An integrated risk tool combining a polygenic risk score with pooled cohort equations yielded an overall net reclassification improvement of 5.9% for incident coronary artery disease compared to pooled cohort equations alone.
Cohort (n=186,451)
Yes
Does an integrated risk tool combining a polygenic risk score with established clinical calculators improve predictive accuracy for coronary artery disease events in the general population?
An integrated risk tool combining polygenic risk scores with standard clinical calculators significantly improves coronary artery disease risk stratification and reclassification.
Effect estimate: NRI 5.9% (95% CI 4.7-7.0)
p-value: p=<0.005
BACKGROUND: There is considerable interest in whether genetic data can be used to improve standard cardiovascular disease risk calculators, as the latter are routinely used in clinical practice to manage preventative treatment. METHODS: Using the UK Biobank resource, we developed our own polygenic risk score for coronary artery disease (CAD). We used an additional 60 000 UK Biobank individuals to develop an integrated risk tool (IRT) that combined our polygenic risk score with established risk tools (either the American Heart Association/American College of Cardiology pooled cohort equations PCE or UK QRISK3), and we tested our IRT in an additional, independent set of 186 451 UK Biobank individuals. RESULTS: The novel CAD polygenic risk score shows superior predictive power for CAD events, compared with other published polygenic risk scores, and is largely uncorrelated with PCE and QRISK3. When combined with PCE into an IRT, it has superior predictive accuracy. Overall, 10.4% of incident CAD cases were misclassified as low risk by PCE and correctly classified as high risk by the IRT, compared with 4.4% misclassified by the IRT and correctly classified by PCE. The overall net reclassification improvement for the IRT was 5.9% (95% CI, 4.7-7.0). When individuals were stratified into age-by-sex subgroups, the improvement was larger for all subgroups (range, 8.3%-15.4%), with the best performance in 40- to 54-year-old men (15.4% 95% CI, 11.6-19.3). Comparable results were found using a different risk tool (QRISK3) and also a broader definition of cardiovascular disease. Use of the IRT is estimated to avoid up to 12 000 deaths in the United States over a 5-year period. CONCLUSIONS: An IRT that includes polygenic risk outperforms current risk stratification tools and offers greater opportunity for early interventions. Given the plummeting costs of genetic tests, future iterations of CAD risk tools would be enhanced with the addition of a person's polygenic risk.
Riveros-Mckay et al. (Tue,) conducted a cohort in Coronary Artery Disease (n=186,451). Integrated risk tool (IRT) combining polygenic risk score (PRS) with pooled cohort equations (PCE) vs. Pooled cohort equations (PCE) alone was evaluated on Net reclassification improvement (NRI) for incident CAD (NRI 5.9%, 95% CI 4.7-7.0, p=<0.005). An integrated risk tool combining a polygenic risk score with pooled cohort equations yielded an overall net reclassification improvement of 5.9% for incident coronary artery disease compared to pooled cohort equations alone.
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