Impact of obesity on heart failure risk is mediated by hypertension: univariable and multivariable Mendelian randomization study

Abstract

Obesity is a risk factor for heart failure, and patients with obesity and heart failure have a better prognosis. We attempted to explain this paradox by exploring the role of hypertension in obesity and heart failure.We performed univariable and multivariable Mendelian randomization (MR) analyses to investigate causal effects of obesity and hypertension on heart failure. Analysis using the inverse-variance weighted (IVW) method showed that obesity Ⅱ (ORIVW = 1.10, 95% CI = 1.05–1.15, P = 2.86 × 10− 5) and obesity Ⅰ (ORIVW = 1.17, 95% CI = 1.11–1.24, P = 8.41 × 10− 8) had a positive effect on the occurrence of heart failure. The IVW method showed a causal effect of obesity Ⅰ (ORIVW = 1.02, 95% CI = 1.00–1.02, P = 2.807× 10− 25) and obesity Ⅱ (ORIVW = 1.01, 95% CI = 1.00–1.02, P = 7.14 × 10− 11) on hypertension. After adjusting for hypertension using multivariate IVW, obesity II was not causally associated with heart failure.Both obesity and hypertension are risk factors for heart failure, and the effect of obesity on heart failure is mediated by hypertension.