Participants with top quintile polygenic risk score had 1.79-fold higher odds of any CAD (CACS>0) and 1.68-fold higher odds of clinically actionable CAD (CACS≥100 or >75th percentile).
Does a high polygenic risk score identify the presence of coronary artery calcium in primary prevention patients with low/moderate absolute CVD risk?
In primary prevention patients with low/moderate clinical risk, a high polygenic risk score significantly increases the odds of having detectable coronary artery calcium, supporting its potential role in triaging patients for CT imaging.
Absolute Event Rate: 0% vs 0%
Abstract Background The identification and targeting of cardiovascular disease (CVD) modifiable risk factors has led to a significant reduction in poor outcomes from coronary artery disease (CAD) at a population level. However, up to 25 percent of individuals presenting with ST elevation myocardial infarction do so in the absence of such risk factors as hypercholesterolaemia, hypertension, diabetes mellitus, and smoking. (1) This highlights the need for novel diagnostic strategies to identify individuals with elevated CAD risk in conjunction with current risk assessment. The ESCALATE clinical trial (ACTRN12622000436774) was initiated as an implementation study, incorporating a CAD polygenic risk score (PRS) into an otherwise standard primary care-based CVD risk assessment. (2) The primary trial outcome is the proportion of participants at low/moderate Absolute CVD Risk, in the Top Quintile PRS risk, with a positive coronary artery calcium score (CACS). Purpose The present study seeks to retrospectively model the performance of this diagnostic pathway in an Australian-based CAD cohort study. Methods The BioHEART-CT Discovery 1000 cohort was utilised for this analysis. CAD PRS was calculated using the GPSMult tool (PGS003725), (3) with genetic information obtained through SNP array using Global Screen Assay (Infinium GSAMD-24v1-0₂0011747A1). The GPSMult 80th percentile was calculated from 333, 274 UK Biobank participants of European ancestry. Baseline outcomes of the ESCALATE trial were analysed. Standard descriptive statistics were used to characterise baseline differences. Group comparisons were completed with Wilcoxon rank sum for continuous measures and Chi square for categorical. Results A cohort of 703 primary prevention BioHEART-CT participants with a low/moderate Absolute CVD Score at the time of enrolment was prepared. 195 participants (27. 7%) were considered "Top Quintile PRS Risk, " with a PRS≥80th percentile. Participants with a top quintile PRS had 1. 79-times odds (95%CI 1. 28-2. 51, p=0. 001) of having CAD defined as CACS0AU compared to non-top quintile participants, A clinically relevant composite of CACS≥100AU or ≥75th CACS percentile was next considered. Participants with Top Quintile PRS had an 1. 68-times increased odds (1. 16-2. 44, p=0. 006) of reaching this composite endpoint. Conclusion In BioHEART-CT participants with no coronary intervention history, and with low/moderate Absolute CVD Risk, PRS appears helpful in identifying those with any CAD (CACS0) or clinically actionable CAD (CACS≥100AU or 75thpercentile). This finding supports the possible role of PRS in a novel clinical pathway, triaging patients into non-invasive imaging and management of identified plaque. Table 1
Gray et al. (Sat,) reported a other. Participants with top quintile polygenic risk score had 1.79-fold higher odds of any CAD (CACS>0) and 1.68-fold higher odds of clinically actionable CAD (CACS≥100 or >75th percentile).