Tyroler H A
Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill 27514.
Am J Prev Med. 1985 Jul-Aug;1(4):18-24.
Despite compelling evidence that elevated plasma total and low-density lipoprotein cholesterol plays a causal role in ischemic heart disease (IHD) (evidence derived from molecular biologic, genetic, animal experimental, and human observational studies), the results of individual clinical trials testing the lipid hypothesis have not been regarded as conclusive. Analyzed in aggregate, however, the trials results indicate a dose-response relationship between amount of cholesterol lowering and reduction of ischemic heart disease risk. This summary analysis predicted the quantitative measure of efficacy in the recently completed Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT). There was a quantitatively similar relationship between the amount of IHD risk reduction associated with amount of total plasma cholesterol reduction within the active drug (cholestyramine) treated group. Further, the risk function relating baseline level of total plasma cholesterol to ischemic heart disease incidence in community-based studies such as Framingham was so similar to the risk function of the LRC-CPPT placebo group that it accurately predicted the ischemic heart disease events in the trial. These findings in aggregate provide strong confirmation of the lipid hypothesis, indicate that lowering total plasma cholesterol in middle-aged hypercholesterolemic men will reduce ischemic heart disease risk, and suggest that some extrapolation of the results to lower levels of plasma cholesterol is appropriate. However, aggregate evidence that supports the lipid hypothesis should be distinguished from that required for intervention and treatment programs. Instituting the latter requires the review and evaluation of the evidence relating cholesterol levels and cholesterol reduction not only to ischemic heart disease, but also to other outcomes.(ABSTRACT TRUNCATED AT 250 WORDS)
尽管有确凿证据表明，血浆总胆固醇和低密度脂蛋白胆固醇升高在缺血性心脏病（IHD）中起因果作用（证据来源于分子生物学、遗传学、动物实验和人体观察研究），但检验脂质假说的个体临床试验结果并未被视为定论。然而，综合分析这些试验结果表明，胆固醇降低量与缺血性心脏病风险降低之间存在剂量反应关系。这一汇总分析预测了最近完成的脂质研究临床中心冠心病一级预防试验（LRC-CPPT）中的疗效定量指标。在活性药物（消胆胺）治疗组中，与血浆总胆固醇降低量相关的缺血性心脏病风险降低量之间存在定量相似的关系。此外，在像弗明汉姆这样的社区研究中，将血浆总胆固醇基线水平与缺血性心脏病发病率相关联的风险函数，与LRC-CPPT安慰剂组的风险函数非常相似，以至于它准确地预测了该试验中的缺血性心脏病事件。这些总体发现有力地证实了脂质假说，表明降低中年高胆固醇血症男性的血浆总胆固醇将降低缺血性心脏病风险，并表明将结果外推至较低血浆胆固醇水平是合适的。然而，支持脂质假说的总体证据应与干预和治疗方案所需的证据区分开来。制定后者需要审查和评估不仅将胆固醇水平及胆固醇降低与缺血性心脏病相关，而且与其他结果相关的证据。（摘要截短于250字）
