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Body Composition and Mortality in a Large Cohort With Preserved Ejection Fraction: Untangling the Obesity Paradox



      To evaluate the effects of body composition as a function of lean mass index (LMI) and body fat (BF) on the correlation between increasing body mass index (BMI; calculated as the weight in kilograms divided by the height in meters squared) and decreasing mortality, which is known as the obesity paradox.

      Patients and Methods

      We retrospectively assessed 47,866 patients with preserved left ventricular ejection fraction (≥50%). We calculated BF by using the Jackson-Pollock equation and LMI using (1 − BF) × BMI. The population was divided according to the sex-adjusted BMI classification, sex-adjusted LMI classification, and sex-adjusted BF tertiles. The population was analyzed by using multivariate analysis for total mortality over a mean follow-up duration of 3.1 years by using the National Death Index, adjusting for left ventricular ejection fraction, left ventricular mass index, age, sex, and relative wall thickness.


      In the entire population, higher BMI was narrowly associated (hazard ratio [HR], 0.99; P<.001) with lower mortality. The higher LMI group was clearly protective (HR, 0.71; P<.001), whereas BF tertile was associated with lower mortality only if no adjustment was made for LMI (HR, 0.87; P<.001 without LMI; HR, 0.97; P=.23 with LMI). In the lean patients, low BMI was clearly associated with higher mortality (HR, 0.92; P<.001) and lower BF tertile was associated with lower mortality only if no adjustment was made for LMI (HR, 0.80; P<.001 without LMI; HR, 1.01; P=.83 with LMI). The underweight patients stratified by BF seemed to have an increased mortality (HR, 1.91; 95% CI, 1.56-2.34) that was independent of LMI. However, in obese patients, both BMI (HR, 1.03; P<.001) and BF (HR, 1.18; P=.003) were associated with higher mortality, even after adjusting for LMI, which remained protective (HR, 0.57; P<.001) independently of BF.


      Body composition could explain the inverse J shape of the mortality curve noted with increasing BMI. Body fat seems to be protective in this cohort only if no adjustment was made for LMI, although being underweight stratified by BF seems to be an independent risk factor. Lean mass index seems to remain protective in obese patients even when BMI is not.

      Abbreviations and Acronyms:

