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The obesity paradox in heart failure patients with preserved versus reduced ejection fraction: a meta-analysis of individual patient data

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Abstract

Background:

In heart failure (HF), obesity, defined as body mass index (BMI) ⩾30 kg m−2, is paradoxically associated with higher survival rates compared with normal-weight patients (the ‘obesity paradox’). We sought to determine if the obesity paradox differed by HF subtype (reduced ejection fraction (HF-REF) versus preserved ejection fraction (HF-PEF)).

Patients and Methods:

A sub-analysis of the MAGGIC meta-analysis of patient-level data from 14 HF studies was performed. Subjects were divided into five BMI groups: <22.5, 22.5–24.9 (referent), 25–29.9, 30–34.9 and ⩾35 kg m−2. Cox proportional hazards models adjusted for age, sex, aetiology (ischaemic or non-ischaemic), hypertension, diabetes and baseline blood pressure, stratified by study, were used to examine the independent association between BMI and 3-year total mortality. Analyses were conducted for the overall group and within HF-REF and HF-PEF groups.

Results:

BMI data were available for 23 967 subjects (mean age, 66.8 years; 32% women; 46% NYHA Class II; 50% Class III) and 5609 (23%) died by 3 years. Obese patients were younger, more likely to receive cardiovascular (CV) drug treatment, and had higher comorbidity burdens. Compared with BMI levels between 22.5 and 24.9 kg m−2, the adjusted relative hazards for 3-year mortality in subjects with HF-REF were: hazard ratios (HR)=1.31 (95% confidence interval=1.15–1.50) for BMI <22.5, 0.85 (0.76–0.96) for BMI 25.0–29.9, 0.64 (0.55–0.74) for BMI 30.0–34.9 and 0.95 (0.78–1.15) for BMI ⩾35. Corresponding adjusted HRs for those with HF-PEF were: 1.12 (95% confidence interval=0.80–1.57) for BMI <22.5, 0.74 (0.56–0.97) for BMI 25.0–29.9, 0.64 (0.46–0.88) for BMI 30.0–34.9 and 0.71 (0.49–1.05) for BMI ⩾35.

Conclusions:

In patients with chronic HF, the obesity paradox was present in both those with reduced and preserved ventricular systolic function. Mortality in both HF subtypes was U-shaped, with a nadir at 30.0–34.9 kg m−2.

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Acknowledgements

FAM is supported by salary awards from Alberta Innovates-Health Solutions and the Capital Health Chair in Cardiovascular Outcomes Research; KKP is supported by a Research Fellowship from the New Zealand Heart Foundation; RND holds the New Zealand Heart Foundation Chair in Heart Health; and MRC is supported by the National Institute for Health Research Cardiovascular Biomedical Research Unit at the Royal Brompton Hospital, London, UK. RP and FAM are supported by an alternate funding plan from the Government of Alberta. The MAGGIC meta-analysis was supported by grants from the New Zealand National Heart Foundation, the University of Auckland and the University of Glasgow.

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Author notes

  1. See appendix.

Authors and Affiliations

  1. Department of Medicine, University of Alberta, Edmonton, Canada

    R Padwal & F A McAlister

  2. BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK

    J J V McMurray

  3. Faculty of Medicine, National Heart and Lung Institute, Imperial College London (Royal Brompton Hospital), London, UK

    M R Cowie

  4. Washington University School of Medicine, St Louis, MO, USA

    M Rich

  5. Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK

    S Pocock & C Ariti

  6. Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    K Swedberg

  7. ANMCO Research Center, Florence, Italy

    A Maggioni

  8. Department of Medicine and National Institute for Health Innovation, University of Auckland, Auckland, New Zealand

    G Gamble, N Earle, K K Poppe & R N Doughty

  9. Faculty of Social and Health Sciences, UNITEC Institute of Technology, Auckland, New Zealand

    G Whalley

  10. Department of Medicine, Hospital Universitari Germans Trias i Pujol UAB, Barcelona, Spain

    A Bayes-Genis

Authors
  1. R Padwal
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  2. F A McAlister
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  3. J J V McMurray
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  4. M R Cowie
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  5. M Rich
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  6. S Pocock
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  7. K Swedberg
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  8. A Maggioni
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  9. G Gamble
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  10. C Ariti
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  11. N Earle
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  12. G Whalley
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  13. K K Poppe
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  14. R N Doughty
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  15. A Bayes-Genis
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Consortia

for the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) Investigators

Corresponding author

Correspondence to R Padwal.

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Competing interests

The authors declare no conflict of interest.

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These sponsors had no role in the design, conduct, data management and analysis, manuscript preparation or review, nor in the authorization for submission.

Appendices

MAGGIC Executive Group:

C Berry, R Doughty, C Granger, L Køber, B Massie, F McAlister, J McMurray, S Pocock, K Poppe, K Swedberg, J Somaratne, G Whalley.

