Researchers Develop Tool That Reliably Predicts Blood Platelet Hyperreactivity and Risk of Stroke

Results of a study published in Nature Communications reveal the association between platelet hyperreactivity and cardiovascular risk in certain patient populations. In their article, the researchers presented a new tool, the Platelet Reactivity ExpreSsion Score (PRESS), which integrates platelet aggregation responses along with RNA sequencing data. Compared with traditional platelet aggregation testing, PRESS provides a consistent and reliable method to predict platelet hyperreactivity, which is associated with increased risk for cardiovascular events, including stroke.

The PACE-PAD study (NCT02106429) included 287 participants with peripheral artery disease (PAD) who received a lower extremity revascularization (LER) at New York University (NYU) Langone Health: Manhattan Campus, Bellevue Hospital, or Veterans Affairs New York Harbor Healthcare System. Prior to the LER procedure, platelet aggregation was measured in 254 participants.

Researchers found that those with a hyperreactive platelet response (>60% aggregation) to 0.4 µM epinephrine had a more than a 50% increased incidence of stroke, heart attack, acute limb ischemia, or major amputation within 30 days following the LER procedure (37.2% vs 15.3% in those without hyperreactivity [adjusted HR, 2.76; 95% CI, 1.5 to 5.1; P=.002]).

Researchers employed RNA sequencing techniques to identify differences in gene expression that correlated with a hyperreactive platelet response from 129 study participants whose genetic material was collected prior to the LER procedure. They found an association between 451 gene transcripts and platelet hyperreactivity and generated a weighted PRESS score for participants in the study.

According to subsequent analysis, the PRESS score was accurate in identifying a platelet hyperreactive phenotype in both patients with PAD (AUC [cross-validation], 0.81; 95% CI, 0.68 to 0.94; n=84) and in an independent cohort of healthy participants (AUC [validation], 0.77; 95% CI 0.75 to 0.79; n=35). Individuals with PAD who had a PRESS score above the median were at higher risk for a future cardiovascular event (adjusted HR, 1.90; CI, 1.07 to 3.36; P=.027).

"Our results demonstrate that our new platelet-centric scoring system can, for the first time and across populations, circumvent aggregometry to reliably predict platelet hyperreactivity and the related risk of cardiovascular events," said Jeffrey Berger, MD, Study Author and Director of the Center for the Prevention of Cardiovascular Disease at NYU Grossman School of Medicine. "PRESS promises to help physicians confine anti-platelet treatment to the people most likely to benefit: those with platelet hyperreactivity."