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Bernhard R Winkelmann

Publications and source records attributed to Bernhard R Winkelmann.

24 records · Page 2Linked to original sources
PubMed2003

Design of the Genetics of Early Onset Cardiovascular Disease (GENECARD) study.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of death and a leading cause of disability in the developed world. Early onset (premature) coronary artery disease (EOCAD) is known to have a particularly strong genetic component. However, the actual genes leading to this increased risk of CAD remain obscure. METHODS: The primary goal of the Genetics of Early Onset Cardiovascular Disease (GENECARD) study is to perform a genetic linkage study in 920 families with at least 1 sibling pair having EOCAD. The study sites include a US network of 15 cardiology practices and 5 additional sites located in Europe and the United States. We propose to identify chromosomal regions associated with increased susceptibility to EOCAD in this large sample of affected sibling pairs and nuclear families, where EOCAD is defined on the basis of having acute coronary syndrome (unstable angina or myocardial infarction), a revascularization procedure, or a positive functional imaging study at or before the age of 50 years in men or 55 years in women. To identify which genomic regions and genes are associated with increased susceptibility to EOCAD, we will use a comprehensive strategy comprising genomic screening, fine mapping, candidate gene analysis, and family-based association studies. RESULTS: Herein we describe the clinical characteristics, family history, and risk factor profiles of the 1168 members from 438 nuclear families included in the first, exploratory analysis. Analysis of the study population revealed a strong concordance of known cardiac risk factors among affected sibling pairs. There was significant concordance (P <. 01) among siblings with EOCAD for presence of diabetes (78% concordance), dyslipoproteinemia (67%), obesity (63%), and hypertension (56%). This level of concordance of risk factors among siblings might be expected, given the significant genetic components demonstrated for these metabolic susceptibility traits. However, there was also substantial sibling pair concordance (P <.01) for smoking history (74%), regular alcohol consumption (81%), and sedentary lifestyle (63%), environmental traits without known inherited predisposition. CONCLUSIONS: Analyses such as these will have implications for stratifying populations for the statistical analysis of the genome scan and on the choice of covariates for the follow-up studies of the initial genome screen analysis.

Adult↗
PubMed2003

Prevalence, predictors, and consequences of unrecognized diabetes mellitus in 3266 patients scheduled for coronary angiography.

BACKGROUND: Previous population-based studies have reported a proportion of undiagnosed diabetes in the range between 25% and 50%. However, data on undiagnosed diabetes in a high-risk population, such as patients scheduled for coronary angiography, are lacking. Therefore, we sought to determine prevalence, predictors, and consequences of unrecognized diabetes in patients scheduled for coronary angiography. METHODS: This analysis involved 3266 patients scheduled for coronary angiography who have been enrolled in the Ludwigshafen Risk and Cardiovascular Health study. RESULTS: Five hundred fifty-six patients (17.0%) had known diabetes. Another 486 patients with previously unrecognized diabetes (17.9%) were diagnosed in the remaining 2710 presumed nondiabetic subjects. Therefore, 486 (46.6%) of a total of 1042 patients with diabetes were previously undiagnosed, raising the diabetic proportion of enrolled patients to 31.9%. In half of the newly diagnosed patients with diabetes, the disease was detectable only by use of glucose challenge. Independent predictors of unrecognized type 2 diabetes were C-reactive protein >5 mg/L, arterial hypertension, body mass index >30 kg/m(2), age >or=65 years, and a positive family history of diabetes. Compared with nondiabetic subjects, patients with unrecognized type 2 diabetes showed a significantly increased risk for coronary artery disease (odds ration [OR] 1.7, 95% CI 1.3-2.3) and multivessel disease (OR 1.4, 95% CI 1.1-1.8), and a borderline association with myocardial infarction (OR 1.2, 95% CI 1.0-1.5). Oral glucose challenge was not superior to fasting glucose in predicting this increased cardiovascular risk. CONCLUSION: In half of the patients scheduled for coronary angiography, diabetes was previously unrecognized. In a high-risk population of patients scheduled for coronary angiography, screening for diabetes should be performed routinely to initiate timely preventive efforts.

Aged↗
PubMed2003

Pharmacogenomics, genetic testing and ethnic variability: tackling the ethical questions.

Dr Winkelmann is the Head of the Cooperation Unit for Pharmacogenomics and Applied Genomics in Heidelberg, which was founded in 2001 by the Department of Internal Medicine VI and the Coordination Centre for Clinical Trials at the University of Heidelberg. His main interests are sophisticated phenotyping procedures for patient characterization and the conduct of multicenter clinical trials according to international standards with state-of-the-art data management. He currently applies new genomic tools in order to achieve progress in personalized medicine using collaborating networks of general practitioners for patient enrollment. The focus of his research group is on the common complex genetic cardiovascular and metabolic diseases ranging from coronary artery disease, dyslipidemia and hypertension, to metabolic syndrome and diabetes mellitus. In collaboration with partners from biotech, the genomic techniques used in clinical studies include haplotyping of candidate genes, gene expression profiling of peripheral leucocytes and proteomics in order to identify new biomarkers of effect in therapeutic studies or pathway/target gene identification in disease-specific family studies using microarray-based linkage approaches. An innovative web-based remote data entry system with an integrated pedigree drawing tool is used in the family studies. Dr Winkelmann is also involved as the clinical database coordinator for a European Framework VI research initiative of leading European centers in cardiovascular genetics for identification of risk genes for atherothrombosis in coronary artery disease by transcriptome and proteome analysis and high throughput exon resequencing at the Wellcome Trust Sanger Institute, Cambridge, UK.

Cardiovascular Diseases↗
PubMed2002

The interleukin-6 G(-174)C promoter polymorphism in the LURIC cohort: no association with plasma interleukin-6, coronary artery disease, and myocardial infarction.

IL-6 plasma levels are predictive of major cardiovascular events. Recently a G/C polymorphism at position -174 in the promoter of the IL-6 gene has been associated with differences in both the IL-6 transcription rate in vitro and IL-6 levels in vivo. We examined the association of this polymorphism with coronary artery disease (CAD) and previous myocardial infarction (MI) in 2559 patients with angiographically documented CAD with ( n=1365) and without ( n=1194) MI and in a control group of 729 individuals in whom CAD had been ruled out angiographically. Assuming dominant or recessive modes of inheritance, carriers of the G allele had odds ratios of 0.98 (95% CI 0.79 - 1.20) and 0.96 (95% CI 0.80 - 1.14), respectively, for CAD, and almost identical ones for previous MI. In subgroups stratified for low cardiovascular risk, the IL-6 promoter polymorphism was also not related to the risk of CAD or MI. In addition, the plasma concentration of IL-6 did not differ between groups with different IL-6 genotypes in 942 randomly selected individuals. We conclude that the IL-6 G(-174)C polymorphism is not associated with the risk of CAD or MI and does not contribute to cardiovascular risk stratification.

Adult↗