Prolongation of PR interval is associated with endothelial dysfunction and activation of vascular repair in high-risk cardiovascular patients

Abstract

Epidemiological studies showed that PR prolongation is associated with increased risk of adverse cardiovascular outcomes. We investigated the relations of PR interval with indices of vascular function and endothelial repair as the underlying mechanisms. The study comprised 348 high-risk patients with prior coronary artery disease, ischemic stroke, and/or diabetes mellitus recruited from medical outpatient clinics and 150 healthy subjects without such a history. PR interval was considered prolonged if >200ms, as determined from resting 12-lead electrocardiogram. Vascular function was assessed by brachial flow-meditated dilatation (FMD) using high-resolution ultrasound. Circulating CD133(+)/KDR(+) endothelial progenitor cell (EPC) levels were measured by flow cytometry. Among healthy subjects, PR interval was inversely associated with FMD (R = -0.20, P = 0.015), but not with the level of circulating CD133(+)/KDR(+) EPC (R = 0.05, P = 0.58). Among high-risk cardiovascular patients, PR prolongation >200ms was more common compared with healthy subjects (45/348 (13%) versus 4/150 (3%), P < 0.001). PR interval was associated inversely with FMD (R = -0.14, P = 0.01) and positively with circulating CD133(+)/KDR(+) EPC level (R = +0.14, P = 0.009). Circulating CD133(+)/KDR(+) EPC level was significantly increased in patients with PR prolongation >200ms (0.87 ± 0.37 versus 0.68 ± 0.42 (log, ×10(-3)/ml), P = 0.005). Adjusted for potential confounders, increased PR interval remained independently associated with increased CD133(+)/KDR(+) EPC by +0.002 (95% confidence interval (CI) 0.000 to 0.004 (log, ×10(-3)/ml), P = 0.011) and depressed FMD (B = -0.014%, 95% CI -0.027 to -0.002, P = 0.026). PR prolongation is associated with endothelial dysfunction and evidence of endothelial repair activation in patients with high cardiovascular risk.