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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.

摘要预测风险对于动脉粥样硬化性心血管疾病的有效一级预防至关重要疾病（ASCVD），但在≥75岁的成人中分类风险仍然非常高挑战性冠状动脉钙（CAC）评分和高敏肌钙蛋白（hs-Tn）是老年人风险分层的有前途的工具，因为它们提供了单一和持久的直接量化累积风险因素暴露和个人风险的组合的快照弹性或脆弱性。联合使用，我们已经表明，CAC和hs-Tn的低值可能对老年人“去风险化”有用，预防性治疗可能无益的预后。然而，尽管有希望观察数据显示，CAC和hs-Tn在老年人中的真正临床价值仍不确定由于缺乏专门的、有足够把握的随机试验。NIA/NHLBI资助老年人降脂事件和益处的评价成人）的实用临床试验，目前正在随机选择20，000名年龄≥75岁的成人，阿托伐他汀40 mg或安慰剂和以下ASCVD事件，提供了理想的测试环境 CAC和hs-Tn联合确定老年人受益最大的关键假设，最少的是他汀类药物。在本提案中，我们寻求执行基线CAC扫描和hs-Tn测量10，000名可预防参与者。审判结束后，我们将进行CAC分层分析，以及CAC和hs-Tn联合分析，把握度>85%，通过生物标志物状态确定他汀类药物效应的异质性。在审判结束时，我们将使用传统风险因素开发全面的ASCVD风险分类模型，CAC，和hs-Tn，并在梅萨和ARIC中验证。然后，我们将构建一个类似于用于计算年龄≥75岁原发性高血压患者中他汀类药物治疗估计获益的LIFE-CVD模型预防人群中，在详细考虑了可预防。总之，我们认为CAC扫描和hs-Tn测量在预防是最迅速和最有指导意义的方式，以填补关键的知识差距，在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，用于告知预防性治疗的个人益处他汀类药物治疗