OBJECTIVE Aberrant neutrophil activation occurs during the advanced stages of atherosclerosis. Once primed, neutrophils can undergo apoptosis or release neutrophil extracellular traps (NETs). This extracellular DNA exerts potent pro-inflammatory, prothrombotic and cytotoxic properties. The goal of this study was to examine the relationships between extracellular DNA formation, coronary atherosclerosis and the presence of a prothrombotic state. APPROACH AND RESULTS In a prospective, observational, cross-sectional cohort of 282 individuals with suspected coronary artery disease (CAD), we examined the severity, extent, and phenotype of coronary atherosclerosis by using coronary computed tomographic angiography (CCTA). Double-stranded DNA, nucleosomes, citrullinated histone H4 and myeloperoxidase (MPO)-DNA complexes, considered in vivo markers of cell death and NETosis, respectively, were established. We further measured various plasma markers of coagulation activation and inflammation. Plasma double-stranded DNA, nucleosomes and MPO-DNA complexes were positively associated with thrombin generation and significantly elevated in patients with severe coronary atherosclerosis or extremely calcified coronary arteries. Multinomial regression analysis, adjusted for confounding factors, identified high plasma nucleosome levels as an independent risk factor of severe coronary stenosis (OR: 2.14, 95% CI 1.26-3.63; p=0.005). Markers of NETs, such as MPO-DNA complexes, predicted the number of atherosclerotic coronary vessels and the occurrence of major adverse cardiac events. CONCLUSIONS Our report provides evidence demonstrating that markers of cell death and NET formation are independently associated with CAD, prothrombotic state and occurrence of adverse cardiac events. These biomarkers could potentially aid in the prediction of cardiovascular risk in patients with chest discomfort.

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 CCTA.

BackgroundCardiologists are often confronted with patients presenting with chest pain, in whom clinical risk profiling is required. We studied four frequently used risk scores in their ability to predict for coronary artery disease (CAD) and major adverse cardiovascular events in patients presenting with stable chest pain at the cardiology outpatient clinic.Methods and ResultsWe enrolled 1,296 stable chest pain patients, who underwent cardiac computed tomographic angiography (CCTA) to assess CAD (any, significant: stenosis ≥50%). Framingham (FRS), PROCAM, SCORE risk score, and Diamond Forrester pre-test probability were calculated. All patients were followed up for a mean 19 ± 9 months for all cardiovascular events (mortality, acute coronary syndrome, revascularization >90 days after CCTA). In ROC-analysis for prediction of significant CAD, the areas under the curve for FRS; 0.68 (95% confidence interval: 0.64-0.72) and for SCORE; 0.69 (95% confidence interval: 0.65-0.72) were significantly higher than for PROCAM; 0.64 (95% confidence interval: 0.61-0.68; P ≤ .001), as well as marginally higher than for Diamond Forrester; 0.65 (95% confidence interval: 0.61-0.68; P ≤ .05). Low FRS category showed the lowest number of patients with significant CAD, compared to patients with low risk using PROCAM, SCORE or Diamond Forrester (P < .001). Also, low FRS category showed less events (compared to PROCAM and SCORE; P < .001, for Diamond Forrester; P = .14).ConclusionOur data show that in a stable chest pain population, the ability of FRS and SCORE to predict for CAD was similar and better compared to PROCAM and Diamond Forrester. The number of low risk patients showing significant CAD or events was lower using FRS. Consequently, risk categorization using FRS seems to be safest to stratify stable chest pain patients prior to CCTA.

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.

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The EAT volume is associated with CAD in DM2, IFG, and control patients. However, EAT is not an independent predictor for CAD in patients presenting with stable chest pain.

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BackgroundBoth end-stage and milder stages of chronic kidney disease (CKD) are associated with an increased risk of adverse cardiovascular events. Several studies found an association between decreasing renal function and increasing coronary artery calcification, but it remains unclear if this association is independent from traditional cardiovascular risk factors. Therefore, the aim of this study was to investigate whether mild to moderate CKD is independently associated with coronary plaque burden beyond traditional cardiovascular risk factors.MethodsA total of 2,038 patients with symptoms of chest discomfort suspected for coronary artery disease underwent coronary CT-angiography. We assessed traditional risk factors, coronary calcium score and coronary plaque characteristics (morphology and degree of luminal stenosis). Patients were subdivided in three groups, based on their estimated glomerular filtration rate (eGFR) Normal renal function (eGFR ≥90 mL/min/1.73 m2); mild CKD (eGFR 60–89 mL/min/1.73 m2); and moderate CKD (eGFR 30–59 mL/min/1.73 m2).ResultsCoronary calcium score increased significantly with decreasing renal function (P<0.001). Coronary plaque prevalence was higher in patients with mild CKD (OR 1.83, 95%CI 1.52–2.21) and moderate CKD (OR 2.46, 95%CI 1.69–3.59), compared to patients with normal renal function (both P<0.001). Coronary plaques with >70% luminal stenosis were found significantly more often in patients with mild CKD (OR 1.67 (95%CI 1.16–2.40) and moderate CKD (OR2.36, 95%CI 1.35–4.13), compared to patients with normal renal function (both P<0.01). After adjustment for traditional cardiovascular risk factors, the association between renal function and the presence of any coronary plaque as well as the association between renal function and the presence of coronary plaques with >70% luminal stenosis becomes weaker and were no longer statistically significant.ConclusionAlthough decreasing renal function is associated with increasing extent and severity of coronary artery disease, mild to moderately CKD is not independently associated with coronary plaque burden after adjustment for traditional cardiovascular risk factors.