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

阿司匹林用于脂蛋白升高患者心血管疾病的一级预防(a)

• 批准号: 10739016
• 负责人: Harpreet Singh Bhatia
• 金额: $ 16.89万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739016
• 关键词: Address; American; Antifibrinolytic Agents; Antisense Oligonucleotides; Aortic Valve Stenosis; Aspirin; Atherosclerosis; Atherosclerosis Risk in Communities; Award; Biometry; Black race; Blood Platelets; Blood specimen; Cardiology; Cardiovascular Diseases; Cardiovascular system; Clinic; Cohort Studies; Collaborations; County; Data; Dedications; Development Plans; Diabetes Mellitus; Dose; Elderly; Epidemiology; Event; FDA approved; Fibrinolysis; Foundations; Funding; Genes; Genetic Polymorphism; Goals; Grant; Guidelines; Heart; Hemorrhage; Individual; Institution; Internal Medicine; Ischemia; Lipids; Lipoprotein (a); Literature; Low-Density Lipoproteins; Measures; Medical; Messenger RNA; Methods; Multi-Ethnic Study of Atherosclerosis; Participant; Patients; Persons; Phase; Placebos; Plasma; Plasminogen; Population; Prevalence; Prevention trial; Preventive; Preventive therapy; Primary Prevention; Probability; Proprotein Convertases; Prospective, cohort study; Random Allocation; Randomized; Recording of previous events; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Sampling; Secondary Prevention; Single Nucleotide Polymorphism; Societies; Specific qualifier value; Subgroup; Subtilisins; Testing; Therapeutic; Thrombosis; Training; United States; Woman; Women' s Health; Work; apolipoprotein B-100; apolipoprotein Lp(a+); atherogenesis; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular risk factor; career; career development; clinical practice; clinical trial analysis; cohort; diabetic; ethnic diversity; experience; genetic analysis; genetic epidemiology; inhibitor; lipid disorder; multi-ethnic; novel; particle; patient subsets; platelet function; preservation; prevention clinical trial; professor; prospective; randomized trial; risk stratification; risk/benefit ratio; secondary analysis; skills; statistics; tool; vascular inflammation

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.

项目摘要 /摘要 脂蛋白（A）[LP（A）]是一种携带脂质的颗粒，当 在升高的水平（估计占人口的30％），但治疗方案有限，尤其是针对初级的 预防。阿司匹林的抗血小板治疗已引起争议 心血管事件，但LP（a）升高的人可能代表一个子组，该亚组受益于 与LP（a），LP（a）与血小板的相互作用以及LP（a）的相互作用与升高的风险以及与 纤维蛋白溶解可能导致总体出血风险降低。该提议旨在解决以下假设 每日低剂量阿司匹林疗法将减少患有患者的动脉粥样硬化心血管疾病（ASCVD）事件 升高的LP（a）。我们将对糖尿病参与者的上升试验进行次要分析（AIM 1）和 通过在储存的血液样本上测量LP（A）对健康的老年参与者的Aspree试验（AIM 2）并评估 阿司匹林治疗对LP（a）水平的ASCVD事件的影响，同时保留随机分组。另外，我们 同样的目的是在多种族的美国前瞻性队列研究（AIM 3）中评估这一假设以研究 人口增强的种族多样性，更反映美国的人口 全世界。使用ASPREE试验的遗传多态性的初步数据提供了可靠的证据证明 在LP升高（a）升高的人中，阿司匹林治疗对初级预防的预期益处。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独立 预防性心脏病学研究者，重点是流行病学，风险分层和预防疗法 与血栓形成和脂质疾病相关，特别是LP（a）。这个奖项和描述的职业 发展计划将使我通过完成拟议的研究并建立建立来实现这些目标 我以前建立的基金会完成了培训计划，以进一步发展脂肪学技能， 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有关新问题的相关问题 使用流行病学和生物统计学中的先进方法来脂肪学。加州大学圣地亚哥分校是世界著名的 学术机构拥有令人难以置信的资源来完成此培训和进行研究， 以及在每个可能的领域中合作的合作者。此外，作为助理教授，部门 心脏病学致力于通过为我提供75％受保护的研究来支持我的研究职业 团队，专门的办公空间和创业资金通过KL2赠款进行研究（每年25,000美元）。