Abstract 505: Circulating Monocyte-Platelet Aggregates are Different Across Phenotypes of Vascular Disease

Abstract

Background: Platelets are a major culprit in the pathogenesis of cardiovascular disease (CVD). Although vascular disease in different arterial beds share common risk factors, the role of platelet activity may differ by vascular bed. Clinical trials suggest that more potent antiplatelet therapy is needed in lower extremity peripheral artery disease (PAD) than coronary artery disease (CAD). We investigated circulating monocyte platelet aggregates (MPA), a reproducible ex vivo measurement of platelet activity, in patients with CVD (PAD, CAD, carotid artery stenosis [CAS], and abdominal aortic aneurysm [AAA]) and disease controls. Methods: Subjects with CVD (n=351) and disease controls (n=73) had MPA measured using strict quality control, all of whom were on aspirin monotherapy. MPA were identified by CD14/CD61 positivity. Data is represented as median (IQR, interquartile range). Wilcoxon rank sum, Wilcoxon signed rank, and multivariable linear regression were used to analyze data. Results: Platelets aggregated with monocytes had a higher platelet surface expression of PAC-1, P-selectin, and CD40 versus platelets not aggregated with monocytes (P<0.05 for each comparison). Compared with controls, MPA was significantly higher in CVD (14.5 [10.3, 27.8] vs. 9.4 [8.2, 11.5], P<0.001) which remained significant after multivariable adjustment for demographics and risk factors (β=9.1 (SER=3.9), P=0.02). For each vascular disease phenotype, MPA was higher than controls ( Figure ). In a multivariable linear regression model including demographics, risk factors and each vascular bed, PAD was the only vascular disease associated with a higher value of MPA (β=10.2 (SER=2.4), P<0.001). Conclusions: Platelets aggregated with monocytes have increased platelet activity and are significantly elevated in subjects with PAD. Future studies understanding the platelet profile in PAD and its clinical relevance are needed.