Platelet reactivity score may predict heart attack, stroke risk beyond BP, cholesterol
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Key takeaways:
- A new genetics-based score identifies people with platelet hyperreactivity.
- The score could be used to better identify who needs antiplatelet therapy to prevent a first heart attack or stroke.
A platelet reactivity score that identifies people with a hyperreactive platelet phenotype can be used to determine those who might be at elevated risk for a cardiovascular event, researchers reported in Nature Communications.
It has been known for more than 3 decades that increased platelet reactivity is associated with long-term risk for CV events and mortality, but technological barriers have prevented platelet reactivity from being measured routinely and becoming a regular part of calculating a patient’s risk, the researchers wrote.
“This score has been close to a decade in the progress,” Jeffrey S. Berger, MD, MS, director of the Center for Prevention of Cardiovascular Disease at NYU Langone Health and associate professor of medicine and surgery at NYU Grossman School of Medicine, told Healio. “It started from a simple question: We know who to give lipid-lowering therapy by measuring someone’s lipids, we know who to give blood pressure-lowering therapy by measuring someone’s blood pressure, but we do not know in many cases who to give platelet-inhibiting drugs to. It is very difficult to measure platelet activity.”
Genetics-based analysis
Instead of measuring platelet activity directly, a genetics-based analysis can be used to provide information on platelet hyperreactivity, he said.
“Platelets are unique cells — they are anuclear, yet have a transcriptome that affects their function,” Berger, a Healio | Cardiology Today Editorial Board member, said. “We compared the platelet transcriptome between patients with platelet hyperreactivity and those without it. We found a group of platelet genes associated with platelet hyperreactivity.”
Development of the Platelet Reactivity Expression Score (PRESS) began with a cohort of 254 patients from the PACE-PAD study who had peripheral artery disease and were about to undergo lower-extremity revascularization and who had platelet aggregation measured. Berger and colleagues determined that elevated platelet reactivity before lower-extremity revascularization was associated with major adverse CV and limb events at 30 days after revascularization. They then found that 796 genes were expressed differently in patients with elevated platelet reactivity (P < .05), and of those, 451 were correlated with percent aggregation to ephedrine 0.4 µM (P < .05). The PRESS for each patient was derived using a combination of weighted expression values from those 451 genes, the researchers wrote.
In the PACE-PAD cohort, PRESS strongly discriminated patients with platelet hyperreactivity from those without it (area under the curve [cross-validation] = 0.81; 95% CI, 0.68-0.94). In a separate cohort of 35 healthy patients, the researchers were able to validate PRESS (AUC [validation] = 0.77; 95% CI, 0.75-0.79) with 80% accuracy, 71% sensitivity and 86% specificity.
“We found that [PRESS] discriminates platelet hyperreactivity really well,” even in healthy people, Berger told Healio. “That gave us a lot of excitement. But then we needed to see if the score can identify people at high risk for platelet-mediated cardiovascular events. The answer was a phenomenal yes.”
In two additional high-risk cohorts, a PRESS score above the median was associated with elevated risk for major adverse CV events — defined as death, MI and stroke — at 18 months compared with a PRESS score below the median (50.7% vs. 31.9%; adjusted HR = 1.9; 95% CI, 1.07-3.36; P = .027), and when the population was stratified into tertiles, the highest tertile were at higher risk for MACE compared with the lowest tertile (54.3% vs. 28.3%; aHR = 2.39; 95% CI, 1.15-4.98; P = .02), Berger and colleagues found.
The HR was significant even after adjusting for lipid and BP levels, which suggests PRESS can provide useful clinical information beyond lipid test results and BP readings, Berger told Healio.
‘A landmark foundational study’
“We know that blood pressure and cholesterol do not identify people with platelet hyperreactivity,” he said. “Now we have done that in what I think is a landmark foundational study. Where I think this will go is that, using PRESS, we will be able to identify people who have platelet hyperreactivity ... who would most likely have the greatest benefit from an antiplatelet therapy drug, or if they were already on it, a more potent antiplatelet therapy drug.”
Now that the ability to identify people with platelet hyperreactivity has been shown, “future studies will need to validate this in larger populations and to examine whether people with high PRESS would benefit from antiplatelet therapy compared with [determining candidates for antiplatelet therapy] based on age, high blood pressure, diabetes, etc,” Berger told Healio. “In the medical community, there is a lot of uncertainty about who should be on antiplatelet therapy for the prevention of a first heart attack or stroke. For the first time, we provide foundational data to suggest that we can use a circulating genetic score to identify people with increased platelet activity where you don’t have the problem of difficulty of measurement.”
For more information:
Jeffrey S. Berger, MD, MS, can be reached at jeffrey.berger@nyulangone.org. X (Twitter): @plateletdoc.
Perspective
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Dominick J. Angiolillo, MD, PhD, FACC, FESC, FSCAI
While this is indeed a very interesting score and represents a further contribution towards risk stratifying patients based on their platelet function, there are some inherent challenges on how this can be incorporated into routine practice.
Overall, the accuracy of this score is very good. Use of scores that consider markers including pharmacodynamic measures of genetic factors can aid with risk stratifying patients beyond what traditional risk factors do. Therefore, anything that can be done to help identify patients at risk for developing a cardiac event is important.
I believe that the score has the potential for moving the field of personalized antiplatelet therapy forward. However, in order to be embraced in clinical practice in a routine fashion, larger datasets are needed. More importantly, randomized studies showing that using the score to make treatment decisions can improve outcomes represents the most important unmet need.
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