[show abstract][hide abstract] ABSTRACT: BACKGROUND: The usual diagnostic work-up of chest pain patients includes clinical risk profiling and exercise-ECG, possibly followed by additional tests. Recently cardiac computed tomographic angiography (CCTA) has been employed. We evaluated the prognostic value of the combined use of exercise-ECG and CCTA for the development of cardiovascular endpoints. METHODS: In 283 patients (143 male, mean age 54±10years) with intermediate pre-test probability for coronary artery disease presenting with stable chest pain, exercise-ECG, CCTA and calcium score were performed. Patients were followed-up for combined endpoint of acute coronary syndrome (ACS) and revascularization. RESULTS: After a median follow-up of 769days (interquartile range 644-1007), 6 ACS and 9 revascularizations were recorded. A positive exercise-ECG predicted for the combined endpoint, [hazard ratio (HR) 5.14 (95% confidence interval (CI) 1.64-16.13), p=0.005], as well as a positive calcium score [HR 4.59 (95% CI 1.30-16.28), p=0.02] and a ≥50% stenosis on CCTA [HR 45.82 (95% CI 6.02-348.54), p<0.001]. ROC-analysis showed an area under the curve (AUC) of 0.79 (95% CI 0.67-0.90) for exercise-ECG, which increased significantly when CCTA was added: 0.91 (95% CI; 0.86-0.97; p=0.006). Multivariable Cox regression showed exercise-ECG predicted independently [HR 3.6, (95% CI 1.1-11.2), p=0.03], as well as CCTA [HR 31.4 (95% CI 4.0-246.6), p=0.001], but not calcium score [HR 0.6 (95% CI 0.2-2.3), p=0.5]. CONCLUSIONS: The combined subsequent use of exercise-ECG for functional information and CCTA for anatomical information provides a high diagnostic yield in stable chest pain patients with an intermediate pre-test probability for coronary artery disease.
International journal of cardiology 01/2012; · 7.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Vitamin K-antagonists (VKA) are treatment of choice and standard care for patients with venous thrombosis and thromboembolic risk. In experimental animal models as well as humans, VKA have been shown to promote medial elastocalcinosis. As vascular calcification is considered an independent risk factor for plaque instability, we here investigated the effect of VKA on coronary calcification in patients and on calcification of atherosclerotic plaques in the ApoE(-/-) model of atherosclerosis.
A total of 266 patients (133 VKA users and 133 gender and Framingham Risk Score matched non-VKA users) underwent 64-slice MDCT to assess the degree of coronary artery disease (CAD). VKA-users developed significantly more calcified coronary plaques as compared to non-VKA users. ApoE(-/-) mice (10 weeks) received a Western type diet (WTD) for 12 weeks, after which mice were fed a WTD supplemented with vitamin K(1) (VK(1), 1.5 mg/g) or vitamin K(1) and warfarin (VK(1)&W; 1.5 mg/g & 3.0 mg/g) for 1 or 4 weeks, after which mice were sacrificed. Warfarin significantly increased frequency and extent of vascular calcification. Also, plaque calcification comprised microcalcification of the intimal layer. Furthermore, warfarin treatment decreased plaque expression of calcification regulatory protein carboxylated matrix Gla-protein, increased apoptosis and, surprisingly outward plaque remodeling, without affecting overall plaque burden.
VKA use is associated with coronary artery plaque calcification in patients with suspected CAD and causes changes in plaque morphology with features of plaque vulnerability in ApoE(-/-) mice. Our findings underscore the need for alternative anticoagulants that do not interfere with the vitamin K cycle.
PLoS ONE 01/2012; 7(8):e43229. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
We studied 1,088 patients (follow-up 2.2 ± 0.8 years) with chest discomfort who underwent coronary calcium scoring and coronary CT-angiography. Traditional cardiovascular risk factors and concentrations of hs-cTnT, N-terminal pro-brain-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.
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, or CT-angiography assessment (HR 3.11; 2.73; 2.47; respectively; all P<0.01). This was not the case for hsCRP and NT-proBNP.
