TY - JOUR
T1 - Accelerated In Vivo Thrombin Formation Independently Predicts the Presence and Severity of CT Angiographic Coronary Atherosclerosis
AU - Borissoff, Julian I.
AU - Joosen, Ivo A.
AU - Versteylen, Mathijs O.
AU - Spronk, Henri M.
AU - ten Cate, Hugo
AU - Hofstra, Leonard
PY - 2012/12
Y1 - 2012/12
N2 - 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. (J Am Coll Cardiol Img 2012; 5: 1201-10)
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. (J Am Coll Cardiol Img 2012; 5: 1201-10)
KW - atherosclerosis
KW - atherothrombosis
KW - coagulation
KW - coronary computed tomography
KW - imaging
KW - thrombin
U2 - 10.1016/j.jcmg.2012.01.023
DO - 10.1016/j.jcmg.2012.01.023
M3 - Article
C2 - 23236969
SN - 1936-878X
VL - 5
SP - 1201
EP - 1210
JO - JACC-Cardiovascular Imaging
JF - JACC-Cardiovascular Imaging
IS - 12
ER -