title: Calprotectin and platelet aggregation in patients with stable coronary artery disease.
abstract: BACKGROUND
  Recent studies suggest that the inflammation-associated protein calprotectin may be implicated in the pathogenesis of coronary artery disease (CAD). However, the impact of calprotectin levels on platelet aggregation in CAD patients has never been investigated.
  
  
  OBJECTIVE
  We investigated the association between calprotectin levels and platelet aggregation in stable, high-risk CAD patients receiving aspirin as mono antiplatelet therapy. Furthermore, we aimed to investigate independent clinical and laboratory determinants of calprotectin levels.
  
  
  METHODS
  We performed a cross-sectional study including 581 stable, high-risk CAD patients. All patients received 75 mg aspirin daily as mono antiplatelet therapy. Platelet aggregation was assessed by 1) impedance aggregometry (Multiplate Analyzer) using arachidonic acid (AA) and collagen as agonists and by 2) the VerifyNow Aspirin Assay. Low-grade inflammation was evaluated by calprotectin, high-sensitive C-reactive-protein (hs-CRP) and interleukin-6. Platelet activation was assessed by soluble P-selectin, and cyclooxygenase-1 inhibition was evaluated by serum thromboxane B2, both measured by ELISA.
  
  
  RESULTS
  Calprotectin levels correlated positively with platelet aggregation according to Multiplate Analyzer (r=0.12, p=0.01). Additionally, calprotectin was positively associated with leukocytes (r=0.33, p<0.0001), hs-CRP (r=0.31, p<0.0001), interleukin-6 (r=0.28, p<0.0001), soluble P-selectin (r=0.10, p=0.02) and serum thromboxane B2 (r=0.10, p=0.02). Type 2 diabetes mellitus was an independent predictor of increased calprotectin levels (p=0.004), and trends were seen for body mass index (p=0.06) and smoking (p=0.07). Compliance with aspirin was confirmed by low serum thromboxane B2 levels in all patients (median [25%;75%]: 1.07 [0.52;1.87] ng/mL).
  
  
  CONCLUSIONS
  Calprotectin levels correlated positively, though weakly, with platelet aggregation and activation as well as serum thromboxane B2 in high-risk, stable CAD patients treated with aspirin.
authors.affiliation: Department of Cardiology, Aarhus University Hospital, DK-8200, Aarhus N, Denmark.
authors.forename: Sanne Bøjet
authors.initials: SB
authors.lastname: Larsen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, DK-8200, Aarhus N, Denmark.
authors.forename: Erik Lerkevang
authors.initials: EL
authors.lastname: Grove
authors.affiliation: Department of Cardiology, Aarhus University Hospital, DK-8200, Aarhus N, Denmark.
authors.forename: Manan
authors.initials: M
authors.lastname: Pareek
authors.affiliation: Department of Cardiology, Aarhus University Hospital, DK-8200, Aarhus N, Denmark; Faculty of Health Sciences, Aarhus University, DK-8200, Aarhus N, Denmark.
authors.forename: Steen Dalby
authors.initials: SD
authors.lastname: Kristensen
authors.affiliation: Faculty of Health Sciences, Aarhus University, DK-8200, Aarhus N, Denmark; Department of Clinical Biochemistry, Aarhus University Hospital, DK-8200, Aarhus N, Denmark.
authors.forename: Anne-Mette
authors.initials: AM
authors.lastname: Hvas
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D039841:Leukocyte L1 Antigen Complex / Q000097:blood*; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D013929:Thromboxane B2 / Q000097:blood
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D039841:Leukocyte L1 Antigen Complex; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D002097:C-Reactive Protein; D001241:Aspirin