R01HL155396

Coronary Artery Calcium in the Pragmatic Evaluation of Events and Benefits of Lipid Lowering in the Elderly: CAC Preventable Ancillary Study - Abstract

Predicting risk is critical for effective primary prevention of atherosclerotic cardiovascular disease (ASCVD). However, classifying risk in adults aged 75 years and older 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 a 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 aged 75 years and older 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 over 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 the estimated benefit of statin therapy in the age 75 and older 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.

Duke University

TO FOSTER HEART AND VASCULAR RESEARCH IN THE BASIC, TRANSLATIONAL, CLINICAL AND POPULATION SCIENCES, AND TO FOSTER TRAINING TO BUILD TALENTED YOUNG INVESTIGATORS IN THESE AREAS, FUNDED THROUGH COMPETITIVE RESEARCH TRAINING GRANTS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

North Carolina United States

State-Wide

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the End Date has been extended from 07/31/26 to 07/31/27 and the total obligations have increased 486% from $1,281,492 to $7,505,536.