Obesity, Galectin‐3, and Incident Heart Failure: The ARIC Study

Background Laboratory data suggest obesity is linked to myocardial inflammation and fibrosis, but clinical data are limited. We aimed to examine the association of obesity with galectin‐3, a biomarker of cardiac inflammation and fibrosis, and the related implications for heart failure (HF) risk. Methods and Results We evaluated 8687 participants (mean age 63 years; 21% Black) at ARIC (Atherosclerosis Risk in Communities) Visit 4 (1996–1998) who were free of heart disease. We used adjusted logistic regression to estimate the association of body mass index (BMI) categories with elevated galectin‐3 (≥75th sex‐specific percentile) overall and across demographic subgroups, with tests for interaction. We used Cox proportional hazards models to assess the combined associations of galectin‐3 and BMI with incident HF (through December 31, 2019). Higher BMI was associated with higher odds of elevated galectin‐3 (odds ratio [OR], 2.32; 95% CI, 1.88–2.86) for severe obesity ([BMI ≥35 kg/m2] versus normal weight [BMI 18.5‐<25 kg/m2]). There were stronger associations of BMI with elevated galectin‐3 among women versus men and White versus Black participants (both P‐for‐interaction <0.05). Elevated galectin‐3 was similarly associated with incident HF among people with and without obesity (HR, 1.49; 95% CI, 1.18–1.88; and HR, 1.71; 95% CI, 1.38–2.11, respectively). People with severe obesity and elevated galectin‐3 had >4‐fold higher risk of HF (HR, 4.19; 95% CI, 2.98–5.88) than those with normal weight and galectin‐3 <25th percentile. Conclusions Obesity is strongly associated with elevated galectin‐3. Additionally, the combination of obesity and elevated galectin‐3 is associated with marked HF risk, underscoring the importance of elucidating pathways linking obesity with cardiac inflammation and fibrosis.