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Clinical Research

Obesity and the paradox of mortality and heart failure hospitalization in heart failure with preserved ejection fraction

Abstract

Background

Limited data exist on the association of obesity with both hospitalization and mortality in patients with heart failure with preserved ejection fraction (HFpEF), especially in the real-world ambulatory setting. We hypothesized that increasing body-mass index (BMI) in ambulatory heart failure with preserved ejection fraction would have a protective effect on these patients leading to decreased mortality and hospitalizations.

Methods

We studied the relationship between BMI and the time to all-cause mortality, time to heart failure (HF) hospitalization, and time to all-cause hospitalization over a 2-year follow-up in a national cohort of 2501 ambulatory HFpEF patients at 153 Veterans Affairs medical centers.

Results

Compared with normal BMI, overweight (HR 0.72; 95% CI 0.57–0.91), obesity class I (HR 0.59; 95% CI 0.45–0.77), obesity class II (HR 0.56; 95% CI 0.40–0.77), and obesity class III (HR 0.53; 95% CI 0.36–0.77) were associated with improved survival after adjustment for demographics and comorbidities. In contrast, the time to HF hospitalization showed an inverse relationship, with shorter time to HF hospitalization with increasing BMI compared with normal BMI; overweight (adjusted HR 1.30; 95% CI 0.88–1.90), obesity class I (HR 1.57; 95% CI 1.05–2.34), obesity class II (HR 1.79; 95% CI 1.15–2.78), and obesity class III (HR 1.96; 95% CI 1.23–3.12). However, time to first all-cause hospitalization was not significantly different by BMI groups.

Conclusions

In a large, national ambulatory HFpEF cohort, despite the presence of the obesity paradox with respect to survival, increasing BMI was independently associated with an increased risk of HF hospitalization and similar risk of all-cause hospitalization. Future longer-term prospective trials evaluating the safety and efficacy of weight loss on morbidity and mortality, in patients with severe obesity and HFpEF are needed.

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Fig. 1: Distribution of HFpEF patients by BMI Category.
Fig. 2: Cumulative mortality of HFpEF patients stratified by BMI.
Fig. 3: Multivariable Cox proportional adjusted hazard model for HF hospitalization stratified by BMI.

References

  1. 1.

    Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999–2000. JAMA. 2002;288:1723–7.

    Article  Google Scholar 

  2. 2.

    Popkin BM, Doak CM. The obesity epidemic is a worldwide phenomenon. Nutr Rev. 1998;56:106–14.

    CAS  Article  Google Scholar 

  3. 3.

    Hales C, Carroll M, Fryar C, Ogden C. Prevalence of obesity among adults and youth: United States. National Health and Nutrition Examination, CDC 2017:288.

  4. 4.

    Kenchaiah S, Evans J, Levy D, Wilson P, Benjamin E, Larson M, et al. Obesity and the risk of heart failure. N Engl J Med. 2002;347:305–13.

    Article  Google Scholar 

  5. 5.

    Obokata M, Reddy Y, Pislaru S, Melenovsky V, Borlaug B. Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction. Circulation. 2017;136:6–19.

    CAS  Article  Google Scholar 

  6. 6.

    Kitzman DW, Shah SJ. The HFpEF obesity phenotype: the elephant in the room. J Am Coll Cardiol. 2016;68:200–3.

    Article  Google Scholar 

  7. 7.

    Aune D, Sen A, Norat T, Janszky I, Romundstad P, Tonstad S, et al. Body mass index, abdominal fatness, and heart failure incidence and mortality. Circulation. 2016;133:639–49.

    Article  Google Scholar 

  8. 8.

    Horwich T, Fonarow G, Clark A. Obesity and the obesity paradox in heart failure. Prog Cardiovasc Dis. 2018;61:151–6.

    Article  Google Scholar 

  9. 9.

    Elagizi A, Kachur S, Lavie C, Carbone S, Pandey A, Ortega F, et al. An overview and update on obesity and the obesity paradox in cardiovascular diseases. Prog Cardiovasc Dis. 2018;61:142–50.

