Skip to main content

Advertisement

Log in

Body mass index and all-cause mortality in heart failure patients with normal and reduced ventricular ejection fraction: a dose–response meta-analysis

  • Review
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Abstract

Background

For patients with heart failure, there is an inverse relation between body mass index (BMI) and mortality, sometimes called the obesity-paradox. However, the relationship might be either U- or J-shaped and might differ between patients with reduced (HFrEF) or preserved left ventricular ejection fraction (HFpEF). We sought to investigate this further in a dose–response meta-analysis of published studies.

Methods

PubMed and Embase from June 1980 to April 2017 were searched for prospective cohort studies evaluating associations between BMI and all-cause mortality in patients with HFrEF (LVEF < 40%) or HFpEF (LVEF ≥ 50%). Summary estimated effect sizes were obtained by using a random-effects model. Potential non-linear relationships were evaluated by using random-effects restricted cubic spline models.

Results

Ten studies were identified that included 96,424 patients of whom 59,263 had HFpEF (mean age 68 years of whom 38% were women) and 37,161 had HFrEF (mean age 60 years of whom 17% were women). For patients with HFpEF, the summary hazard ratio (HR) for all-cause mortality was: 0.93 (95% CI 0.89–0.97) per 5 units increase in BMI (I2 = 75.8%, p for heterogeneity = 0.01 and Begg’s test, p = 1.0, Egger’s test, p = 0.29) but the association was U-shaped (p for non-linearity < 0.01) with the nadir of risk at a BMI of 32–33 kg/m2. For patients with HFrEF, the summary HR for all-cause mortality was: 0.96 (95% CI 0.92–0.99) (I2 = 95%, p for heterogeneity < 0.001 and Begg’s test, p = 0.45, Egger’s test, p = 0.01). The relationship was also U-shaped (p < 0.01), although ‘flatter’ than for HFpEF, with the nadir at a BMI of 33 kg/m2.

Conclusions

For patients with heart failure, the relation between BMI and mortality is U-shaped with a similar nadir of risk for HFpEF and HFrEF at a BMI of 32–33 kg/m2. Whether interventions that alter weight in either direction can alter risk is unknown.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Horwich TB, Fonarow GC, Hamilton MA, MacLellan WR, Woo MA, Tillisch JH (2001) The relationship between obesity and mortality in patients with heart failure. J Am Coll Cardiol 38(3):789–95

    Article  CAS  PubMed  Google Scholar 

  2. Osman AF, Mehra MR, Lavie CJ, Nunez E, Milani RV (2000) The incremental prognostic importance of body fat adjusted peak oxygen consumption in chronic heart failure. J Am Coll Cardiol 36(7):2126–2131

    Article  CAS  PubMed  Google Scholar 

  3. Kapoor JR, Heidenreich PA (2010) Obesity and survival in patients with heart failure and preserved systolic function: a U-shaped relationship. Am Heart J 159(1):75–80

    Article  PubMed  Google Scholar 

  4. Oreopoulos A, Padwal R, Kalantar-Zadeh K, Fonarow GC, Norris CM, McAlister FA (2008) Body mass index and mortality in heart failure: a meta-analysis. Am Heart J 156(1):13–22

    Article  PubMed  Google Scholar 

  5. Zamora E, Lupon J, Urrutia A, Gonzalez B, Mas D, Pascual T, Domingo M, Valle V (2007) Does body mass index influence mortality in patients with heart failure?. Rev Esp Cardiol 60(11):1127–1134

    Article  PubMed  Google Scholar 

  6. Shah RV, Murthy VL, Abbasi SA, Blankstein R, Kwong RY, Goldfine AB, Jerosch-Herold M, Lima JA, Ding J, Allison MA (2014) Visceral adiposity and the risk of metabolic syndrome across body mass index: the MESA Study. JACC Cardiovasc Imaging 7(12):1221–1235

