Biomarker BMP10 profiles suggest an association of female and age with atrial endomysial fibrosis: Results from the ISOLATION AF ablation registry

Abstract

Abstract Background/Introduction Atrial fibrillation has a complex pathophysiology such as inflammation, myocyte injury, collagen and lipid infiltration. Different biomarkers reflect these pathophysiological pathways. The biomarker Bone Morphogenetic Protein 10 (BMP10) is a secreted protein, expressed by myocytes, and is required for myocyte growth and development. BMP10 is associated with PITX2 and endomysial fibrosis. We recently demonstrated that BMP10 is independently associated with left atrial andomysial fibrosis. Purpose To analyze the correlation between the blood-based biomarker BMP10 with sex and age in patients with atrial fibrillation. Methods A cross-sectional analysis was conducted of atrial fibrillation patients scheduled for catheter ablation included from July 2020 through May 2022 in the prospective multicenter ISOLATION cohort study (NCT04342312). Clinical characteristics and routine tests were collected before ablation. Blood samples were taken before ablation and were analyzed for BMP10 among other known and novel cardiovascular biomarkers. We investigated the correlation between BMP10 and age in a univariate analysis and in a multivariate analysis including differences in clinical traits. In addition, we investigated the difference in BMP10 levels between males and females. Results Blood samples from 509 patients were analyzed. Their mean age was 64±9 years, and 31.2% were female. 352 patients (69.2%) had paroxysmal AF and 152 patients (29.9%) had persistent AF. Heart failure was reported in 77 patients (15%). 357 (70%) patients were in sinus rhythm at the time the blood was drawn (table 1). Univariate analysis showed that BMP10 levels increased with age (figure 1). After adjusting for sex, type of AF, heart failure and rhythm at blood drawing, BMP10 remained higher in older patients (Beta coefficient 0.77, standard error 0.14, p-value <0.001). In addition, univariate analysis showed that BMP10 was significantly higher in women than in men (2.16 ng/L versus 1.95 ng/l, P< 0.001). After adjusting for age, BMP10 remained higher in women than in men. Conclusion Elevated BMP10 levels suggest that in older patients possibly more atrial fibrosis is present and thus more substrate for AF. In addition, the different biomarker profile suggests that AF in women may more often be associated with atrial fibroses than in men.