Obesity-related traits were associated with higher heart failure (HF) risk in a systematic review and meta-analysis of Mendelian randomization (MR) studies published in Frontiers in Cardiovascular Medicine. The review synthesized genetic epidemiology evidence on body mass index (BMI), related anthropometric traits, and HF outcomes. 

Multiple databases, including PubMed, Google Scholar, Web of Science, Embase, and the Cochrane Library, were searched for eligible studies published up to October 2025. Included studies applied MR methodology to assess associations between genetic instruments for obesity traits and HF outcomes. Study quality was evaluated, and pooled estimates were calculated using random-effects models where feasible.

Genetically predicted adult body mass index (BMI) was significantly related to increased HF risk across populations. In European ancestry cohorts, the odds ratio per standard deviation (ORSD) was 1.79 (95% CI: 1.64-1.94), while in East Asian populations, the odds ratio per kg/m² increase was 2.17 (95% CI: 1.79-2.63). A significant association was also reported for HF with preserved ejection fraction (HFpEF) in European ancestry individuals (ORSD: 2.68; 95% CI: 1.07–4.28). 

Childhood body size traits were associated with HF risk (ORSD: 1.30; 95% CI: 1.21-1.39). Additional adiposity-related measures, including fat mass, waist circumference (WC), waist-to-hip ratio (WHR), and unfavorable adiposity, were identified as causal contributors. Tissue-specific analyses indicated that genetic instruments for BMI derived from both brain and adipose tissues were linked to increased HF risk.

These findings support obesity-related traits as potential contributors to HF across diverse populations. Further MR studies in non-European populations may help clarify generalizability.