Associations of body mass index with mortality in heart failure with preserved ejection fraction patients with ischemic versus non-ischemic etiology

Shan Zeng, Xingming Cai, Yuxiang Zheng, Xiao Liu, Min Ye, Shan Zeng, Xingming Cai, Yuxiang Zheng, Xiao Liu, Min Ye

Abstract

Background: Obesity could paradoxically improve prognosis in patients with heart failure (HF), termed the "obesity paradox." Whether HF etiology could modify the "obesity paradox" is still controversial. In the present study, we aimed to assess the relationship between obesity and death in patients with heart failure with preserved ejection fraction (HFpEF) with non-ischemic versus ischemic etiologies.

Methods: We analyzed 3,360 HFpEF patients from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial. Cox regression models were used to assess the association of obesity assessed by body mass index (BMI) with short-term and long-term death risk.

Results: Overweight and obesity were associated with a lower risk of long-term all-cause death in patients with non-ischemic HFpEF, even in those with class III obesity (adjusted HR: 0.61, 95% CI 0.38-0.97). However, in the ischemic subgroup, as obesity advanced, this paradoxical relationship was gradually attenuated and disappeared in class III obesity (adjusted HR: 0.93, 95% CI 0.56-1.57). Restricted cubic spline analyses confirmed the differential relationship of baseline BMI with risk of long-term death with a BMI higher than 30 kg/m2 in non-ischemic versus ischemic HFpEF. In the short-term follow-up, the beneficial effects of overweight and obesity on survival were consistently observed in all the BMI categories, with the nadirs of all-cause death risk at class III obesity category both in non-ischemic and ischemic subgroups.

Conclusion: "Obesity paradox" was evident both in non-ischemic and ischemic HFpEF during short-term follow-up, even in those with class III obesity. However, the beneficial effect of class III obesity disappeared during long-term follow-up in ischemic HFpEF.

Clinical trial registration: [https://ichgcp.net/clinical-trials-registry/NCT00094302" title="See in ClinicalTrials.gov">NCT00094302].

Keywords: HFpEF; body mass index; death; etiology; obesity paradox.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Zeng, Cai, Zheng, Liu and Ye.

Figures

FIGURE 1
FIGURE 1
Crude death rates in HFpEF patients with non-ischemic and ischemic etiology according to baseline BMI categories. (A) All-cause death; (B) cardiovascular death.
FIGURE 2
FIGURE 2
Kaplan–Meier survival curves for all-cause death (A,B) and cardiovascular death (C,D) according to baseline BMI categories in HFpEF patients with non-ischemic and ischemic etiology. (A,C) Non-ischemic HFpEF; (B,D) ischemic HFpEF.
FIGURE 3
FIGURE 3
Association of baseline BMI with long-term all-cause death (A,B) and cardiovascular death (C,D) in HFpEF patients according to HF etiology, using restricted cubic spline models. (A,C) Non-ischemic HFpEF; (B,D) ischemic HFpEF.

