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.
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.
Authors: Rajashree Rana; Tianfang Huang; Georgios Koukos; Elizabeth K Fletcher; Susan E Turner; Andrew Shearer; Paul A Gurbel; Jeffrey J Rade; Carey D Kimmelstiel; Kevin P Bliden; Lidija Covic; Athan Kuliopulos Journal: Arterioscler Thromb Vasc Biol Date: 2018-04-05 Impact factor: 8.311
Authors: Julian I Borissoff; Ivo A Joosen; Mathijs O Versteylen; Alexander Brill; Tobias A Fuchs; Alexander S Savchenko; Maureen Gallant; Kimberly Martinod; Hugo Ten Cate; Leonard Hofstra; Harry J Crijns; Denisa D Wagner; Bas L J H Kietselaer Journal: Arterioscler Thromb Vasc Biol Date: 2013-07-01 Impact factor: 8.311
Authors: Ivo A Joosen; Frank Schiphof; Mathijs O Versteylen; Eduard M Laufer; Mark H Winkens; Patricia J Nelemans; Jeroen P Kooman; Leonard Hofstra; Joachim E Wildberger; Tim Leiner Journal: PLoS One Date: 2012-10-10 Impact factor: 3.240
Authors: Julian I Borissoff; Jeroen J T Otten; Sylvia Heeneman; Peter Leenders; René van Oerle; Oliver Soehnlein; Sarah T B G Loubele; Karly Hamulyák; Tilman M Hackeng; Mat J A P Daemen; Jay L Degen; Hartmut Weiler; Charles T Esmon; Joanne van Ryn; Erik A L Biessen; Henri M H Spronk; Hugo ten Cate Journal: PLoS One Date: 2013-02-07 Impact factor: 3.240