Combining polygenic risk score and high platelet reactivity for incremental predictive value of acute myocardial infarction in patients with coronary artery disease with 10-year follow-up
Y Yao, N Xu, X F Lu, J Q Yuan, X Y ZhaoAbstract
Background
Genetic risk affect prognosis of coronary heart disease. High platelet reactivity(HPR) under antiplatelet treatment is associated with increased risks of adverse cardiovascular events.
Purpose
Our study aims to explore whether combining polygenic risk and HPR can provide incremental predictive value for acute myocardial infarction(AMI) risk in patients with 10-year follow-up after percutaneous coronary intervention(PCI).
Methods
Our study included patients who underwent PCI in 2013 and both had Thromboelastography(TEG) platelet function test results and coronary heart disease risk genes genotyping results. HPR was defined as adenosine diphosphate induced platelet-fibrin maximum clot strength(MAADP) > 47mm in TEG test. The risk genes included test were according to the “polygenic risk score model(metaPRS) of coronary artery disease in Chinese cohort” which containing 540 single nucleotide polymorphism sites[1]. Patients were grouped based on the percentiles of metaPRS, evaluated the prognostic value of metaPRS alone or combined HPR in predicting 10-year AMI risk.
Results
A total of 2615 patients were included, among them 760 (29.1%) had HPR, 243(9.3%) occurred AMI. The results showed that metaPRS was independently associated with 10-year AMI risk, and the risk increased with higher percentiles of metaPRS. When grouped as quintiles of metaPRS, the patients of top quintile compared to patients of bottom quintile, the hazard ratio(HR) of AMI were 1.96(95% CI 1.28-2.99, P = 0.001). While other HR of AMI in different percentiles of metaPRS were 1.37 (median), 1.74 (tertiles), and 1.86 (quartiles), respectively. There was no significant association between HPR and 10-year AMI risk (P=0.254). However, when combined with HPR based on metaPRS, the prediction efficiency of AMI risk significantly improved, with HR increasing to 1.58 (median), 1.76 (tertiles), 2.38 (quartiles), and 2.64 (quintiles), respectively. After adjusting for clinical confounding factors by Cox regression analysis, the predictive power was further enhanced. Further dividing patients into six groups according to metaPRS (quintiles) and HPR status (Figure 1), Kaplan-Meier analysis showed significant differences in 10-year cumulative incidence of AMI between six groups (P=0.034). Compared with patients with non-HPR and lowest metaPRS(bottom quintile of the metaPRS), patients with both highest metaPRS (top quintile of the metaPRS) and HPR had the highest risk of myocardial infarction (HR=2.71, 95%CI 1.44-5.07, P=0.002). Notably, regardless of whether with HPR, patients with the lowest metaPRS (bottom quintile of the metaPRS) had lower 10-year AMI risk.
Conclusions
Polygenic risk scores are independent predictors of 10-year AMI risk after PCI in patients with coronary heart disease, and the risk increases with higher scores. Based on polygenic risk scores, combining high platelet reactivity status provides significant incremental prognostic value.