Greater collagen-induced platelet aggregation following cyclooxygenase 1 inhibition predicts incident acute coronary syndromes

Clin Transl Sci. 2015 Feb;8(1):17-22. doi: 10.1111/cts.12195. Epub 2014 Jul 25.

Abstract

Greater ex vivo platelet aggregation to agonists may identify individuals at risk of acute coronary syndromes (ACS). However, increased aggregation to a specific agonist may be masked by inherent variability in other activation pathways. In this study, we inhibited the cyclooxygenase-1 (COX1) pathway with 2-week aspirin therapy and measured residual aggregation to collagen and ADP to determine whether increased aggregation in a non-COX1 pathway is associated with incident ACS. We assessed ex vivo whole blood platelet aggregation in 1,699 healthy individuals with a family history of early-onset coronary artery disease followed for 6±1.2 years. Incident ACS events were observed in 22 subjects. Baseline aggregation was not associated with ACS. After COX1 pathway inhibition, collagen-induced aggregation was significantly greater in participants with ACS compared with those without (29.0 vs. 23.6 ohms, p < 0.001). In Cox proportional hazards models, this association remained significant after adjusting for traditional cardiovascular risk factors (HR = 1.10, 95%CI = 1.06-1.15; p < 0.001). In contrast, ADP-induced aggregation after COX1 inhibition was not associated with ACS. After COX1 pathway inhibition, subjects with greater collagen-induced platelet aggregation demonstrated a significant excess risk of incident ACS. These data suggest that platelet activation related to collagen may play an important role in the risk of ACS.

Keywords: acute coronary syndromes; aspirin; collagen; platelet aggregation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood*
  • Acute Coronary Syndrome / epidemiology*
  • Adult
  • Collagen / pharmacology*
  • Confidence Intervals
  • Cyclooxygenase 1 / metabolism*
  • Cyclooxygenase Inhibitors / pharmacology*
  • Female
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Platelet Aggregation / drug effects*
  • Proportional Hazards Models

Substances

  • Cyclooxygenase Inhibitors
  • Collagen
  • Cyclooxygenase 1