Aspirin, Lp(a) and Primary Prevention of Cardiovascular Events

阿司匹林、Lp(a) 和心血管事件的一级预防

基本信息

批准号：
10720757
负责人：
SOTIRIOS TSIMIKAS
金额：
$ 76.35万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10720757
关键词：
Adult Affect Antifibrinolytic Agents Apolipoproteins B Aspirin Biological Assay Blood Platelets Blood Vessels Cardiovascular Diseases Cardiovascular system Cessation of life Clinical Clinical Research Collaborations Coronary heart disease Data Diabetes Mellitus Elderly Enrollment Equipoise Event Exclusion Family history of Genetic Grant Individual Inflammation Intracranial Hemorrhages Ischemic Stroke Lipoprotein (a)Low-Density Lipoproteins Measures Mediating Meta-Analysis Modernization Myocardial Infarction Non-Insulin-Dependent Diabetes Mellitus Outcome Patients Persons Phospholipids Physicians Placebos Plasma Populations at Risk Prevention therapy Primary Prevention Randomized Research Personnel Risk Risk Factors Risk Reduction Role Secondary Prevention Single Nucleotide Polymorphism Stroke Subgroup Testing Transient Ischemic Attack United States Woman Women&apos s Health apolipoprotein Lp(a+)cardiovascular disorder prevention cardiovascular disorder risk cardiovascular risk factor clinical development efficacy outcomes follow-up high risk inhibitor men pharmacologic platelet function prospective prospective test randomized placebo controlled trial randomized trial receptor response

项目摘要

PROJECT Summary Lp(a) is a highly prevalent, independent, genetic and likely causal risk factor for cardiovascular disease. The population at risk represents 20-30% of individuals in the United States, or >100,000,000 people, and an estimated 1.4 billion people globally. Lp(a) is associated with increased CVD risk in primary prevention settings and in patients on statins and PCSK9 inhibitors in secondary prevention settings. Lp(a) is a preferential carrier of OxPL, the content of which in plasma can be measured by the assay OxPL-apoB. There are no approved pharmacological therapies to treat elevated Lp(a). In primary prevention settings, clinical equipoise exists in the use of aspirin in adults with elevated Lp(a) (>30 mg/dL or >75 nmol/L), and physicians do not have enough information to treat such patients with aspirin, particularly those with a strong family history of CVD. We hypothesize that elevated Lp(a) will identify a large subgroup of individuals that may benefit from aspirin in primary prevention settings and propose to test this hypothesis in the ASPREE and ASCEND trials. We propose to test the hypothesis that aspirin modifies the risk of incident atherothrombotic CVD events in high-risk primary prevention settings to a different extent in people with high Lp(a) or OxPL-apoB levels than in people with lower Lp(a) levels. SubAim 1 will test this hypothesis in elderly individuals in the ASPREE trial. SubAim 2 will test this hypothesis in individuals with type 2 diabetes in the ASCEND trial. We will also perform a meta-analyses of the effects of aspirin on the risk of incident atherothrombotic CVD events in high-risk primary prevention settings in people with high versus lower Lp(a) levels and in people with high versus lower OxPL-apoB levels in the ASPREE and ASCEND trials, using the most comprehensive relevant outcome in each trial, as used in Aim 1 and Aim 2.

项目摘要 LP（A）是心血管疾病的高度普遍，独立，遗传和可能的因果风险因素。处于危险中的人口占美国个人的20-30％，> 100,000,000人，一个全球估计有14亿人。 LP（a）与初级预防设置中的CVD风险增加有关以及在二级预防环境中他汀类药物和PCSK9抑制剂的患者中。 LP（a）是优先载体 OXPL，血浆中的含量可以通过测定OXPL-APOB测量。没有批准治疗升高LP（A）的药理疗法。在初级预防环境中，存在于在LP升高（a）（> 30 mg/dl或> 75 nmol/l）的成年人中使用阿司匹林，并且医生没有足够以治疗阿司匹林的患者，特别是患有CVD家族史的患者的信息。我们假设升高的LP（a）将识别一个可能受益于主要预防中阿司匹林的个体亚组设置并建议在Aspree和上升试验中检验这一假设。我们建议检验假设阿司匹林将高风险初级预防设置中的动脉粥样硬化性CVD事件改变为 LP（A）或OXPL-APOB水平高的人的程度与LP较低（a）水平的人不同。 Subaim 1 Will 在ASPREE试验中，在老年人中检验这一假设。 Subaim 2将在患有上升试验中的2型糖尿病。我们还将对阿司匹林的影响进行荟萃分析在高风险的初级预防环境中事件中的动脉粥样硬化CVD事件， LP（a）水平以及在Aspree和Aspend试验中具有较高OXPL-APOB水平的人，使用该水平在AIM 1和AIM 2中使用的每个试验中最全面的相关结果。