Abstract Body: Background: Osteoprotegerin (OPG), a protein involved in bone metabolism, is associated with left ventricular remodeling and fibrosis. Circulating OPG levels correlate with left ventricular mass index and plasma brain natriuretic peptide levels in humans. The association with incident heart failure (HF) has not been elucidated.
Methods: Among 7581 participants in the Framingham Heart Study Third Generation (Gen 3, Visit 1) and Offspring (OS, Visit 7) cohorts, we investigated the association of plasma OPG levels with incident HF using multivariable Cox proportional hazard models. Heart failure was defined based on FHS criteria and carefully adjudicated. OPG was measured with a commercially available quantitative ELISA kit. The primary model was adjusted for age, sex, body mass index, systolic blood pressure, anti-hypertensive medication use, diabetes, current smoking status, and estimated glomerular filtration rate (eGFR). In the secondary model, we additionally added prevalent and incident coronary heart disease (CHD).
Results: Overall, mean age was 50±14 years, 54% were women, and all participants were White. Higher OPG levels were observed in association with older age, female sex, higher systolic blood pressure, diabetes, smoking and lower eGFR (all p <0.05). Over a median of 16 years follow-up (25^th-75^th %ile:14-18), there were 345 incident HF. In multivariable models, higher serum OPG levels were associated with greater risk of incident HF (hazard ratio per 1 SD increase: 1.29 [95% confidence interval (CI), 1.18–1.40]; Figure). This association remained significant after further adjustment for prevalent and incident CHD as a time dependent variable (HR 1.28 [95% CI 1.18-1.39]).
Conclusion: In this large community-based cohort, higher plasma OPG levels were significantly associated with incident HF, adjusting for traditional cardiovascular risk factors and incident coronary heart disease. Further studies are warranted to clarify whether OPG could be a new therapeutic target for HF prevention.