissions (adjusted OR 0.22, 95% < sion for HF in 2000 were 0.9%, 1.9%, 2.84%, and 3.48% at CI 0.19 to 0.25, p 0.001 for percutaneous coronary inter- < 30 days, 90 days, 180 days, and 1 year, respectively. At 5 years vention and OR 0.44, 95% CI 0.38 to 0.51, p 0.001 for CABG). of follow-up, the decline was more pronounced than at 1 year from 7.21% to 1.4%, an 80% versus 60% decline at 1 year. Discussion The rate of HF in patients with AMI discharged in 2015 was This study shows a 60% decrease in rate of admission for significantly lower, 0.67% 1.1%, 1.3%, and 1.4% at 30 days, HF in patients discharged alive after a first AMI from 2000 90 days, 180 days, 1 year, and 5 years, respectively, than those to 2015 with follow-up periods up to 1 year and 80% at 5 discharged in 2000 (Table 2). Figure 1 displays the trend in years. Similar declines were observed for all-cause death and HF admission rates in patients discharged alive after a first for the combined end point of admission for HF or death. To AMI between the years 2000 and 2015. All-cause death, as our knowledge, this is the first study to report data from a well as the combined end point of admission for HF or death, statewide all-inclusive database. This study is in agreement also showed a decreasing trend. with older studies that were not based on a defined popula- Estimates from logistic regression models adjusted for all tion. These studies reported a decline in the incidence of HF risk factors listed earlier are presented in Figure 2. Older age, ranging from 10% to 40% between 1990 and 2002.7,8 A decline female gender, history of diabetes, Medicare (vs commercial in the occurrence of HF after myocardial infarction (MI) insurance), history of hypertension, CKD, and COPD were between 1979 and 1994 was observed in the Olmsted County associated with a higher risk of admission for HF or death (p Study.10 A more recent study from Denmark reported a de- <0.001) at follow-up. History of disorder of lipid metabo- crease in HF incidence and mortality at 90 days after MI lism showed a negative association for HF. Cox regression between 1997 and 201011 and in Western Australia between hazard ratios for admission for HF yielded results similar to the periods 1996 to 1998 and 2005 to 2007.12 Similar trends the logistic regressions (Figure 3). There was no significant were observed in a national sample of Medicare beneficiaries where hospitalization for HF after MI decreased from 1998 Table 1 to 2010 and in a study from Sweden where HF declined 13,14 Demographics of acute myocardial infarction patients between 1993 and 2004. An increase in the incidence of HF after MI between 1975 and 2001, in the Worcester Heart Mean/SD; % Attack Study, was attributed to the survival of patients with Mean Age (Years) at First AMI Admission +/− S.D. 63.3 + /−14.4 more severe MIs because of new treatments.15 Women 34.9% An explanation for the decline in HF incidence after AMI Insurance (%) may be the use of increasingly sensitive biomarkers for the Commercial 53.8% diagnosis of AMI that would result in the diagnosis of smaller Medicare 37.3% AMIs with a lower risk of developing HF.16–18 Improved treat- Medicaid/Self-Pay/Other 8.9% ment methods for AMI and HF, more frequent use of HF Number of AMI Patients 109,717 medications, and prompt reperfusion therapy may also have AMI = acute myocardial infarction. contributed to the decreasing incidence of HF. A similar effect Coronary Artery Disease/Heart Failure After Myocardial Infarction 3

Figure 1. Decreasing rate of HF admission (left panel), all-cause death (middle panel), and the combined end point of HF admission or death (right panel) in patients discharged alive after a ﬁrst AMI from 2000 to 2015.

