Lowe G, Rumley A, Norrie J, Ford I, Shepherd J, Cobbe S, Macfarlane P, Packard C
Department of Medicine, University of Glasgow, UK.
Thromb Haemost. 2000 Oct;84(4):553-8.
The West of Scotland Coronary Prevention Study (WOSCOPS) showed that pravastatin reduced the risk of coronary heart disease (CHD) events in 6,595 middle-aged hypercholesterolaemic men aged 45-64 years without prior myocardial infarction followed for an average of 4.9 years. We hypothesised prospectively (a) that baseline levels of haemorheological variables were related to baseline and incident CHD and to mortality; and (b) that reduction in lipoproteins by pravastatin would lower plasma and blood viscosity, a potential contributory mechanism to CHD events. We therefore studied plasma and blood viscosity, fibrinogen, haematocrit, and blood cell counts at baseline and 1 year. At baseline, plasma and blood viscosity were related to risk factors, CHD measures, and claudication. On univariate analysis, baseline levels of all rheological variables (except platelet count) were related to incident CHD; CHD mortality; and total mortality. On multivariate analysis including baseline CHD and risk factors, plasma and blood viscosity, haematocrit and white cell count each remained significantly associated with incident CHD; while fibrinogen remained an independent predictor of mortality (all p < 0.03). After one year, lipoprotein reduction by pravastatin was associated with significant reductions (about one quarter of a standard deviation) in plasma viscosity (mean difference 0.02 mPa.s, p <0.001) and in blood viscosity (mean difference 0.06 mPa.s, p<0.001), but was not associated with significant changes in other rheological variables. We therefore suggest that pravastatin therapy, which reduces elevated lipoproteins in hypercholesterolaemic men, may lower risks of CHD and mortality partly by lowering plasma and blood viscosity. Further studies are required to test this hypothesis.
苏格兰西部冠心病预防研究(WOSCOPS)表明,普伐他汀降低了6595名年龄在45 - 64岁、无心肌梗死病史的中年高胆固醇血症男性患冠心病(CHD)事件的风险,这些男性平均随访了4.9年。我们前瞻性地假设:(a)血液流变学变量的基线水平与基线及新发冠心病和死亡率相关;(b)普伐他汀降低脂蛋白水平会降低血浆和血液粘度,这是冠心病事件的一个潜在促成机制。因此,我们在基线和1年时研究了血浆和血液粘度、纤维蛋白原、血细胞比容和血细胞计数。在基线时,血浆和血液粘度与危险因素、冠心病指标和跛行相关。单因素分析显示,所有流变学变量(血小板计数除外)的基线水平均与新发冠心病、冠心病死亡率和总死亡率相关。多因素分析纳入基线冠心病和危险因素后,血浆和血液粘度、血细胞比容和白细胞计数各自仍与新发冠心病显著相关;而纤维蛋白原仍是死亡率的独立预测因素(所有p<0.03)。1年后,普伐他汀降低脂蛋白水平与血浆粘度显著降低(平均差异0.02 mPa.s,p<0.001)和血液粘度显著降低(平均差异0.06 mPa.s,p<0.001)相关,但与其他流变学变量的显著变化无关。因此,我们认为,普伐他汀治疗可降低高胆固醇血症男性升高的脂蛋白水平,可能部分通过降低血浆和血液粘度来降低冠心病和死亡风险。需要进一步研究来验证这一假设。