References

    1. Campbell DJ, Gong FF, Jelinek MV, Castro JM, Coller JM, McGrady M, et al. Threshold body mass index and sex-specific waist circumference for increased risk of heart failure with preserved ejection fraction. Eur J Prev Cardiol. (2019) 26:1594–602. 10.1177/2047487319851298
    1. Piché M-E, Tchernof A, Després J-P. Obesity phenotypes, diabetes, and cardiovascular diseases. Circ Res. (2020) 126:1477–500. 10.1161/CIRCRESAHA.120.316101
    1. Horwich TB, Fonarow GC, Clark AL. Obesity and the obesity paradox in heart failure. Prog Cardiovasc Dis. (2018) 61:151–6. 10.1016/j.pcad.2018.05.005
    1. Zhang J, Begley A, Jackson R, Harrison M, Pellicori P, Clark AL, et al. Body mass index and all-cause mortality in heart failure patients with normal and reduced ventricular ejection fraction: a dose-response meta-analysis. Clin Res Cardiol. (2019) 108:119–32. 10.1007/s00392-018-1302-7
    1. Elagizi A, Kachur S, Lavie CJ, Carbone S, Pandey A, Ortega FB, et al. An overview and update on obesity and the obesity paradox in cardiovascular diseases. Prog Cardiovasc Dis. (2018) 61:142–50. 10.1016/j.pcad.2018.07.003
    1. Simonenko M. Obesity paradox in heart failure: a matter of debate. Eur J Prev Cardiol. (2019) 26:1748–50. 10.1177/2047487319861473
    1. Lavie CJ, Ventura HO. The obesity paradox in heart failure: is it all about fitness, fat, or sex? JACC Heart Fail. (2015) 3:927–30. 10.1016/j.jchf.2015.07.009
    1. Arena R, Myers J, Abella J, Pinkstaff S, Brubaker P, Moore B, et al. Influence of etiology of heart failure on the obesity paradox. Am J Cardiol. (2009) 104:1116–21. 10.1016/j.amjcard.2009.05.059
    1. Zamora E, Lupón J, de Antonio M, Urrutia A, Coll R, Díez C, et al. The obesity paradox in heart failure: is etiology a key factor? Int J Cardiol. (2013) 166:601–5. 10.1016/j.ijcard.2011.11.022
    1. Gentile F, Sciarrone P, Zamora E, De Antonio M, Santiago E, Domingo M, et al. Body mass index and outcomes in ischaemic versus non-ischaemic heart failure across the spectrum of ejection fraction. Eur J Prev Cardiol. (2020) 2020:2047487320927610. 10.1177/2047487320927610
    1. Lee DS, Gona P, Vasan RS, Larson MG, Benjamin EJ, Wang TJ, et al. Relation of disease pathogenesis and risk factors to heart failure with preserved or reduced ejection fraction: insights from the framingham heart study of the national heart, lung, and blood institute. Circulation. (2009) 119:3070–7. 10.1161/CIRCULATIONAHA.108.815944
    1. Powell-Wiley TM, Ngwa J, Kebede S, Lu D, Schulte PJ, Bhatt DL, et al. Impact of body mass index on heart failure by race/ethnicity from the get with the guidelines-heart failure (GWTG-HF) Registry. JACC Heart Fail. (2018) 6:233–42.
    1. Desai AS, Lewis EF, Li R, Solomon SD, Assmann SF, Boineau R, et al. Rationale and design of the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial: a randomized, controlled study of spironolactone in patients with symptomatic heart failure and preserved ejection fraction. Am Heart J. (2011) 162:966.e–72.e. 10.1016/j.ahj.2011.09.007
    1. Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. (2014) 370:1383–92. 10.1056/NEJMoa1313731
    1. Zhu W, Wu Y, Zhou Y, Liang W, Xue R, Wu Z, et al. CHA2DS2-VASc and ATRIA scores and clinical outcomes in patients with heart failure with preserved ejection fraction. Cardiovasc Drugs Ther. (2020) 34:763–72. 10.1007/s10557-020-07011-y
    1. Pfeffer MA, Claggett B, Assmann SF, Boineau R, Anand IS, Clausell N, et al. Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation. (2015) 131:34–42. 10.1161/CIRCULATIONAHA.114.013255
    1. Who. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. (2000) 894 i–xii:1–253.
    1. Dekker FW, de Mutsert R, van Dijk PC, Zoccali C, Jager KJ. Survival analysis: time-dependent effects and time-varying risk factors. Kidney Int. (2008) 74:994–7. 10.1038/ki.2008.328
    1. Kenchaiah S, Pocock SJ, Wang D, Finn PV, Zornoff LAM, Skali H, et al. Body mass index and prognosis in patients with chronic heart failure: insights from the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) program. Circulation. (2007) 116:627–36. 10.1161/CIRCULATIONAHA.106.679779
    1. Oreopoulos A, Padwal R, Kalantar-Zadeh K, Fonarow GC, Norris CM, McAlister FA. Body mass index and mortality in heart failure: a meta-analysis. Am Heart J. (2008) 156:13–22. 10.1016/j.ahj.2008.02.014
    1. 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) 115:1428–34. 10.1016/j.amjcard.2015.02.024
    1. Qin W, Liu F, Wan C. A U-shaped association of body mass index and all-cause mortality in heart failure patients: a dose-response meta-analysis of prospective cohort studies. Cardiovasc Ther. (2017) 35:12232. 10.1111/1755-5922.12232
    1. Shah R, Gayat E, Januzzi JL, Sato N, Cohen-Solal A, diSomma S, et al. GREAT (Global Research on Acute Conditions Team) Network, Body mass index and mortality in acutely decompensated heart failure across the world: a global obesity paradox. J Am Coll Cardiol. (2014) 63:778–85. 10.1016/j.jacc.2013.09.072
    1. Vest AR, Wu Y, Hachamovitch R, Young JB, Cho L. The heart failure overweight/obesity survival paradox: the missing sex link. JACC Heart Fail. (2015) 3:917–26. 10.1016/j.jchf.2015.06.009
