Aspirin for Primary Prevention of Cardiovascular Disease in Patients with Elevated Lipoprotein(a)

项目摘要/摘要 脂蛋白(A)[Lp(A)]是一种载脂颗粒，在以下情况下会显著增加心血管疾病的风险 处于较高水平(估计占人口的30%)，但治疗选择有限，特别是对初级患者 预防。阿司匹林的抗血小板治疗在一级预防高血压方面存在争议。 心血管事件，但Lp(A)升高的人可能代表着受益于 与Lp(A)升高、Lp(A)S与血小板的相互作用以及Lp(A)与S的相互作用相关的未解决风险 纤溶作用，可能导致总体出血风险较低。这项提议试图解决这样一个假设： 每日小剂量阿司匹林治疗将减少患有动脉粥样硬化性心血管疾病(ASCVD)的患者事件 Lp(A)升高。我们将对糖尿病参与者的ASCEND试验(目标1)和 健康老年受试者的ASPREE试验(目标2)通过测定储存的血液样本中的Lp(A)并评估 阿司匹林治疗对ASCVD事件影响的Lp(A)水平与随机化。此外，我们 类似地，目的是在多种族美国人前瞻性队列研究(目标3)中评估这一假设，以研究 种族多样性增强的人口，更能反映美国的人口和 全世界。ASPREE试验中使用基因多态的初步数据提供了强有力的证据 阿司匹林治疗Lp(A)升高患者一级预防的预期益处。我在以下方面有专业知识 内科、心脏病学、流行病学和统计学。我的职业目标是成为一名独立人士 预防心脏病学研究员，重点研究流行病学、风险分层和预防治疗 与血栓形成和血脂紊乱有关，特别是Lp(A)。这一奖项和所描述的职业生涯 发展计划将使我能够通过完成拟议的研究和在 我之前建立的基础，通过完成进一步发展血脂技能的培训计划， 生物统计学和遗传流行病学。通过这个计划，我将开发工具来提出与此相关的新问题 利用流行病学和生物统计学中的先进方法进行血脂学研究。加州大学圣地亚哥分校举世闻名 学术机构拥有大量资源来完成这项培训和进行研究， 以及所有可能合作的领域的合作者。此外，作为助理教授，该司 致力于支持我的研究事业，为我提供75%的受保护研究 团队、专用办公空间和启动资金，用于通过KL2赠款进行研究(每年25,000美元)。

PROJECT SUMMARY / ABSTRACT Lipoprotein(a) [Lp(a)] is a lipid-carrying particle that contributes significantly to cardiovascular disease risk when at elevated levels (estimated 30% of the population), but has limited options for therapy, especially for primary prevention. Anti-platelet therapy with aspirin has become controversial for the primary prevention of cardiovascular events, but people with elevated Lp(a) may represent a subgroup that derives benefit due to the unaddressed risk associated with elevated Lp(a), Lp(a)’s interaction with platelets, and Lp(a)’s interaction with fibrinolysis which may result in lower overall bleeding risk. This proposal seeks to address the hypothesis that daily low-dose aspirin therapy will reduce atherosclerotic cardiovascular disease (ASCVD) events in people with elevated Lp(a). We will perform secondary analyses of the ASCEND trial of diabetic participants (Aim 1) and the ASPREE trial of healthy elderly participants (Aim 2) by measuring Lp(a) on stored blood samples and evaluating the effect of aspirin therapy on ASCVD events by Lp(a) level while preserving randomization. Additionally, we similarly aim to evaluate this hypothesis in multi-ethnic American prospective cohort studies (Aim 3) to study a population with enhanced ethnic diversity that is more reflective of the population in the United States and worldwide. Preliminary data using genetic polymorphisms from the ASPREE trial provides robust evidence of an anticipated benefit of aspirin therapy for primary prevention in people with elevated Lp(a). I have expertise in internal medicine, cardiology, epidemiology, and statistics. My career goal is to become an independent investigator in preventive cardiology with a focus on epidemiology, risk stratification and preventive therapies in association with thrombosis and lipid disorders, particularly Lp(a). This award and the described career development plan will allow me to achieve these goals by completing the proposed studies and by building on my previously established foundation by completing the training plan to further develop skills in lipidology, biostatistics and genetic epidemiology. Through this plan, I will develop the tools to ask novel questions related to lipidology using advanced methods in epidemiology and biostatistics. UC San Diego is a world-renown academic institution with an incredible array of resources for completing this training and performing research, as well as collaborators in every possible field to work with. Additionally, as an Assistant Professor, the Division of Cardiology has committed to supporting my research career by providing me with 75% protected research team, dedicated office space and startup funding to conduct research ($25,000 per year) through a KL2 grant.