    Article  Google Scholar 

  10. 10.

    Ather S, Chan W, Bozkurt B, Aguilar D, Ramasubbu K, Zachariah A, et al. Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction. J Am Coll Cardiol. 2012;59:998–1005.

    Article  Google Scholar 

  11. 11.

    Deswal A, Petersen N, Urbauer D, Wright S, Beyth R. Racial variations in quality of care and outcomes in an ambulatory heart failure cohort. Am Heart J. 2006;152:348–54.

    Article  Google Scholar 

  12. 12.

    Padwal R, McAlister F, McMurray J, Cowie M, Rich M, Pocock S, et al. The obesity paradox in heart failure patients with preserved versus reduced ejection fraction: a meta-analysis of individual patient data. Int J Obes. 2014;38:1110–4.

    Article  Google Scholar 

  13. 13.

    Kenchaiah S, Pocock S, Wang D, Finn P, Zornoff L, 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.

    Article  Google Scholar 

  14. 14.

    Haass M, Kitzman D, Anand I, Miller A, Zile M, Massie B, et al. Body mass index and adverse cardiovascular outcomes in heart failure patients with preserved ejection fraction: results from the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial. Circ Heart Fail. 2011;4:324–31.

    Article  Google Scholar 

  15. 15.

    Mandviwala T, Khalid U, Deswal A. Obesity and cardiovascular disease: a risk factor or a risk marker? Curr Atheroscler Rep. 2016;18:21.

    Article  Google Scholar 

  16. 16.

    Tsujimoto T, Kajio H. Abdominal obesity is associated with an increased risk of all-cause mortality in patients with HFpEF. J Am Coll Cardiol. 2017;70:2739–49.

    Article  Google Scholar 

  17. 17.

    Flegal KM, Shepherd JA, Looker AC, Graubard BI, Borrud LG, Ogden CL, et al. Comparisons of percentage body fat, body mass index, waist circumference, and waist-stature ratio in adults. Am J Clin Nutr. 2009;89:500–8.

    CAS  Article  Google Scholar 

  18. 18.

    Blew RM, Sardinha LB, Milliken LA, Teixeira PJ, Going SB, Ferreira DL, et al. Assessing the validity of body mass index standards in early postmenopausal women. Obes Res. 2002;10:799–808.

    Article  Google Scholar 

  19. 19.

    Clark AL, Fonarow GC, Horwich TB. Waist circumference, body mass index, and survival in systolic heart failure: the obesity paradox revisited. J Cardiac Fail. 2011;17:374–80.

    Article  Google Scholar 

  20. 20.

    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.

    CAS  Article  Google Scholar 

  21. 21.

    Alexander JK, Dennis EW, Smith WG, Amad KH, Duncan WC, Austin RC. Blood volume, cardiac output, and distribution of systemic blood flow in extreme obesity. Cardiovasc Res Cent Bull. 1962;1:39–44.

    PubMed  Google Scholar 

  22. 22.

    Nagarajan V, Cauthen C, Starling R, Tang W. Prognosis of morbid obesity patients with advanced heart failure. Congest Heart Fail. 2013;19:160–4.

    CAS  Article  Google Scholar 

  23. 23.

    Haykowsky M, Kouba E, Brubaker P, Nicklas B, Eggebean J, Kitzman D. Skeletal muscle composition and its relation to exercise intolerance in older patients with heart failure and preserved ejection fraction. J Am Coll Cardiol. 2014;7:1211–6.

    Article  Google Scholar 

  24. 24.

    Paulus W, Tschope C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol. 2013;62:263–71.

    Article  Google Scholar 

  25. 25.

    Dalos D, Mascherbauer J, Zotter-Tufaro C, Duca F, Kammerlander A, Aschauer S, et al. Functional status, pulmonary artery pressure, and clinical outcomes in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2016;68:189–99.

