LIFE'S ESSENTIAL 8 AND THE PROGRESSION, RISK, AND PREVENTION OF PERIPHERAL ARTERY DISEASE IN THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY

Background: Peripheral artery disease (PAD) is an atherosclerotic disease of the extremities that is associated with significant morbidity and mortality. Although global PAD prevalence and incidence have increased in recent decades, much of the recent literature focuses on treatment rather than early identification, risk factors, and prevention. This dissertation aims to: (1) identify distinct ankle-brachial index (ABI) trajectories from mid- to late-life; (2) explore cardiovascular (CV) health profiles across trajectory groups; (3) assess the association between the American Heart Association’s Life’s Essential 8 (LE8) framework, combining blood glucose, blood pressure, BMI, cholesterol, diet, physical activity, sleep, and tobacco use into an overall CV health score, and incident PAD; and (4) estimate the impact of hypothetical lifestyle-oriented interventions improving CV health and modifiable risk factors on incident PAD. Methods: Each aim utilized data from the Atherosclerosis Risk in Communities (ARIC) study, a longitudinal cohort of adults aged 45-65 years of age at baseline. Aim 1 analyzed ABI trajectories among participants with ≥3 ABI measurements using group-based trajectory modeling. Aim 2 compared demographic, social determinants of health, and CV health metrics across trajectory groups. Aim 3 assessed the relationship between categorical LE8 (poor, moderate, ideal) and incident PAD using Aalen-Johansen estimators accounting for death as a competing risk. Aim 4 used the parametric g-formula to simulate realistic improvements in CV health and modifiable risk factors and estimate PAD risk reduction. Results: We identified three distinct trajectories of ABI from mid- to late-life. Participants with a declining ABI trajectory had worse baseline CV health than the other trajectories. Women were more likely to experience declining ABI with delayed onset compared to men. Black participants experienced earlier, faster, and more severe ABI decline than White participants. The 25-year cumulative PAD incidence was significantly higher for participants with poor versus moderate or ideal CV health. Hypothetical interventions improving CV health and modifiable risk factors resulted in a meaningful reduction in 25-year PAD risk. Conclusions: Targeted ABI screening for early PAD identification, coupled with modest population-level improvements in CV health, could reduce PAD-related morbidity, mortality, and incidence.