Syvänne M, Taskinen M R, Manninen V, Kesäniemi Y A, Pasternack A, Nawrocki J W, Haber H, Frick M H
Lopid Coronary Angiography Trial Investigators, Helsinki, Finland.
Control Clin Trials. 1997 Feb;18(1):93-119. doi: 10.1016/s0197-2456(96)00091-8.
Several clinical trials have shown that reducing serum cholesterol levels retards the progression of coronary atherosclerosis assessed by serial angiography. By contrast, as yet no studies have addressed the impact of increasing high density lipoprotein (HDL) cholesterol levels on progression of coronary artery disease (CAD). As HDL cholesterol is inversely related to the risk of CAD, we hypothesize that an intervention that raises low HDL cholesterol concentrations may have a beneficial effect on the course of CAD. Lopid Coronary Angiography Trial (LOCAT) was designed to test this hypothesis. Three hundred and ninety-five men, aged < or = 70 years, all of whom had previously undergone coronary bypass surgery, were randomly assigned to receive either slow-release gemfibrozil, 1200 mg once daily, or a matching placebo for on average 2 1/2 years. The lipid inclusion criteria were HDL cholesterol concentration < or = 1.1 mmol/L, low density lipoprotein (LDL) cholesterol < or = 4.5 mmol/L, and serum triglyceride < or = 4.0 mmol/L. Subjects were not accepted if they had manifest diabetes, body mass index > 30 kg/m2, uncontrolled hypertension, or if they were regular smokers. All randomized subjects underwent baseline coronary angiography, which will be repeated at the end of the study. The angiograms will be analyzed using the Cardiovascular Measurement System, a validated computer-assisted image-analysis and quantitation package. The primary endpoints are the changes in the per-patient mean of 1) the average diameter of evaluable native coronary segments, and 2) the minimal luminal diameter of evaluable stenoses, and 3) the appearance of new lesions. Extensive lipoprotein and other metabolic studies and analyses of genetic polymorphisms are carried out to study the determinants of CAD progression. At baseline, the study subjects were 59.1 +/- 6.8 (mean +/- standard deviation) years old, had a body mass index 26.4 +/- 2.2 kg/m2, and serum triglyceride, serum cholesterol, HDL cholesterol, and LDL cholesterol concentrations 1.64 +/- 0.64, 5.17 +/- 0.64, 0.82 +/- 0.14, and 3.61 +/- 0.53 mmol/L, respectively.
多项临床试验表明，通过系列血管造影评估，降低血清胆固醇水平可延缓冠状动脉粥样硬化的进展。相比之下，目前尚无研究探讨提高高密度脂蛋白（HDL）胆固醇水平对冠状动脉疾病（CAD）进展的影响。由于HDL胆固醇与CAD风险呈负相关，我们推测提高低HDL胆固醇浓度的干预措施可能对CAD病程产生有益影响。洛匹特冠状动脉造影试验（LOCAT）旨在验证这一假设。395名年龄≤70岁且均曾接受冠状动脉搭桥手术的男性被随机分配，分别接受每日一次1200毫克的缓释吉非贝齐或匹配的安慰剂，平均治疗2.5年。血脂纳入标准为HDL胆固醇浓度≤1.1毫摩尔/升、低密度脂蛋白（LDL）胆固醇≤4.5毫摩尔/升、血清甘油三酯≤4.0毫摩尔/升。若受试者患有显性糖尿病、体重指数>30千克/平方米、高血压未得到控制或为经常吸烟者，则不被纳入。所有随机分组的受试者均接受了基线冠状动脉造影检查，并将在研究结束时重复进行。血管造影将使用心血管测量系统进行分析，该系统是一个经过验证的计算机辅助图像分析和定量软件包。主要终点是以下各项患者平均值的变化：1）可评估的自身冠状动脉节段的平均直径；2）可评估狭窄病变的最小管腔直径；3）新病变的出现。还进行了广泛的脂蛋白及其他代谢研究以及基因多态性分析，以研究CAD进展的决定因素。在基线时，研究对象的年龄为59.1±6.8（均值±标准差）岁，体重指数为26.4±2.2千克/平方米，血清甘油三酯、血清胆固醇、HDL胆固醇和LDL胆固醇浓度分别为1.64±0.64、5.17±0.64、0.82±0.14和3.61±0.53毫摩尔/升。