    Article  Google Scholar 

  26. 26.

    Kitzman D, Brubaker P, Morgan T. The effect of calortic restriction or aerobic exercise training on peak oxygen consumption and quality of life in older obese patients with heart failure with preserved ejection fraction. JAMA. 2016;315:36–46.

    CAS  Article  Google Scholar 

  27. 27.

    Miranda W, Batsis J, Sarr M, Collazo-Clavell M, Clark M, Somers V. Impact of bariatric surgery on quality of life, functional capacity, and symptoms in patients with heart failure. Obes Surg. 2013;23:1011–115.

    Article  Google Scholar 

  28. 28.

    Shimada Y, Tsugawa Y, Brown D, Hasegawa K. Bariatric surgery and emergency department visits and hospitalizatins for heart failure exacerbation: population-based, self-controlled series. J Am Coll Cardiol. 2016;67:895–903.

    Article  Google Scholar 

  29. 29.

    Kapoor J, Heidenreich P. Obesity and survival in patients with heart failure and preserved systolic function: a U-shaped relationship. Am Heart J. 2010;159:75–80.

    Article  Google Scholar 

  30. 30.

    Oreopoulos A, Padwal R, Kalantar-Zadeh K, Fonarow G, Norris C, McAlister F. Body mass index and mortality in heart failure: a meta-analysis. Am Heart J. 2008;156:13–22.

    Article  Google Scholar 

  31. 31.

    Stavrakis S, Pakala A, Thomas J, Chaudhry M, Thadani U. Obesity, brain natriuretic peptide levels and mortality in patients hospitalized with heart failure and preserved left ventricular systolic function. Am J Med Sci. 2013;345:211–7.

    Article  Google Scholar 

  32. 32.

    Lavie C, Ventura H. Weighing in on obesity and the obesity paradox in heart failure. J Card Fail. 2011;17:381–3.

    Article  Google Scholar 

  33. 33.

    Wolk R, Bertolet M, Singh P, Brooks M, Pratley R, Frye R, et al. Prognostic value of adipokines in predicting cardiovascular outcome: explaining the obesity paradox. Mayo Clin Proc. 2016;91:858–66.

    CAS  Article  Google Scholar 

  34. 34.

    Heo S, Moser D, Pressler S, Dunbar S, Lee K, Kim J, et al. Association between obesity and heart failure symptoms in male and female patients. Clin Obes. 2017;7:77–85.

    CAS  Article  Google Scholar 

  35. 35.

    Pocock S, McMurray J, Dobson J, Yusuf S, Granger C, Michelson E, et al. Weight loss and mortality risk in patients with chronic heart failure in the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) programme. Eur Heart J. 2008;29:2641–50.

    Article  Google Scholar 

  36. 36.

    Lavie C, Cahalin L, Chase P, Myers J, Bensimhon D, Peberdy M, et al. Impact of cardiorespiratory fitness on the obesity paradox in patients with heart failure. Mayo Clinic Proc. 2013;88:251–8.

    Article  Google Scholar 

  37. 37.

    Hegde SM, Claggett B, Shah AM, Lewis EF, Anand I, Shah SJ, et al. Physical activity and prognosis in the TOPCAT Trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist). Circulation. 2017;136:982–92.

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank the Office of Quality and Performance of the Veterans Health Administration for providing EPRP data. The views expressed in this report are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs.

Funding

This study was supported in part by VA Health Services Research & Development Service #IIR 02-082-1.

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Correspondence to Anita Deswal.

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None of the authors have any financial or other relations that could lead to a conflict of interest. AD is supported in part by the Ting Tsung and Wei Fong Chao Distinguished Chair at the MD Anderson Cancer Center.

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Mandviwala, T.M., Basra, S.S., Khalid, U. et al. Obesity and the paradox of mortality and heart failure hospitalization in heart failure with preserved ejection fraction. Int J Obes 44, 1561–1567 (2020). https://doi.org/10.1038/s41366-020-0563-1

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