Influence of irregular heart rhythm on radiation exposure, image quality and diagnostic impact of cardiac computed tomography angiography in 4,339 patients. Data from the German Cardiac Computed Tomography Registry.

BACKGROUND: Coronary computed tomography angiography (coronary CTA) provides non-invasive evaluation of the coronary arteries with high precision for the detection of significant coronary artery disease (CAD). AIM: To investigate whether irregular heart rhythm including atrial fibrillation and premature beats during data acquisition influences (i) radiation and contrast media exposure, (ii) number of non-evaluable coronary segments and (iii) diagnostic impact of coronary CTA. METHODS: Twelve tertiary care centers with ≥64 slice CT scanners and ≥5 years of experience with cardiovascular imaging participated in this registry. Between 2009 and 2014, 4339 examinations were analysed in patients who underwent clinically indicated coronary CTA for suspected CAD. Clinical and epidemiologic data were gathered from all patients. In addition, clinical presentation, heart rate and rhythm during the scan, Agatston score, radiation and contrast media exposure and the diagnostic impact of coronary CTA were systematically analysed. RESULTS: Of 4339 patients in total, 260 (6.0%) had irregular heart rhythm, whereas the remaining 4079 (94.0%) had stable sinus rhythm. Patients with irregular heart rhythm were older (63.2 ± 12.5yrs versus 58.6 ± 11.4yrs. p < 0.001), exhibited a higher rate of pathologic stress tests before CTA (37.1% versus 26.1%, p < 0.01) and higher heart rates during CTA compared to those with sinus rhythm (62.5 ± 11.6bpm versus 58.9 ± 8.5bpm, p < 0.001). Both contrast media exposure and radiation exposure were significantly higher in patients with irregular heart rhythm (90 mL (95%CI = 80-110 mL) versus 80 mL (95%CI = 70-90 mL) and 6.2 mSv (95%CI = 2.5-11.7) versus 3.3 mSv (95%CI = 1.7-6.9), p < 0.001 for both). Coronary CTA excluded significant CAD less frequently in patients with irregular heart rhythm (32.9% versus 44.8%, p < 0.001). This was attributed to the higher rate of examinations with at least one non-diagnostic coronary segment in patients with irregular heart rhythm (10.8% versus 4.6%, p < 0.001). Subsequent invasive angiography could be avoided in 47.2% of patients with irregular heart rhythm compared to 52.9% of patients with sinus rhythm (p = NS), whereas downstream stress testing was recommended in 3.2% of patients with irregular heart rhythm versus 4.0% of patients with sinus rhythm (p = NS). CONCLUSION: A significant number of patients scheduled for coronary CTA have irregular heart rhythm in a real-world clinical setting. In such patients, heart rate during coronary CTA is higher, possibly resulting in (i) higher radiation and contrast agent exposure and (ii) more frequent coronary CTA examinations with at least one non-diagnostic coronary artery segment. However, this does not seem to lead to increased downstream stress testing or subsequent invasive procedures.

Declining radiation dose of coronary computed tomography angiography: German cardiac CT registry experience 2009-2014.

