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Circulating monocyte-platelet aggregates are a robust marker of platelet activity in cardiovascular disease

  • Author Footnotes
    1 These authors contributed equally to this work.
    Nicole Allen
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY, USA
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Tessa J. Barrett
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY, USA
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  • Yu Guo
    Affiliations
    Division of Biostatistics, Department of Population Health, New York University School of Medicine, New York, NY, USA
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  • Michael Nardi
    Affiliations
    Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY, USA
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  • Bhama Ramkhelawon
    Affiliations
    Division of Vascular Surgery, Department of Surgery, New York University School of Medicine, New York, NY, USA
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  • Caron B. Rockman
    Affiliations
    Division of Vascular Surgery, Department of Surgery, New York University School of Medicine, New York, NY, USA
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  • Judith S. Hochman
    Affiliations
    Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY, USA
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  • Jeffrey S. Berger
    Correspondence
    Corresponding author. Center for the Prevention of Cardiovascular Disease, The Leon H. Charney Division of Cardiology, Marc and Ruti Bell Program in Vascular Biology, New York University School of Medicine, 530 First Ave, SKI-9R, New York, NY, 10016, USA.
    Affiliations
    Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY, USA

    Division of Vascular Surgery, Department of Surgery, New York University School of Medicine, New York, NY, USA

    Division of Hematology, Department of Medicine, New York University School of Medicine, New York, NY, USA
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  • Author Footnotes
    1 These authors contributed equally to this work.

      Highlights

      • Monocyte-platelet aggregates (MPA) are a robust marker of platelet activity and inflammatory monocytes.
      • MPA are higher in patients with cardiovascular disease.
      • MPA are highest in patients with peripheral artery disease (PAD).

      Abstract

      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.

      Graphical abstract

      Keywords

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