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  • 1
    Keywords: COMBINATION ; MODEL ; MODELS ; FOLLOW-UP ; INFORMATION ; DISEASE ; DISEASES ; RISK ; HEART ; TIME ; MARKER ; ASSOCIATION ; ASSAY ; DESIGN ; PLASMA ; NUMBER ; AGE ; meta-analysis ; smoking ; DATABASE ; C-REACTIVE PROTEIN ; MYOCARDIAL-INFARCTION ; HEART-DISEASE ; vascular disease ; REGRESSION ; ASSOCIATIONS ; ISCHEMIC-STROKE ; CORONARY-HEART-DISEASE ; METAANALYSIS ; LEVEL ; methods ; EXTENT ; ARTERY-DISEASE ; MIDDLE-AGED MEN ; ACTIVATING-FACTOR-ACETYLHYDROLASE ; ATHEROSCLEROSIS RISK ; lipoprotein-associated phospholipase A(2) ; LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE-A2 ; REPEAT
    Abstract: Background A large number of observational epidemiological studies have reported generally positive associations' between circulating mass and activity levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA(2) markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors. Objectives By combination of data from individual participants from all relevant observational studies in a systematic,meta-analysis, with correction for regression dilution (using available data on serial measurements of Lp-PLA(2)), the Lp-PLA(2) Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA(2) with coronary heart disease (and, where data are sufficient with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA(2) and cardiovascular outcomes. Methods A central database is being established containing data on circulating Lp-PLA(2) values, sex and other potential confounding factors, age at baseline Lp-PLA(2) Measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA(2) will yield information on a total of about 15 000 cardiovascular disease endpoints
    Type of Publication: Journal article published
    PubMed ID: 17301621
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  • 2
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Kongress Medizin und Gesellschaft 2007; 20070917-20070921; Augsburg; DOC07gmds287 /20070906/
    Publication Date: 2007-09-07
    Keywords: adipokines ; asthma ; allergy ; children ; ddc: 610
    Language: English
    Type: conferenceObject
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  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Kongress Medizin und Gesellschaft 2007; 20070917-20070921; Augsburg; DOC07gmds205 /20070906/
    Publication Date: 2007-09-07
    Keywords: epidemiology ; inflammation ; genetics ; C-reactive protein ; myocardial infarction ; ddc: 610
    Language: English
    Type: conferenceObject
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  • 4
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    German Medical Science; Düsseldorf, Köln
    In:  123. Kongress der Deutschen Gesellschaft für Chirurgie; 20060502-20060505; Berlin; DOC06dgch5575 /20060502/
    Publication Date: 2006-05-09
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 5
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    German Medical Science; Düsseldorf, Köln
    In:  50. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 12. Jahrestagung der Deutschen Arbeitsgemeinschaft für Epidemiologie; 20050912-20050915; Freiburg im Breisgau; DOC05gmds050 /20050908/
    Publication Date: 2005-09-09
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 6
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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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  • 7
    Abstract: OBJECTIVE: Chronic kidney disease (CKD) increases risk of coronary heart disease (CHD), but the impact of using different equations for estimating kidney function on CHD is not clear yet. This study described the prognostic value of CKD as defined by various creatinine- (Cr-eGFR) and cystatin C-based estimating (Cys-eGFR) equations and their combinations on subsequent cardiovascular disease (CVD) events in patients with CHD. DESIGN: Cohort study. SETTING: Patients with coronary heart disease in in-patient rehabilitation and long-term follow-up (mean 63.4 months). SUBJECTS: 1050 patients with coronary heart disease aged 30-70 years at baseline. METHODS: CKD was defined as eGFR〈60mL/min/1.73m(2) (CKD stages 3-5) estimated by three Cr-eGFR equations (Cockroft-Gault equation adjusted for body surface area (CG/BSA), Modification of Diet in Renal Disease Study (MDRD) equation, CKD-EPIcrea) and by two Cys-eGFR equations (Arnal-Dade equation, CKD-EPIcys) and a combination. The primary endpoint of our study was subsequent CVD events. RESULTS: During follow-up 118 patients (11.2%) experienced the outcome of our study. CKD assessed by the CG/BSA, MDRD, and CKD-EPIcrea equations showed no statistically significant association with subsequent CVD events after adjustment for multiple covariates (hazard ratio (HR) 1.45 [95% CI, 0.81-2.59], HR 1.47 [95% CI, 0.84-2.60], and HR 1.31 [95% CI, 0.72-2.83], respectively). By contrast, the Cys-eGFR equations were much stronger associated with subsequent CVD endpoints (Arnal-Dade: HR, 2.01 [95% CI, 1.34-3.04]; CKD-EPIcys HR, 2.22 [95% CI, 1.46-3.37]). The CKD-EPIcys also provided the highest area under the curve value. CONCLUSION: Our study shows that prevalent CKD is an independent risk factor for subsequent CVD in patients with prevalent CHD and implies that Cys-eGFR equations show a better clinical utility compared to the Cr-eGFR equations. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
    Type of Publication: Journal article published
    PubMed ID: 20347445
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  • 8
    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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  • 9
    Keywords: BLOOD-PRESSURE ; ALL-CAUSE MORTALITY ; OLDER-ADULTS ; GENERAL-POPULATION ; GLOMERULAR-FILTRATION-RATE ; CARDIOVASCULAR RISK ; RISK POPULATION COHORTS ; COLLABORATIVE METAANALYSIS ; URINARY ALBUMIN EXCRETION ; CYSTATIN C
    Abstract: Context Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial. Objective To evaluate possible effect modification (interaction) by age of the association of eGFR and albuminuria with clinical risk, examining both relative and absolute risks. Design, Setting, and Participants Individual-level meta-analysis including 2 051 244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australasia, Europe, and North/South America, conducted in 1972-2011 with a mean follow-up time of 5.8 years (range, 0-31 years). Main Outcome Measures Hazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholesterol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates. Results Mortality (112 325 deaths) and ESRD (8411 events) risks were higher at lower eGFR and higher albuminuria in every age category. In general and high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age; eg, adjusted HRs at an eGFR of 45 mL/min/1.73 m(2) vs 80 mL/min/1.73 m(2) were 3.50 (95% CI, 2.55-4.81), 2.21 (95% CI, 2.02-2.41), 1.59 (95% CI, 1.42-1.77), and 1.35 (95% CI, 1.23-1.48) in age categories 18-54, 55-64, 65-74, and 〉= 75 years, respectively (P 〈 .05 for age interaction). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0-12.8], 12.2 [95% CI, 10.3-14.3], 13.3 [95% CI, 9.0-18.6], and 27.2 [95% CI, 13.5-45.5] excess deaths per 1000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age was less evident, while differences in absolute risk were higher in older age categories (7.5 [95% CI, 4.3-11.9], 12.2 [95% CI, 7.9-17.6], 22.7 [95% CI, 15.3-31.6], and 34.3 [95% CI, 19.5-52.4] excess deaths per 1000 person-years, respectively by age category, at an albumin-creatinine ratio of 300 mg/g vs 10 mg/g). In CKD cohorts, adjusted relative hazards of mortality did not decrease with age. In all cohorts, ESRD relative risks and absolute risk differences at lower eGFR or higher albuminuria were comparable across age categories. Conclusions Both low eGFR and high albuminuria were independently associated with mortality and ESRD regardless of age across a wide range of populations. Mortality showed lower relative risk but higher absolute risk differences at older age.
    Type of Publication: Journal article published
    PubMed ID: 23111824
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  • 10
    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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