PMID- 23236969
OWN - NLM
STAT- MEDLINE
DCOM- 20130521
LR  - 20161125
IS  - 1876-7591 (Electronic)
IS  - 1876-7591 (Linking)
VI  - 5
IP  - 12
DP  - 2012 Dec
TI  - Accelerated in vivo thrombin formation independently predicts the presence and 
      severity of CT angiographic coronary atherosclerosis.
PG  - 1201-10
LID - S1936-878X(12)00683-3 [pii]
LID - 10.1016/j.jcmg.2012.01.023 [doi]
AB  - OBJECTIVES: 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.
CI  - Copyright (c) 2012 American College of Cardiology Foundation. Published by Elsevier 
      Inc. All rights reserved.
FAU - Borissoff, Julian I
AU  - Borissoff JI
AD  - Laboratory for Clinical Thrombosis and Haemostasis, Department of Internal 
      Medicine, Cardiovascular Research Institute Maastricht, Maastricht University 
      Medical Center, Maastricht, the Netherlands.
FAU - Joosen, Ivo A
AU  - Joosen IA
FAU - Versteylen, Mathijs O
AU  - Versteylen MO
FAU - Spronk, Henri M
AU  - Spronk HM
FAU - ten Cate, Hugo
AU  - ten Cate H
FAU - Hofstra, Leonard
AU  - Hofstra L
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - JACC Cardiovasc Imaging
JT  - JACC. Cardiovascular imaging
JID - 101467978
RN  - 0 (Biomarkers)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Atherosclerosis/*blood/diagnostic imaging
MH  - Biomarkers/blood
MH  - Coronary Angiography/*methods
MH  - Coronary Artery Disease/*blood/diagnostic imaging
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Retrospective Studies
MH  - Severity of Illness Index
MH  - Thrombin/*metabolism
MH  - *Tomography, X-Ray Computed
EDAT- 2012/12/15 06:00
MHDA- 2013/05/23 06:00
CRDT- 2012/12/15 06:00
PHST- 2011/12/07 00:00 [received]
PHST- 2012/01/13 00:00 [revised]
PHST- 2012/01/18 00:00 [accepted]
PHST- 2012/12/15 06:00 [entrez]
PHST- 2012/12/15 06:00 [pubmed]
PHST- 2013/05/23 06:00 [medline]
AID - S1936-878X(12)00683-3 [pii]
AID - 10.1016/j.jcmg.2012.01.023 [doi]
PST - ppublish
SO  - JACC Cardiovasc Imaging. 2012 Dec;5(12):1201-10. doi: 10.1016/j.jcmg.2012.01.023.