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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Mainz//2011; 56. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 6. Jahrestagung der Deutschen Gesellschaft für Epidemiologie (DGEpi); 20110926-20110929; Mainz; DOC11gmds161 /20110920/
    Publication Date: 2011-09-20
    Keywords: Troponin ; Cardiovascular Disease ; Cohort Study ; ddc: 610
    Language: English
    Type: conferenceObject
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  • 2
    Abstract: Background Smoking has recently been suggested to synergistically interact with alcohol intake as a determinant of serum gamma-glutamyltransferase (g-GT), an emergent powerful predictor of disease and mortality. This study investigated whether this also applies to higher smoking and alcohol exposure ranges and to body mass index (BMI), which likewise is strongly associated with g-GT. Methodology/Principal Findings Analyses were based on occupational health examinations of more than 15,000 German male workers aged 16-64 years, predominantly from the construction industry. Sociodemographics and other health-related information were collected during the exam. Joint associations of smoking and alcohol consumption or BMI with elevated or log-transformed g-GT were examined by tabulation and multiple adjusted regression models. Cigarette smoking exerted no effect on g-GT in teetotalers, but there was a statistically significant effect of smoking among participants with higher alcohol consumption intensity, odds of elevated g-GT being increased by 24% and 27% per additional 10 cigarettes smoked per day in subjects drinking 61-90 and 〉90 gram alcohol per day, respectively (P for interaction = 0.039). The interaction was opposite for BMI, where no association was seen in obese subjects, whereas odds of elevated g-GT were increased by 24% per 10 cigarettes below 25 kg/m2 (P for interaction = 0.040). This novel interaction was replicable in an independent cohort. Conclusion The evidence for opposite interactions of smoking with alcohol and BMI as determinants of serum g-GT suggests that different physiological pathways are responsible for the associations between these factors.
    Type of Publication: Journal article published
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  • 3
    Keywords: CANCER ; MORTALITY ; mechanisms ; genetics ; DNA methylation ; SMOKERS ; HUMAN-DISEASE ; HYPERMETHYLATION ; EPIGENETICS ; PROMOTER METHYLATION ; MULTIPLE GENES ; GENOME-WIDE ASSOCIATION ; CARDIOVASCULAR RISK
    Abstract: Tobacco smoking is responsible for substantial morbidity and mortality worldwide, in particular through cardiovascular, pulmonary, and malignant pathology. CpG methylation might plausibly play a role in a variety of smoking-related phenomena, as suggested by candidate gene promoter or global methylation studies. Arrays allowing hypothesis-free searches on a scale resembling genome-wide studies of SNPs have become available only very recently. Methylation extents in peripheral-blood DNA were assessed at 27,578 sites in more than 14,000 gene promoter regions in 177 current smokers, former smokers, and those who had never smoked, with the use of the Illumina HumanMethylation 27K BeadChip. This revealed a single locus, cg03636183, located in F2RL3, with genome-wide significance for lower methylation in smokers (p = 2.68 x 10(-31)). This was similarly significant in 316 independent replication samples analyzed by mass spectrometry and Sequenom EpiTyper (p = 6.33 x 10(-34)). Our results, which were based on a rigorous replication approach, show that the gene coding for a potential drug target of cardiovascular importance features altered methylation patterns in smokers. To date, this gene had not attracted attention in the literature on smoking.
