BACKGROUND: Underlying mechanisms of PR-interval prolongation leading to increased risk of adverse cardiovascular outcomes, including atrial fibrillation, are unclear. This study aims to investigate the relation between PR interval and changes in vascular function. HYPOTHESIS: We hypothesize that there exists an intermediate pathological stage between electrocardiographic PR prolongation and adverse cardiovascular outcomes, which could be reflected by changes in surrogate measurements of vascular function. METHODS: We recruited 88 healthy subjects (mean age 57.5 ± 9.8 y, 46% male) from a community-based health screening program who had no history of cardiovascular disease or diabetes mellitus. PR interval was determined from a resting 12-lead electrocardiogram. Vascular function was noninvasively assessed by flow-mediated dilation (FMD) using high-resolution ultrasound and brachial-ankle pulse wave velocity (PWV) using a vascular profiling system. RESULTS: Only 3 subjects had a PR-interval length longer than the conventional cutoff of 200 ms. The PR-interval length was associated inversely with FMD (Pearson r = -0.30, P = 0.004) and positively with PWV (r = 0.40, P < 0.001). Adjusting for potential confounders, increased PR-interval length by each 25 ms was independently associated with reduced FMD by -1 unit (absolute %, B = -0.04 [95% confidence interval: -0.080 to -0.002, P = 0.040)] and increased PWV by +103 cm/second (B = +4.1 [95% confidence interval: 0.6-7.6, P = 0.023]). CONCLUSIONS: This study shows that PR-interval length, even in the conventionally normal range, is independently associated with endothelial dysfunction and increased arterial stiffness in healthy subjects free of atherosclerotic disease. This suggests the presence of a systemic, intermediate pathologic stage of the vasculature in PR prolongation before clinically manifest cardiovascular events, and could represent a mediating mechanism.
BACKGROUND: Underlying mechanisms of PR-interval prolongation leading to increased risk of adverse cardiovascular outcomes, including atrial fibrillation, are unclear. This study aims to investigate the relation between PR interval and changes in vascular function. HYPOTHESIS: We hypothesize that there exists an intermediate pathological stage between electrocardiographic PR prolongation and adverse cardiovascular outcomes, which could be reflected by changes in surrogate measurements of vascular function. METHODS: We recruited 88 healthy subjects (mean age 57.5 ± 9.8 y, 46% male) from a community-based health screening program who had no history of cardiovascular disease or diabetes mellitus. PR interval was determined from a resting 12-lead electrocardiogram. Vascular function was noninvasively assessed by flow-mediated dilation (FMD) using high-resolution ultrasound and brachial-ankle pulse wave velocity (PWV) using a vascular profiling system. RESULTS: Only 3 subjects had a PR-interval length longer than the conventional cutoff of 200 ms. The PR-interval length was associated inversely with FMD (Pearson r = -0.30, P = 0.004) and positively with PWV (r = 0.40, P < 0.001). Adjusting for potential confounders, increased PR-interval length by each 25 ms was independently associated with reduced FMD by -1 unit (absolute %, B = -0.04 [95% confidence interval: -0.080 to -0.002, P = 0.040)] and increased PWV by +103 cm/second (B = +4.1 [95% confidence interval: 0.6-7.6, P = 0.023]). CONCLUSIONS: This study shows that PR-interval length, even in the conventionally normal range, is independently associated with endothelial dysfunction and increased arterial stiffness in healthy subjects free of atherosclerotic disease. This suggests the presence of a systemic, intermediate pathologic stage of the vasculature in PR prolongation before clinically manifest cardiovascular events, and could represent a mediating mechanism.