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Freiburg, Germany

Kleber M.E.,LURIC Study Nonprofit LLC | Renner W.,Medical University of Graz | Marz W.,University of Heidelberg
BMC Medical Genetics | Year: 2010

Background: C-reactive protein is a well established marker of inflammation and has been used to predict future cardiovascular disease. It is still controversial if it plays an active role in the development of cardiovascular disease. Recently, polymorphisms in the gene for HNF1α have been linked to the levels of C-reactive protein and coronary artery disease.Methods: We investigated the association of the rs2259816 polymorphism in the HNF1A gene with the circulating level of C-reactive protein and the hazard of coronary artery disease in the LURIC Study cohort.Results: Compared to CC homozygotes, the level of C-reactive protein was decreased in carriers of at least one A-allele. Each A-allele decreased CRP by approximately 15%. The odds ratio for coronary artery disease was only very slightly increased in carriers of the A-allele and this association did not reach statistical significance.Conclusions: In the LURIC Study cohort the A-allele of rs2259816 is associated with decreased CRP but not with coronary artery disease. © 2010 Kleber et al; licensee BioMed Central Ltd.

De Boer S.P.M.,Erasmus University Rotterdam | Cheng J.M.,Erasmus University Rotterdam | Garcia-Garcia H.M.,Erasmus University Rotterdam | Oemrawsingh R.M.,Erasmus University Rotterdam | And 10 more authors.
EuroIntervention | Year: 2014

Aims: The European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis - Intravascular Ultrasound (ATHEROREMOIVUS) study aims to investigate the relations of genetic profile and novel circulating biomarkers with coronary plaque phenotype and vulnerability as determined by intravascular ultrasound (IVUS). Methods and results: ATHEROREMOIVUS is a prospective, observational cohort study of 846 patients with stable angina pectoris or acute coronary syndrome (ACS) who are referred for coronary angiography. Prior to the catheterisation procedure, blood samples are drawn for biomarker measurements and genetic analyses. During the catheterisation procedure, IVUS is performed in a nonculprit coronary artery. The primary endpoint is the presence of vulnerable plaque as determined by IVUS virtual histology. Secondary endpoints include the incidence of major adverse cardiac events during longterm followup. Conclusions: Results from ATHEROREMOIVUS are expected to improve our knowledge of the role of genetic profile and circulating biomarkers in relation to the development of atherosclerosis and vulnerable plaques. Assessment and early validation of the prognostic value of novel biomarkers and intracoronary imaging techniques will be performed.

Murr C.,Innsbruck Medical University | Pilz S.,Medical University of Graz | Grammer T.B.,University of Heidelberg | Kleber M.E.,University of Heidelberg | And 6 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2012

Background: Low vitamin D concentrations are detected in patients suffering from various clinical conditions which are characterized also by inflammation and immune activation. We investigated whether vitamin D levels in patients with coronary artery disease (CAD) are related to markers of immune activation. Methods: Serum concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and the immune activation markers neopterin and high sensitivity C-reactive protein (hsCRP) were measured in 2015 patients derived from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, a cohort study among patients referred for coronary angiography. Results: Serum concentrations of 25(OH)D and 1,25(OH)2D did not differ between patients with CAD [mean±SD: 25(OH)D: 17.4±9.4 μg/L; 1,25(OH)2D: 34.4±13.3 ng/L] and controls [25(OH)D: 18.4±11.7 μg/L; 1,25(OH)2D: 35.3±12.7 ng/L; Welch's t-test: p=n.s.] but CAD patients had higher neopterin (8.6±7.4 nmol/L) and hsCRP (9.6±19.6 mg/L) concentrations compared to controls (neopterin: 7.5±4.8 nmol/L; p=0.0004; hsCRP: 5.4±10.0 mg/L; p<0.0001). There was an inverse correlation between serum 25(OH)D or 1,25(OH)2D concentrations and serum neopterin [Spearman's rank correlation: 25(OH)D: r s=-0.183; 1,25(OH)2D: rs=-0.230] and hsCRP [25(OH)D: rs=-0.142; 1,25(OH)2D: rs=-0.130; all p<0.0001] concentrations. Conclusions: Our results indicate increased inflammatory processes in patients with low vitamin D status. Further studies should clarify the underlying mechanisms for the observed associations of vitamin D status and inflammatory parameters. Copyright © 2012 by Walter de Gruyter.