    Type of Publication: Journal article published
    PubMed ID: 21457905
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  • 4
    Keywords: validation ; ASSOCIATION ; ALZHEIMERS-DISEASE ; PERFORMANCE ; HEALTH ; DESIGN ; IMPAIRMENT ; OLDER-ADULTS ; Dose-response relationship ; Epidemiological study ; 25-Hydroxy vitamin D3 ; 25-HYDROXYVITAMIN D LEVELS ; Adult cognitive functioning ; Telephone interview
    Abstract: OBJECTIVES: To examine the relationship of serum 25-hydroxy vitamin D3 with cognitive functioning in higher age, using an instrument covering multiple cognitive domains in a population-based study. DESIGN: Follow-up study with measurement of vitamin D levels at baseline and assessment of cognitive functioning at year 5 follow-up. SETTING AND PARTICIPANTS: A subgroup of 1639 participants of the ongoing epidemiological ESTHER study of the elderly general population in Saarland State, Germany, aged 65+ years at baseline (2000-2002). INTERVENTION: Observational study. MEASUREMENTS: Cognitive functioning was assessed by the COGTEL phone interview developed by Kliegel et al., which was administered 5years after ESTHER baseline. Vitamin D in baseline samples was measured by chemiluminescence methods. Additional information was obtained by standardised questionnaires. RESULTS: In multiple linear regression adjusted for important confounders, women in the lowest sex-specific quintile of vitamin D showed an on average 2.1 (95% confidence interval: 0.4 to 3.9) units lower COGTEL score than women in the highest quintile. A similar, albeit slightly weaker, association was seen in males (difference of 1.7 [-0.4 to 3.8] units). Spline regression suggested non-linearity with a distinct decline in cognitive performance in the lower range of vitamin D levels. CONCLUSIONS: Our findings support suggestions that low levels of vitamin D may be associated with reduced cognitive functioning in the elderly.
    Type of Publication: Journal article published
    PubMed ID: 22123431
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  • 5
    Keywords: RISK ; MARKER ; MYOCARDIAL-INFARCTION ; ISCHEMIA ; REGISTRY ; COMMITTEE ; PLASMA-CONCENTRATIONS ; EUROPEAN-SOCIETY ; EARLY-DIAGNOSIS ; I ASSAY
    Abstract: BACKGROUND: The clinical relevance of slightly increased circulating troponin concentrations in patients with stable coronary heart disease (CHD) several weeks after an acute event or CABG has not been fully evaluated. METHODS: Baseline plasma concentrations of troponin T were measured with a high-sensitivity assay (hs-cTnT) (Roche Elecsys) in a cohort of 1050 CHD patients from 30 to 70 years of age. The prognostic value of hs-cTnT on a combined cardiovascular disease (CVD) end point after adjustment for covariates was determined with Cox proportional hazards modeling. RESULTS: The median hs-cTnT concentration was 10.9 ng/L (interquartile range, 5.1-18.9 ng/L). Increased hs-cTnT concentrations were associated with an older age, history of hypertension and diabetes, more advanced coronary artery disease, and other CHD risk factors. Furthermore, hs-cTnT concentration was strongly correlated with N-terminal pro B-type natriuretic peptide (NT-proBNP) and cystatin C (rho = 0.61, and rho = 0.32, respectively; both P values 〈0.0001). During a median follow-up of 8.1 years, 150 patients (14.3%) experienced a secondary CVD event. In a multivariate model, hs-cTnT was associated with a hazard ratio (HR) for secondary events of 2.83 (95% CI, 1.68-4.79) when the extreme quartiles were compared. Further adjustment for cystatin C, NT-proBNP, and C-reactive protein attenuated this association only slightly (HR, 2.27; 95% CI, 1.31-3.95); P for trend 〈 0.002). ROC curve analysis of a clinical model that added hs-cTnT to a baseline model showed nonsignificant improvement in the area under the curve (0.69 vs 0.67), whereas the net reclassification improvement was 17.2% (P = 0.029). CONCLUSIONS: Slightly increased hs-cTnT concentrations in stable CHD patients are associated with several cardiovascular disorders and predict long-term CVD events.
    Type of Publication: Journal article published
    PubMed ID: 22634379
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  • 6
    Keywords: INHIBITION ; ALZHEIMERS-DISEASE ; MOUSE ; IMPAIRMENT ; AMYLOID-BETA OLIGOMERS ; PRPC
    Abstract: OBJECTIVES: Recent animal studies have suggested a key role for cellular prion protein (PrPc) in the pathological consequences of amyloid plaque formation, the hallmark of Alzheimer's disease. This epidemiological study investigated whether serum concentrations of PrPc are associated with cognitive functioning in humans. DESIGN, SETTING, PARTICIPANTS: Cross-sectional study of 1,322 participants from the elderly general population in Germany, aged 65+ years at baseline (2000-2002). MEASUREMENTS: Cognitive functioning was assessed by the COGTEL phone interview 5years after baseline. Serum PrPc was determined by a commercial immunoassay. RESULTS: In multiple linear regression adjusted for important confounders, subjects in higher PrPc quintiles appeared to have lower cognitive functioning scores than those in the lowest PrPc quintile. Spline regression suggested pronounced non-linearity with an inverse association between PrPc and cognitive functioning levelling off beyond median PrPc. Cognitive subdomain-specific models produced somewhat heterogeneous results. CONCLUSION: The findings are suggestive of an independent association of PrPc with cognitive functioning in humans. Confirmatory and longitudinal studies are needed to elucidate the potential of PrPc for applications in early risk stratification for cognitive impairment.
