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

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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.