    Article  PubMed  PubMed Central  Google Scholar 

  7. Clark AL, Coats AJS, Krum H, Katus HA, Mohacsi P, Salekin D, Schultz MK, Packer M, Anker SD (2017) Effect of beta-adrenergic blockade with carvedilol on cachexia in severe chronic heart failure: results from the COPERNICUS trial. J Cachexia Sarcopenia Muscle 8(4):549–556

    Article  PubMed  PubMed Central  Google Scholar 

  8. Padwal R, McAlister FA, McMurray JJ, Cowie MR, Rich M, Pocock S, Swedberg K, Maggioni A, Gamble G, Ariti C, Earle N, Whalley G, Poppe KK, Doughty RN, Bayes-Genis A (2014) Meta-analysis Global Group in Chronic Heart F. The obesity paradox in heart failure patients with preserved versus reduced ejection fraction: a meta-analysis of individual patient data. Int J Obes (Lond) 38(8):1110–1114

    Article  Google Scholar 

  9. Somaratne JB, Berry C, McMurray JJ, Poppe KK, Doughty RN, Whalley GA (2009) The prognostic significance of heart failure with preserved left ventricular ejection fraction: a literature-based meta-analysis. Eur J Heart Fail 11(9):855–62

    Article  PubMed  Google Scholar 

  10. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational Studies in Epidemiology (MOOSE) group. JAMA 283(15):2008–2012

    Article  CAS  PubMed  Google Scholar 

  11. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement. Open Med 3(3):e123-30

    PubMed  Google Scholar 

  12. Organization WH (2009) Principles for modelling dose–response for the risk assessment of chemicals. World Health Organization, Geneva

    Google Scholar 

  13. Shah R, Gayat E, Januzzi JL Jr, Sato N, Cohen-Solal A, diSomma S, Fairman E, Harjola VP, Ishihara S, Lassus J, Maggioni A, Metra M, Mueller C, Mueller T, Parenica J, Pascual-Figal D, Peacock WF, Spinar J, van Kimmenade R, Mebazaa A, Network G (2014) Body mass index and mortality in acutely decompensated heart failure across the world: a global obesity paradox. J Am Coll Cardiol 63(8):778–85

    Article  PubMed  Google Scholar 

  14. Bozkurt B, Deswal A (2005) Obesity as a prognostic factor in chronic symptomatic heart failure. Am Heart J 150(6):1233–1239

    Article  PubMed  Google Scholar 

  15. Hamaguchi S, Tsuchihashi-Makaya M, Kinugawa S, Goto D, Yokota T, Goto K, Yamada S, Yokoshiki H, Takeshita A, Tsutsui H, Investigators J-C (2010) Body mass index is an independent predictor of long-term outcomes in patients hospitalized with heart failure in Japan. Circ J 74(12):2605–2611

    Article  PubMed  Google Scholar 

  16. Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose–response data, with applications to meta-analysis. Am J Epidemiol 135(11):1301–1309

    Article  CAS  PubMed  Google Scholar 

  17. Orsini N, Li R, Wolk A, Khudyakov P, Spiegelman D (2012) Meta-analysis for linear and nonlinear dose–response relations: examples, an evaluation of approximations, and software. Am J Epidemiol 175(1):66–73

    Article  PubMed  Google Scholar 

  18. Orsini N (2009) From floated to conventional confidence intervals for the relative risks based on published dose–response data. Comput Methods Programs Biomed 88(1):90–93

    Article  Google Scholar 

  19. Clark AL, Fonarow GC, Horwich TB (2015) Impact of cardiorespiratory fitness on the obesity paradox in patients with systolic heart failure. Am J Cardiol 115(2):209–13

    Article  PubMed  Google Scholar 

  20. Orsini NBR, Greenland S (2006) Generalized least squares for trend estimation of summarized dose–response data. Stat J 6:40–57

    Article  Google Scholar 

  21. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  22. Begg CBMM. (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101

