Abstract 4147347: The value of Coronary Artery Disease Polygenic Risk Score (CAD PRS) and Coronary Artery Calcium Score (CACS) in the prediction of Atherosclerotic Cardiovascular Diseases (ASCVD)

Introduction: Atherosclerotic cardiovascular disease (ASCVD) is a complex disease process, and an early diagnosis of high-risk patients will decrease morbidity and mortality. In our study, we evaluated Coronary Artery Disease Polygenic Risk Score (CAD PRS) and Coronary Artery Calcium Score (CACS) and their combination in the prediction of ASCVD, represented by peripheral vascular disease, aortic sclerosis, severe aortic stenosis, and stroke. Method: Our population was individuals enrolled in the Sanford Heart Screening Program and genotyped using the Illumina Global Screening Array version 1. CAD PRS was calculated using a literature-derived list of 180 single nucleotide polymorphisms (SNP). Patients were classified into two groups based on CAD PRS: High PRS (>=85 th percentile) or low/intermediate PRS (<85 th percentile). CACS was classified as high risk with a value of ≥ 300 and a non-high score when <300. We used hierarchical logistic regression to assess CAD PRS, CACS, and their combination in predicting ASCVD. Results: In a sample of 689 patients, CACS was associated with sclerosis (OR=2.29 [1.18, 4.30], p<.05), aortic stenosis (OR=10.0 [2.14, 70.6], p<.01), PVD (OR=2.52 [1.23, 4.97], p<.01) but not a stroke (OR=1.63 [0.62, 3.87], p=.3). A high PRS was shown not to be significantly associated with aortic sclerosis (OR=1.23 [0.52, 2.60], p=.60), PVD (OR=1.09 [0.40, 2.52], p=.8), or stroke (OR=1.5 [0.49, 3.84], p=.4), but was marginally associated with aortic stenosis (OR=4.31 [0.84, 19.8], p=.058). When holding a high CACS constant, a high PRS failed to show any significant hierarchical utility in predicting aortic stenosis (OR=3.10 [0.59, 14.7], p=.20). Conclusion: The combination of high CAD PRS to high CACS was not clinically significant in improving predictive value for atherosclerotic cardiovascular diseases, although was noted to be marginally significant for aortic stenosis. Increasing sample size might increase the power and show clinical significance in future assessment