Dangas G, Smith D A, Unger A H, Shao J H, Meraj P, Fier C, Cohen A M, Fallon J T, Badimon J J, Ambrose J A
Cardiovascular Institute, Mount Sinai Medical Center, Cardiovascular Research Foundation, New York, NY 10022, USA.
Thromb Haemost. 2000 May;83(5):688-92.
Lipid-lowering with statins reduces blood thrombogenicity. However, it is unknown whether this is purely due to LDL-cholesterol reduction, or it is related to a statin or agent specific effect. We investigated the relationship between reduction in blood thrombogenicity and the magnitude of low-density lipoprotein cholesterol (LDL-C) during pravastatin therapy. We prospectively followed for 6 months 57 hyperlipidemic patients who initiated therapy with pravastatin, and 36 patients who were randomized into placebo plus diet. Pravastatin-treated patients were grouped according to the LDL-C reduction at 6 months; (i) "adequate LDL-C reduction": LDL-C reduction >30% from baseline or LDL-C<125 mg/dl (n = 38; LDL-C reduction 74 +/- 4 mg/dl; 6-month LDL-C 119 +/- 5 mg/dl); (ii) "inadequate LDL-C reduction": neither of the above criteria (n = 19; LDL-C reduction 31 +/- 5 mg/dl; 6-month LDL-C 158 +/- 6 mg/dl). Placebo patients were divided into those "with LDL-C reduction" (n = 17, mean reduction 21 +/- 5 mg/dl) and those "without LDL reduction" (n = 19). The following parameters were altered at 6 months in both patients with "adequate" and "inadequate" LDL-C reduction: (1) tissue plasminogen activator decreased by 1.4 +/- 0.4 and 1.5 +/- 0.5 ng/ml respectively (p = NS); (2) plasminogen activator inhibitor-1 decreased by 8.7 +/- 2.0 and 10.1 +/- 2.7 ng/ml respectively (p = NS); (3) thrombus formation under dynamic flow conditions decreased by 3.5 +/- 0.9 and 2.8 +/- 1.2 microm2 x 10(3) respectively (p = NS). In contrast, no significant changes from baseline were noted in placebo-treated patients, regardless of their LDL-C reduction category, and multivariate analysis eliminated LDL-C reduction as an independent predictor of reduction in thrombogenicity. Therefore, the reduction in thrombogenicity was not proportional to the magnitude of LDL-C reduction suggesting that a class or agent specific property is primarily responsible for the pro-fibrinolytic/antithrombotic effects observed.
他汀类药物降低血脂可减少血液的血栓形成性。然而，尚不清楚这纯粹是由于低密度脂蛋白胆固醇（LDL-C）降低所致，还是与他汀类药物或药物的特定效应有关。我们研究了普伐他汀治疗期间血液血栓形成性降低与低密度脂蛋白胆固醇（LDL-C）降低幅度之间的关系。我们前瞻性地随访了57例开始使用普伐他汀治疗的高脂血症患者以及36例随机接受安慰剂加饮食治疗的患者，为期6个月。接受普伐他汀治疗的患者根据6个月时LDL-C的降低情况分组：（i）“LDL-C充分降低”：LDL-C较基线降低>30%或LDL-C<125mg/dl（n = 38；LDL-C降低74±4mg/dl；6个月时LDL-C为119±5mg/dl）；（ii）“LDL-C降低不足”：不符合上述任何标准（n = 19；LDL-C降低31±5mg/dl；6个月时LDL-C为158±6mg/dl）。安慰剂组患者分为“LDL-C降低”组（n = 17，平均降低21±5mg/dl）和“LDL-C未降低”组（n = 19）。在“LDL-C充分降低”和“LDL-C降低不足”的患者中，6个月时以下参数均发生了改变：（1）组织纤溶酶原激活物分别降低1.4±0.4和1.5±0.5ng/ml（p =无显著性差异）；（2）纤溶酶原激活物抑制剂-1分别降低8.7±2.0和10.1±2.7ng/ml（p =无显著性差异）；（3）动态血流条件下的血栓形成分别减少3.5±0.9和2.8±1.2μm2×10(3)（p =无显著性差异）。相比之下，无论LDL-C降低类别如何，安慰剂治疗患者与基线相比均未观察到显著变化，多变量分析排除了LDL-C降低作为血栓形成性降低的独立预测因素。因此，血栓形成性的降低与LDL-C降低幅度不成比例，这表明某类药物或药物的特定特性是观察到的促纤溶/抗血栓作用的主要原因。
