Adiposity-related anthropometrics, cardiovascular outcomes, and finerenone in heart failure and chronic kidney disease with type 2 diabetes: a FINE-HEART analysis

Abstract Background Excess/dysfunctional adiposity is a core pathophysiological mechanism intersecting cardiovascular (CV), kidney, and metabolic (CKM) disorders. However, the association between different adiposity-related anthropometrics and CV outcomes has not been rigorously explored in this population. Purpose To explore CV outcomes and treatment effects of finerenone according to baseline body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and waist-hip ratio (WHR). Methods In this prespecified participant-level FINE-HEART pooled analysis of FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF, CV outcomes and treatment effects of finerenone according to BMI, WC, WHtR, and WHR were evaluated using multivariable-adjusted Cox proportional hazards regression models and Poisson regression with restricted cubic splines. Independent and combined effects of BMI and WHtR were also assessed. Results Among 18,759 participants with available data for all anthropometrics, 52% had a BMI ≥30 kg/m2 (8% with BMI ≥40 kg/m2), 77% had an elevated WC, 64% had an elevated WHtR, and 91% had an elevated WHR. Among those with BMI 30 kg/m2, WC and WHtR were elevated in 62% and 35%, respectively. Female and older participants were more likely to have elevated WC and WHtR. Higher BMI, WC, WHtR, and WHR were each significantly associated with a wide range of CV outcomes, including CV death or heart failure (HF) hospitalization (Figure) and its individual components, major adverse cardiovascular events, and new-onset atrial fibrillation. A U-shaped association was observed between BMI and CV death, but not WC, WHtR, or WHR, for which more linear associations were observed. BMI-adjusted WHtR (adjusted hazard ratio aHR, 1.09 per 0.05 increase; 95% CI, 1.03 to 1.11) and WHtR-adjusted BMI (aHR, 1.13 per 5 kg/m2 increase above 30 kg/m2; 95% CI, 1.04 to 1.22) were each associated with a higher rate of CV death or HF hospitalization, and participants with elevated BMI and WHtR experienced a higher rate of CV death or HF hospitalization compared with those with elevated BMI or WHtR alone (Table). Benefits of finerenone on CV death or HF hospitalization were consistent irrespective of baseline BMI (Pinteraction=0.27) or WHtR (Pinteraction=0.26), with greater absolute benefits among participants with higher BMI (absolute rate reduction ARR for BMI ≥40 kg/m2, 1.3 per 100 person-years; ARR for BMI 18.5-25 kg/m2, 0.6 per 100 person-years) and WC (ARR for elevated WC, 0.7 per 100 person-years; ARR for non-elevated WC, 0.5 per 100 person-years). Conclusions These findings support assessment of anthropometrics capturing abdominal adiposity, in addition to BMI, to enhance risk stratification among individuals with CKM conditions. Higher BMI and abdominal adiposity may additionally identify individuals with potential to derive greater absolute CV benefits with finerenone.Figure Table