No abstract

Introduction: Genetic predisposition for CAD is well established. Polygenic risk scores are emerging as tools which attempt to quantify the genomic component of an individual’s risk for CAD. However, clinical utility for individual risk stratification is unclear. Hypothesis: 180 SNPs previously identified in Caucasian Genome Wide-Association Studies for CAD were used to construct a weighted restricted polygenic risk score (PRS; normalized range 11.18 -17.58). This study hypothesizes that high PRS (>=85th percentile) is associated with high (>400) coronary artery calcium (CAC) score, & a low PRS(< 85th percentile) is associated with low (<100) CAC. Methods: Between January 2018 and March 2020, 21,784 patients underwent CAC screening and/or PRS testing. Caucasian patients with both PRS and CAC scores were reviewed. Patients with CAC 100-400 were excluded. Fisher’s exact test for high/low PRS and high/low CAC was utilized. Results: 2,752 patients were identified to have low (<100) or high (>400) CAC; 306 (11.1%) had a high CAC (table 1). Odds ratio of high PRS associated with high CAC and low PRS associated with low CAC was 1.54 (95% CI: 1.07-2.19; p=0.017). Conclusion: Our real-world experience in a Caucasian cohort shows that high PRS is associated with a high CAC, as is a low PRS with low CAC. Concordance between PRS and CAC lends support for incorporating PRS in the clinical setting, especially for early identification of individuals at high risk for CAD. Larger, ethnically diverse studies are needed.

Introduction: Genetic predisposition for CAD is well established. Polygenic risk scores are emerging as tools which attempt to quantify the genomic component of an individual’s risk for CAD. However, their clinical utility for individual risk stratification is unclear. Hypothesis: 180 SNPs previously identified in Caucasian Genome Wide-Association Studies for CAD were used to construct a weighted restricted polygenic risk score (PRS; normalized range 11.18 -17.58). This study hypothesizes a gender-specific association between high PRS (>=85th percentile) and high coronary artery calcium score (CAC) score, defined as >400. Methods: Between January 2018 & March 2020, 21,784 patients underwent CAC screening and/or PRS testing. Caucasian patients with both PRS and CAC scores were identified. Fisher’s exact test was utilized to test the association between high PRS and high CAC in men and women. Results: Both PRS and CAC were available for 3,197 Caucasian patients, out of which 2,106 (65.8%) were women (figure 1: gender adjusted PRS distribution). Odds ratio of high PRS and high CAC was 1.64 (95% CI: 0.86-2.97; p >0.05) in women and 1.59 (95% CI: 0.98 - 2.53; p>0.05) in men. Conclusions: There is no statistically significant, gender-specific association between high PRS and high CAC in our Caucasian cohort. However, there is a trend suggestive of a positive correlation in women. This clinical data is the first of its kind in a real world setting on the use of PRS for CAD risk assessment. Larger, ethnically diverse studies are needed.

Introduction: Genetic predisposition for CAD is well established. Polygenic risk scores are emerging as tools to quantify the genomic component of an individual’s risk for CAD. However, their clinical utility for individual risk stratification is unclear. Hypothesis: 180 SNPs previously identified in Caucasian Genome Wide-Association Studies for CAD were used to construct a weighted restricted polygenic risk score (PRS; normalized range 11.18 -17.58). This study hypothesizes that a low PRS (<85th percentile) is associated with coronary calcium score (CAC) of zero. Methods: Between January 2018 & March 2020, 21,784 patients underwent CAC screening and/or PRS testing. Caucasian patients with both PRS and CAC scores were identified. Fisher’s exact test was utilized to test the association between low PRS and CAC score of zero. Results: 3,197 Caucasian patients had both PRS and CAC calculated, 1597 (49.9%) of whom had CAC greater than zero. Characteristics are summarized in table 1. Odds ratio of low PRS associated with CAC zero was 1.34 (95% CI 1.08 - 1.67; p=0.0079). Conclusions: In our Caucasian cohort, there is a statistically significant correlation between a low PRS and absence of coronary artery calcium. This is a real-world analysis incorporating genomic data for individual CAD risk stratification. Further studies on a larger, ethnically diverse cohort are needed.