BACKGROUND: Coronary computed tomography angiography (CTA) is increasingly used as a test to rule out coronary artery disease (CAD) in patients with a low to intermediate pre-test probability of the disease. We used the database of the German CT registry, collected between 2009 and 2014 in a broad patient population, to analyze contemporary radiation dose associated with coronary CTA in clinical practice. PATIENTS AND METHODS: The prospective observational registry included a total of 7061 patients ≥18 years, referred to 12 participating centers for a clinically indicated cardiac CT examination. All centers were cardiology units well experienced in CTA and used multi-slice CT scanners with at least 64 rows. Coronary CTA was performed in a subset of 5001 patients, 59.6 ± 11.8 years, body mass index (BMI) 26.9 ± 4.5 kg/m2, 38% females. Three time periods with approximately equal numbers of patients were created (01/09-03/10, 04/10-03/11, 04/11-07/14). The dose-length product of all examinations and derived effective dose in mSv (conversion factor k = 0.014) as well as the influence of patient characteristics on dose were compared for the three time periods. RESULTS: BMI and proportion of female patients remained stable over time, and mean heart rate decreased from 60.3 ± 9.0 to 58.5 ± 9.3 bpm from the first to the last time period (p < 0.001). Overall, the mean effective dose of coronary CTA was 3.6 mSv (Q1 1.8 mSv, Q3 7.4 mSv). Within the three time periods, it declined from 5.6 (2.7, 8.6) mSv during the first to 4.8 (2.1, 8.2) mSv during the second and 2.5 (1.3, 4.6) mSv during the last time period (p < 0.001). Paralleling the decline in radiation dose over time, the proportion of prospectively ECG-triggered examinations increased (68, 79, 83%; p < 0.001), and the proportion of examinations with retrospective gating and no tube current modulation decreased (5.3, 4.0, 1.6%; p < 0.001). Tube current (mAs) and voltage (kV) both decreased over time. In multivariable analysis, besides earlier time period, further independent predictors of an increased radiation dose were older age, higher heart rate, and higher BMI as well as the technical factors higher mAs, higher kV, and retrospective gating. At three sites, CT scanners with improved technology were installed during the last time period. CONCLUSIONS: In current clinical practice among German cardiology units with specific expertise in cross-sectional cardiovascular imaging, overall radiation dose of coronary CTA was comparably low. Over time, a decline in radiation dose was demonstrated, probably due to a combination of improvements in data acquisition protocols and patient preparation as well as installation of new CT scanners with advanced technology.

Sitagliptin plus granulocyte colony-stimulating factor in patients suffering from acute myocardial infarction: A double-blind, randomized placebo-controlled trial of efficacy and safety (SITAGRAMI trial).

OBJECTIVE: In animal models, G-CSF based progenitor cell mobilization combined with a DPP4 inhibitor leads to increased homing of bone marrow derived progenitor cells to the injured myocardium via the SDF1/CXCR4 axis resulting in improved ejection fraction and survival after acute myocardial infarction (AMI). RESEARCH DESIGN AND METHODS: After successful revascularization in AMI, 174 patients were randomized 1:1 in a multi-centre, prospective, placebo-controlled, parallel group, double blind, phase III efficacy and safety trial to treatment with G-CSF and Sitagliptin (GS) or placebo. Diabetic and non-diabetic patients were included in our trial. The primary efficacy endpoint hierarchically combined global left and right ventricular ejection fraction changes from baseline to 6 months of follow-up (ΔLVEF, ΔRVEF), as determined by cardiac MRI. RESULTS: At follow-up ΔLVEF as well as ΔRVEF did not differ between the GS and placebo group. Patients in the placebo group had a similar risk for a major adverse cardiac event within 12 months of follow-up as compared to patients under GS. CONCLUSION: Progenitor cell therapy comprising the use of G-CSF and Sitagliptin after successfully revascularized acute myocardial infarction fails to show a beneficial effect on cardiac function and clinical events after 12 months. (EudraCT: 2007-003,941-34; ClinicalTrials.gov: NCT00650143, funding: Heinz-Nixdorf foundation).

Magnetic resonance myocardial perfusion imaging at 3.0 Tesla for the identification of myocardial ischaemia: comparison with coronary catheter angiography and fractional flow reserve measurements.

