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 NG-monomethyl-Larginine 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 (37μg/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.