Abstract 43: Genetic, Sociodemographic, Lifestyle, and Clinical Risk Factors of Coronary Artery Disease Recurrent Events: Population-Based Cohort Study

Introduction: Contemporary guidelines remain to uniformly classify patients with established atherosclerotic cardiovascular disease as high risk despite substantial heterogeneities in risk factors distributions. We examined the independent associations and relative predictabilities of genetic, sociodemographic, lifestyle, and clinical risk factors on coronary artery disease (CAD) recurrence. Methods: From population-based UK Biobank cohort, we identified 7,024 participants aged 40-69 years with established CAD at enrollment. Based on multivariable Cox regression model, we evaluated the hazard ratio (HR) and discrimination index of age at enrollment, age at first CAD diagnosis, sex, smoking, physical activity, diet, sleep, socioeconomic deprivation, body mass index, blood pressure, lipids, glucose, lipoprotein(a), C-reactive protein, estimated glomerular filtration rate, statin prescription, and CAD polygenic risk score (PRS) on first CAD recurrence since enrollment. Results: Over a median [IQR] follow-up of 11.6 [4.0] years, 2,003 (28.5%) recurrent CAD events occurred. Of studied risk factors, the HR [95% CI] for CAD recurrence was the most pronounced with current smoking (1.35 [1.13-1.61]) and per SD increase in age at first CAD (0.74 [0.67-0.82]). Moreover, age at enrollment, Townsend Deprivation Index, sleep quality, cholesterols, glucose, renal function, C-reactive protein, and CAD PRS also significantly associated with recurrence. CAD PRS (C index: 0.58 [0.57-0.59]) largely predicted CAD recurrence, followed by high-density lipoprotein (HDL) cholesterol (0.57 [0.57-0.58]) and age at first CAD (0.57 [0.56-0.57]). In addition to traditional risk factors, a comprehensive model improved the C index from 0.64 [0.63-0.65] to 0.68 [0.67 to 0.69]. Conclusion: Genetic risk, age at first CAD event, and HDL cholesterol contributed the most to CAD recurrence. These features may identify high risk subgroups for treatment intensification or trials for new therapeutic strategies among those with CAD.