Anderson T J, Meredith I T, Yeung A C, Frei B, Selwyn A P, Ganz P
Cardiovascular Division, Brigham and Women's Hospital, Boston.
N Engl J Med. 1995 Feb 23;332(8):488-93. doi: 10.1056/NEJM199502233320802.
Patients with coronary artery disease and abnormalities of serum lipids often have endothelial vasodilator dysfunction, which may contribute to ischemic cardiac events. Whether cholesterol-lowering or antioxidant therapy can restore endothelium-dependent coronary vasodilation is unknown.
We randomly assigned 49 patients (mean serum cholesterol level, 209 +/- 33 mg per deciliter [5.40 +/- 0.85 mmol per liter]) to receive one of three treatments: an American Heart Association Step 1 diet (the diet group, 11 patients); lovastatin and cholestyramine (the low-density lipoprotein [LDL]-lowering group, 21 patients); or lovastatin and probucol (the LDL-lowering-antioxidant group, 17 patients). Endothelium-dependent coronary-artery vasomotion in response to an intracoronary infusion of acetylcholine (10(-8) to 10(-6) M) was assessed at base line and after one year of therapy. Vasoconstrictor responses to these doses of acetylcholine are considered to be abnormal.
Treatment resulted in significant reductions in LDL cholesterol levels of 41 +/- 22 percent in the LDL-lowering-antioxidant group and 38 +/- 20 percent in the LDL-lowering group (P < 0.001 vs. the diet group). The maximal changes in coronary-artery diameter with acetylcholine at base line and at follow-up were -19 and -2 percent, respectively, in the LDL-lowering-antioxidant group, -15 and -6 percent in the LDL-lowering group, and -14 and -19 percent in the diet group (P < 0.01 for the LDL-lowering-antioxidant group vs. the diet group; P = 0.08 for the LDL-lowering group vs. the diet group). (The negative numbers indicate vasoconstriction). Thus, the greatest improvement in the vasoconstrictor response was seen in the LDL-lowering-antioxidant group.
The improvement in endothelium-dependent vasomotion with cholesterol-lowering and antioxidant therapy may have important implications for the activity of myocardial ischemia and may explain in part the reduced incidence of adverse coronary events that is known to result from cholesterol-lowering therapy.
冠心病患者及血脂异常患者常存在内皮血管舒张功能障碍，这可能促使缺血性心脏事件的发生。降低胆固醇或抗氧化治疗能否恢复内皮依赖性冠状动脉舒张尚不清楚。
我们将49例患者（平均血清胆固醇水平为209±33mg/dl[5.40±0.85mmol/L]）随机分为三组接受以下治疗之一：美国心脏协会第一步饮食方案（饮食组，11例患者）；洛伐他汀和考来烯胺（降低低密度脂蛋白[LDL]组，21例患者）；或洛伐他汀和普罗布考（降低LDL-抗氧化组，17例患者）。在基线及治疗1年后，评估冠状动脉对冠状动脉内注入乙酰胆碱（10⁻⁸至10⁻⁶M）的内皮依赖性血管运动。对这些剂量乙酰胆碱的血管收缩反应被认为是异常的。
治疗使降低LDL-抗氧化组的LDL胆固醇水平显著降低41±22%，降低LDL组降低38±20%（与饮食组相比，P<0.001）。在降低LDL-抗氧化组中，基线和随访时乙酰胆碱引起的冠状动脉直径最大变化分别为-19%和-2%，降低LDL组为-15%和-6%，饮食组为-14%和-19%（降低LDL-抗氧化组与饮食组相比，P<0.01；降低LDL组与饮食组相比，P=0.08）。（负数表示血管收缩）。因此，在降低LDL-抗氧化组中血管收缩反应改善最大。
降低胆固醇和抗氧化治疗使内皮依赖性血管运动得到改善，这可能对心肌缺血活动具有重要意义，并且可能部分解释了降低胆固醇治疗已知能降低不良冠状动脉事件发生率的原因。
