Impaired coronary blood flow response to acetylcholine in patients with coronary risk factors and proximal atherosclerotic lesions.

Abstract

We examined whether coronary risk factors and atherosclerotic lesions in the study artery were associated with impaired endothelium-dependent dilation of coronary resistance arteries. Acetylcholine (ACH) at graded doses (1, 3, 10 and 30 micrograms/min) and papaverine (10 mg) were selectively infused into the left anterior descending coronary artery of 28 patients, in whom the study artery was angiographically normal (n = 16) or with mild stenosis < or = 40% (n = 12). Coronary blood flow (CBF) was estimated from the product of mean CBF velocity measured by an intracoronary Doppler catheter and the arterial cross-sectional area of the study artery determined by quantitative arteriography. ACH increased CBF in a dose-dependent manner. However, the maximum CBF response to ACH varied widely among patients (from 50% to 660%). By multivariate analysis, the presence of atherosclerotic lesions in the study artery was an independent predictor for impaired CBF response to ACH (P < 0.01). Hypertension (P < 0.001), hypercholesterolemia (r = -0.52, P < 0.005), age > or = 50 yr (P < 0.01) and total number of coronary risk factors (r = -0.62, P < 0.001) were associated with the impaired increase in CBF with ACH by univariate analysis. The percent increase in CBF evoked with papaverine did not correlate with these risk factors. The results suggest that mild atherosclerotic lesions in the study artery and coronary risk factors are accompanied by impaired endothelium-dependent dilation of coronary resistance arteries evoked with ACH. Endothelial dysfunction of coronary resistance arteries may result in altered regulation of myocardial perfusion in patients with mild coronary atherosclerosis and coronary risk factors.