AIMS: To assess image quality and diagnostic performance of 3.0 Tesla (3T) cardiac magnetic resonance (CMR) myocardial perfusion imaging with a dual radiofrequency source to detect functional relevant coronary artery disease (CAD), using coronary angiography and invasive pressure-derived fractional flow reserve (FFR) as reference standard. METHODS AND RESULTS: We included 116 patients with suspected or known CAD, who underwent 3T adenosine myocardial perfusion CMR (resolution 2.97 × 2.97 mm) and coronary angiography plus FFR measurements in intermediate lesions. Image quality of myocardial perfusion CMR was graded on a 4-point scale (1 = poor to 4 = excellent). Diagnostic accuracy was assessed by ROC analyses using a 16-myocardial segment-based summed perfusion score (0 = normal to 3 = transmural perfusion defect) and by determining sensitivity, specificity, positive and negative predictive value on the coronary vessel territory and the patient level. Diagnostic image quality was achieved for all stress myocardial perfusion CMR studies with an average quality score of 2.5, 3.1, and 3.0 for LAD, LCX, and RCA territories. The ability of the myocardial perfusion CMR perfusion score to detect significant coronary artery stenosis yielded an area under the curve of 0.93 on ROC analysis. Values for sensitivity, specificity, positive and negative predictive value on a vessel territory level and the patient level were 89, 95, 87, 96% and 85, 87, 77, 92%, respectively. CONCLUSION: In patients with suspected or known significant CAD, 3T myocardial perfusion CMR with standard perfusion protocols provides consistently high image quality and an excellent diagnostic performance.

Circulating concentrations of GLP-1 are associated with coronary atherosclerosis in humans.

BACKGROUND: 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. METHODS: GLP-1 serum levels were assessed in a cohort of 303 patients receiving coronary CT-angiography due to typical or atypical chest pain. RESULTS: 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). CONCLUSION: Circulating GLP-1 was found to be positivity associated with coronary atherosclerosis in humans. The clinical relevance of this observation needs further investigations.

Myocardium: dynamic versus single-shot CT perfusion imaging.

PURPOSE: To determine the diagnostic accuracy of dynamic computed tomographic (CT) perfusion imaging of the myocardium for the detection of hemodynamically relevant coronary artery stenosis compared with the accuracy of coronary angiography and fractional flow reserve (FFR) measurement. MATERIALS AND METHODS: This study was approved by the institutional review board and the Federal Radiation Safety Council (Bundesamt für Strahlenschutz). All patients provided written informed consent. Thirty-two consecutive patients in adenosine stress conditions underwent dynamic CT perfusion imaging (14 consecutive data sets) performed by using a 256-section scanner with an 8-cm detector and without table movement. Time to peak, area under the curve, upslope, and peak enhancement were determined after calculation of time-attenuation curves. In addition, myocardial blood flow (MBF) was determined quantitatively. Results were compared with those of coronary angiography and FFR measurement by using a receiver operating characteristic (ROC) analysis. In addition, threshold values based on the Youden index and sensitivity and specificity were calculated. RESULTS: Area under the ROC curve, sensitivity, and specificity, respectively, were 0.67, 41.4% (95% confidence interval [CI]: 23.5%, 61.1%), and 86.6% (95% CI: 76.0%, 93.7%) for time to peak; 0.74, 58.6% (95% CI: 38.9%, 76.5%), and 83.6% (95% CI: 72.5%, 91.5%) for area under the curve; 0.87, 82.8% (95% CI: 64.2%, 94.1%), and 88.1% (95% CI: 77.8%, 94.7%) for upslope; 0.83, 82.8% (95% CI: 64.2%, 94.1%), and 89.6% (95% CI: 79.6%, 95.7%) for peak enhancement; and 0.86, 75.9% (95% CI: 56.5%, 89.7%), and 100% (95% CI: 94.6%, 100%) for MBF. The thresholds determined by using the Youden index were 148.5 HU · sec for area under the curve, 12 seconds for time to peak, 2.5 HU/sec for upslope, 34 HU for peak enhancement, and 1.64 mL/g/min for MBF. CONCLUSION: The semiquantitative parameters upslope and peak enhancement and the quantitative parameter MBF showed similar high diagnostic accuracy. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13121441/-/DC1.

Fully automated derivation of coronary artery calcium scores and cardiovascular risk assessment from contrast medium-enhanced coronary CT angiography studies.

