BENEFICIAL-EFFECTS OF CHOLESTEROL-LOWERING THERAPY ON THE CORONARY ENDOTHELIUM IN PATIENTS WITH CORONARY-ARTERY DISEASE
BENEFICIAL-EFFECTS OF CHOLESTEROL-LOWERING THERAPY ON THE CORONARY ENDOTHELIUM IN PATIENTS WITH CORONARY-ARTERY DISEASE
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DOI：
10.1056/nejm199502233320801
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发表时间：
1995-02-23
影响因子：
158.5
通讯作者：
ALEXANDER, RW
中科院分区：
文献类型：
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作者：
TREASURE, CB;KLEIN, JL;ALEXANDER, RW
背景。内皮介导的舒张受损会导致冠状动脉疾病患者的血管痉挛和心肌缺血。我们假设使用 3-羟基-3-甲基戊二酰辅酶 A 还原酶抑制剂洛伐他汀进行降胆固醇治疗可以改善冠状动脉粥样硬化患者的内皮介导的反应。方法。在一项随机、双盲、安慰剂对照试验中，我们研究了 23 名患者的冠状动脉内皮反应，这些患者被随机分配到洛伐他汀（40 毫克，每天两次；11 名患者）或安慰剂（12 名患者）加降脂饮食（美国心脏协会第 1 步饮食）。患者在随机分组后 12 天进行研究，并在 5% 月份再次进行研究。这些患者的总胆固醇水平为 160 至 300 毫克每分升（4.1 至 7.8 毫摩尔每升），并且正在接受冠状动脉血管成形术。在初始和后续研究中，患者接受连续冠状动脉内输注（在未进行血管成形术的冠状动脉中）乙酰胆碱以评估内皮介导的血管舒张作用。通过定量血管造影分析冠状血管的反应。结果。安慰剂组和洛伐他汀组的患者在平均治疗 12 天时对乙酰胆碱有相似的反应（表示为对 10(-9) M、10(-8) M、10(-7) M 和 10(-6) M 乙酰胆碱剂量的直径变化百分比）。在安慰剂组中，各自的平均 (+/-SE) 变化分别为 1+/-2、0+/-2、-2+/-4 和 -19+/-4%；在洛伐他汀组中，它们分别为-2+/-2、-4+/-4、-12+/-5 和-16+/-7% (P=0.32)。 （冠状动脉收缩以负数反映。）平均 5.5 个月的治疗后，安慰剂组对乙酰胆碱的反应分别为 -3+/-3、-1+/-2、-8+/-4 和 -18+/-5%。洛伐他汀组有显着改善，反应率为 3+/-3、3+/-3、0+/-2 和 0+/-3% (P = 0.004)。结论。洛伐他汀降低胆固醇可显着改善动脉粥样硬化患者冠状动脉内皮介导的反应。冠状动脉张力局部调节的这种改善可能会缓解缺血症状并标志着动脉粥样硬化斑块的稳定。
Background. Impaired endothelium-mediated relaxation contributes to vasospasm and myocardial ischemia in patients with coronary artery disease. We hypothesized that cholesterol-lowering therapy with the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor lovastatin could improve endothelium-mediated responses in patients with coronary atherosclerosis.Methods. In a randomized, double-blind, placebo-controlled trial, we studied coronary endothelial responses in 23 patients randomly assigned to either lovastatin (40 mg twice daily; 11 patients) or placebo (12 patients) plus a lipid-lowering diet (American Heart Association Step 1 diet). Patients were studied 12 days after randomization and again at 5% months. These patients had total cholesterol levels ranging from 160 to 300 mg per deciliter (4.1 to 7.8 mmol per liter) and were undergoing coronary angioplasty. At the initial and follow-up studies, patients received serial intracoronary infusions (in a coronary artery not undergoing angioplasty) of acetylcholine to assess endothelium-mediated vasodilatation. The responses of the coronary vessels were analyzed with quantitative angiography.Results. The patients in the placebo and lovastatin groups had similar responses to acetylcholine at a mean of 12 days of therapy (expressed as the percentage of change in diameter in response to acetylcholine doses of 10(-9) M, 10(-8) M, 10(-7) M, and 10(-6) M). In the placebo group, the respective mean (+/-SE) changes were 1+/-2, 0+/-2, -2+/-4, and -19+/-4 percent; in the lovastatin group, they were -2+/-2, -4+/-4, -12+/-5, and -16+/-7 percent (P=0.32). (Coronary-artery constriction is reflected by negative numbers.) The responses to acetylcholine in the placebo group after a mean of 5.5 months of therapy were -3+/-3, -1+/-2, -8+/-4, and -18+/-5 percent, respectively; there was significant improvement in the lovastatin group, which had responses of 3+/-3, 3+/-3, 0+/-2, and 0+/-3 percent (P = 0.004).Conclusions. Cholesterol lowering with lovastatin significantly improved endothelium-mediated responses in the coronary arteries of patients with atherosclerosis. Such improvement in the local regulation of coronary arterial tone could potentially relieve ischemic symptoms and signal the stabilization of the atherosclerotic plaque.