      BF (body fat), BMI (body mass index), CHD (coronary heart disease), HF (heart failure), HR (hazard ratio), LMI (lean mass index), LVEF (left ventricular ejection fraction), LVMI (left ventricular mass index), RWT (relative wall thickness)
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        • Uretsky S.
        • Messerli F.H.
        • Bangalore S.
        • et al.
        Obesity paradox in patients with hypertension and coronary artery disease.
        Am J Med. 2007; 120: 863-870
        • Lavie C.J.
        • Milani R.V.
        • Ventura H.O.
        Obesity and cardiovascular disease.
        J Am Coll Cardiol. 2009; 53: 1925-1932
        • Habbu A.
        • Lakkis N.M.
        • Dokainish H.
        The obesity paradox: fact or fiction?.
        Am J Cardiol. 2006; 98: 944-948
        • Goel K.
        • Thomas R.J.
        • Squires R.W.
        • et al.
        Combined effect of cardiorespiratory fitness and adiposity on mortality in patients with coronary artery disease.
        Am Heart J. 2011; 161: 590-597
        • De Schutter A.
        • Lavie C.J.
        • Arce C.
        • Menendez S.G.
        • Milani R.V.
        Correlation and discrepancies between obesity by body mass index and body fat in patients with coronary heart disease.
        J Cardiopulm Rehabil Prev. 2013; 33: 77-83
        • Romero-Corral A.
        • Somers V.K.
        • Sierra-Johnson J.
        • et al.
        Accuracy of body mass index in diagnosing obesity in the adult general population.
        Int J Obes (Lond). 2008; 32: 959-966
        • De Schutter A.
        • Lavie C.J.
        • Gonzalez J.
        • Milani R.V.
        Body composition in coronary heart disease: how does body mass index correlate with body fatness?.
        Ochsner J. 2011; 11: 220-225
        • Kalantar-Zadeh K.
        • Streja E.
        • Kovesdy C.P.
        • et al.
        The obesity paradox and mortality associated with surrogates of body size and muscle mass in patients receiving hemodialysis.
        Mayo Clin Proc. 2010; 85: 991-1001
        • Morse S.A.
        • Gulati R.
        • Reisin E.
        The obesity paradox and cardiovascular disease.
        Curr Hyperten Rep. 2010; 12: 120-126
        • Lavie C.J.
        • Ventura H.O.
        • Milani R.V.
        The “obesity paradox”: is smoking/lung disease the explanation?.
        Chest. 2008; 134: 896-898
        • Oreopoulos A.
        • Kalantar-Zadeh K.
        • Sharma A.M.
        • Fonarow G.C.
        The obesity paradox in the elderly: potential mechanisms and clinical implications.
        Clin Geriatr Med. 2009; 25 (viii): 643-659
        • Lea J.P.
        • Crenshaw D.O.
        • Onufrak S.J.
        • Newsome B.B.
        • McClellan W.M.
        Obesity, end-stage renal disease, and survival in an elderly cohort with cardiovascular disease.
        Obesity (Silver Spring). 2009; 17 (2216-2222)
        • Casas-Vara A.
        • Santolaria F.
        • Fernández-Bereciartúa A.
        • González-Reimers E.
        • García-Ochoa A.
        • Martínez-Riera A.
        The obesity paradox in elderly patients with heart failure: analysis of nutritional status.
        Nutrition. 2012; 28: 616-622
        • Clark A.L.
        • Chyu J.
        • Horwich T.B.
        The obesity paradox in men versus women with systolic heart failure.
        Am J Cardiol. 2012; 110: 77-82
        • Clark A.L.
        • Fonarow G.C.
        • Horwich T.B.
        Waist circumference, body mass index, and survival in systolic heart failure: the obesity paradox revisited.
        J Card Fail. 2011; 17: 374-380
        • Lavie C.J.
        • De Schutter A.
        • Patel D.A.
        • Romero-Corral A.
        • Artham S.M.
        • Milani R.V.
        Body composition and survival in stable coronary heart disease.
        J Am Coll Cardiol. 2012; 60: 1374-1380
        • Lavie C.J.
        • De Schutter A.
        • Patel D.
        • Artham S.M.
        • Milani R.V.
        Body composition and coronary heart disease mortality—an obesity or a lean paradox?.
        Mayo Clin Proc. 2011; 86: 857-864
        • McAuley P.A.
        • Artero E.G.
        • Sui X.
        • et al.
        The obesity paradox, cardiorespiratory fitness, and coronary heart disease.
        Mayo Clin Proc. 2012; 87: 443-451
        • Lavie C.J.
        • Osman A.F.
        • Milani R.V.
        • Mehra M.R.
        Body composition and prognosis in chronic systolic heart failure: the obesity paradox.
        Am J Cardiol. 2003; 91: 891-894
        • Lavie C.J.
        • Alpert M.A.
        • Arena R.
        • Mehra M.R.
        • Milani R.V.
        • Ventura H.O.
        Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure.
        JACC Heart Fail. 2013; 1: 93-102
        • Després J.P.
        Excess visceral adipose tissue/ectopic fat the missing link in the obesity paradox?.
        J Am Coll Cardiol. 2011; 57: 1887-1889
        • Coutinho T.
        • Goel D.
        • Corrêa de Sá R.E.
        • et al.
        Combining body mass index with measures of central obesity in the assessment of mortality in subjects with coronary disease: role of ‘normal weight central obesity.
        J Am Coll Cardiol. 2013; 61: 553-560
        • Jackson A.S.
        • Pollock M.L.
        • Ward A.
        Generalized equations for predicting body density of women.
        Med Sci Sports Exerc. 1980; 12: 175-181
        • Jackson A.
        • Pollock M.
        Practical assessment of body composition.
        Physician Sports Med. 1985; : 76-90
        • Xavier Pi-Sunyer F.
        • Dietz W.H.
        • Becker D.M.
        • et al.
        • National Institutes of Health
        Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report.
        National Heart, Lung, and Blood Institute in cooperation with the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD1998
        • Romero-Corral A.
        • Montori V.M.
        • Somers V.K.
        • et al.
        Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies.
        Lancet. 2006; 368: 666-678
        • Das S.R.
        • Alexander K.P.
        • Chen A.Y.
        • et al.
        Impact of body weight and extreme obesity on the presentation, treatment, and in-hospital outcomes of 50,149 patients with ST-segment elevation myocardial infarction.
        J Am Coll Cardiol. 2011; 58: 2642-2650
        • Dhoot J.
        • Tariq S.
        • Erande A.
        • Amin A.
        • Patel P.
        • Malik S.
        Effect of morbid obesity on in-hospital mortality and coronary revascularization outcomes after acute myocardial infarction in the United States.
        Am J Cardiol. 2013; 111: 1104-1110
        • McAuley P.A.
        • Kokkinos P.F.
        • Oliveira R.B.
        • Emerson B.T.
        • Myers J.N.
        Obesity paradox and cardiorespiratory fitness in 12,417 male veterans aged 40 to 70 years.
        Mayo Clin Proc. 2010; 85: 115-121
        • De Schutter A.
        • Lavie C.J.
        • Patel D.
        • Artham S.M.
        • Milani R.V.
        Relation of body fat categories by Gallagher classification and by continuous variables to mortality in patients with coronary heart disease.
        Am J Cardiol. 2013; 111: 657-660
        • Flegal K.M.
        • Kit B.K.
        • Orpana H.
        • Graubard B.I.
        Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis.
        JAMA. 2013; 309: 71-82
        • Lavie C.J.
        • Cahalin L.
        • Chase P.
        • et al.
        Impact of cardiorespiratory fitness on the obesity paradox in patients with heart failure.
        Mayo Clin Proc. 2013; 88: 251-258
        • Lavie C.J.
        • De Schutter A.
        • Patel D.A.
        • Milani R.V.
        Does fitness completely explain the obesity paradox?.
        Am Heart J. 2013; 166: 1-3
        • Coutinho T.
        • Goel K.
        • Corrêa de Sá D.
        • et al.
        • Central obesity and survival in subjects with coronary artery disease: a systematic review of the literature and collaborative analysis with individual subject data
        J Am Coll Cardiol. 2011; 57: 1877-1886