OBJECTIVES: Performance evaluation of a fully automated system for calculating computed tomography (CT) coronary artery calcium scores from contrast medium-enhanced coronary CT angiography (cCTA) studies. METHODS: One hundred and twenty-seven patients (58 ± 11 years, 71 men) who had undergone cCTA as well as an unenhanced CT calcium scoring study where included. Calcium scores were computed from cCTA by an automated image processing algorithm and compared with calcium scores obtained by standard manual assessment of unenhanced CT calcium scoring studies. Results were compared vis-a-vis (1) absolute calcium score values, (2) age-, gender- and race-dependent percentiles, and (3) commonly used calcium score risk classification categories. RESULTS: One hundred and nineteen out of 127 (93.7%) studies were successfully processed. Mean Agatston calcium score values obtained by traditional non-contrast CT calcium scoring studies and derived from contrast medium-enhanced cCTA did not significantly differ (235.6 ± 430.5 vs 262.0 ± 499.5; P > 0.05). Calcium score risk categories and Multi-Ethnic Study of Atherosclerosis (MESA) percentiles showed very high correlation (Spearman rank correlation coefficient = 0.97, P < 0.0001/0.95, P < 0.0001) between the two approaches. CONCLUSIONS: Calcium score values automatically computed from cCTA are highly correlated with standard unenhanced CT calcium scoring studies. These results suggest a radiation dose- and time-saving potential when deriving calcium scores from cCTA studies without a preceding unenhanced CT calcium scoring study.

Lipoprotein (a) is independently correlated with coronary artery calcification.

INTRODUCTION: Lipoprotein a (Lp(a)) has been recognized as a risk factor for both coronary heart diseases and for cardiovascular events. Coronary artery calcification (CAC) is a well proven marker for coronary artery disease and risk factor for cardiovascular events. Still there are conflicting data regarding the relationship of Lp(a) and CAC. We therefore wanted to evaluate the influence of Lp(a) on CAC. METHODS: 1560 European patients (1123 men, age 59.3 ± 20.8 years) with typical or atypical chest pain underwent CAC scoring by a multi-slice CT-scanner, using a standard protocol. Blood samples were evaluated the same day using an automated particle enhanced immunoturbidimetric assay to determine Lp(a) serum levels. RESULTS: There was a positive correlation between CAC score, age, and common cardiovascular risk factors. Lp(a) serum levels were not associated with age but a positive correlation between Lp(a) serum levels and CAC was found. In the multivariate analysis age, diabetes, statin therapy, and Lp(a) could be identified as independent risk factors for CAC. (p<0.001). BMI, smoking, hypertension and LDL-C were not independently associated with CAC. CONCLUSION: Lp (a) could be identified as an independent predictor of CAC, a marker of coronary atherosclerosis. Further a positive correlation between increasing Lp (a) levels and CAC scores was found.

CT evaluation of coronary artery stents with iterative image reconstruction: improvements in image quality and potential for radiation dose reduction.

OBJECTIVES: Comparison of coronary artery stent assessment with cardiac CT angiography (cCTA) using traditional filtered back projection (FBP) and sinogram affirmed iterative reconstruction (SAFIRE), in both full- and half-radiation dose image data. METHODS: Dual-source cCTA studies of 37 implanted stents were reconstructed at full- and half-radiation dose with FBP and SAFIRE. Half-dose data were based on projections from one DSCT detector. In-stent noise, signal-to-noise ratio (SNR), and stent-lumen attenuation increase ratio (SAIR) were measured and image quality graded. Stent volumes were measured to gauge severity of beam hardening artefacts. RESULTS: Full-dose SAFIRE reconstructions were superior to full-dose FBP vis-à-vis in-stent noise (21.2 ± 6.6 vs. 35.7 ± 17.5; P < 0.05), SNR (22.1 ± 8.6 vs. 14.3 ± 6.7; P < 0.05), SAIR (19.6 ± 17.6 vs. 33.4 ± 20.4%; P < 0.05), and image quality (4.2 ± 0.86 vs. 3.5 ± 1.0; P < 0.05). Stent volumes were lower measured with SAFIRE (119.9 ± 53.7 vs. 129.8 ± 65.0 mm(3); P > 0.05). Comparing half-dose SAFIRE with full-dose FBP, in-stent noise (26.7 ± 13.0 vs. 35.7 ± 17.5; P < 0.05) and SNR (18.2 ± 6.9 vs. 14.3 ± 6.7; P < 0.05) improved significantly. SAIR (31.6 ± 24.3 vs. 33.4 ± 20.4%; P > 0.05), stent volume (129.6 ± 57.3 vs. 129.8 ± 65.0 mm(3); P > 0.05), and image quality (3.5 ± 1.0 vs. 3.7 ± 1.1; P > 0.05) did not differ. Radiation dose decreased from 8.7 ± 5.2 to 4.3 ± 2.6 mSv. CONCLUSIONS: Iterative reconstruction significantly improves imaging of coronary artery stents by CT compared with FBP, even with half-radiation-dose data.

