脂蛋白(a)与多民族队列前瞻性研究的长期心血管风险。

Lipoprotein(a) and Long-Term Cardiovascular Risk in a Multi-Ethnic Pooled Prospective Cohort.

机构信息

Division of Cardiology, University of California-Irvine, Irvine, California, USA; Department of Epidemiology and Biostatistics, University of California-Irvine, Irvine, California, USA.

出版信息

J Am Coll Cardiol. 2024 Apr 23;83(16):1511-1525. doi: 10.1016/j.jacc.2024.02.031.

DOI:10.1016/j.jacc.2024.02.031

PMID:38631771

Abstract

BACKGROUND: Lipoprotein(a) (Lp[a]) is a causal genetic risk factor for atherosclerotic cardiovascular disease (ASCVD). There are limited long-term follow-up data from large U.S. population cohorts. OBJECTIVES: This study examined the relationship of Lp(a) with ASCVD outcomes in a large, pooled, multi-ethnic U.S. METHODS: The study included data on Lp(a) and ASCVD outcomes from 5 U.S. PROSPECTIVE STUDIES: MESA (Multi-Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults), JHS (Jackson Heart Study), FHS-OS (Framingham Heart Study-Offspring), and ARIC (Atherosclerosis Risk In Communities). Lp(a) levels were classified on the basis of cohort-specific percentiles. Multivariable Cox regression related Lp(a) with composite incident ASCVD events by risk group and diabetes status. RESULTS: The study included 27,756 persons without previous ASCVD who were aged 20 to 79 years, including 55.0% women, 35.6% Black participants, and 7.6% patients with diabetes, with mean follow-up of 21.1 years. Compared with Lp(a) levels <50th percentile, Lp(a) levels in the 50th to <75th, 75th to <90th, and ≥90th percentiles had adjusted HRs of 1.06 (95% CI: 0.99-1.14), 1.18 (95% CI: 1.09-1.28), and 1.46 (95% CI: 1.33-1.59), respectively for ASCVD events. Elevated Lp(a) predicted incident ASCVD events similarly by risk group, sex, and race or ethnic groups, but more strongly in patients with vs without diabetes (interaction P = 0.0056), with HRs for Lp(a) levels ≥90th percentile of 1.92 (95% CI: 1.50-2.45) and 1.41 (95% CI: 1.28-1.55), respectively. Lp(a) also individually predicted myocardial infarction, revascularization, stroke, and coronary heart disease death, but not total mortality. CONCLUSIONS: The study shows, in a large U.S. pooled cohort, that higher Lp(a) levels are associated with an increased ASCVD risk, including in patients with diabetes.

摘要

背景：脂蛋白(a)[Lp(a)]是动脉粥样硬化性心血管疾病（ASCVD）的一个因果遗传风险因素。目前，美国大型人群队列的长期随访数据有限。

目的：本研究旨在一个大型的、多族裔的美国人群队列中，研究脂蛋白(a)与 ASCVD 结局之间的关系。

方法：这项研究纳入了来自 5 项美国前瞻性研究的数据：多民族动脉粥样硬化研究（MESA）、冠状动脉风险发展（青年）研究（CARDIA）、杰克逊心脏研究（JHS）、弗雷明汉心脏研究后代队列（FHS-OS）和社区动脉粥样硬化风险研究（ARIC）。根据队列特异性百分位数对 Lp(a)水平进行分类。多变量 Cox 回归分析将 Lp(a)与复合首发 ASCVD 事件相关，并按风险组和糖尿病状态进行分层。

结果：这项研究纳入了 27756 名无 ASCVD 病史、年龄在 20 至 79 岁之间的患者，其中 55.0%为女性，35.6%为黑人参与者，7.6%为糖尿病患者，平均随访时间为 21.1 年。与 Lp(a)水平低于第 50 百分位相比，第 50 至第 75 百分位、第 75 至第 90 百分位和第 90 百分位以上的 Lp(a)水平的校正 HR 分别为 1.06（95%CI：0.99-1.14）、1.18（95%CI：1.09-1.28）和 1.46（95%CI：1.33-1.59），分别用于 ASCVD 事件。Lp(a)水平升高同样预示着 ASCVD 事件的发生，且与风险组、性别和种族或民族有关，但在有糖尿病和无糖尿病的患者中，其预测作用更强（交互 P=0.0056），Lp(a)水平处于第 90 百分位以上的患者发生 ASCVD 的 HR 分别为 1.92（95%CI：1.50-2.45）和 1.41（95%CI：1.28-1.55）。Lp(a)还可以单独预测心肌梗死、血运重建、卒中和冠心病死亡，但不能预测全因死亡率。

结论：这项研究表明，在一个大型的美国人群队列中，较高的 Lp(a)水平与 ASCVD 风险增加相关，包括在有糖尿病的患者中。