Body Mass Index, Clinical Outcomes, and Mortality in Heart Failure: A Mendelian Randomization Study

作者：Sunderland N, Asselin G, Henry A, Nelson CP, Lemieux Perreault LP, Asselbergs FW, Boersma E, Cappola TP, Chazara O, Chutkow W, Cyr MC, Gkatzionis A, Gui H, Haefliger C, Hedman ÅK, Hillege H, Hyde CL, Kamanu FK, Kardys I, Koekemoer AL, Kraus WE, Lang CC, Malarstig A, Margulies KB, Marston NA, Melloni GEM, Morley MP, O'Donoghue ML, Owens AT, Paul DS, Tilling K, van der Harst P, van Setten J, van Vugt M, Verweij N, Veluchamy A, Wallentin L, Wang X, Xing H, Yang Y, White HD, Zannad F, Smith JG, Brunner-La Rocca HP, Lanfear DE, Mann DL, de Denus S, Tardif JC, Voors AA, Samani NJ, Ellinor PT, Ruff CT, Sabatine MS, Sattar N, McMurray JJV, Paternoster L, Dubé MP, Lumbers RT · 发表于：Journal of the American College of Cardiology · 年份：2026 · DOI：10.1016/j.jacc.2026.02.5093

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: The mean BMI was 29.2 ± 5.8 kg/m2. Over a median follow-up of 27.0 months, all-c...