Waist-hip ratio and mortality in heart failure; contradicting the obesity paradox

Aims: A higher body mass index (BMI) is associated with better survival in heart failure (HF) patients, also known as the obesity paradox. However, BMI does not account for body composition. We therefore analysed the association between abdominal fat, measured via waist-hip ratio (WHR), BMI and all-cause mortality in patients with HF. Methods: For this analysis 1738 patients from The Scottish BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) validation study were included. Patients without waist and hip measurements were excluded. WHR was defined as waist circumference/hip circumference, divided into tertiles and split for sex. A linear regression of principal components from an extensive panel of biomarkers was performed to provide insight in the pathophysiology behind a higher WHR. Results: In total, 1479 patients with were included, of which 33% were female and mean age was 75±11 years. A higher WHR was independently associated with a higher BMI, a higher prevalence of diabetes and higher functional NYHA class. There was a significant interaction between sex and WHR on its association with mortality (P<0.001). In women, a higher WHR was associated with a higher mortality risk (HR 2.01; 95% confidence interval (CI) 1.33-3.02, P=0.001), whereas no significant association was found in men (HR 1.21, 95% CI 0.87-1.69, P=0.262). We found a strong association between a higher WHR and elevated markers of inflammation and MAPK cascade in women, while in men these associations were less profound. Conclusions: A higher WHR was associated with a higher risk of death in female, but not in male HF patients. These findings challenge the obesity paradox, and suggest that fat deposition is pathophysiologically harmful and may be a target for therapy in female patients with HF.