Aortic valve calcium score as a predictor for outcome after TAVI using the CoreValve revalving system.

BACKGROUND: TAVI is a novel treatment option for patients at too high risk for surgery. Risk scores for surgical valve replacement failed to accurately predict outcomes after TAVI and alternative risk parameters are lacking so far. OBJECTIVE: We evaluated the CT-derived aortic valve calcification score as a predictor for outcome during and after TAVI. METHODS: Transfemoral TAVI using the CoreValve device was performed in 68 patients, in whom the aortic valve calcium score was determined from preprocedural 64-sclice ECG gated CT-scans. RESULTS: 30-day MACE rate (death, stroke, MI) was 10.3%, 1-year mortality was 11.8%. Using linear regression analysis the aortic valve calcium score was the only significant predictor for 30-day MACE and for 1-year mortality and was also associated with the incidence and severity of post procedural aortic regurgitation (r=0.33, p<0.05). Patients withvalve calcium scores >750 had a significant lower 1-year survival rate compared to patients with scores <750 (58% vs. 98%, p<0.05). The aortic valve calcium score is also inversely associated with the absolute improvement of NYHA-class after TAVI (regression coefficient=-0.43, p<0.02). CONCLUSION: The degree of aortic valve calcification is associated with post procedural aortic regurgitation, procedural complications, 1-year mortality and with the degree of functional improvement of patients who underwent TAVI using the CoreValve device. Due to the fact that the aortic valve calcium score can be determined from CT-datasets that are used for preprocedural planning, this parameter may be incorporated in the general work up and may be used for risk stratification and patient selection.

Cryoballoon in AF ablation: impact of PV ovality on AF recurrence.

INTRODUCTION: Complete occlusion of the pulmonary veins (PV) is crucial for successful PV isolation. While two different sizes of cryoballoons (23 and 28 mm) are available, complete occlusion is not always achieved in any given PV. We investigated the role of PV ostial anatomy during cryoballoon PV occlusion grading and atrial fibrillation (AF) recurrence rate. METHODS: PV ostial diameter was analyzed in 168 consecutive patients (111 men, 61 ± 10 years, 124 paroxysmal (px) and 44 persistent AF) using cardiac computed tomography (CT) prior to procedure. The ovality index at the PV ostial level was calculated in any given PV. During follow-up, 7-day holter monitors were performed at 1, 3, 6, 9, 12, 18 and 24 months post-ablation. RESULTS: The success rate at 12 ± 6 months follow-up was 69% including a 3-month blanking period (px AF: 66%; persistent AF 77%). The ovality index of the left-sided PVs was significantly larger ("more oval") than that of the right-sided PVs (p<0.001). An optimized PV occlusion in all individual PVs (complete occlusion, grading 4/4) was achieved during ablation in 49% of patients with AF recurrence and in 73% of patients without AF recurrence (p=0.004). Patients with AF recurrence had "more oval" left-sided PVs compared to patients free from AF recurrence (LSPV 0.40 ± 0.2 vs. 0.33 ± 0.2; p=0.04 and LIPV 0.41 ± 0.3 vs. 0.32 ± 0.2; p=0.03), whereas no significant association was found for right sided PVs. CONCLUSION: The ostial PV anatomy seems to have an important impact on clinical outcome and should be considered when planning and performing cryoballoon AF ablation procedures.

