BACKGROUND. 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.

    METHODS. 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.

    RESULTS. 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.

    CONCLUSIONS. 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.

    背景：患冠心病和血脂水平异常的患者，常有内皮血管舒张功能失调，这可引起缺血性心肌疾病。降胆固醇或抗氧化治疗可否恢复依赖内皮的冠状血管舒张是未知的。

    方法：49例高胆固醇血症患者随机分为三组：
        美国心脏协会标准饮食组（饮食组，11例）
        洛伐他汀和消胆胺组（降低LDL组，21例）
        洛伐他汀和普罗布考组（降低LDL+抗氧化组，17例）
    治疗一年后，冠状动脉内注射乙酰胆碱（10-8~10-6 M），测定冠状动脉舒缩性在基线上的变化。

    结果：治疗后胆固醇：
        降低LDL+抗氧化组          降低  41±22%；
        降低LDL组                 降低  38±20%
        与标准饮食组比 P<0.001
        冠状动脉直径在基线上最大收缩 
                                                                                                                                        

       组 别                   用乙酰胆碱时      随访时                      P 
                                                                                                                        

降低LDL+抗氧化组         19%                 2%           <0.01, 与饮食组比
   降低LDL组                    15%                 6%           =0.08, 与饮食组比
   饮食组                            14%                 19%
                                                                                                                        

    结论：普罗布考可明显改善冠状动脉的舒缩性，对改善心肌缺血和减少冠脉病事件有重要意义。

    讨论：(1) 用乙酰胆碱时和随访时的冠状动脉收缩值之差是乙酰胆碱血管收缩作用过后的血管舒张值，降低LDL组的血管舒缩与饮食组比无显著性差异，因此，降低LDL+抗氧化组的明显改善血管舒缩作用主要是由抗氧化作用即普罗布考的作用引起，也说明普罗布考可明显抗动脉粥样硬化。
    (2) 降低LDL组与降低LDL+抗氧化组均使用了洛伐他汀，所不同的是前者又使用了消胆胺，后者又使用了普罗布考，两组洛伐他汀的影响应是一样的，治疗效果的差异主要应是消胆胺与普罗布考的差异，即普罗布考有明显改善冠状动脉舒缩性作用，而消胆胺则没有。
    (3) 氧化LDL较天然LDL更易损伤内皮功能并引起动脉粥样硬化，普罗布考结合入脂蛋白内，阻止脂蛋白的氧化，从而保护了内皮功能，抗动脉粥样硬化。
    (4) 氧游离基使NO形成过氧化氮而灭活NO的内皮功能保护作用，普罗布考能清除氧游离基，从而起到保护内皮功能作用。