Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
J Am Coll Cardiol. 2022 Oct 4;80(14):1287-1298. doi: 10.1016/j.jacc.2022.07.027.
BACKGROUND: The role of aspirin in reducing lipoprotein(a)-mediated atherothrombotic events in primary prevention is not established. OBJECTIVES: This study sought to assess whether low-dose aspirin benefits individuals with elevated plasma lipoprotein(a)-associated genotypes in the setting of primary prevention. METHODS: The study analyzed 12,815 genotyped individuals ≥70 years of age of European ancestry and without prior cardiovascular disease events enrolled in the ASPREE (ASPirin in Reducing Events in the Elderly) randomized controlled trial of 100 mg/d aspirin. We defined lipoprotein(a)-associated genotypes using rs3798220-C carrier status and quintiles of a lipoprotein(a) genomic risk score (LPA-GRS). We tested for interaction between genotypes and aspirin allocation in Cox proportional hazards models for incidence of major adverse cardiovascular events (MACE) and clinically significant bleeding. We also examined associations in the aspirin and placebo arms of the trial separately. RESULTS: During a median 4.7 years (IQR: 3.6-5.7 years) of follow-up, 435 MACE occurred, with an interaction observed between rs3798220-C and aspirin allocation (P = 0.049). rs3798220-C carrier status was associated with increased MACE risk in the placebo group (HR: 1.90; 95% CI: 1.11-3.24) but not in the aspirin group (HR: 0.54; 95% CI: 0.17-1.70). High LPA-GRS (vs low) was associated with increased MACE risk in the placebo group (HR: 1.70; 95% CI: 1.14-2.55), with risk attenuated in the aspirin group (HR: 1.41; 95% CI: 0.90-2.23), but the interaction was not statistically significant. In all participants, aspirin reduced MACE by 1.7 events per 1,000 person-years and increased clinically significant bleeding by 1.7 events per 1,000 person-years. However, in the rs3798220-C and high LPA-GRS subgroups, aspirin reduced MACE by 11.4 and 3.3 events per 1,000 person-years respectively, without significantly increased bleeding risk. CONCLUSIONS: Aspirin may benefit older individuals with elevated lipoprotein(a) genotypes in primary prevention.
背景：在一级预防中，阿司匹林降低脂蛋白(a)介导的动脉粥样血栓事件的作用尚未确定。
目的：本研究旨在评估在一级预防中，高血浆脂蛋白(a)相关基因型的个体服用低剂量阿司匹林是否获益。
方法：本研究分析了 12815 名年龄≥70 岁、无心血管疾病既往史的欧洲血统个体，他们参加了 ASPREE（阿司匹林减少老年人事件）随机对照试验，每天服用 100mg 阿司匹林。我们使用 rs3798220-C 携带状态和脂蛋白(a)基因组风险评分（LPA-GRS）五分位数来定义脂蛋白(a)相关基因型。我们在 Cox 比例风险模型中检验了基因型与阿司匹林分配之间的交互作用，以评估主要不良心血管事件（MACE）和临床显著出血的发生率。我们还分别在试验的阿司匹林组和安慰剂组中进行了相关性分析。
结果：在中位 4.7 年（IQR：3.6-5.7 年）的随访期间，发生了 435 例 MACE，rs3798220-C 与阿司匹林分配之间存在交互作用（P=0.049）。rs3798220-C 携带状态与安慰剂组 MACE 风险增加相关（HR：1.90；95%CI：1.11-3.24），但与阿司匹林组无关（HR：0.54；95%CI：0.17-1.70）。高 LPA-GRS（与低相比）与安慰剂组 MACE 风险增加相关（HR：1.70；95%CI：1.14-2.55），但在阿司匹林组中风险降低（HR：1.41；95%CI：0.90-2.23），但交互作用无统计学意义。在所有参与者中，阿司匹林使每 1000 人年的 MACE 减少 1.7 例，使临床显著出血每 1000 人年增加 1.7 例。然而，在 rs3798220-C 和高 LPA-GRS 亚组中，阿司匹林使每 1000 人年的 MACE 分别减少 11.4 和 3.3 例，且出血风险无显著增加。
结论：阿司匹林可能使一级预防中高脂蛋白(a)基因型的老年个体获益。
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