Abstract
Background: Cell derived microparticles (MP) are useful biomarkers in various thrombotic and inflammatory disorders. However, MP are heterogeneous in their phenotypes, functional properties, and origin. Platelet-derived microparticles (PMP) have been shown to be elevated in acute coronary syndromes but different species of PMP have not been compared. We performed a study to compare two subspecies of PMP, those identified by anti-GP-IIb/IIIa vs. those by CD31+/CD42+, for predicting adverse outcomes in patients with chest pain of possible ischemic cause.Methods: The study population consisted of 105 patients who presented to the emergency department with chest pain, non-diagnostic electrocardiograms and negative serial cardiac troponin I levels. Blood was obtained after the third negative troponin result for determination of levels of GP-IIb/IIIa positive PMP (PMPIIb/IIIa) and CD31+/CD42+ PMP (PMP31). All treatment decisions were left at the caregiver's discretion. Telephone follow-up was done at 6 months for the development of a combined endpoint of death, myocardial infarction or need for cardiac catheterization or revascularization. The mean age of our patients was 57.5 years. The age, diabetes, hypertension, smoking and history of coronary artery disease was not significantly different between patients who reached an endpoint at 6 months versus those who did not. Overall 19% reached an endpoint at 6 months. The endpoint was largely driven by the need for cardiac catheterization due to positive stress test results.Results: On univariate analysis, patients who reached an endpoint at 6 months had higher levels of PMPIIb/IIIa than those who did not (geometric means 2059.6 vs. 924.4 counts/μL; p=0.04; medians 2157.5 vs 1764.0 counts/μL; p=0.009). When adjusted for age, diabetes, hypertension, dyslipidemia, aspirin use and current smoking by analysis of covariance, the difference persisted (adjusted geometric means: 2484.9 vs. 829.5 counts/μL; p=0.01). In contrast, PMP31 levels were not significantly different between patients who reached an endpoint at 6 months versus those who did not (5908 ±7990 vs. 3812 ±3109 counts/μL; p=0.26).Conclusions: Our findings suggest that different subspecies of PMPs may reflect different pathophysiological phenomena. PMP31 levels did not correlate with the risk of adverse outcomes in this population. In contrast, GpIIb/IIIa-positive PMP appear to be promising prognostic indicators in chest pain patients with negative troponins and nondiagnostic EKGs. Our results are consistent with prior studies showing association between PMP and thrombosis, but suggest that not all PMP are equal. Further research is needed to investigate a possible role of PMP in the pathogenesis of ACS, and as prognostic markers in current stratification strategies. Assay of different species of MP is likely to provide more discriminating diagnostic and prognostic information.
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