Adiposity, fat-free mass and incident heart failure in 500 000 individuals

Background and aims The independent role of body fat distribution and fat-free mass in heart failure (HF) risk is unclear. We investigated the role of different body composition compartments in risk of HF. Methods Present analyses include 428 087 participants (mean age 55.9 years, 44% male) from the UK Biobank. Associations of long-term average levels of body composition measures with incident HF were determined using adjusted Cox proportional hazards regression models. Results Over a median follow-up of 13.8 years, there were 10 455 first-ever incident HF events. Overall, HF risk was more strongly associated with central adiposity (waist circumference (WC) adjusted for body mass index (BMI); HR 1.38, 95% CI 1.32 to 1.45) than general adiposity (BMI adjusted for WC; HR 1.22, 95% CI 1.16 to 1.27). Although dual X-ray absorptiometry-derived body fat remained positively related to HF after adjustment for fat-free mass (HR 1.37, 95% CI 1.18 to 1.59), the association of fat-free mass with HF was substantially attenuated by fat mass (HR 1.12, 95% CI 1.01 to 1.26) while visceral fat (VAT) remained associated with HF independent of subcutaneous fat (HR 1.20, 95% CI 1.09 to 1.33). In analyses of HF subtypes, HF with preserved ejection fraction was independently associated with all fat measures (eg, VAT: HR 1.23, 95% CI 1.12 to 1.35; body fat: HR 1.36, 95% CI 1.17 to 1.57) while HF with reduced ejection fraction was not independently associated with fat measures (eg, VAT: HR 1.29, 95% CI 0.98 to 1.68; body fat: HR 1.29, 95% CI 0.80 to 2.07). Conclusions This large-scale study shows that excess adiposity and fat mass are associated with higher HF risk while the association of fat-free mass with HF could be explained largely by its correlation with fat mass. The study also describes the independent relevance of body fat distribution to HF subtypes, suggesting different mechanisms may be driving their aetiopathogenesis.