A Platelet Reactivity ExpreSsion Score derived from patients with peripheral artery disease predicts cardiovascular risk

Jeffrey S. Berger (), Macintosh G. Cornwell, Yuhe Xia, Matthew A. Muller, Nathaniel R. Smilowitz, Jonathan D. Newman, Florencia Schlamp, Caron B. Rockman, Kelly V. Ruggles, Deepak Voora, Judith S. Hochman and Tessa J. Barrett ()
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Jeffrey S. Berger: New York University Grossman School of Medicine
Macintosh G. Cornwell: New York University Grossman School of Medicine
Yuhe Xia: New York University Grossman School of Medicine
Matthew A. Muller: New York University Grossman School of Medicine
Nathaniel R. Smilowitz: New York University Grossman School of Medicine
Jonathan D. Newman: New York University Grossman School of Medicine
Florencia Schlamp: New York University Grossman School of Medicine
Caron B. Rockman: New York University Grossman School of Medicine
Kelly V. Ruggles: New York University Grossman School of Medicine
Deepak Voora: Duke University School of Medicine
Judith S. Hochman: New York University Grossman School of Medicine
Tessa J. Barrett: New York University Grossman School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract Platelets are key mediators of atherothrombosis, yet, limited tools exist to identify individuals with a hyperreactive platelet phenotype. In this study, we investigate the association of platelet hyperreactivity and cardiovascular events, and introduce a tool, the Platelet Reactivity ExpreSsion Score (PRESS), which integrates platelet aggregation responses and RNA sequencing. Among patients with peripheral artery disease (PAD), those with a hyperreactive platelet response (>60% aggregation) to 0.4 µM epinephrine had a higher incidence of the 30 day primary cardiovascular endpoint (37.2% vs. 15.3% in those without hyperreactivity, adjusted HR 2.76, 95% CI 1.5–5.1, p = 0.002). PRESS performs well in identifying a hyperreactive phenotype in patients with PAD (AUC [cross-validation] 0.81, 95% CI 0.68 –0.94, n = 84) and in an independent cohort of healthy participants (AUC [validation] 0.77, 95% CI 0.75 –0.79, n = 35). Following multivariable adjustment, PAD individuals with a PRESS score above the median are at higher risk for a future cardiovascular event (adjusted HR 1.90, CI 1.07–3.36; p = 0.027, n = 129, NCT02106429). This study derives and validates the ability of PRESS to discriminate platelet hyperreactivity and identify those at increased cardiovascular risk. Future studies in a larger independent cohort are warranted for further validation. The development of a platelet reactivity expression score opens the possibility for a personalized approach to antithrombotic therapy for cardiovascular risk reduction.

Date: 2024
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DOI: 10.1038/s41467-024-50994-7

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