Anthropometric measures and long-term mortality in heart failure with reduced ejection: debunking the obesity paradox

Abstract Background In patients with heart failure (HF), an "obesity-survival paradox" has been reported. Although body mass index (BMI) is the most commonly used anthropometric measure to assess adiposity, alternative indices such as the waist-to-height ratio may better reflect the location and amount of ectopic fat as well as the weight of the skeleton. Purpose To examine and compare the prognostic value of several alternative anthropometric measures with that of BMI in patients with non-ischemic HF with reduced ejection fraction (HFrEF) enrolled in the DANISH trial. Patients were eligible if they had non-ischemic HFEF, a left ventricular ejection fraction of <35%, New York Heart Association functional class II-III (IV if cardiac resynchronization therapy was planned), and elevated natriuretic peptides. The outcomes of interest were all-cause mortality and cardiovascular death. The association between anthropometric measures and all-cause death was examined with Cox regression models, adjusted for prognostic variables, including natriuretic peptides. Results Among 1,116 patients with non-ischemic HFrEF, there was no evidence for a BMI-related "obesity-survival paradox" during a median follow-up of 9.5 years (25th-75th percentile, 7.9-10.9 years). Indeed, compared to patients with a BMI 18.5-24.9 kg/m2 (N=363), those with a BMI >35 kg/m2 (N=91) had a significantly higher risk of all-cause death (HR 1.78 [95% CI 1.28-2.48]). Greater waist-to-height ratio (as an exemplar of indices not incorporating weight) was also associated with a higher risk of all-cause death, with a HR of 2.11 (95% CI, 1.53-2.92) for the highest quintile (N=205) compared with the lowest quintile (N=196). In the minimally adjusted restricted cubic spline models, the association between adiposity and all-cause death was more apparent for waist-to-height ratio than for BMI. A similar pattern was seen for cardiovascular death (Figure). Conclusion In patients with HFrEF, there was no evidence for an "obesity-survival paradox". Indeed, there was a clear association between adiposity and higher long-term mortality, which appeared to be stronger for waist-to-height ratio than for BMI. There is a need to test the potential benefits of intentional weight loss in patients with HFrEF and obesity.