title: Greater collagen-induced platelet aggregation following cyclooxygenase 1 inhibition predicts incident acute coronary syndromes.
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.
authors: GeneSTAR Research Program, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Rehan
authors: R
authors: Qayyum
authors: Diane M
authors: DM
authors: Becker
authors: Lisa R
authors: LR
authors: Yanek
authors: Nauder
authors: N
authors: Faraday
authors: Dhananjay
authors: D
authors: Vaidya
authors: Rasika
authors: R
authors: Mathias
authors: Brian G
authors: BG
authors: Kral
authors: Lewis C
authors: LC
authors: Becker
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000453:epidemiology*; D000328:Adult; D003094:Collagen / Q000494:pharmacology*; D016001:Confidence Intervals; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D016016:Proportional Hazards Models
chemical_list: D016861:Cyclooxygenase Inhibitors; D003094:Collagen; D051545:Cyclooxygenase 1
keywords: acute coronary syndromes; aspirin; collagen; platelet aggregation