MAGGIC Steering Group:

A Ahmed, B Andersson, A Bayes-Genis, C Berry, M Cowie, R Cubbon, R Doughty, J Ezekowitz, J Gonzalez-Juanatey, M Gorini, I Gotsman, L Grigorian-Shamagian, M Guazzi, M Kearney, L Køber, M Komajda, A di Lenarda, M Lenzen, D Lucci, S Macín, B Madsen, A Maggioni, M Martínez-Sellés, F McAlister, F Oliva, K Poppe, M Rich, M Richards, M Senni, I Squire, G Taffet, L Tarantini, C Tribouilloy, R Troughton, H Tsutsui, G Whalley.

MAGGIC Coordinating Centre:

R Doughty, N Earle, GD Gamble, K Poppe, G Whalley, the University of Auckland, New Zealand.

MAGGIC Statistical Group:

C Ariti, J Dobson, GD Gamble, S Pocock, K Poppe.

Studies included:

AHFMS: RN Doughty, G Whalley; Andersson (2 data sets): B Andersson, C Hall; BATTLESCARRED and Richards: AM Richards, R Troughton, J Lainchbury; Berry: C Berry, K Hogg, J Norrie, K Stevenson, M Brett, J McMurray; CHARM: MA Pfeffer, K Swedberg, CB Granger, P Held, JJV McMurray, EL Michelson, B Olofsson, J Östergren, S Yusuf for the CHARM Investigators and Committees; Diamond and ECHOS: L Køber, C Torp-Pedersen; DIG Trial: DIG limited access data, Ali Ahmed; Euro HF Survey: MJ Lenzen, WJM Scholte op Reimer, E Boersma, PJMJ Vantrimpont, F Follath, K Swedberg, J Cleland, M Komajda; Gotsman: I Gotsman, D Zwas, D Planer, T Azaz-Livshits, D Admon, C Lotan, A Keren; Grigorian-Shamagian: L Grigorian-Shamagian, A Varela-Roman, P Mazón-Ramos, P Rigeiro-Veloso, MA Bandin-Dieguez, JR Gonzalez-Juanatey; Guazzi: M Guazzi, J Myers, R Arena; Heart Failure Clinic Edmonton: FA McAlister, J Ezekowitz, PW Armstrong, Bibiana Cujec, Ian Paterson; Hillingdon: MR Cowie, DA Wood, AJS Coats, SG Thompson, V Suresh, PA Poole-Wilson, GC Sutton; HOLA: M Martínez-Sellés, JAG Robles, L Prieto, MD Muñoa, E Frades, O Díaz-Castro, J Almendral; Italian HF Registry (IN-CHF): L Tarantini, P Faggiano, M Senni, D Lucci, D Bertoli, M Porcu, C Opasich, L Tavazzi, AP Maggioni; Kirk: V Kirk, M Bay, J Parner, K Krogsgaard, TM Herzog, S Boesgaard, C Hassager, OW Nielsen, J Aldershvile, H Nielsen L Kober; Macin: SM Macín, ER Perna, JP Cimbaro Canella, P Alvarenga, R Pantich, N Ríos, EF Farias, JR Badaracco; Madsen: BK Madsen, JF Hansen, KH Stokholm, J Brons, D Husum, LS Mortensen; MUSIC: A Bayes-Genis, R Vazquez, T Puig, C Fernandez-Palomeque, A Bardají, D Pascual-Figal, J Ordoñez-Llanos, M Valdes, A Gabarrus, R Pavon, L Pastor, JR Gonzalez-Juanatey, J Almendral, M Fiol,V Nieto, C Macaya, J Cinca, A Bayes de Luna; Newton: JD Newton, HM Blackledge, IB Squire; NPC I: SP Wright, GA Whalley, RN Doughty; Rich (data set 1): R Kerzner, BF Gage, KE Freedland, MW Rich: Rich (data set 2): BC Huynh, A Rovner, KE Freedland, RM Carney, MW Rich; Taffet: GE Taffet, TA Teasdale, AJ Bleyer, NJ Kutka, RJ Luchi; Tribouilloy: C Tribouilloy, D Rusinaru, H Mahjoub, V Soulière, F Lévy, M Peltier; Tsutsui: H Tsutsui, M Tsuchihashi, A Takeshita; UK Heart Study: PA MacCarthy, MT Kearney, J Nolan, AJ Lee, RJ Prescott, AM Shah, WP Brooksby, KAA Fox; Varela-Roman: A Varela-Roman, JR Gonzalez-Juanatey, P Basante, R Trillo, J Garcia-Seara, JL Martinez-Sande, F Gude.

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Padwal, R., McAlister, F., McMurray, J. 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 38, 1110–1114 (2014). https://doi.org/10.1038/ijo.2013.203

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