CORONARY ARTERY CALCIFICATION IN THE 75-AND-OLDER POPULATION: IMPLICATIONS ON HEALTHY VASCULAR AGING AND CARDIOVASCULAR DISEASE PREVENTION
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Wang, Frances M.
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Although age is a strong predictor of vascular disease burden, vascular health is heterogenous within the older adult population. Because studies have traditionally focused on unhealthy vascular aging outcomes (e.g., cardiovascular disease and myocardial infarction), little is understood about optimal vascular aging. This dissertation examines the epidemiology and predictors of healthy vascular aging, characterized by coronary artery calcium (CAC), a strong marker of vascular disease burden, in the 75-and-older population. First, we designed and conducted a survey to understand perceptions surrounding benefit and harm outcomes related to statin and aspirin, two major cardiovascular disease prevention therapies, in older adults age 65-84 and found that older adults generally considered outcomes related to cardiovascular disease prevention therapy benefits, stroke and heart attack, more important than their harms (e.g., muscle pain or bleeding). Second, we characterized the distribution of CAC in the 75-and-older population since data are sparse. The prevalence of zero CAC was 11%, and we found that the current CAC >100 threshold for high atherosclerotic cardiovascular disease risk would categorize most adults 75-and-older at high risk. This aim established age, sex, race specific percentiles for CAC in adults 75-and-older that can be used in clinical practice. Third, we examined the association between 30-year mid-to-late life cumulative average traditional cardiovascular risk factors to zero CAC at age ~75 years-and-older. Favorable cumulative risk factors (lower total cholesterol, higher high-density lipoprotein-cholesterol [HDL-C], lower systolic blood pressure, and not smoking [but not necessarily lower fasting glucose]) were associated with zero CAC, more so than mid-life or late-life timepoints alone. When we compared risk factor profiles at mid-life vs. late-life, the former was more evidently associated with zero CAC. Fourth, we assessed mid-life and late-life proteomic associations with zero CAC to identify proteins and protein pathways associated with healthy vascular aging. We identified seven proteins (one at mid-life and six at late-life) for zero CAC and described protein pathways, networks and upstream regulators which may be important for maintaining healthy vascular aging. These proteins were not identified in previous proteomic studies focusing on clinical cardiovascular events. As a whole, the results of this work advocate for the importance of cardiovascular disease prevention and presents a system for using CAC to understand atherosclerotic disease burden in the 75-and-older population, highlights the importance of primordial prevention to optimize vascular health over the life course, and presents potential proteins and biological mechanisms for healthy vascular aging.