    1. Zamora E, Lupón J, Enjuanes C, Pascual-Figal D, de Antonio M, Domingo M, et al. No benefit from the obesity paradox for diabetic patients with heart failure. Eur J Heart Fail. (2016) 18:851–8.
    1. Mehra MR, Uber PA, Park MH, Scott RL, Ventura HO, Harris BC, et al. Obesity and suppressed B-type natriuretic peptide levels in heart failure. J Am Coll Cardiol. (2004) 43:1590–5. 10.1016/j.jacc.2003.10.066
    1. Krauser DG, Lloyd-Jones DM, Chae CU, Cameron R, Anwaruddin S, Baggish AL, et al. Effect of body mass index on natriuretic peptide levels in patients with acute congestive heart failure: a ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) substudy. Am Heart J. (2005) 149:744–50. 10.1016/j.ahj.2004.07.010
    1. Pan W, Hindler K, Lee V-V, Vaughn WK, Collard CD. Obesity in diabetic patients undergoing coronary artery bypass graft surgery is associated with increased postoperative morbidity. Anesthesiology. (2006) 104:441–7. 10.1097/00000542-200603000-00010
    1. Sharma A, Vallakati A, Einstein AJ, Lavie CJ, Arbab-Zadeh A, Lopez-Jimenez F, et al. Relationship of body mass index with total mortality, cardiovascular mortality, and myocardial infarction after coronary revascularization: evidence from a meta-analysis. Mayo Clin Proc. (2014) 89:1080–100. 10.1016/j.mayocp.2014.04.020
    1. Romero-Corral A, Montori VM, Somers VK, Korinek J, Thomas RJ, Allison TG, et al. Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies. Lancet. (2006) 368:666–78. 10.1016/S0140-6736(06)69251-9
    1. Lancefield T, Clark DJ, Andrianopoulos N, Brennan AL, Reid CM, Johns J, et al. MIG (Melbourne Interventional Group) registry, is there an obesity paradox after percutaneous coronary intervention in the contemporary era? an analysis from a multicenter australian registry. JACC Cardiovasc Interv. (2010) 3:660–8. 10.1016/j.jcin.2010.03.018
    1. Wang ZJ, Zhou YJ, Galper BZ, Gao F, Yeh RW, Mauri L. Association of body mass index with mortality and cardiovascular events for patients with coronary artery disease: a systematic review and meta-analysis. Heart. (2015) 101:1631–8. 10.1136/heartjnl-2014-307119
    1. Ma W-Q, Sun X-J, Wang Y, Han X-Q, Zhu Y, Liu N-F. Does body mass index truly affect mortality and cardiovascular outcomes in patients after coronary revascularization with percutaneous coronary intervention or coronary artery bypass graft? A systematic review and network meta-analysis. Obes Rev. (2018) 19:1236–47. 10.1111/obr.12713
    1. 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) 111:1104–10. 10.1016/j.amjcard.2012.12.033
    1. Lavie CJ, De Schutter A, Milani RV. Body composition and the obesity paradox in coronary heart disease: can heavier really be healthier? Heart. (2015) 101:1610–1. 10.1136/heartjnl-2015-307966
    1. Oreopoulos A, McAlister FA, Kalantar-Zadeh K, Padwal R, Ezekowitz JA, Sharma AM, et al. The relationship between body mass index, treatment, and mortality in patients with established coronary artery disease: a report from APPROACH. Eur Heart J. (2009) 30:2584–92. 10.1093/eurheartj/ehp288
    1. 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) 1:93–102. 10.1016/j.jchf.2013.01.006
    1. Parto P, Lavie CJ, Ventura HO. Reducing heart failure risks in obese patients. Curr Cardiovasc Risk Rep. (2016) 10:15. 10.1007/s12170-016-0498-1
    1. Cottam DR, Mattar SG, Barinas-Mitchell E, Eid G, Kuller L, Kelley DE, et al. The chronic inflammatory hypothesis for the morbidity associated with morbid obesity: implications and effects of weight loss. Obes Surg. (2004) 14:589–600. 10.1381/096089204323093345
    1. Lin G-M, Li Y-H, Lin C-L, Wang J-H, Han C-L. Relation of body mass index to mortality among Asian patients with obstructive coronary artery disease during a 10-year follow-up: a report from the ET-CHD registry. Int J Cardiol. (2013) 168:616–20. 10.1016/j.ijcard.2013.01.204
    1. Li Y-H, Lin G-M, Lin C-L, Wang J-H, Han C-L. Relation of body mass index to mortality among patients with percutaneous coronary intervention longer than 5 years follow-up: a meta-analysis. Int J Cardiol. (2013) 168:4315–8. 10.1016/j.ijcard.2013.04.174
    1. Ivert T, Huttunen K, Landou C, Björk VO. Angiographic studies of internal mammary artery grafts 11 years after coronary artery bypass grafting. J Thorac Cardiovasc Surg. (1988) 96:1–12.
    1. Mahaffey KW, Tonev ST, Spinler SA, Levine GN, Gallo R, Ducas J, et al. SYNERGY Trial Investigators, Obesity in patients with non-ST-segment elevation acute coronary syndromes: results from the SYNERGY trial. Int J Cardiol. (2010) 139:123–33. 10.1016/j.ijcard.2008.10.008
    1. Schmiegelow M, Torp-Pedersen C, Gislason GH, Andersson C, Lyngbæk S, Pedersen S, et al. Relation of body mass index to risk of stent thrombosis after percutaneous coronary intervention. Am J Cardiol. (2012) 110:1592–7. 10.1016/j.amjcard.2012.07.029
    1. Parto P, Lavie CJ. Obesity and cardiovasculardiseases. Curr Probl Cardiol. (2017) 42:376–94. 10.1016/j.cpcardiol.2017.04.004
    1. Jerant A, Franks P. Body mass index, diabetes, hypertension, and short-term mortality: a population-based observational study, 2000–2006. J Am Board Fam Med. (2012) 25:422–31. 10.3122/jabfm.2012.04.110289

Source: PubMed

3
Sottoscrivi