Circulating Monocyte-platelet Aggregates Are a Robust Marker of Platelet Activity in Cardiovascular Disease

Background And Aims: Platelets are a major culprit in the pathogenesis of cardiovascular disease (CVD). Circulating monocyte-platelet aggregates (MPA) represent the crossroads between atherothrombosis and inflammation. However, there is little understanding of the platelets and monocytes that comprise MPA and the prevalence of MPA in different CVD phenotypes. We aimed to establish (1) the reproducibility of MPA over time in circulating blood samples from healthy controls, (2) the effect of aspirin, (3) the relationship between MPA and platelet activity and monocyte subtype, and (4) the association between MPA and CVD phenotype (coronary artery disease, peripheral artery disease [PAD], abdominal aortic aneurysm, and carotid artery stenosis).

Methods And Results: MPA were identified by CD14 monocytes positive for CD61 platelets in healthy subjects and in patients with CVD. We found that MPA did not significantly differ over time in healthy controls, nor altered by aspirin use. Compared with healthy controls, MPA were significantly higher in CVD (9.4% [8.2, 11.1] vs. 21.8% [11.5, 44.1], p < 0.001) which remained significant after multivariable adjustment (β = 9.1 [SER = 3.9], p = 0.02). We found PAD to be associated with a higher MPA in circulation (β = 19.3 [SER = 6.0], p = 0.001), and among PAD subjects, MPA was higher in subjects with critical limb ischemia (34.9% [21.9, 51.15] vs. 21.6% [15.1, 40.6], p = 0.0015), and significance remained following multivariable adjustment (β = 14.77 (SE = 4.35), p = 0.001).

Conclusions: Circulating MPA are a robust marker of platelet activity and monocyte inflammation, unaffected by low-dose aspirin, and are significantly elevated in subjects with CVD, particularly those with PAD.