Accuracy of 64-multidetector computed tomography coronary angiography in patients with symptomatic atrial fibrillation prior to pulmonary vein isolation.

AIMS: Aim of our study was to investigate the value of multidetector computed tomography (MDCT) for detecting significant stenoses of coronary arteries in patients with symptomatic atrial fibrillation (AF) prior to pulmonary vein (PV) ablation (PVA). BACKGROUND: Many patients undergoing PVA for AF receive three-dimensional computed tomography or magnetic resonance tomography imaging for improving anatomical orientation. METHODS: One-hundred and eighty-one patients with AF refractory to antiarrhythmic treatment underwent ECG-gated 64-MDCT for identification of PV anatomy and simultaneous assessment of coronary vessels before PVA. No additional radiation was incurred for MDCT coronary angiography during MDCT scan. Pretest probability for obstructive coronary artery disease (CAD) was estimated. Invasive coronary angiography (ICA) was performed in all patients with at least intermediate risk of CAD. RESULTS: Eighty-six out of 181 patients (48%) had ICA and MDCT, 95 patients (52%) underwent MDCT alone. ICA revealed significant stenoses in 9% of the catheterized patients (8/86). MDCT investigation lead to a sensitivity of 90% (9/10), specificity of 98% (829/844 lesions), positive predictive value (PPV) of 39% (9/24), and negative predictive value (NPV) of 100% (829/830 lesions) for the detection of >50% stenoses seen on ICA. All patients with a significant stenosis were classified as patients with CAD. Overall prevalence of significant CAD detected by MDCT was found to be low with 10% of patients and 2% of all segments. CONCLUSION: MDCT coronary angiography is sensitive and highly specific in patients presenting for PVA. In this group a negative scan reliably excludes significant CAD. These data suggest that MDCT coronary angiography can replace ICA prior to PVA.

MMP-1 serum levels predict coronary atherosclerosis in humans.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: MMP-1 serum levels are associated with total plaque burden but do not allow a specification of plaque morphology.

Chemerin is associated with markers of inflammation and components of the metabolic syndrome but does not predict coronary atherosclerosis.

OBJECTIVES: Chemerin is a recently discovered adipokine that regulates adipocyte differentiation and modulates chemotaxis and activation of dendritic cells and macrophages. Given the convergence of adipocyte and macrophage function, chemerin may provide an interesting link between obesity, inflammation and atherosclerosis in humans. We sought to examine the relationship of i) chemerin and markers of inflammation, ii) chemerin and components of the metabolic syndrome, and iii) chemerin and coronary atherosclerotic plaque burden and morphology. DESIGN: Serum chemerin levels were determined 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. RESULTS: Chemerin levels were highly correlated with high sensitivity C-reactive protein (r=0.44, P<0.0001), interleukin-6 (r=0.18, P=0.002), tumor necrosis factor-alpha (r=0.24, P<0.0001), resistin (r=0.28, P<0.0001), and leptin (r=0.36, P<0.0001) concentrations. Furthermore, chemerin was associated with components of the metabolic syndrome including body mass index (r=0.23, P=0.0002), triglycerides (r=0.29, P<0.0001), HDL-cholesterol (r=-0.18, P=0.003), and hypertension (P<0.0001). In bivariate analysis, chemerin levels were weakly correlated with coronary plaque burden (r=0.16, P=0.006) and the number of non-calcified plaques (r=0.14, P=0.02). These associations, however, were lost after adjusting for established cardiovascular risk factors (odds ratio, OR 1.17, 95% confidence interval (CI) 0.97-1.41, P=0.11 for coronary plaque burden; OR 1.06, 95% CI 0.96-1.17, P=0.22 for non-calcified plaques). CONCLUSIONS: Chemerin is strongly associated with markers of inflammation and components of the metabolic syndrome. However, chemerin does not predict coronary atherosclerosis.