Hs-cTnT is a useful prognostic biomarker in patients with chest discomfort suspected for coronary artery disease. In addition, hs-cTnT was an independent predictor for cardiac events when corrected for cardiovascular risk profiling, calcium score and CT-angiography results.
PLoS ONE 01/2012; 7(4):e35059. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Both 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.
A 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 m(2)); mild CKD (eGFR 60-89 mL/min/1.73 m(2)); and moderate CKD (eGFR 30-59 mL/min/1.73 m(2)).
Coronary 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.
Although 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.
PLoS ONE 01/2012; 7(10):e47267. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study explored the relationship between coronary atherosclerotic plaque burden and quantifiable circulating levels of troponin measured with a recently introduced high sensitive cardiac troponin T (hs-cTnT) assay.
Cardiac patients suspected of having coronary artery disease (CAD) but without acute coronary syndrome were studied. Cardiac troponin T levels were assessed using the fifth-generation hs-cTnT assay. All patients (n=615) underwent cardiac computed tomographic angiography (CCTA). On the basis of CCTA, patients were classified as having no CAD or mild (<50% lesion), moderate (50% to 70% lesion), severe (>70% lesion), or multivessel CAD (multiple >70% lesions). As a comparison, high-sensitivity C-reactive protein levels were measured. Progressively increasing hs-cTnT levels were found in patients with mild (median, 4.5 ng/L), moderate (median, 5.5 ng/L), severe (median, 5.7 ng/L), and multivessel (median, 8.6 ng/L) CAD compared with patients without CAD (median, 3.7 ng/L) (all P<0.01). For high-sensitivity C-reactive protein and N-terminal pro-B-type natriuretic peptide, no such relationship was observed. In patients without CAD, 11% showed hs-cTnT levels in the highest quartile, compared with 62% in the multivessel disease group (P<0.05). Multivariance analysis identified hs-cTnT as an independent risk factor for the presence of CAD.
In patients without acute coronary syndrome, even mild CAD is associated with quantifiable circulating levels of hs-cTnT.
[show abstract][hide abstract] ABSTRACT: Endurance exercise is frequently associated with cardiac troponin (cTn) concentrations, otherwise corresponding to minor myocardial infarction. However, research on the underlying mechanisms has been limited because of assay restraints in the low concentration range.
Using the pre-commercial, highly sensitive hs-cTnT assay, cTnT concentrations were measured in samples from recreational runners obtained before and after running 5 km (trained, n = 43/untrained, n = 122), 15 km (n = 38), 21 km (n = 10), and 42 km (n = 85) (all trained). The percentage of runners with elevated cTnT concentrations after the run increased with running distance (0, 11, 13, 40, and 86%), in contrast to NT-proBNP (2, 7, 0, 0, 5). Median (IQR) cTnT post-run concentrations were 0.004 microg/L (0.003), 0.006 microg/L (0.008), 0.010 microg/L (0.006), 0.014 microg/L (0.019), and 0.030 microg/L (0.029), respectively.
We found, using a novel hs-cTnT assay, the distance of recreational competitive running to be positively related to asymptomatic increases in cTnT post-run concentrations. In contrast, NT-proBNP showed no increase. In addition, the data indicated that a relatively short running distance of 5 km resulted in cTnT release of untrained participants, in contrast to trained participants, which underlines the necessity of sufficient training. Further effort is needed to clarify the significance of exercise-induced cardiac biomarker elevations.
Clinical Research in Cardiology 03/2010; 99(6):385-91. · 3.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: The ability to identify atherosclerotic plaques that are prone to rupture, also called vulnerable plaques, may provide a major step forward in the recognition of patients that have a high risk of developing acute myocardial infarction. Current clinical risk profiling algorithms, such as the Framingham and Procam risk scores, have reasonable predictive value in the assessment of the 10 year risk. These clinical risk profiling scores typically classify patients into low risk (10-year risk, less than 5%), intermediate risk (5% to 20% risk), and high risk (greater than 20%). The challenge to imagers is to identify the risk that is beyond 2% yearly risk. Molecular imaging may help identify plaque inflammation and apoptosis of inflammatory cells, which are obligatory components of the plaque instability. These processes offer specific biological targets that can potentially be exploited to obtain biological information on atherosclerosis development in the individual patient.