Body Mass Index, Clinical Outcomes, and Mortality in Heart Failure: A Mendelian Randomization Study.
Nicholas, S., Geraldine, A., Albert, H., P, N.C., Louis-Philippe, L.P., W, A.F., Eric, B., P, C.T., Olympe, C., William, C., Marie-Christyne, C., Apostolos, G., Hongsheng, G., Carolina, H., K, H.Å., Hans, H., L, H.C., K, K.F., Isabella, K., . . . Thomas, L.R. (2026). Body Mass Index, Clinical Outcomes, and Mortality in Heart Failure: A Mendelian Randomization Study.. J Am Coll Cardiol. https://doi.org/10.1016/j.jacc.2026.02.5093
Nicholas S, Geraldine A, Albert H, P NC, Louis-Philippe LP, W AF, et al. Body Mass Index, Clinical Outcomes, and Mortality in Heart Failure: A Mendelian Randomization Study.. J Am Coll Cardiol. 2026; doi: 10.1016/j.jacc.2026.02.5093
Nicholas S, Geraldine A, Albert H, et al. Body Mass Index, Clinical Outcomes, and Mortality in Heart Failure: A Mendelian Randomization Study.[J]. J Am Coll Cardiol. 2026. DOI: 10.1016/j.jacc.2026.02.5093.
@article{nicholas2026,
author = {Sunderland Nicholas and Asselin Geraldine and Henry Albert and Nelson Christopher P and Lemieux Perreault Louis-Philippe and Asselbergs Folkert W and Boersma Eric and Cappola Thomas P and Chazara Olympe and Chutkow William and Cyr Marie-Christyne and Gkatzionis Apostolos and Gui Hongsheng and Haefliger Carolina and Hedman Åsa K and Hillege Hans and Hyde Craig L and Kamanu Frederick K and Kardys Isabella and Koekemoer Andrea L and Kraus William E and Lang Chim C and Malarstig Anders and Margulies Kenneth B and Marston Nicholas A and Melloni Giorgio E M and Morley Michael P and O'Donoghue Michelle L and Owens Anjali T and Paul Dirk S and Tilling Kate and van der Harst Pim and van Setten Jessica and van Vugt Marion and Verweij Niek and Veluchamy Abirami and Wallentin Lars and Wang Xiaosong and Xing Heming and Yang Yifan and White Harvey D and Zannad Faiez and Smith J Gustav and Brunner-La Rocca Hans-Peter and Lanfear David E and Mann Douglas L and de Denus Simon and Tardif Jean-Claude and Voors Adriaan A and Samani Nilesh J and Ellinor Patrick T and Ruff Christian T and Sabatine Marc S and Sattar Naveed and McMurray John J V and Paternoster Lavinia and Dubé Marie-Pierre and Lumbers R Thomas},
title = {Body Mass Index, Clinical Outcomes, and Mortality in Heart Failure: A Mendelian Randomization Study.},
journal = {J Am Coll Cardiol},
year = {2026},
doi = {10.1016/j.jacc.2026.02.5093},
note = {PMID: 42017882},
}
TY - JOUR AU - Sunderland Nicholas AU - Asselin Geraldine AU - Henry Albert AU - Nelson Christopher P AU - Lemieux Perreault Louis-Philippe AU - Asselbergs Folkert W AU - Boersma Eric AU - Cappola Thomas P AU - Chazara Olympe AU - Chutkow William AU - Cyr Marie-Christyne AU - Gkatzionis Apostolos AU - Gui Hongsheng AU - Haefliger Carolina AU - Hedman Åsa K AU - Hillege Hans AU - Hyde Craig L AU - Kamanu Frederick K AU - Kardys Isabella AU - Koekemoer Andrea L AU - Kraus William E AU - Lang Chim C AU - Malarstig Anders AU - Margulies Kenneth B AU - Marston Nicholas A AU - Melloni Giorgio E M AU - Morley Michael P AU - O'Donoghue Michelle L AU - Owens Anjali T AU - Paul Dirk S AU - Tilling Kate AU - van der Harst Pim AU - van Setten Jessica AU - van Vugt Marion AU - Verweij Niek AU - Veluchamy Abirami AU - Wallentin Lars AU - Wang Xiaosong AU - Xing Heming AU - Yang Yifan AU - White Harvey D AU - Zannad Faiez AU - Smith J Gustav AU - Brunner-La Rocca Hans-Peter AU - Lanfear David E AU - Mann Douglas L AU - de Denus Simon AU - Tardif Jean-Claude AU - Voors Adriaan A AU - Samani Nilesh J AU - Ellinor Patrick T AU - Ruff Christian T AU - Sabatine Marc S AU - Sattar Naveed AU - McMurray John J V AU - Paternoster Lavinia AU - Dubé Marie-Pierre AU - Lumbers R Thomas TI - Body Mass Index, Clinical Outcomes, and Mortality in Heart Failure: A Mendelian Randomization Study. T2 - J Am Coll Cardiol PY - 2026 DO - 10.1016/j.jacc.2026.02.5093 AN - PMID:42017882 ER -
Excess adiposity, most commonly indexed through body mass index (BMI), is strongly associated with the development of heart failure (HF). Weight loss therapies improve outcomes in patients with obesity and HF with preserved left ventricular ejection fraction (LVEF), but their effects in HF with reduced LVEF remain unclear. The aim of this work is to determine whether higher BMI is associated with adverse clinical outcomes in patients with HF and whether there is effect modification by LVEF subgroup. Two-sample Mendelian randomization (MR) was used, with genome-wide significant loci associated with BMI as instrumental variables and outcome data from a genome-wide association study (GWAS) of time-to-event clinical outcomes in patients with HF. A total of 50,636 individuals of European ancestry with established HF from 22 cohorts were included in the genetic analysis: 12 HF trials, 1 prospective case-cohort study, 9 cohorts nested within non-HF cardiovascular trials, and 1 population-based cohort derived from the UK Biobank. The exposure was genetically predicted BMI and the outcome measures were all-cause mortality and a composite of cardiovascular mortality or HF hospitalization. Genetic associations for the outcomes were derived from our GWAS and MR was used to estimate the unbiased association of genetically predicted BMI with these clinical outcomes. The mean BMI was 29.2 ± 5.8 kg/m2. Over a median follow-up of 27.0 months, all-cause mortality occurred in 11,454 patients (23%), and 11,360 participants (22%) experienced the composite endpoint. Genetically predicted BMI was associated with an increased rate of both all-cause mortality (HR per SD [4.8 BMI units] 1.21; 95% CI: 1.13-1.29; P = 9 × 10-8) and the composite outcome (HR 1.29; 95% CI: 1.20-1.38; P = 8 × 10-13). Associations were consistent across LVEF ≤40% and >40%: for all-cause mortality, HR: 1.16 (95% CI: 0.99-1.37) and 1.20 (95% CI: 0.94-1.53); and for the composite outcome, HR: 1.30 (95% CI: 1.15-1.48) and 1.57 (95% CI: 1.29-1.91), respectively. Among patients with HF, higher BMI was associated with increased all-cause mortality and cardiovascular death or HF hospitalization, supporting the potential role of weight-management strategies across the ejection fraction spectrum.