Abstract 18300: Association Between a Genetic Risk Score for Clinical CAD and Early Stage Lesions in the Coronary and Aorta Provides Insights Into the Pathophysiology of Atherosclerosis
Autopsy studies suggest that the fatty streak is the earliest identifiable lesion of atherosclerosis. However, not all fatty streaks progress to more advanced lesions of atherosclerosis. Furthermore, the correlation between the extent of fatty streaks in younger persons and the extent of more advanced lesions in older persons as well as the community rates of CAD is substantially lower for the aorta compared to the coronaries. These observations suggest that the pathophysiologic processes leading to the formation of fatty streaks and raised atherosclerotic lesions may differ between the two vascular beds. To test this hypothesis, we analyzed genetic data from 564 white participants of the Pathobiological Determinants of Atherosclerosis in Youth study between the age of 15 and 34 at the time of accidental death. We ranked subjects by the percent surface area of involvement of fatty streaks and raised lesions in their right coronary artery, thoracic aorta, and abdominal aorta, respectively, on post-mortem examination. We then defined cases within each lesion type and artery location as subjects with a sex specific ranking that was in the top quartile. We found a genetic risk score (GRS) composed of high-risk alleles at 32 loci for clinical CAD operating independent of traditional risk factors to be robustly associated with the probability of being a case for both fatty streaks and raised atherosclerotic lesions in the right coronary artery (Table). In contrast, the same GRS exhibited no association with case status for fatty streaks in the aorta and only a weak trend for association with case status for raised lesions in the aorta. Our findings support the notion that not all fatty streaks are equivalent in their predisposition to atherosclerosis and suggest that some atherosclerosis susceptibility loci uncovered through GWAS studies of clinical CAD may only be active in the coronary tree.
- Coronary artery disease
- Peripheral artery disease (PAD)
- Genome-wide association studies (GWAS)
Author Disclosures: E.L. Salfati: None. D.M. Herrington: None. T.L. Assimes: None.
- © 2015 by American Heart Association, Inc.