Diabetes Status Modifies the Association Between Different Measures of Obesity and Heart Failure Risk Among Older Adults: A Pooled Analysis of Community-Based NHLBI Cohorts

Background: Obesity and diabetes are associated with a higher risk of heart failure (HF). The inter-relationships between different measures of adiposity—overall obesity, central obesity, fat mass (FM)—and diabetes status for HF risk are not well-established. Methods: Participant-level data from ARIC(visit-5) and CHS(visit-1) cohorts were obtained from the NHLBI BioLINCC, harmonized, and pooled for the present analysis, excluding individuals with prevalent HF. FM was estimated in all participants using established anthropometric prediction equations additionally validated using the bioelectrical impedance-based FM in the ARIC subgroup. Incident HF events on follow-up were captured across both cohorts using similar adjudication methods. Multivariable-adjusted Fine-Gray models were created to evaluate the associations of body mass index (BMI), waist circumference (WC), and FM with risk of HF in the overall cohort as well as among those with vs. without diabetes at baseline. The population attributable risk of overall obesity (BMI≥30 kg/m 2 ), abdominal obesity (WC>88 and 102 cm in women and men, respectively), and high FM (above sex-specific median) for incident HF was evaluated among participants with and without diabetes. Results: The study included 10,387 participants (52.9% ARIC; 25.1% diabetes; median age: 74 years). The correlation between predicted and bioelectrical impedance-based FM was high (R 2 =0.90; n=5,038). Over a 5-year follow-up, 447 participants developed HF (4.3%). Higher levels of each adiposity measure were significantly associated with higher HF risk (HR [95% CI] per 1-SD higher BMI=1.19[1.09-1.31], WC=1.27[1.14-1.41]; FM=1.17[1.06-1.29]). A significant interaction was noted between diabetes status and measures of BMI (p-interaction=0.04) and WC (p-interaction=0.004) for the risk of HF. In stratified analysis, higher measures of each adiposity parameter were significantly associated with higher HF risk in individuals with diabetes (HR[95% CI] per 1-SD higher BMI=1.29[1.14-1.47], WC=1.48[1.29-1.70]; FM=1.25[1.09-1.43]) but not those without diabetes, including participants with prediabetes and euglycemia. The population attributable risk percentage of overall obesity, abdominal obesity, and high FM for incident HF was higher among participants with diabetes (12.8%, 29.9%, 13.7%, respectively) vs. those without diabetes (≤1% for each). Conclusions: Higher BMI, WC, and FM are strongly associated with greater risk of HF among older adults, particularly among those with prevalent diabetes.