Platelet Reactivity ExpreSsion Score Predicts Cardiovascular Risk

Platelets are key mediators of atherothrombosis; yet, limited tools exist to identify individuals with a hyperreactive platelet phenotype. Here we derive and validate a Platelet Reactivity ExpreSsion Score (PRESS) integrating platelet aggregation responses and RNA sequencing in multiple cohorts. PRESS performs well in identifying a hyperreactive phenotype in patients with cardiovascular disease (AUC [cross-validation] 0.81, 95% CI 0.68 to 0.94), with similar discrimination in an independent cohort of healthy participants (AUC [validation] 0.77, 95% CI 0.75 to 0.79); accuracy 80%, sensitivity 71%, and specificity 86%. Next, we validate PRESS in multiple cohorts of patients with platelet RNASeq available. Following multivariable adjustment, PRESS was significantly higher in MI (β=1.8, p=0.02), and individuals with a score above the median more frequently develop a future cardiovascular event (adjusted HR 1.90, CI 1.07 to 3.36), p=0.027). Altogether, we provide strong evidence that PRESS is a robust prognostic marker, which could have an essential role in facilitating a personalized approach to cardiovascular risk management.