Title: Impact of Obesity on the Prevalence and Prognosis in Heart Failure It is Not Always Just Black and White

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1 Accepted Manuscript Title: Impact of Obesity on the Prevalence and Prognosis in Heart Failure It is Not Always Just Black and White Author: Carl J. Lavie, Hector O. Ventura PII: S (16) DOI: /j.cardfail Reference: YJCAF 3778 To appear in: Journal of Cardiac Failure Received date: Accepted date: Please cite this article as: Carl J. Lavie, Hector O. Ventura, Impact of Obesity on the Prevalence and Prognosis in Heart Failure It is Not Always Just Black and White, Journal of Cardiac Failure (2016), /j.cardfail This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

2 Impact of Obesity on the Prevalence and Prognosis in Heart Failure It is Not Always Just Black and White Carl J. Lavie, M.D., Hector O. Ventura, M.D. Department of Cardiovascular Diseases, John Ochsner Heart and Vascular Institute, Ochsner Clinical School-University of Queensland School of Medicine New Orleans, LA No conflicts of interest to declare. Corresponding author: Carl J. Lavie, M.D., FACC, FACP, FCCP Medical Director, Cardiac Rehabilitation Director, Exercise Laboratories John Ochsner Heart and Vascular Institute Ochsner Clinical School - The University of Queensland School of Medicine 1514 Jefferson Highway New Orleans, LA (504) Phone (504) Fax clavie@ochsner.org Page 1 of 6

3 For many decades, the prevalence of overweightness and obesity increased in epidemic proportions; currently statistics indicate that almost 3 of 4 adults in the United States are either overweight or obese. 1 Clearly, obesity worsens most of the cardiovascular disease (CVD) risk factors, especially hypertension (HTN), dyslipidemia, glucose abnormalities, including metabolic syndrome and diabetes mellitus, and inflammation, which all increase the prevalence of coronary heart disease, a strong contributor along with HTN to the risk of heart failure (HF). 1 Considering also the adverse effects that obesity have on cardiac structure and function, increasing both systolic and, more so, diastolic ventricular dysfunction, it is not surprising that HF is markedly increased in the setting of obesity. 1-3 Nevertheless, many studies, including from our group, 4,5 have indicated an obesity paradox in HF, where overweight and obese HF patients have a better short- and medium-term prognosis compared with leaner HF patients. 6-8 Many studies have also focused on racial disparities in CVD, indicating that African Americans (AAs) have a significantly higher risk of CVD and its associated mortality compared with their Caucasian American (CA) counterparts. 9 The 2013 overall death rate attributable to CVD was 223 per 100,000 Americans, but was considerably higher for AA males (357 vs 271 per 100,000) and AA females (247 vs 184 per 100,000) compared with CAs. 10 Certainly, obesity rates are considerably higher in AAs compared with CAs, 10 which places AAs at higher risk of HF. However, as discussed by Krishnamoorthy and colleagues 11 in this issue of Journal Cardiac Failure (JCF), the relationship between obesity and mortality in AAs is unclear, with possibly a paradoxical lower risk of death in AAs with obesity compared with obesity in other populations. Likewise, although the association of obesity with HF is well-known, 1-3,6,9 this relationship has not been well described in AAs. Page 2 of 6

4 In the present issue of JCF, 11 using data from the Jackson Heart Study, these investigators studied 5,301 AA participants, including 5,292 for mortality and 5,184 for hospitalizations. They observed a higher frequency of HF as BMI increased (p < 0.001). There was also a significant increase in HF hospitalizations as BMI increased, with the highest rate noted in the morbidly obese group (9%) compared with the lowest rate in the mildly obese participants (5.9%). For each one unit increase in BMI up to 32 kg/m 2, the adjusted hazard of HF hospitalization decreased by 4% (p = 0.03), whereas with BMI > 32 kg/m 2, each one unit increase in BMI was associated with a 5% increase in HF hospitalizations (p < 0.001). These investigators did not show an increase in all-cause mortality with increases in BMI in either unadjusted or adjusted analyses, despite the higher risk of HF and HF hospitalizations discussed above. In fact, for each one unit increase in BMI up to 27 kg/m 2, the adjusted hazard of all-cause mortality decreased by 9%. However, there was no statistically significant association with mortality per one unit increase in BMI > 27 kg/m 2. In fact, in a categorical comparison with normal BMI AAs, the multivariable adjusted rate of all-cause mortality was 34% lower in the overweight, 30% lower in the obese, and even 34% lower in the morbidly obese AA group. We recently performed a meta-analysis of 6 HF studies (n=22,807) and demonstrated the highest risk of adverse events, including CVD mortality, all-cause mortality, and rehospitalizations at 3- year follow-up, were in those with the lowest BMIs, whereas the lowest risk occurred in the overweight BMI (Figure). 5 The results in the Jackson Heart Study, however, in AAs demonstrated a discordant impact of obesity, especially severe obesity, to increase HF prevalence and hospitalizations, but not mortality, showing lower rates of mortality even among the more severely obese. Although recent studies indicate good survival in overweight and mildly obese, 1,12,13 these results in AAs are different, Page 3 of 6