Low adiponectin levels are an independent predictor of mixed and non-calcified coronary atherosclerotic plaques.

BACKGROUND: 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. CONCLUSIONS/SIGNIFICANCE: 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.

Predictive value of coronary calcifications for future cardiac events in asymptomatic patients with diabetes mellitus: a prospective study in 716 patients over 8 years.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Predictive value of coronary calcifications for future cardiac events in asymptomatic individuals.

BACKGROUND: Reliable risk stratification is crucial for efficient prevention of coronary artery disease. The following prospective study determined the predictive value of coronary calcifications for future cardiovascular events. METHODS: We included 1726 asymptomatic individuals (1018 men, 708 women, age 57.7 +/- 13.3 years) referred for a cardiological examination. Coronary calcifications were determined with the Imatron C 150 XP electron beam computed tomography scanner. For quantification of coronary calcifications, we calculated the Agatston score. Over a mean observation period of 40.3 +/- 7.3 months we registered the event rate for cardiac death (CD) and myocardial infarction (MI). RESULTS: The Agatston score in patients who died of CD (n = 65) or had an MI (n = 114) was significantly higher compared with those without cardiac events (458 +/- 228 vs 206 +/- 201, P < .01). An Agatston score above the 75th percentile was associated with a significantly higher annualized event rate for MI (3.6% vs 1.6%, P < .05) and for CD (2.2% vs 0.9%) compared with patients with scores below the 75th percentile. No cardiac events were observed in patients where coronary calcifications could be excluded. CONCLUSIONS: By determination of coronary calcifications, patients at risk for future MI and CD could be identified within an asymptomatic population independent of concomitant risk factors. At the same time, future cardiovascular events could be excluded in patients without coronary calcifications.

Comparison of progression of coronary calcium in postmenopausal women on versus not on estrogen/progestin therapy.

The prophylactic effect of postmenopausal hormone replacement therapy on coronary atherosclerosis remains controversial. We, therefore, examined the influence of combined estrogen/progestin therapy on the progression of coronary calcium as a marker of coronary atherosclerosis. We determined the extent of coronary calcium in 277 women (age 57 +/- 6 years, time after menopause 3.9 +/- 2.4 years, group I) at the beginning of hormone replacement therapy using multislice computed tomography. For quantification, we calculated the volume score. After an observation period of 3 years, we determined the progression of coronary calcium in a second scan. The results were compared with those from an age- and risk factor-adjusted group of postmenopausal women without hormone substitution (group II). No significant difference was found in the volume score (59 +/- 95 vs 58 +/- 88) or risk factor distribution between the 2 groups on study entry. In 56 women of group I and 52 women of group II, coronary calcium could be excluded on the initial scan (p = NS). After a mean observation time of 38.5 +/- 4.9 months, we observed no significant difference between the 2 groups regarding an increase in volume score (17 +/- 24 vs 19 +/- 27, p = NS) or the fraction of women with an increase in volume score (82.2% vs 84.2%). In conclusion, a reduced progression of coronary calcium in postmenopausal women on combined estrogen/progestin therapy could not be observed compared with a matched group of women without hormone substitution.

Multislice computed tomography for determination of coronary artery disease in a symptomatic patient population.