    Type of Publication: Journal article published
    PubMed ID: 22967749
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  • 7
    Keywords: IMPLEMENTATION ; SECONDHAND SMOKE ; 4 COUNTRY SURVEY ; IRELAND ; RESTRICTIONS ; CROSS-SECTIONAL SURVEY ; CHILD EXPOSURE ; SCOTLAND ; LAW ; HOUSEHOLDS
    Abstract: ObjectivesTo measure changes in prevalence and predictors of home smoking bans (HSBs) among smokers in four European countries after the implementation of national smoke-free legislation.DesignTwo waves of the International Tobacco Control Policy Evaluation Project Europe Surveys, which is a prospective panel study. Pre- and post-legislation data were used from Ireland, France, Germany and the Netherlands. Two pre-legislation waves from the UK were used as control.Participants4634 respondents from the intervention countries and 1080 from the control country completed both baseline and follow-up and were included in the present analyses.MethodsMultiple logistic regression models to identify predictors of having or of adopting a total HSB, and Generalised Estimating Equation models to compare patterns of change after implementation of smoke-free legislation to a control country without such legislation.ResultsMost smokers had at least partial smoking restrictions in their home, but the proportions varied significantly between countries. After implementation of national smoke-free legislation, the proportion of smokers with a total HSB increased significantly in all four countries. Among continuing smokers, the number of cigarettes smoked per day either remained stable or decreased significantly. Multiple logistic regression models indicated that having a young child in the household and supporting smoking bans in bars were important correlates of having a pre-legislation HSB. Prospective predictors of imposing a HSB between survey waves were planning to quit smoking, supporting a total smoking ban in bars and the birth of a child. Generalised Estimating Equation models indicated that the change in total HSB in the intervention countries was greater than that in the control country.ConclusionsThe findings suggest that smoke-free legislation does not lead to more smoking in smokers homes. On the contrary, our findings demonstrate that smoke-free legislation may stimulate smokers to establish total smoking bans in their homes.
    Type of Publication: Journal article published
    PubMed ID: 22331456
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  • 8
    Keywords: SAMPLE ; POLYMORPHISMS ; ASSAY ; PLASMA ; cancer risk ; SERUM ; DETERMINANTS ; GENOME-WIDE ASSOCIATION ; 25-hydroxyvitamin D ; GC-GLOBULIN
    Abstract: Background: Vitamin D insufficiency is common among older adults. Genome-wide association studies have found an association between variants in the vitamin D binding protein and serum levels of vitamin D. The quantification of this association among older women and men and its potential variation by season remain unexplored. Methods: Serum levels of 25-hydroxyvitamin D [25(OH)D] and genetic variants in the vitamin D binding protein were analyzed in 2160 women and 1581 men age 50 to 74 years participating in a large population-based cohort study (ESTHER study-epidemiologic study assessing chances of prevention and early detection of various chronic diseases, including cancer among older adults) in Germany. Serum levels of 25(OH)D were assessed in relation to four single nucleotide polymorphisms (SNPs; rs4588, rs2282679, rs1155563, and rs12512631) by descriptive and multivariate analysis. Results: Both heterozygous and homozygous women and men carrying the rare allele with SNPs rs4588, rs2282679, or rs1155563 had lower levels of 25(OH)D in summer months than those homozygous for the wild-type alleles. Adjusted differences ranged from 5.1 to 5.4 nmol/l among heterozygous carriers of the rare alleles and from 8.8 to 9.6 nmol/l among homozygous carriers of the rare alleles. During winter months, 25(OH)D differences by genotype were smaller among women and not apparent among men. Conclusions: Older women and men living in a high-latitude region and carrying the rare alleles of SNPs rs4588, rs2282679, or rs1155563 seem to benefit less from higher levels of ultraviolet radiation during the summer season.