5 suggesting good survival even in the group with more obesity. Nevertheless, this study did not evaluate mortality long-term (e.g., years), nor did it specifically determine mortality in those with HF, different etiologies of HF, and those hospitalized with HF related to different BMIs. Clearly, obesity is related to significant comorbidities and reduces quality of life, in addition to increased medical costs, including the very expensive costs of HF. 1,6-8 Finally, my colleagues and I have focused on the fact that fitness may be more important than fatness for many health outcomes, including mortality, an observation applicable for those with CVD, including HF. 1,3,7,8,14 We have demonstrated that not only do AAs have lower levels of fitness than do CAs, AAs also appear to have less of an improvement in fitness following an exercise training program than do CAs. 9,14-17 Since fitness is an important predictor of the development of HF and impacts its prognosis, 18 potentially very applicable to AAs would be increasing efforts to prevent severe and morbid obesity and increasing levels of fitness, more so than preventing overweightness and obesity per se. As is true in many aspects of medicine, the relationship between obesity and outcomes is not always "black and white." References 1. Lavie CJ, De Schutter A, Parto P, Jahangir E, Kokkinos P, Ortega FB, et al. Obesity and prevalence of cardiovascular diseases and prognosis: the obesity paradox updated. Prog Cardiovasc Dis 2016:58: Alpert MA, Omram J, Mehra A, Ardhanari S. Impact of obesity and weight loss on cardiac performance and morphology in adults. Prog Cardiovasc Dis 2014;56: Lavie CJ, Alpert MA, Arena R, Mehra MR, Milani RV, Ventura HO. Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure. JACC Heart Fail 2013;1: Page 4 of 6

6 4. Lavie CJ, Osman AF, Milani RV, Mehra MR. Body composition and prognosis in chronic systolic heart failure: the obesity paradox. Am J Cardiol 2003;91: Sharma A, Lavie CJ, Borer JS, Vallakati A, Goel S, Lopez-Jimenez F, et al. Meta-analysis of the relation of body mass index to all-cause and cardiovascular mortality and hospitalization in patients with chronic heart failure. Am J Cardiol 2015;115: Clark AL, Fonarow GC, Horwich TB. Obesity and obesity paradox in heart failure. Prog Cardiovasc Dis 2014;56: Lavie CJ, Sharma A, Alpert MA, De Schutter A, Lopez-Jimenez F, Milani RV, et al. Update on obesity and obesity paradox in heart failure. Prog Cardiovasc Dis 2016;58: Lavie CJ, Ventura HO. The obesity paradox in heart failure: is it all about fitness, fat, or sex? JACC Heart Fail 2015;3: Lavie CJ, Ventura HO. The obesity paradox in heart failure: is it all about fitness, fat, or sex? JACC Heart Fail 2015;3: Swift DL, Staiano AE, Johannsen NM, Lavie CJ, Earnest CP, Katzmarzyk PT, et al. Low cardiorespiratory fitness in African Americans: a health disparity risk factor. Sports Med 2013;43: Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al; on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive Summary: Heart Disease and Stroke Statistics: 2016 update: a report from the Heart Association. Circulation 2016;133: Krishnamoorthy A, Greiner MA, Bertoni AG, Eapen ZJ, O'Brien EC, Curtis LH, et al. The obesity and heart failure epidemics among African Americans: insights from the Jackson Heart Study. J Card Fail 2016; doi: /j.cardfail [Epub ahead of print] Page 5 of 6

7 12. Flegal KM, Kit BK, Orpana H, Graubard BL. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA 2013;309: Afzal S, Tybjærg-Hansen A, Jensen GB, Nordestgaard BG. Change in body mass index associated with lowest mortality in Denmark, JAMA 2016;315: Lavie CJ, McAuley PA, Church TS, Milani RV, Blair SN. Obesity and cardiovascular diseases: implications regarding fitness, fatness, and severity in the obesity paradox. J Am Coll Cardiol 2014;63: Swift DL, Johannsen NM, Lavie CJ, Earnest CP, Johnson WD, Blair SN, et al. Racial differences in the response of cardiorespiratory fitness to aerobic exercise training in Caucasian and African American postmenopausal women. J Appl Physiol 2013;114: Shook RP, Hand GA, Wang X, Paluch AE, Moran R, Hébert JR, et al. Low fitness partially explains resting metabolic rate differences between African American and white women. Am J Med 2014;127: Lavie CJ, Kuruvanka T, Milani RV, Prasad A, Ventura HO. Exercise capacity in adult African- Americans referred for exercise stress testing: is fitness affected by race. Chest 2004;126: Pandey A, Berry JD, Lavie CJ. Cardiometabolic disease leading to heart failure: better fat and fit than lean and lazy. Curr Heart Fail Rep 2015;12: Figure Legend Figure. Meta-analysis of six studies (n=22,807) on impact of body mass index on cardiovascular mortality, all-cause mortality, and hospitalizations in heart failure. Reproduced with permission from Sharma A et al, Am J Cardiol. 5 Page 6 of 6