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

项目总结/摘要 脂蛋白（a）[Lp（a）]是一种携带脂质的颗粒，当 水平升高（估计占人口的30%），但治疗选择有限，尤其是原发性 预防阿司匹林的抗血小板治疗在一级预防中已成为有争议的。 心血管事件，但Lp（a）升高的人可能代表一个亚组，由于Lp（a）升高而获益。 与Lp（a）升高、Lp（a）与血小板的相互作用以及Lp（a）与 纤维蛋白溶解，这可能导致总体出血风险降低。本提案旨在解决以下假设： 每日低剂量阿司匹林治疗将减少动脉粥样硬化性心血管疾病（ASCVD）事件， Lp（a）升高。我们将对糖尿病受试者的ASCEND试验（目标1）和 ASPREE健康老年受试者试验（目的2），通过测量储存血液样本的Lp（a）并评估 在保持随机化的情况下，按Lp（a）水平评估阿司匹林治疗对ASCVD事件的影响。另外我们 类似地，旨在评估多种族美国前瞻性队列研究（目标3）中的这一假设，以研究 种族多样性增强的人口，更能反映美国的人口， 国际吧使用ASPREE试验的遗传多态性的初步数据提供了强有力的证据， 阿司匹林治疗对脂蛋白（a）升高人群的一级预防的预期益处。我有专业知识 内科、心脏病学、流行病学和统计学。我的职业目标是成为一个独立的 预防心脏病学研究者，重点是流行病学，危险分层和预防治疗， 与血栓形成和脂质紊乱相关，特别是Lp（a）。这个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建立在 我以前建立的基础，通过完成培训计划，以进一步发展在脂质学的技能， 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。 使用流行病学和生物统计学的先进方法进行脂质学研究。加州大学圣地亚哥分校是一个世界闻名的 学术机构拥有令人难以置信的资源来完成这项培训和进行研究， 以及各个领域的合作者。此外，作为助理教授，该司 心脏病学研究所致力于支持我的研究事业，为我提供75%的受保护研究 团队，专门的办公空间和启动资金进行研究（每年25，000美元）通过KL 2赠款。

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.