Bone morphogenetic protein 10: clinical correlates and risk of incident atrial fibrillation

Bone morphogenetic protein-10 (BMP10), a protein predominantly secreted by atrial cardiomyocytes, has emerged as a promising biomarker in patients with atrial fibrillation (AF) and as a marker of atrial stress in patients with heart failure. Its clinical correlates in community-dwelling adults and its association with incident AF remain unexplored. BMP10 was measured in 5,883 participants from the Prevention of Renal and Vascular End-stage Disease (PREVEND) community-based cohort (mean age 53.6 yr; 51.5% females). The mean BMP10 concentration was 2.20 ± 0.43 ng/mL. In multivariable linear regression analyses, the strongest positive correlates of BMP10 were female sex [standardized beta-(Sβ): 0.34], high-density lipoprotein cholesterol (HDL-C; Sβ: 0.16), total cholesterol (Sβ: 0.13), and N-terminal pro-B-type natriuretic peptide (NT-proBNP; Sβ: 0.13). The strongest negative correlates were relative fat mass (Sβ: -0.21), C-reactive protein (CRP; Sβ: -0.16), and estimated glomerular filtration rate (eGFR; Sβ: -0.13); P for all < 0.001. BMP10 was not significantly associated with prevalent hypertension, myocardial infarction, stroke, or heart failure. Over a median follow-up of 6.4 years, 154 participants (2.6%) developed incident AF, corresponding to 4.2 cases per 1,000 person years. In a multivariable Cox-regression model, higher BMP10 levels were significantly associated with incident AF (Hazard ratio per 1SD increase: 1.58; 95%CI: 1.23-2.04). In summary, among community-dwelling adults, BMP10 levels are higher in women, positively associated with HDL-C and NT-proBNP, and inversely associated with fat mass, inflammation, and kidney function. Although not linked to prevalent cardiovascular disease, higher BMP10 levels are independently associated with incident AF.NEW & NOTEWORTHY This is the first population-based study of circulating bone morphogenetic protein 10 (BMP10), a heart-specific protein mainly secreted by atrial cardiomyocytes. In over 5,800 community-dwelling adults, BMP10 showed distinct physiological and pathophysiological correlates, including higher levels in women, an inverse association with fat mass and inflammation (CRP), and a positive association with incident atrial fibrillation. These findings represent an important first step toward understanding the role of BMP10 in atrial biology and disease.