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

Abstract

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.

Keywords: bone-vascular axis; calcification; conduction disorders; osteocalcin; osteogenic endothelial progenitor cells; rheumatoid arthritis.