title: Accelerated in vivo thrombin formation independently predicts the presence and severity of CT angiographic coronary atherosclerosis.
abstract: OBJECTIVE
  This study sought to investigate the association between thrombin generation in plasma and the presence and severity of computed tomography angiographically defined coronary atherosclerosis in patients with suspected coronary artery disease (CAD).
  
  
  BACKGROUND
  Besides its pivotal role in thrombus formation, experimental data indicate that thrombin can induce an array of pro-atherogenic and plaque-destabilizing effects. Although thrombin plays a role in the pathophysiology of atherosclerosis progression and vascular calcification, the clinical evidence remains limited.
  
  
  METHODS
  Using 64-slice coronary computed tomographic angiography, we assessed the presence and characteristics of CAD in patients (n = 295; median age 58 years) with stable chest pain. Coronary artery calcification was graded as absent (Agatston score 0), mild (Agatston score 1 to 100), moderate (Agatston score 101 to 400), and severe (Agatston score >400). Calibrated automated thrombography was used to assess endogenous thrombin potential in plasma in vitro. Thrombin-antithrombin complex (TATc) levels were measured as a marker for thrombin formation in vivo.
  
  
  RESULTS
  TATc plasma levels were substantially higher in patients with CAD versus patients without CAD (p = 0.004). Significant positive correlations were observed between steadily increasing TATc levels and the severity of CAD (r = 0.225, p < 0.001). In multinomial logistic regression models, after adjusting for established risk factors, TATc levels predicted the degree of coronary artery calcification: mild (odds ratio: 1.56, p = 0.006), moderate (odds ratio: 1.56, p = 0.007), and severe (odds ratio: 1.67, p = 0.002). Trends were comparable between the groups when stratified according to the degree of coronary luminal stenosis.
  
  
  CONCLUSIONS
  This study provides novel clinical evidence indicating a positive independent association between enhanced in vivo thrombin generation and the presence and severity of coronary atherosclerosis, which may suggest that thrombin plays a role in the pathophysiology of vascular calcification and atherosclerosis progression.
authors.affiliation: Laboratory for Clinical Thrombosis and Haemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Julian I
authors.initials: JI
authors.lastname: Borissoff
authors.forename: Ivo A
authors.initials: IA
authors.lastname: Joosen
authors.forename: Mathijs O
authors.initials: MO
authors.lastname: Versteylen
authors.forename: Henri M
authors.initials: HM
authors.lastname: Spronk
authors.forename: Hugo
authors.initials: H
authors.lastname: ten Cate
authors.forename: Leonard
authors.initials: L
authors.lastname: Hofstra
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood* / Q000000981:diagnostic imaging; D015415:Biomarkers / Q000097:blood; D017023:Coronary Angiography / Q000379:methods*; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013917:Thrombin / Q000378:metabolism*; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D013917:Thrombin