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

• 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
• 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' 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

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 脂蛋白（a）是心血管疾病的一个高度流行、独立、遗传和可能的因果危险因素。 处于风险中的人群占美国个体的20-30%，或> 100，000，000人， 估计全球有14亿人。Lp（a）与一级预防环境中CVD风险增加相关 以及在二级预防环境中接受他汀类药物和PCSK 9抑制剂的患者中。Lp（a）是一种 OxPL，其在血浆中的含量可以通过测定OxPL-apoB来测量。没有批准的 药物治疗以治疗升高的Lp（a）。在一级预防环境中，临床平衡存在于 在Lp（a）升高（>30 mg/dL或>75 nmol/L）的成人中使用阿司匹林，并且医生没有足够的 这是一个用阿司匹林治疗这些患者的信息，特别是那些有强烈的CVD家族史的患者。我们假设 Lp（a）升高将确定一个大的亚组个体，可能受益于阿司匹林的一级预防 并建议在ASPREE和ASCEND试验中检验这一假设。我们打算检验这个假设 阿司匹林可以改变高风险一级预防中动脉粥样硬化血栓形成性心血管事件的风险， 高Lp（a）或OxPL-apoB水平的人与低Lp（a）水平的人相比，其程度不同。SubAim 1将 在ASPREE试验的老年人中检验这一假设。SubAim 2将在以下个体中检验这一假设： ASCEND试验中的2型糖尿病。我们还将对阿司匹林对以下风险的影响进行荟萃分析： 高风险与低风险人群中高风险一级预防环境中发生的动脉粥样硬化血栓性CVD事件 在ASPREE和ASCEND试验中，使用 目标1和目标2中使用的每项试验中最全面的相关结局。