Author + information
- Received December 7, 2011
- Revision received January 13, 2012
- Accepted January 18, 2012
- Published online December 1, 2012.
- Julian I. Borissoff, MD, PhD⁎,
- Ivo A. Joosen, MD†,
- Mathijs O. Versteylen, MD†,
- Henri M. Spronk, PhD⁎,
- Hugo ten Cate, MD, PhD⁎ and
- Leonard Hofstra, MD, PhD‡,⁎ ( )()
- ↵⁎Reprint requests and correspondence:
Dr. Leonard Hofstra, Cardiology Center Netherlands–Utrecht, Herculesplein 379, 3584 AA, Utrecht, the Netherlands
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.
This study was supported by a Marie Curie fellowship (MEST-CT-2005-020706) from the European Commission (to Dr. Borissoff). Dr. Borissoff is a recipient of a Kootstra Talent Fellowship (2011) from Maastricht University and is supported by a Rubicon fellowship (825.11.019) granted by the Netherlands Organization for Scientific Research (NWO). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Borissoff and Joosen contributed equally to this work.
- Received December 7, 2011.
- Revision received January 13, 2012.
- Accepted January 18, 2012.
- American College of Cardiology Foundation