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1.  Circulating concentrations of GLP-1 are associated with coronary atherosclerosis in humans 
GLP-1 is an incretine hormone which gets secreted from intestinal L-cells in response to nutritional stimuli leading to pancreatic insulin secretion and suppression of glucagon release. GLP-1 further inhibits gastric motility and reduces appetite which in conjunction improves postprandial glucose metabolism. Additional vasoprotective effects have been described for GLP-1 in experimental models. Despite these vasoprotective actions, associations between endogenous levels of GLP-1 and cardiovascular disease have yet not been investigated in humans which was the aim of the present study.
GLP-1 serum levels were assessed in a cohort of 303 patients receiving coronary CT-angiography due to typical or atypical chest pain.
GLP-1 was found to be positively associated with total coronary plaque burden in a fully adjusted model containing age, sex, BMI, hypertension, diabetes mellitus, smoking, triglycerides, LDL-C (low density lipoprotein cholesterol), hsCRP (high-sensitive C-reactive protein), and eGFR (estimated glomerular filtration rate) (OR: 2.53 (95% CI: 1.12 – 6.08; p = 0.03).
Circulating GLP-1 was found to be positivity associated with coronary atherosclerosis in humans. The clinical relevance of this observation needs further investigations.
PMCID: PMC3765863  PMID: 23953602
GLP-1; Atherosclerosis; Coronary CT angiography
2.  Cost-effectiveness of cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary artery disease in Germany 
Recent studies have demonstrated a superior diagnostic accuracy of cardiovascular magnetic resonance (CMR) for the detection of coronary artery disease (CAD). We aimed to determine the comparative cost-effectiveness of CMR versus single-photon emission computed tomography (SPECT).
Based on Bayes’ theorem, a mathematical model was developed to compare the cost-effectiveness and utility of CMR with SPECT in patients with suspected CAD. Invasive coronary angiography served as the standard of reference. Effectiveness was defined as the accurate detection of CAD, and utility as the number of quality-adjusted life-years (QALYs) gained. Model input parameters were derived from the literature, and the cost analysis was conducted from a German health care payer’s perspective. Extensive sensitivity analyses were performed.
Reimbursement fees represented only a minor fraction of the total costs incurred by a diagnostic strategy. Increases in the prevalence of CAD were generally associated with improved cost-effectiveness and decreased costs per utility unit (ΔQALY). By comparison, CMR was consistently more cost-effective than SPECT, and showed lower costs per QALY gained. Given a CAD prevalence of 0.50, CMR was associated with total costs of €6,120 for one patient correctly diagnosed as having CAD and with €2,246 per ΔQALY gained versus €7,065 and €2,931 for SPECT, respectively. Above a threshold value of CAD prevalence of 0.60, proceeding directly to invasive angiography was the most cost-effective approach.
In patients with low to intermediate CAD probabilities, CMR is more cost-effective than SPECT. Moreover, lower costs per utility unit indicate a superior clinical utility of CMR.
PMCID: PMC3688498  PMID: 23574690
Cost-effectiveness; Cardiovascular magnetic resonance; Scintigraphy; Coronary angiography; Coronary artery disease
5.  Visualization of anomalous origin and course of coronary arteries in 748 consecutive symptomatic patients by 64-slice computed tomography angiography 
Coronary artery anomalies (CAAs) are currently undergoing profound changes in understanding potentially pathophysiological mechanisms of disease. Aim of this study was to investigate the prevalence of anomalous origin and course of coronary arteries in consecutive symptomatic patients, who underwent cardiac 64-slice multidetector-row computed tomography angiography (MDCTA).
Imaging datasets of 748 consecutive symptomatic patients referred for cardiac MDCTA were analyzed and CAAs of origin and further vessel course were grouped according to a recently suggested classification scheme by Angelini et al.