BACKGROUND: Multislice computed tomography (MSCT) has started to replace Electron beam CT for quantitation of coronary artery calcium. However no study has evaluated the diagnostic accuracy of MSCT for prediction of coronary artery disease (CAD) in a symptomatic patient population using the volume score. METHODS AND RESULTS: 1347 symptomatic subjects (male = 803, mean age = 62 years) with suspected CAD underwent MSCT studies 1 +/- 2 days before the coronary angiogram. The Agatston (ACS) and Volumetric calcium score (VCS) were calculated using a proprietary workstation. Statistical analyses included the Pearson's correlation coefficient and the nonparametric Mann-Whitney U-test to compare the calcium score in different age groups and between men and women. Sensitivity, specificity and predictive accuracy were calculated for different calcium thresholds for prediction of CAD. ROC curve analyses were used to establish relations between the coronary calcium score and presence or absence of CAD. In 720 (53%) subjects (male = 419) angiography revealed a minimal lumen diameter stenosis greater than 50%. Patients with significant CAD had significantly higher total calcium score values than patients without CAD (P = 0.001). ACS and VCS demonstrate a close correlation for the whole study group, r = 0.99. The overall sensitivity of any calcium to predict stenosis was 99%, specificity = 32%. Exclusion of calcium was highly accurate for exclusion of CAD in subjects older than 50 years (predictive accuracy = 98%). An absolute cutoff >100 and an age and sex specific threshold (score over 75th percentile) were identified as the cutoff levels with the highest sensitivities (86-89%) and lowest false positive rates (20-22%). ROC analyses revealed MSCT calcium scanning as a good clinical test which can be performed with similar accuracy in all age groups with an area under the curve of 0.84. CONCLUSION: Determination of coronary calcium with MSCT is an accurate imaging modality for prediction of significant CAD in a patient population with intermediate likelihood of CAD. Exclusion of any calcium provided strong evidence that patients older than 50 years did not have obstructive CAD. ACS and VCS show an equivalent diagnostic accuracy.

[Diabetes mellitus type 2: coronary calcifications as a predictor of coronary artery disease]. / Diabetes mellitus Typ 2: Koronarkalk als unabhängiger Prädiktor einer koronaren Herzkrankheit.

BACKGROUND AND PURPOSE: Patients with diabetes mellitus have an increased risk of developing cardiovascular disease. Therefore, coronary artery disease (CAD) is the most common cause of mortality in these patients. The early and reliable diagnosis of coronary atherosclerosis is crucial for an effective treatment. Determination of coronary calcifications with multislice computed tomography offers the possibility to detect coronary calcifications as a sign of early coronary atherosclerosis. The present study examined the possibility to predict CAD in patients with diabetes mellitus by determination of coronary calcifications. PATIENTS AND METHODS: 632 patients (417 men, 215 women, age 54.6 +/- 17.3 years) with diabetes mellitus and suspected CAD were examined. All patients underwent coronary angiography. Coronary stenoses with lumen narrowing > 50% were regarded as significant CAD. Within 3 days coronary multislice computed tomography (Sensation 4, Siemens Medical Solutions, Forchheim, Germany) was performed and coronary calcifications were quantified using the volume score. Sensitivity, specificity, negative and positive predictive value for prediction of CAD were determined for different cutpoints. RESULTS: 440 patients showed a significant CAD, 315 patients underwent coronary transluminal angioplasty and 57 patients coronary artery bypass surgery. Mean volume score was 421 +/- 461. Volume score increased from 2 +/- 6 for patients < 40 years to 751 +/- 801 for patients > 70 years. Women showed a significantly lower score in all age groups. The mean volume score was significantly higher in patients with CAD compared to those without CAD (587 +/- 642 compared to 40 +/- 53; p < 0.01). In all patients without coronary calcifications, CAD could be ruled out angiographically. Using score 0, 10, 100 as cutoff points for the prediction of CAD, a sensitivity of 100%, 97%, and 87% at a specificity of 25%, 69%, and 82% was calculated. Best results were achieved using the 75th percentile as cutoff point with a sensitivity of 91% and a specificity of 84%. In total, CAD could be diagnosed correctly by quantification of coronary calcifications in 94% of all patients. CONCLUSION: Determination of coronary calcifications by multislice computed tomography could be used in patients with diabetes mellitus to detect coronary atherosclerosis and allows the early and exact diagnosis of CAD.