    Type of Publication: Journal article published
    PubMed ID: 23191998
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  • 9
    Keywords: INHIBITOR ; PLASMA ; C-REACTIVE PROTEIN ; NITRIC-OXIDE SYNTHESIS ; L-ARGININE ; ARTERY-DISEASE ; GLOMERULAR-FILTRATION-RATE ; STAGE RENAL-DISEASE ; MEDIA THICKNESS ; ADMA
    Abstract: BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor, which has been associated with total and cardiovascular mortality in various clinical settings. Studies on its structural isomer, symmetric dimethylarginine (SDMA), are scarce. This study aimed to determine the associations of both ADMA and SDMA levels with secondary cardiovascular disease events and all-cause mortality in patients with stable coronary heart disease (CHD). METHODS: In the observational prospective cohort study KAROLA, 1,148 CHD patients were followed for a median of 8.1 years. ADMA and SDMA were determined by liquid chromatography-tandem mass spectrometry. Baseline ADMA and SDMA levels were categorized in quartiles or standardized by their respective standard deviation, and appropriate hazard ratios and 95 % confidence intervals (HR [95 % CI]) were estimated in Cox proportional hazards models. RESULTS: 150 patients experienced secondary cardiovascular disease events (CVD) and 121 patients died. After adjustment for confounders, ADMA was not associated with the risk of secondary CVD events (HR per standard deviation increase: 1.02 [95 %CI: 0.86-1.21]), whereas an association was suggested for SDMA (HR 1.17 [1.00-1.37]). Higher hazard ratios were observed in all-cause mortality models (ADMA: HR 1.15 [0.95-1.37]; SDMA: HR 1.29 [1.09-1.52]). CONCLUSIONS: Our results suggest that especially SDMA might possibly have potential as a risk marker for all-cause mortality and to a lesser extent for secondary cardiovascular events. Future studies are needed to quantify these associations more precisely and should, in particular, further address the possibility of residual confounding by impaired kidney function.
    Type of Publication: Journal article published
    PubMed ID: 23073705
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  • 10
    Keywords: CANCER ; CELLS ; EXPRESSION ; ASSOCIATION ; CIGARETTE-SMOKING ; CORONARY-HEART-DISEASE ; CARDIOVASCULAR RISK ; THROMBIN ; ACTIVATED RECEPTOR 4 ; MARTINGALE-BASED RESIDUALS
    Abstract: Background: Smoking is a major cause of morbidity and mortality. Smoking-related epigenetic biomarkers may open new avenues to better quantify the adverse health effects of smoking, and to better understanding of the underlying mechanisms. We aimed to evaluate the clinical implications of F2RL3 methylation, a novel epigenetic biomarker of smoking exposure disclosed by recent genome-wide methylation studies. Methods: Blood DNA methylation at F2RL3 (also known as PAR-4) was quantified in baseline samples of 3588 participants aged 50-75 years in a large population-based prospective cohort study by MALDI-TOF mass spectrometry. Deaths were recorded during a median follow-up of 10.1 years. The associations of methylation intensity and of smoking with all-cause, cardiovascular, cancer and other mortality were assessed by Cox's proportional hazards regression, controlling for potential confounding factors. Results: Lower methylation intensity at F2RL3 was strongly associated with mortality. After adjustment for multiple covariates including smoking, hazard ratios [95% confidence interval (CI)] for death from any cause, cardiovascular disease, cancer or other causes were 2.60 (95% CI, 1.81-3.74), 2.45 (95% CI, 1.28-4.68), 2.94 (95% CI, 1.68-5.14) and 2.39 (95% CI, 1.11-5.16), respectively, in subjects in the lowest quartile of methylation intensity compared with subjects in the highest quartile. The associations with mortality outcomes were much stronger among men than among women. In addition, strong positive associations of smoking with each of the outcomes were substantially weakened, and almost disappeared when controlling for F2RL3 methylation intensity. Conclusions: F2RL3 methylation is a strong predictor of mortality, including all-cause, cardiovascular, cancer and other mortality. Systemic adverse effects of smoking may be mediated by pathways associated with F2RL3 methylation.
    Type of Publication: Journal article published
    PubMed ID: 24510982
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