Long-term Cigarette Smoking Impairs Endothelium-Dependent Coronary Arterial Vasodilator Function

Abstract

Background Smoking is a primary risk factor for coronary and peripheral vascular disease. Because the endothelium is a principal target for the effects of risk factors early in the pathogenesis of atherosclerosis, we investigated whether long-term smoking is associated with impaired endothelial vasodilator function of epicardial conductance vessels regardless of the presence or absence of atherosclerotic lesions. Methods and Results Using quantitative coronary angiography, we measured epicardial artery diameter at baseline, after maximal increases in coronary blood flow that caused flow-mediated dilation (which is strictly endothelium dependent), and after intracoronary injection of nitroglycerin (an endothelium-independent dilator) in 96 patients. Endothelium-dependent, flow-mediated dilation was significantly ( P <.0001) blunted in smokers (n=46) compared with nonsmokers (n=50). The ratio of flow-dependent dilation to nitroglycerin-induced dilation was significantly ( P <.001) lower in smokers (0.34±0.32) compared with nonsmokers (0.59±0.23), indicating that the blunted dilator response to increased blood flow was out of proportion to the mildly impaired dilator response to nitroglycerin in smokers. In the presence of angiographically visible atherosclerosis, flow-dependent dilation was essentially absent (3.0±6.5%) in smokers. Multivariate analysis revealed that luminal irregularities by angiography ( P <.0001) and smoking ( P <.001) were the only variables to be independently associated with a reduced flow-dependent dilator response of epicardial arteries. Intracoronary ultrasound demonstrated that flow-dependent dilation progressively decreased with increasing atherosclerotic plaque load ( r =−.82, P <.0001; n=24). However, over the entire range of wall thickening, segments from smokers exhibited a significantly ( P <.01) impaired flow-dependent dilator response compared with those of nonsmokers. Conclusions Long-term cigarette smoking is associated with impaired endothelium-dependent coronary vasodilation regardless of the presence or absence of coronary atherosclerotic lesions.