    Article  CAS  PubMed  Google Scholar 

  23. Egger MDSG., Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. De Schutter A, Lavie CJ, Kachur S, Patel DA, Milani RV (2014) Body composition and mortality in a large cohort with preserved ejection fraction: untangling the obesity paradox. Mayo Clin Proc 89(8):1072–1079

    Article  PubMed  Google Scholar 

  25. Wu AH, Eagle KA, Montgomery DG, Kline-Rogers E, Hu YC, Aaronson KD (2009) Relation of body mass index to mortality after development of heart failure due to acute coronary syndrome. Am J Cardiol 103(12):1736–1740

    Article  PubMed  Google Scholar 

  26. Vest AR, Wu Y, Hachamovitch R, Young JB, Cho L (2015) The heart failure overweight/obesity survival paradox: the missing sex link. JACC Heart Fail 3(11):917–26

    Article  PubMed  Google Scholar 

  27. Haass M, Kitzman DW, Anand IS, Miller A, Zile MR, Massie BM, Carson PE (2011) 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 4(3):324–31

    Article  PubMed  PubMed Central  Google Scholar 

  28. Curtis JP, Selter JG, Wang Y, Rathore SS, Jovin IS, Jadbabaie F, Kosiborod M, Portnay EL, Sokol SI, Bader F, Krumholz HM (2005) The obesity paradox: body mass index and outcomes in patients with heart failure. Arch Intern Med 165(1):55–61

    Article  PubMed  Google Scholar 

  29. Zafrir B, Goren Y, Salman N, Amir O (2015) Comparison of body mass index and body surface area as outcome predictors in patients with systolic heart failure. Cardiol J 22(4):375–81

    Article  PubMed  Google Scholar 

  30. McAuley P, Myers J, Abella J, Froelicher V (2007) Body mass, fitness and survival in veteran patients: another obesity paradox? Am J Med 120(6):518–24

    Article  PubMed  Google Scholar 

  31. Alpert MA (2016) Severe obesity and acute decompensated heart failure: new insights into prevalence and prognosis. JACC Heart Fail 4(12):932–934

    Article  PubMed  Google Scholar 

  32. Agarwal SK, Chambless LE, Ballantyne CM, Astor B, Bertoni AG, Chang PP, Folsom AR, He M, Hoogeveen RC, Ni H, Quibrera PM, Rosamond WD, Russell SD, Shahar E, Heiss G (2012) Prediction of incident heart failure in general practice: the Atherosclerosis Risk in Communities (ARIC) Study. Circ Heart Fail 5(4):422–429

    Article  PubMed  PubMed Central  Google Scholar 

  33. Miro O, Gil VI, Martin-Sanchez FJ, Jacob J, Herrero P, Alquezar A, Llauger L, Aguilo S, Martinez G, Rios J, Dominguez-Rodriguez A, Harjola VP, Muller C, Parissis J, Peacock WF, Llorens P (2018) Research Group on Acute Heart Failure of the Spanish Society of Emergency Medicine R. Short-term outcomes of heart failure patients with reduced and preserved ejection fraction after acute decompensation according to the final destination after emergency department care. Clin Res Cardiol. https://doi.org/10.1007/s00392-018-1237-z

    Article  PubMed  Google Scholar 

  34. Tschope C, Birner C, Bohm M, Bruder O, Frantz S, Luchner A, Maier L, Stork S, Kherad B, Laufs U (2018) Heart failure with preserved ejection fraction: current management and future strategies: Expert opinion on the behalf of the Nucleus of the “Heart Failure Working Group” of the German Society of Cardiology (DKG). Clin Res Cardiol 107(1):1–19

    Article  PubMed  Google Scholar 

  35. Chau K, Girerd N, Magnusson M, Lamiral Z, Bozec E, Merckle L, Leosdottir M, Bachus E, Frikha Z, Ferreira JP, Despres JP, Rossignol P, Boivin JM, Zannad F (2018) Obesity and metabolic features associated with long-term developing diastolic dysfunction in an initially healthy population-based cohort. Clin Res Cardiol. https://doi.org/10.1007/s00392-018-1259-6