Figure 2. ORs for risk factors of readmission for HF after AMI for 30-day (left upper panel), 90-day (middle upper panel), 180-day (right upper panel), 1-year (left lower panel), and 5-year (right lower panel) follow-up periods. was observed in the Framingham Heart Study, where a higher elevation MI in patients undergoing percutaneous coronary incidence of first AMI between 1970 and 1999 was associ- intervention.19 Significant predictors of HF in the Choles- ated with a decrease in mortality after AMI. terol and Recurrent Events trial were age and left ventricular In the current study, the development of HF was associ- ejection fraction. Additional predictors included diabetes, ated with older age, female gender, history of diabetes, and history of hypertension, previous MI, and baseline heart rate.20 history of CKD, confirming some of the co-morbidities as- Older age, anterior MI, lower systolic blood pressure, lower sociated with HF in previous studies.7,8 In addition, pulse pressure, and diabetes were predictors of HF in pa- revascularization with either percutaneous coronary inter- tients who received intravenous thrombolytic therapy in the vention or CABG was associated with a marked decrease in Thrombolysis and Angioplasty in Myocardial Infarction trials.21 HF admissions. Patient demographics and co-morbid condi- Hellermann et al identified older age, female gender, diabe- tions were associated with the development of HF after AMI tes, and increased heart rate as the most consistent risk factors in previous studies, including the HORIZONS-AMI trial, for the development of HF after MI.7 where HF at 1 year was associated with diabetes, dyslipidemia, Only a few studies examined the association of COPD, previous AMI, previous revascularization, and anterior ST- CKD, and Medicare (vs commercial insurance) with the 4 The American Journal of Cardiology (www.ajconline.org)

Figure 3. Cox regression for admission for HF after AMI (hazard ratio, 95% CI). development of HF after AMI as was observed in our study.22–24 creased markedly from 2000 to 2015. It is in agreement with Patients with CKD have accelerated cardiovascular disease, older, smaller studies. Further exploration of trends in the in- experience poorer outcomes, and have a high prevalence of cidence of HF after AMI on a national level may lead to greater developing AMI and HF.22,23 Medicare insurance was also as- understanding of the reasons behind the rate changes in HF sociated with increased risk of developing HF compared with incidence and ultimately lead to strategies to decrease mor- commercial insurance. This interesting association may be bidity and mortality from HF. examined on a national level to confirm the association and determine potential causes. Interestingly, patients with disorders of lipid metabolism Disclosures were found to have a negative association with developing The authors have no conflicts of interest to disclose. HF in our study in contrast to the finding in the HORIZONS- AMI trial.19 This may, in part, be due to the protective effect of statin therapy of patients diagnosed with dyslipidemia. De 1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman Gennaro et al reported that statin therapy does not decrease M, de Ferranti S, Després JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu all-cause death but does significantly decrease the rate of hos- S, Mackey RH, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, 25 pitalization for worsening HF. Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan There are several limitations to the study. MIDAS, al- L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi though comprehensive and including all nonfederal admissions A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB, Ameri- can Heart Association Statistics Committee and Stroke Statistics for AMI in New Jersey, does not provide information on Subcommittee. Heart disease and stroke statistics-2015 update: a report smoking status, medications, the etiology of HF hospitaliza- from the American Heart Association. Circulation 2015;131:e29– tion, the severity of HF, hospitalization or deaths outside the e322. doi:10.1161/CIR.0000000000000152. state, and the influence of unknown confounders. However, 2. Ryan TJ, Antman EM, Brooks NH, Califf RM, Hillis LD, Hiratzka LF, this study has significant strengths because it includes all ad- Rapaport E, Riegel B, Russell RO, Smith EE III, Weaver WD. 1999 update: ACC/AHA guidelines for the management of patients with acute missions in the state and all deaths were identified with a high myocardial infarction. A report of the American College of Cardiology/ level of accuracy. American Heart Association Task Force on Practice Guidelines. JAm Better understanding of risk factors for developing HF, ef- Coll Cardiol 1999;34:890–911. fective and early implementation of HF therapies, and lifestyle 3. Briffa T, Hickling S, Knuiman M, Hobbs M, Hung J, Sanfilippo FM, Jamrozik K, Thompson PL. Long term survival after evidence based modification will lead to improved outcomes. This state- treatment of acute myocardial infarction and revascularization: follow- wide study indicates that the rate of admission for HF after up of population based Perth Monica cohort, 1984–2005. BMJ discharge for a first AMI as well as all-cause death de- 2009;338:b36. doi:10.1136/bmj.b36. Coronary Artery Disease/Heart Failure After Myocardial Infarction 5

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