Combining European and US risk prediction models with polygenic risk scores to refine cardiovascular prevention: the CoLaus|PsyCoLaus Study
Combining European and US risk prediction models with polygenic risk scores to refine cardiovascular prevention: the CoLaus|PsyCoLaus Study
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DOI：
10.1093/eurjpc/zwad012
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发表时间：
2023-02-01
影响因子：
8.3
通讯作者：
Vaucher，Julien
中科院分区：
文献类型：
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作者：
de La Harpe，Roxane;Thorball，Christian W.;Vaucher，Julien
AimsA多基因风险评分（PRS）具有改善个体动脉粥样硬化性心血管疾病（ASCVD）风险评估的潜力。为了确定PRS与两种临床风险评分相结合，系统冠状动脉风险评估2 （SCORE2）和合并队列方程（PCE）是否能改善ASCVD的预测。方法和结果采用以人群为基础的欧洲前瞻性队列，在基线（2003-2006年）有6733名参与者，将具有最佳预测准确性的PRS与SCORE2和PCE结合，评估它们在预测ASCVD方面的联合性能。4218名受试者（53%为女性，中位年龄53.4岁），363名ASCVD流行和发生率，用于比较4种PRSs。metaGRS_CAD PRS具有最佳的预测能力（AUROC = 0.77），并用于以下分析。3383名受试者（中位随访14.4年），其中190名首次发生ASCVD，用于ASCVD风险预测。SCORE2和PCE模型与metaGRS_CAD与SCORE2和PCE联合模型的C统计量变化分别为0.008 （95% CI, - 0.00008-0.02，P= 0.05）和0.007 （95% CI, 0.005-0.01，P= 0.03）。对于临床判定为中度危险的患者，两项临床评分的重新分类都得到了改善[SCORE2和PCE的NRI分别为9.6% （95% CI, 0.3-18.8）和12.0% (95% CI, 1.5-22.6)]。结论将PRS与临床风险评分相结合，可显著提高临床确定的中等风险类别受试者发生ASCVD风险的重新分类。在临床实践中引入PRSs可以改善预防策略不确定的亚组患者的心血管预防。
AimsA polygenic risk score (PRS) has the potential to improve individual atherosclerotic cardiovascular disease (ASCVD) risk assessment. To determine whether a PRS combined with two clinical risk scores, the Systematic COronary Risk Evaluation 2 (SCORE2) and the Pooled Cohort Equation (PCE) improves the prediction of ASCVD.Methods and resultsUsing a population-based European prospective cohort, with 6733 participants at the baseline (2003–2006), the PRS presenting the best predictive accuracy was combined with SCORE2 and PCE to assess their joint performances for predicting ASCVD Discrimination, calibration, Cox proportional hazard regression, and net reclassification index were assessed. : 4218 subjects (53% women; median age, 53.4 years), with 363 prevalent and incident ASCVD, were used to compare four PRSs. The metaGRS_CAD PRS presented the best predictive capacity (AUROC = 0.77) and was used in the following analyses. 3383 subjects (median follow-up of 14.4 years), with 190 first-incident ASCVD, were employed to test ASCVD risk prediction. The changes in C statistic between SCORE2 and PCE models and those combining metaGRS_CAD with SCORE2 and PCE were 0.008 (95% CI, −0.00008–0.02,P= 0.05) and 0.007 (95% CI, 0.005–0.01,P= 0.03), respectively. Reclassification was improved for people at clinically determined intermediate-risk for both clinical scores [NRI of 9.6% (95% CI, 0.3–18.8) and 12.0% (95% CI, 1.5–22.6) for SCORE2 and PCE, respectively].ConclusionCombining a PRS with clinical risk scores significantly improved the reclassification of risk for incident ASCVD for subjects in the clinically determined intermediate-risk category. Introducing PRSs in clinical practice may refine cardiovascular prevention for subgroups of patients in whom prevention strategies are uncertain.