Abstract 10769: Osteoprotegerin and Incident Heart Failure: The Atherosclerosis Risk in Communities Study

Abstract

Background: Osteoprotegerin (OPG), a protein involved in bone metabolism, is associated with cardiac fibrosis and remodeling in animal models. Circulating OPG levels correlate with left ventricular mass index and plasma brain natriuretic peptide levels in humans, but the association with incident heart failure (HF) is not known. Methods: Among 10,261 participants in the community-based Atherosclerosis Risk in Communities (ARIC) Study free of prevalent HF at study Visit 3, we investigated the association of plasma OPG levels at Visit 3 with incident HF hospitalization post-Visit 3 using multivariable Cox proportional hazard models. OPG was measured using a high-throughput DNA aptamer-based proteomic platform (Somalogic, Boulder, CO), and relative fluorescence unit values were log2 transformed. All models adjusted for age, sex, race, study field center, body mass index, hypertension, diabetes, estimated glomerular filtration rate, smoking status, prevalent coronary artery disease, and atrial fibrillation. Results: Mean age was 60±6 years, 54% were women, and 20% of participants were Black. Higher OPG levels were associated with older age, female gender, Black race, and higher prevalence of hypertension, diabetes, and smoking (all p <0.001). Over a median of 15.0 years follow-up (interquartile range: 13-15), there were 1301 incident HF hospitalizations. In multivariable models, higher serum OPG levels were associated with greater risk of incident HF (hazard ratio per 1 SD increase: 1.20 [95% confidence interval, 1.13-1.27]; Figure). This association persisted after further adjustment for NT-proBNP (HR 1.19 [95% CI 1.12-1.26], p<.001). Conclusion: In this large community-based cohort, higher plasma OPG levels were significantly associated with incident HF hospitalization, independent of traditional cardiovascular risk factors and NT-proBNP. Further studies are warranted to clarify whether OPG could be a new therapeutic target for HF prevention.