An overall of 17/748 patients (2.3%) showed CAA of origin and further vessel course. According to aforementioned classification scheme no Subgroup 1- (absent left main trunk) and Subgroup 2- (anomalous location of coronary ostium within aortic root or near proper aortic sinus of Valsalva) CAA were found. Subgroup 3 (anomalous location of coronary ostium outside normal "coronary" aortic sinuses) consisted of one patient with high anterior origin of both coronary arteries. The remaining 16 patients showed a coronary ostium at improper sinus (Subgroup 4). Latter group was subdivided into a right coronary artery arising from left anterior sinus with separate ostium (subgroup 4a; n = 7) and common ostium with left main coronary artery (subgroup 4b; n = 1). Subgroup 4c consisted of one patient with a single coronary artery arising from the right anterior sinus (RAS) without left circumflex coronary artery (LCX). In subgroup 4d, LCX arose from RAS (n = 7).
Prevalence of CAA of origin and further vessel course in a symptomatic consecutive patient population was similar to large angiographic series, although these patients do not reflect general population. However, our study supports the use of 64-slice MDCTA for the identification and definition of CAA.
PMCID: PMC2799381  PMID: 20003347
6.  MMP-1 serum levels predict coronary atherosclerosis in humans 
Myocardial infarction results as a consequence of atherosclerotic plaque rupture, with plaque stability largely depending on the lesion forming extracellular matrix components. Lipid enriched non-calcified lesions are considered more instable and rupture prone than calcified lesions. Matrix metalloproteinases (MMPs) are extracellular matrix degrading enzymes with plaque destabilisating characteristics which have been implicated in atherogenesis. We therefore hypothesised MMP-1 and MMP-9 serum levels to be associated with non-calcified lesions as determined by CT-angiography in patients with coronary artery disease.
260 patients with typical or atypical chest pain underwent dual-source multi-slice CT-angiography (0.6-mm collimation, 330-ms gantry rotation time) to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed or non-calcified.
In multivariable regession analysis, MMP-1 serum levels were associated with total plaque burden (OR: 1.37 (CI: 1.02-1.85); p < 0.05) in a model adjusted for age, sex, BMI, classical cardiovascular risk factors, hsCRP, adiponectin, pericardial fat volume and medication. Specification of plaque morphology revealed significant association of MMP-1 serum levels with non-calcified plaques (OR: 1.16 (CI: 1.0-1.34); p = 0.05) and calcified plaques (OR: 1.22 (CI: 1,03-1.45); p < 0.05) while association with mixed plaques was lost in the fully adjusted model. No associations were found between MMP9 serum levels and total plaque burden or plaque morphology.
MMP-1 serum levels are associated with total plaque burden but do not allow a specification of plaque morphology.
PMCID: PMC2754422  PMID: 19751510
7.  Low Adiponectin Levels Are an Independent Predictor of Mixed and Non-Calcified Coronary Atherosclerotic Plaques 
PLoS ONE  2009;4(3):e4733.
Atherosclerosis is the primary cause of coronary artery disease (CAD). There is increasing recognition that lesion composition rather than size determines the acute complications of atherosclerotic disease. Low serum adiponectin levels were reported to be associated with coronary artery disease and future incidence of acute coronary syndrome (ACS). The impact of adiponectin on lesion composition still remains to be determined.
Methodology/Principal Findings
We measured serum adiponectin levels in 303 patients with stable typical or atypical chest pain, who underwent dual-source multi-slice CT-angiography to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed or non-calcified. In bivariate analysis adiponectin levels were inversely correlated with total coronary plaque burden (r = −0.21, p = 0.0004), mixed (r = −0.20, p = 0.0007) and non-calcified plaques (r = −0.18, p = 0.003). No correlation was seen with calcified plaques (r = −0.05, p = 0.39). In a fully adjusted multivariate model adiponectin levels remained predictive of total plaque burden (estimate: −0.036, 95%CI: −0.052 to −0.020, p<0.0001), mixed (estimate: −0.087, 95%CI: −0.132 to −0.042, p = 0.0001) and non-calcified plaques (estimate: −0.076, 95%CI: −0.115 to −0.038, p = 0.0001). Adiponectin levels were not associated with calcified plaques (estimate: −0.021, 95% CI: −0.043 to −0.001, p = 0.06). Since the majority of coronary plaques was calcified, adiponectin levels account for only 3% of the variability in total plaque number. In contrast, adiponectin accounts for approximately 20% of the variability in mixed and non-calcified plaque burden.
