Profiling Cardiovascular Events and Biomarkers in the Very Old to Improve Personalized Approaches for the Prevention of Cardiac and Vascular Disease

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Although older individuals have the highest absolute risk for cardiovascular disease (CVD) events, U.S. cholesterol and blood pressure guidelines recommend lower-intensity, less-aggressive treatment in this high- risk population based on limited clinical trial data and potential for more side effects. The current risk prediction equation does not include individuals aged >79 years, nor does it include heart failure (HF), a more common CVD event in older individuals than myocardial infarction or stroke. Recent trials have demonstrated greater absolute CVD risk reduction in older high-risk participants, underscoring the need for improved risk assessment to inform treatment decisions and patient–physician discussions regarding therapy. Cardiac biomarkers have been shown to identify higher-risk individuals and to improve HF risk prediction beyond traditional risk factors in middle-aged adults in the Atherosclerosis Risk in Communities (ARIC) Study. In the proposed work, we will develop risk prediction tools for atherosclerotic CVD and HF tailored for very old adults, including cardiac biomarker measurements, to provide more comprehensive CVD risk assessment and to allow more precise assessment of potential benefits and risks of therapy as well as midlife lifestyle, demographic, and clinical factors that lead to healthy cardiovascular aging. In addition to data on traditional risk factors and CVD events from ARIC, we propose to measure biomarkers of cardiac injury, stress, fibrosis, and inflammation in all ARIC participants who attended the most recent visit (visit 5: 2011–2013; most aged ≥70 years) and the upcoming visits (visit 6: n=4,214, 2016–2017, most aged ≥75 years; visit 7: n=3,827, 2018–2019) to address our aims: 1: To assess the performance of the Pooled Cohort Equation risk calculator for atherosclerotic CVD in very old adults and to develop an improved risk calculator using the best circulating biomarkers and risk factor panel; 2: To quantify and compare risk of HF versus atherosclerotic CVD, develop risk prediction tools for incident HF in very old adults and a comprehensive tool for HF, myocardial infarction, and stroke for primary prevention; 3: To identify major midlife factors leading to “healthy cardiovascular aging,” defined as the absence of clinical CVD events and elevated cardiac biomarkers.