Zeiher A M, Schächinger V, Minners J
Department of Internal Medicine IV, Johann Wolfgang Goethe-University, Frankfurt, Germany.
Circulation. 1995 Sep 1;92(5):1094-100. doi: 10.1161/01.cir.92.5.1094.
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.
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 non-smokers (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.
Long-term cigarette smoking is associated with impaired endothelium-dependent coronary vasodilation regardless of the presence or absence of coronary atherosclerotic lesions.
吸烟是冠状动脉疾病和外周血管疾病的主要危险因素。由于内皮是动脉粥样硬化发病机制早期危险因素作用的主要靶点，我们研究了长期吸烟是否与心外膜传导血管内皮依赖性血管舒张功能受损相关，而不考虑是否存在动脉粥样硬化病变。
我们使用定量冠状动脉造影术，在96例患者中测量了基线时的心外膜动脉直径、在冠状动脉血流最大增加导致血流介导的舒张（严格依赖内皮）后以及冠状动脉内注射硝酸甘油（一种不依赖内皮的舒张剂）后的直径。与不吸烟者（n = 50）相比，吸烟者（n = 46）的内皮依赖性血流介导的舒张明显减弱（P <.0001）。吸烟者（0.34 ± 0.32）与不吸烟者（0.59 ± 0.23）相比，血流依赖性舒张与硝酸甘油诱导的舒张的比值显著降低（P <.001），表明吸烟者对血流增加的舒张反应减弱与对硝酸甘油的舒张反应轻度受损不成比例。在存在血管造影可见的动脉粥样硬化的情况下，吸烟者基本不存在血流依赖性舒张（3.0 ± 6.5%）。多变量分析显示，血管造影显示的管腔不规则（P <.0001）和吸烟（P <.001）是与心外膜动脉血流依赖性舒张反应降低独立相关的唯一变量。冠状动脉内超声显示，血流依赖性舒张随着动脉粥样硬化斑块负荷的增加而逐渐降低（r = -.82，P <.0001；n = 24）。然而，在整个管壁增厚范围内，与不吸烟者相比，吸烟者的节段血流依赖性舒张反应明显受损（P <.01）。
无论是否存在冠状动脉粥样硬化病变，长期吸烟都与内皮依赖性冠状动脉舒张功能受损相关。