Kleber M.E.,LURIC Study Nonprofit LLC | Renner W.,Medical University of Graz | Linsel-Nitschke P.,University of Lubeck | Boehm B.O.,University of Ulm | And 4 more authors.
Atherosclerosis | Year: 2010

Objective: The rs599839 polymorphism A/G in the vicinity of the sortilin 1 gene has been reported to be associated with low density lipoprotein cholesterol (LDL-C) and coronary artery disease (CAD). The objective of this study was to further characterize the protective effect of the minor allele by analyzing the association with a variety of quantitative traits. Methods: Association of rs599839 with plasma levels of different parameters of LDL and triglyceride (TRIG) metabolism as well as the risk of CAD was tested in the LURIC study cohort. Results: Compared to AA homozygotes, the levels of LDL-C, low density lipoprotein triglycerides (LDL-TRIG) and apolipoprotein B were decreased in carriers of at least one G-allele. The G-allele was also associated with an increasing radius of the LDL particles. Regarding TRIG metabolism we observed a significant decrease in the level of triglycerides for homozygous carriers of the G-allele as well as decreased levels of free fatty acids (FFA), free glycerol and free cholesterol. With each G-allele the prevalence of CAD (multivariate OR 0.806; 95% CI: 0.692. -0.940, P=0.006) decreased significantly whereas we observed only a marginal decrease for MI which did not reach significance.For GG homozygotes, the OR for CAD was 0.588 (95% CI: 0.394. -0.877; P=0.009) and the OR for previous myocardial infarction (MI) was 0.693 (95% CI: 0.490. -0.980; P=0.038). These associations were independent of cardiovascular risk factors. Conclusion: In the LURIC Study the G-allele of rs599839 is associated with LDL and TRIG metabolism and the risk of coronary artery disease and myocardial infarction. © 2009 Elsevier Ireland Ltd.

Marx N.,RWTH Aachen | Silbernagel G.,University of Tubingen | Brandenburg V.,RWTH Aachen | Burgmaier M.,RWTH Aachen | And 8 more authors.
Diabetes Care | Year: 2013

OBJECTIVEdC-peptide is a proinsulin cleavage product released from the pancreas in amounts equimolar to insulin, and elevated levels of C-peptide have been found in patients with insulin resistance and early type 2 diabetes mellitus. Recent data suggest that C-peptide could play a causal role in the pathophysiology of vascular disease, but nothing is known about the prognostic value of C-peptide concentrations in the circulation. RESEARCH DESIGNANDMETHODSdWe examined whether C-peptide is associated with cardiovascular and total mortality in 2,306 patients from the Ludwigshafen Risk and Cardiovascular Health Study who underwent coronary angiography at baseline (1997-2000). RESULTSdDuring amean follow-up of 7.6 years, 440 deaths (19.1%) occurred, 252 (10.9%) of which were due to cardiovascular causes. Age-and sex-adjusted hazard ratios (HRs) in the third compared with the first tertile of C-peptide were 1.46 (95%CI 1.15-1.85; P = 0.002) for all cause and 1.58 (1.15-2.18; P = 0.005) for cardiovascular mortality. After further adjustment for common risk factors as well as markers of glucosemetabolism, these HRs remained significant at 1.46 (1.10-1.93; P = 0.008) and 1.55 (1.07-2.24; P = 0.022), respectively. Moreover, patients in higher tertiles of C-peptide exhibited higher levels of markers of endothelial dysfunction and atherosclerosis as well as a more severe extent of coronary lesions. CONCLUSIONSdIn patients undergoing coronary angiography, C-peptide levels are independently associated with all cause and cardiovascular mortality as well as presence and severity of coronary artery disease. Further studies are needed to examine a potential causal role of Cpeptide in atherogenesis in humans. Copyright © 2013 by the American Diabetes Association.

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