Accelerated In Vivo Thrombin Formation Independently Predicts the Presence and Severity of CT Angiographic Coronary Atherosclerosis

ObjectivesThis 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).BackgroundBesides 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.MethodsUsing 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.ResultsTATc 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.ConclusionsThis 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

High-Sensitivity Cardiac Troponin T: Risk Stratification Tool in Patients with Symptoms of Chest Discomfort

Background: Recent studies have demonstrated the association between increased concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and the incidence of myocardial infarction, heart failure, and mortality. However, most prognostic studies to date focus on the value of hs-cTnT in the elderly or general population. The value of hs-cTnT in symptomatic patients visiting the outpatient department remains unclear. The aim of this study was to investigate the prognostic value of hs-cTnT as a biomarker in patients with symptoms of chest discomfort suspected for coronary artery disease and to assess its additional value in combination with other risk stratification tools in predicting cardiac events. Methods: We studied 1,088 patients (follow-up 2.260.8 years) with chest discomfort who underwent coronary calcium scoring and coronary CT-angiography. Traditional cardiovascular risk factors and concentrations of hs-cTnT, N-terminal probrain-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP) were assessed. Study endpoint was the occurrence of late coronary revascularization (.90 days), acute coronary syndrome, and cardiac mortality. Results: Hs-cTnT was a significant predictor for the composite endpoint (highest quartile [Q4].6.7 ng/L, HR 3.55; 95%CI 1.88–6.70; P,0.001). Survival analysis showed that hs-cTnT had significant predictive value on top of current risk stratification tools (Chi-square change P,0.01). In patients with hs-cTnT in Q4 versus,Q4, a 2- to 3-fold increase in cardiovascular risk was noticed, either when corrected for high or low Framingham risk score, coronary calcium scoring, o

Additive value of semiautomated quantification of coronary artery disease using cardiac computed tomographic angiography to predict future acute coronary syndrome

The purpose of this study was to investigate whether the use of a semiautomated plaque quantification algorithm (reporting volumetric and geometric plaque properties) provides additional prognostic value for the development of acute coronary syndromes (ACS) as compared with conventional reading from cardiac computed tomography angiography (CCTA). CCTA enables the visualization of coronary plaque characteristics, of which some have been shown to predict ACS. A total of 1,650 patients underwent 64-slice CCTA and were followed up for ACS for a mean 26 ± 10 months. In 25 patients who had ACS and 101 random controls (selected from 993 patients with coronary artery disease but without coronary event), coronary artery disease was evaluated using conventional reading (calcium score, luminal stenosis, morphology), and then independently quantified using semiautomated software (plaque volume, burden area [plaque area divided by vessel area times 100%], noncalcified percentage, attenuation, remodeling). Clinical risk profile was calculated with Framingham risk score (FRS). There were no significant differences in conventional reading parameters between controls and patients who had ACS. Semiautomated plaque quantification showed that compared to controls, ACS patients had higher total plaque volume (median: 94 mm(3) vs. 29 mm(3)) and total noncalcified volume (28 mm(3) vs. 4 mm(3), p ≤ 0.001 for both). In addition, per-plaque maximal volume (median: 56 mm(3) vs. 24 mm(3)), noncalcified percentage (62% vs. 26%), and plaque burden (57% vs. 36%) in ACS patients were significantly higher (p <0.01 for all). A receiver-operating characteristic model predicting for ACS incorporating FRS and conventional CCTA reading had an area under the curve of 0.64; a second model also incorporating semiautomated plaque quantification had an area under the curve of 0.79 (p <0.05). The semiautomated plaque quantification algorithm identified several parameters predictive for ACS and provided incremental prognostic value over clinical risk profile and conventional CT reading. The application of this tool may improve risk stratification in patients undergoing CCT