Coronary Heart Disease Cholesteryl Ester Transfer Protein and Mortality in Patients Undergoing Coronary Angiography Background—The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is still open to debate. In the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial, inhibition of CETP in patients with high cardiovascular risk was associated with increased high-density lipoprotein levels but increased risk of cardiovascular morbidity and mortality. In this report, we present a prospective observational study of patients referred to coronary angiography in which CETP was examined in relation to morbidity and mortality. Methods and Results— CETP concentration was determined in 3256 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study who were referred to coronary angiography at baseline between 1997 and 2000. Median follow-up time was 7.75 years. Primary and secondary end points were cardiovascular and all-cause mortality, respectively. CETP levels were higher in women and lower in smokers, in diabetic patients, and in patients with unstable coronary artery disease, respectively. In addition, CETP levels were correlated negatively with high-sensitivity C-reactive protein and interleukin-6. After adjustment for age, sex, medication, coronary artery disease status, cardiovascular risk factors, and diabetes mellitus, the hazard ratio for death in the lowest CETP quartile was 1.33 (1.07 to 1.65; P=0.011) compared with patients in the highest CETP quartile. Corresponding hazard ratios for death in the second and third CETP quartiles were 1.17 (0.92 to 1.48; P=0.19) and 1.10 (0.86 to 1.39; P=0.46), respectively. Conclusions— We interpret our data to suggest that low endogenous CETP plasma levels per se are associated with increased cardiovascular and all-cause mortality, challenging the rationale of pharmacological CETP inhibition. 胆固醇酯转运蛋白和冠状动脉造影患者的死亡率 背景：胆固醇酯转运蛋白（CETP）在动脉粥样硬化发展中的作用仍值得商榷。控制血脂水平以理解其在动脉粥样硬化事件中的影响的试验（ILLUMINATE）研究中，抑制心血管疾病高风险患者的CETP，伴随高密度脂蛋白水平的升高，但心血管发病率和死亡率的风险增加。在这份报告中，我们展示一项前瞻性观察研究，进行冠状动脉造影的患者，我们检查CETP水平，观察CETP与发病率和死亡率的关系。 方法和结果：1997 年至2000年间，我们测定了3256名参加路德维希港风险和心血管健康（LURIC）研究且基线时曾进行冠状动脉造影患者的CETP浓度。中位随访时间为7.75年。一级及二级终点分别是心血管病死亡率和全因死亡率。CETP水平在女性中较高，在吸烟者、糖尿病患者、不稳定性冠心病患者中都较低。此外，CETP水平与hs-CRP和IL-6呈负相关。在校正了年龄、性别、用药、冠状动脉疾病情况、心血管危险因素、糖尿病等因素后，与CETP水平最高四分位患者相比，最低四分位患者的死亡风险比为1.33（1.07至1.65; P = 0.011）在第二和三四分位数的患者死亡风险比分别为1.17（0.92至1.48，P = 0.19）和1.10（0.86〜1.39; P = 0.46）。 结论：我们理解我们的数据表明低内源性CETP血浆水平本质上与心血管死亡率及全因死亡率增加相关，挑战了药理学上CETP抑制剂使用的理论。 |
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