Adiponectin levels predict mixed and non-calcified coronary atherosclerotic plaque burden. Low adiponectin levels may contribute to coronary plaque vulnerability and may thus play a role in the pathophysiology of ACS.
PMCID: PMC2649379  PMID: 19266101
8.  Predictive value of coronary calcifications for future cardiac events in asymptomatic patients with diabetes mellitus: A prospective study in 716 patients over 8 years 
To establish an efficient prophylaxis of coronary artery disease reliable risk stratification is crucial, especially in the high risk population of patients suffering from diabetes mellitus. This prospective study determined the predictive value of coronary calcifications for future cardiovascular events in asymptomatic patients with diabetes mellitus.
We included 716 patients suffering from diabetes mellitus (430 men, 286 women, age 55.2 ± 15.2 years) in this study. On study entry all patients were asymptomatic and had no history of coronary artery disease. In addition, all patients showed no signs of coronary artery disease in ECG, stress ECG or echocardiography. Coronary calcifications were determined with the Imatron C 150 XP electron beam computed tomograph. For quantification of coronary calcifications we calculated the Agatston score. After a mean observation period of 8.1 ± 1.1 years patients were contacted and the event rate of cardiac death (CD) and myocardial infarction (MI) was determined.
During the observation period 40 patients suffered from MI, 36 patients died from acute CD. The initial Agatston score in patients that suffered from MI or died from CD (475 ± 208) was significantly higher compared to those without cardiac events (236 ± 199, p < 0.01). An Agatston score above 400 was associated with a significantly higher annualised event rate for cardiovascular events (5.6% versus 0.7%, p < 0.01). No cardiac events were observed in patients with exclusion of coronary calcifications. Compared to the Framingham risk score and the UKPDS score the Agatston score showed a significantly higher diagnostic accuracy in the prediction of MI with an area under the ROC curve of 0.77 versus 0.68, and 0.71, respectively, p < 0.01.
By determination of coronary calcifications patients at risk for future MI and CD could be identified within an asymptomatic high risk group of patients suffering from diabetes mellitus. On the other hand future events could be excluded in patients without coronary calcifications.
PMCID: PMC2569906  PMID: 18847481
9.  Dual-source CT for chest pain assessment 
European Radiology  2007;18(4):773-780.
Comprehensive CT angiography protocols offering a simultaneous evaluation of pulmonary embolism, coronary stenoses and aortic disease are gaining attractiveness with recent CT technology. The aim of this study was to assess the diagnostic accuracy of a specific dual-source CT protocol for chest pain assessment. One hundred nine patients suffering from acute chest pain were examined on a dual-source CT scanner with ECG gating at a temporal resolution of 83 ms using a body-weight-adapted contrast material injection regimen. The images were evaluated for the cause of chest pain, and the coronary findings were correlated to invasive coronary angiography in 29 patients (27%). The files of patients with negative CT examinations were reviewed for further diagnoses. Technical limitations were insufficient contrast opacification in six and artifacts from respiration in three patients. The most frequent diagnoses were coronary stenoses, valvular and myocardial disease, pulmonary embolism, aortic aneurysm and dissection. Overall sensitivity for the identification of the cause of chest pain was 98%. Correlation to invasive coronary angiography showed 100% sensitivity and negative predictive value for coronary stenoses. Dual-source CT offers a comprehensive, robust and fast chest pain assessment.
PMCID: PMC2270358  PMID: 18034246
Chest pain; CT angiography; Coronary artery disease; Pulmonary; Embolism; Aortic dissection

Results 1-9 (9)