Abstract 3119: Angiographic Burden Of Coronary Atherosclerosis Contributes To Adverse ASCVD Outcomes Independent Of Traditional Risk Factors

Abstract

Background: Coronary artery disease (CAD) is a major contributor to cardiovascular morbidity (including myocardial infarction [MI] and heart failure [HF]), and mortality. Although burden of CAD (number and degree of coronary artery stenosis) has been observationally linked to these outcomes, the causal contribution (and independence from traditional cardiovascular risk factors) has been poorly defined. Methods: The primary exposure for this experiment was a genetic instrument for burden of CAD that was constructed from a GWAS of semi-quantitative CAD burden among VA Million Veteran Program participants undergoing coronary angiography. Two-sample Mendelian randomization (MR) was performed to test 1) bidirectional associations between traditional ASCVD risk factors (including blood lipids, blood pressure, diabetes, obesity, and smoking) and CAD burden and 2) between CAD burden and adverse cardiovascular outcomes (MI, HF, and parental longevity as a proxy of lifespan). Multivariable MR (MVMR) for mediation was then performed to determine whether traditional risk factors mediate the association between CAD burden and adverse outcomes. Results: As expected, traditional cardiovascular risk factors including lipid levels, diabetes and obesity were associated with increased burden of CAD, MI, HF, and lifespan. Angiographic CAD burden was associated with increased risk of MI, HF, and lifespan. MVMR demonstrated experiment wide independent contributions of CAD burden to HF (OR 1.13 [95% CI 1.08-1.19], p = 2.3E-6), lifespan (b = -0.06, se = 0.01, p = 9.7E-05) and MI (OR 1.74 [95% CI 1.55-1.95], p = 3.4E-21), after accounting for traditional ASCVD risk factors. The effects of lipids on HF and lifespan were partially mediated by angiographic burden of CAD. Conclusion: This study suggests that increased angiographic burden of coronary artery disease is associated with adverse cardiovascular outcomes, with an independent contribution beyond traditional cardiovascular risk factors. More aggressive primary prevention of traditional cardiovascular risk factors may be indicated to prevent development and progression/growth of coronary plaques and mitigate subsequent adverse cardiovascular outcomes.