    Article  PubMed  Google Scholar 

  36. Sze S, Pellicori P, Kamzi S, Anton A, Clark AL (2018) Effect of beta-adrenergic blockade on weight changes in patients with chronic heart failure. Int J Cardiol 264:104–112

    Article  PubMed  Google Scholar 

  37. Oldenburg O, Wellmann B, Bitter T, Fox H, Buchholz A, Freiwald E, Horstkotte D, Wegscheider K (2018) Adaptive servo-ventilation to treat central sleep apnea in heart failure with reduced ejection fraction: the Bad Oeynhausen prospective ASV registry. Clin Res Cardiol. https://doi.org/10.1007/s00392-018-1239-x

    Article  PubMed  Google Scholar 

  38. Streng KW, Voors AA, Hillege HL, Anker SD, Cleland JG, Dickstein K, Filippatos G, Metra M, Ng LL, Ponikowski P, Samani NJ, van Veldhusen DJ, Zwinderman AH, Zannad F, Damman K, van der Meer P, Lang CC (2018) Waist–hip ratio and mortality in heart failure. Eur J Heart Fail (In press)

  39. Ebong IA, Goff DC Jr, Rodriguez CJ, Chen H, Bertoni AG (2014) Mechanisms of heart failure in obesity. Obes Res Clin Pract 8(6):e540–e548

    Article  Google Scholar 

  40. Backhaus T, Fach A, Schmucker J, Fiehn E, Garstka D, Stehmeier J, Hambrecht R, Wienbergen H (2018) Management and predictors of outcome in unselected patients with cardiogenic shock complicating acute ST-segment elevation myocardial infarction: results from the Bremen STEMI Registry. Clin Res Cardiol 107(5):371–379

    Article  PubMed  Google Scholar 

  41. Stiermaier T, Santoro F, Graf T, Guastafierro F, Tarantino N, De Gennaro L, Caldarola P, Di Biase M, Thiele H, Brunetti ND, Moller C, Eitel I (2018) Prognostic value of N-terminal Pro-B-type natriuretic peptide in Takotsubo syndrome. Clin Res Cardiol. https://doi.org/10.1007/s00392-018-1227-1

    Article  PubMed  Google Scholar 

  42. Clark AL, Chyu J, Horwich TB (2012) The obesity paradox in men versus women with systolic heart failure. Am J Cardiol 110(1):77–82

    Article  PubMed  PubMed Central  Google Scholar 

  43. Fonarow GC, Srikanthan P, Costanzo MR, Cintron GB, Lopatin M, Committee ASA (2007) Investigators. An obesity paradox in acute heart failure: analysis of body mass index and inhospital mortality for 108,927 patients in the Acute Decompensated Heart Failure National Registry. Am Heart J 153(1):74–81

    Article  PubMed  Google Scholar 

  44. Abdin A, Poss J, Fuernau G, Ouarrak T, Desch S, Eitel I, de Waha S, Zeymer U, Bohm M, Thiele H (2018) Revision: prognostic impact of baseline glucose levels in acute myocardial infarction complicated by cardiogenic shock-a substudy of the IABP-SHOCK II-trial. Clin Res Cardiol. https://doi.org/10.1007/s00392-018-1213-7

    Article  PubMed  Google Scholar 

  45. Shah M, Patnaik S, Patel B, Ram P, Garg L, Agarwal M, Agrawal S, Arora S, Patel N, Wald J, Jorde UP (2018) Trends in mechanical circulatory support use and hospital mortality among patients with acute myocardial infarction and non-infarction related cardiogenic shock in the United States. Clin Res Cardiol 107(4):287–303

    Article  PubMed  Google Scholar 

  46. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P, Group ESCSD (2016) 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 37(27):2129–2200

