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

项目摘要 Lp(A)是一种非常普遍的、独立的、遗传的、可能导致心血管疾病的危险因素。 高危人群占美国个人的20%-30%，即1亿人，而 据估计，全球有14亿人。Lp(A)与一级预防环境中心血管疾病风险的增加有关 在二级预防环境中使用他汀类药物和PCSK9抑制剂的患者。Lp(A)是优先承运人 OXPL，其血浆中的含量可用OXPL-apoB法测定。没有审批通过的 治疗Lp(A)升高的药物治疗。在初级预防环境中，临床平衡存在于 脂蛋白(A)升高的成年人使用阿司匹林(&gt；30 mg/dL或&gt；75nmol/L)，医生服用的量不够 使用阿司匹林治疗这类患者的信息，特别是那些有强烈心血管疾病家族史的患者。我们假设 升高的Lp(A)将确定在一级预防中可能受益于阿司匹林的一大群个体 并建议在ASPREE和ASCEND试验中检验这一假说。我们建议检验这一假设 阿司匹林将高危一级预防环境中动脉粥样硬化性血栓事件发生的风险修改为 Lp(A)或OxPL-apoB水平高的人群与Lp(A)水平低的人群相比程度不同。子目标1将 在ASPREE试验中，在老年人身上测试这一假设。SubAim 2将在患有以下疾病的人身上测试这一假设 Ascend试验中的2型糖尿病。我们还将对阿司匹林对糖尿病风险的影响进行荟萃分析。 高风险一级预防环境中高风险人群与低风险人群的动脉粥样硬化血栓形成心血管事件 在ASPREE和ASCEND试验中，Lp(A)水平以及OxPL-apoB水平高与低的人群中，使用 每次试验中最全面的相关结果，如目标1和目标2所用。

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.