Coronary Artery Calcium in the PRagmatic EValuation of evENTs And Benefits of Lipid lowering in the Elderly: CAC PREVENTABLE Ancillary Study

冠状动脉钙对老年人降脂事件和益处的实用评估：CAC 可预防的辅助研究

基本信息

批准号：
10674482
负责人：
MICHAEL J BLAHA
金额：
$ 224.42万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10674482
关键词：
Accounting Adult Age Age Years Ancillary Study Atherosclerosis Biological Assay Biological Markers Calcium Cardiac Cardiovascular Diseases Cardiovascular system Chronology Classification Clinical Coronary Arteriosclerosis Data Data Analyses Dedications Dementia Disease Outcome Educational workshop Elderly Epidemiology Evaluation Event Funding Future Generations Goals Heart Heterogeneity Individual Infrastructure Injury Knowledge Life Life Expectancy Lipids Low-Density Lipoproteins Malignant Neoplasms Measurement Measures Modeling Modernization Myocardial National Heart, Lung, and Blood Institute Observational Study Older Population Outcome Participant Patients Phase Phenotype Placebos Population Pragmatic clinical trial Predisposition Preventive Preventive therapy Primary Prevention Prognosis Randomized Randomized, Controlled Trials Risk Risk Assessment Risk Estimate Risk Factors Risk Marker Risk Reduction Scanning Serum Serum Markers Subgroup Testing Treatment outcome Troponin Weight X-Ray Computed Tomography atorvastatin cardiovascular disorder risk clinical care coronary artery calcium coronary calcium scoring disability ethnic diversity healthy aging high risk human old age (65+)individual variation middle age mortality older patient overtreatment pragmatic trial precision medicine racial diversity randomized trial resilience risk prediction risk prediction model risk stratification tool trial design

项目摘要

ABSTRACT Predicting risk is critical for effective primary prevention of atherosclerotic cardiovascular disease (ASCVD), however classifying risk in adults ≥75 years of age remains extremely challenging. Coronary artery calcium (CAC) scoring and high-sensitivity troponin (hs-Tn) are promising tools for risk stratification in older adults because they provide singular and enduring snapshots that directly quantify a composite of cumulative risk factor exposure and individual resiliency or vulnerability. Used jointly, we have shown that low values of CAC and hs-Tn may be useful for “de-risking” older populations, identifying individuals with highly favorable prognosis in whom preventive therapy may not be beneficial. However, despite promising observational data, the true clinical value of CAC and hs-Tn in older adults remains uncertain due to lack of a dedicated, adequately powered randomized trial. The NIA/NHLBI-funded PREVENTABLE (PRagmatic EValuation of evENTs And Benefits of Lipid-lowering in oldEr adults) pragmatic clinical trial, which is currently randomizing 20,000 adults ≥75 years of age to atorvastatin 40mg or placebo and following for ASCVD events, provides the ideal setting to test the critical hypothesis that CAC and hs-Tn jointly identify older adults who will benefit the most, and the least, from statin therapy. In this proposal, we seek to perform baseline CAC scanning and hs-Tn measurement in 10,000 PREVENTABLE participants. At trial conclusion, we will conduct analyses stratified by CAC, and jointly by CAC and hs-Tn, with >85% power to determine heterogeneity of statin effect by biomarker status. At the end of the trial, we will develop a comprehensive ASCVD risk classification model using traditional risk factors, CAC, and hs-Tn and validate this in MESA and ARIC. We will then construct an online tool similar to the LIFE-CVD model for calculating estimated benefit of statin therapy in the age ≥75 primary prevention population, after detailed accounting for non-CVD competing risks observed in PREVENTABLE. In summary, we believe that CAC scanning and hs-Tn measurement in PREVENTABLE is the most expeditious and instructive way to fill critical knowledge gaps about subclinical ASCVD in an older primary prevention population and to determine the value of a biomarker-guided precision medicine approach for informing individual benefit of preventive statin therapy.

抽象的预测风险对于动脉粥样硬化心血管疾病的有效一级预防至关重要疾病（ASCVD），但是对 75 岁以上成人的风险分类仍然极其严重冠状动脉钙（CAC）评分和高敏肌钙蛋白（hs-Tn）具有挑战性。老年人风险分层的有前途的工具，因为它们提供了独特和持久的量化累积风险因素暴露和个人风险因素组合的快照结合使用弹性或脆弱性，我们已经证明 CAC 和 hs-Tn 的低值可能会导致对于“降低”老年人群的风险、识别具有高度优势的个人非常有用然而，尽管有希望，但预防性治疗可能无益于预后。观察数据显示，CAC 和 hs-Tn 对老年人的真实临床价值仍不确定由于缺乏 NIA/NHLBI 资助的专门的、足够有力的随机试验。可预防（对老年人降脂的事件和益处进行务实评估）成人）实用临床试验，目前正在随机分组 20,000 名 75 岁以上的成年人阿托伐他汀 40 毫克或安慰剂及后续 ASCVD 事件，提供了理想的测试环境 CAC 和 hs-Tn 共同确定受益最大的老年人的关键假设，最重要的是，来自他汀类药物治疗。在本提案中，我们寻求进行基线 CAC 扫描。在试验结束时，我们将在 10,000 名可预防的参与者中进行 hs-Tn 测量。进行 CAC 分层分析，以及 CAC 和 hs-Tn 联合分析，具有 >85% 的功效在试验结束时，我们将通过生物标志物状态确定他汀类药物效果的异质性。使用传统风险因素 CAC 开发全面的 ASCVD 风险分类模型和 hs-Tn 并在 MESA 和 ARIC 中验证这一点，然后我们将构建一个类似于的在线工具。 LIFE-CVD 模型，用于计算 75 岁以上原发性患者他汀类药物治疗的估计获益在详细考虑了观察到的非 CVD 竞争风险后，预防人群总之，我们认为 CAC 扫描和 hs-Tn 测量可以预防。 PREVENTABLE 是填补关键知识空白的最快捷、最具指导性的方法老年一级预防人群中的亚临床 ASCVD 并确定生物标志物引导的精准医学方法，用于告知个人预防的益处他汀类药物治疗。