Osteogenic circulating endothelial progenitor cells are linked to electrocardiographic conduction abnormalities in rheumatic patients

• Published in: Annals of noninvasive electrocardiology 2019-09, Vol.24 (5), p.e12651-n/a
• Main Authors: Chan, Yap‐Hang, Ngai, Michael Cheong, Chen, Yan, Wu, Mei‐Zhen, Yu, Yu‐Juan, Zhen, Zhe, Lai, Kevin, Cheung, Tommy, Ho, Lai‐Ming, Chung, Ho‐Yin, Lau, Chak‐Sing, Lau, Chu‐Pak, Tse, Hung‐Fat, Yiu, Kai‐Hang
• Format: Article
• Language: English
• Subjects: Abnormalities; Aged; Arthritis; Arthritis, Rheumatoid - complications; Biomedical materials; Bone turnover; bone–vascular axis; Calcification; Cardiac Conduction System Disease - diagnosis; Cardiac Conduction System Disease - etiology; Cardiovascular system; CD34 antigen; Cells (biology); Conduction; conduction disorders; Degeneration; Disorders; Electrocardiography; Endothelial Progenitor Cells - pathology; Female; Fibrillation; Flow Cytometry; Heart; Humans; Male; Metabolism; Middle Aged; Original; Osteocalcin; Osteocalcin - metabolism; osteogenic endothelial progenitor cells; Osteoprogenitor cells; Patients; Progenitor cells; Rheumatoid arthritis
• ISSN: 1082-720X; 1542-474X
• DOI: 10.1111/anec.12651

Background Osteogenic circulating endothelial progenitor cells (EPC) play a pathogenic role in cardiovascular system degeneration through promulgating vasculature calcification, but its role in conduction disorders as part of the cardiovascular degenerative continuum remained unknown. Aim To investigate the role of osteocalcin (OCN)‐expressing circulating EPCs in cardiac conduction disorders in the unique clinical sample of rheumatoid arthritis (RA) susceptible to both abnormal bone metabolism and cardiac conduction disorders. Methods We performed flow cytometry studies in 134 consecutive asymptomatic patients with rheumatoid arthritis to derive osteogenic circulating OCN‐positive (OCN+) CD34+KDR+ vs. CD34+CD133+KDR+ conventional EPC. Study endpoint was the prespecified combined endpoint of electrocardiographic conduction abnormalities. Results Total prevalence of cardiac conduction abnormality was 9% (n = 12). All patients except one had normal sinus rhythm. One patient had atrial fibrillation. No patient had advanced atrioventricular (AV) block. Prevalence of first‐degree heart block (>200 ms), widened QRS duration (>120 ms) and right bundle branch block were 6.7%, 2.1%, and 2.2% respectively. Circulating osteogenic OCN+CD34+KDR+ EPCs were significantly higher among patients with cardiac conduction abnormalities (p = 0.039). Elevated OCN+CD34+KDR+ EPCs> 75th percentile was associated with higher prevalence of cardiac conduction abnormalities (58.3% vs. 20.02%, p = 0.003). Adjusted for potential confounders, elevated OCN+CD34+KDR+ EPCs> 75th percentile remained independently associated with increased risk of cardiac conduction abnormalities (OR = 4.4 [95%CI 1.2–16.4], p = 0.028). No significant relation was found between conventional EPCs CD34+CD133+KDR+ and conduction abnormalities (p = 0.36). Conclusions Elevated osteogenic OCN+CD34+KDR+ EPCs are independently associated with the presence of electrocardiographic conduction abnormalities in patients with rheumatoid arthritis, unveiling a potential novel pathophysiological mechanism.