    Article  PubMed  Google Scholar 

  47. Shah RV, Abbasi SA, Yamal JM, Davis BR, Barzilay J, Einhorn PT, Goldfine AB, Group ACR (2014) Impaired fasting glucose and body mass index as determinants of mortality in ALLHAT: is the obesity paradox real? J Clin Hypertens (Greenwich) 16(6):451–458

    Article  Google Scholar 

  48. Costanzo P, Cleland JG, Pellicori P, Clark AL, Hepburn D, Kilpatrick ES, Perrone-Filardi P, Zhang J, Atkin SL (2015) The obesity paradox in type 2 diabetes mellitus: relationship of body mass index to prognosis: a cohort study. Ann Intern Med 162(9):610–618

    Article  PubMed  Google Scholar 

  49. Sinning C, Ojeda F, Wild PS, Schnabel RB, Schwarzl M, Ohdah S, Lackner KJ, Pfeiffer N, Michal M, Blettner M, Munzel T, Kempf T, Wollert KC, Kuulasmaa K, Blankenberg S, Salomaa V, Westermann D, Zeller T (2017) Midregional proadrenomedullin and growth differentiation factor-15 are not influenced by obesity in heart failure patients. Clin Res Cardiol 106(6):401–410

    Article  CAS  PubMed  Google Scholar 

  50. Sandhu RK, Ezekowitz J, Andersson U, Alexander JH, Granger CB, Halvorsen S, Hanna M, Hijazi Z, Jansky P, Lopes RD, Wallentin L (2016) The ‘obesity paradox’ in atrial fibrillation: observations from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Eur Heart J 37(38):2869–2878

    Article  PubMed  Google Scholar 

  51. Abdin A, Poss J, Fuernau G, Ouarrak T, Desch S, Eitel I, de Waha S, Zeymer U, Bohm M, Thiele H (2018) Revision: prognostic impact of baseline glucose levels in acute myocardial infarction complicated by cardiogenic shock-a substudy of the IABP-SHOCK II-trial. Clin Res Cardiol 107(6):517–523

    Article  CAS  PubMed  Google Scholar 

  52. Wang ZJ, Zhou YJ, Galper BZ, Gao F, Yeh RW, Mauri L (2015) Association of body mass index with mortality and cardiovascular events for patients with coronary artery disease: a systematic review and meta-analysis. Heart 101(20):1631–1638

    Article  CAS  PubMed  Google Scholar 

  53. Futter JE, Cleland JG, Clark AL (2011) Body mass indices and outcome in patients with chronic heart failure. Eur J Heart Fail 13(2):207–13

    Article  PubMed  Google Scholar 

  54. Palazzuoli A, Ruocco G, Beltrami M, Nuti R, Cleland JG (2018) Combined use of lung ultrasound, B-type natriuretic peptide, and echocardiography for outcome prediction in patients with acute HFrEF and HFpEF. Clin Res Cardiol. https://doi.org/10.1007/s00392-018-1221-7

    Article  PubMed  Google Scholar 

  55. Fu M, Ahrenmark U, Berglund S, Lindholm CJ, Lehto A, Broberg AM, Tasevska-Dinevska G, Wikstrom G, Agard A, Andersson B (2017) All investigators of the HRHFs. Adherence to optimal heart rate control in heart failure with reduced ejection fraction: insight from a survey of heart rate in heart failure in Sweden (HR-HF study). Clin Res Cardiol 106(12):960–973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kenchaiah S, Pocock SJ, Wang D, Finn PV, Zornoff LA, Skali H, Pfeffer MA, Yusuf S, Swedberg K, Michelson EL, Granger CB, McMurray JJ, Solomon SD, Investigators C (2007) 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 116(6):627–36

    Article  PubMed  Google Scholar 

  57. Chan MM, Lam CS (2013) How do patients with heart failure with preserved ejection fraction die? Eur J Heart Fail 15(6):604–13

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jufen Zhang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, J., Begley, A., Jackson, R. 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 108, 119–132 (2019). https://doi.org/10.1007/s00392-018-1302-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-018-1302-7

Keywords

Navigation