Diurnal Variation in Endothelium-Dependent Vasodilatation Is Not Apparent in Coronary Artery Disease

Abstract

Background —Acute coronary syndromes present with an increased incidence from 6:00 am to 12:00 noon. Whether endothelial function follows a diurnal rhythm and whether this rhythm is impaired in coronary artery disease (CAD) has not previously been studied. Methods and Results —Diurnal variation in endothelium-dependent vasodilatation was examined in 10 CAD patients and 10 control subjects. Forearm blood flow responses to acetylcholine, sodium nitroprusside, and N G -monomethyl- l -arginine were determined by plethysmography at 8:00 am , 2:00 pm , and 8:00 pm . Heart rate, blood pressure, plasma cortisol, and inflammatory markers were also determined. Heart rate and the low-frequency component of heart rate variability were greatest in the morning in control subjects, suggesting a diurnal variation in sympathetic activity. Basal forearm blood flows were significantly reduced in control subjects at 8:00 pm compared with 8:00 am and 2:00 pm (1.2±0.2 versus 2.1±0.2 [8:00 am ] and 2.1±0.3 [2:00 pm ] mL · 100 mL −1 · min −1 ; P <0.05) but unchanged in the CAD group. Acetylcholine (37 μg/min) responses were greater at 8:00 am than at 8:00 pm in control subjects (12.5±3.7 versus 19.6±2.9 mL · 100 mL −1 · min −1 , respectively; P <0.05), but these responses were not time dependent in the CAD group. Responses to sodium nitroprusside were similar at all time points and between those with and without CAD. Conclusions —Thus, normal volunteers have a diurnal variation in their endothelium-dependent vasodilatation that may counteract other, potentially adverse, diurnal variations in hemodynamic and other parameters. In contrast, CAD patients who had presented with acute coronary syndromes showed a loss of this protective mechanism.