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  • 1
    Keywords: FOLLOW-UP ; MORTALITY ; RISK ; BIOMARKERS ; C-REACTIVE PROTEIN ; PREDICTION ; PROGNOSTIC VALUE ; FAILURE ; GENERAL-POPULATION ; CARDIOVASCULAR EVENTS
    Abstract: Objective To assess the prognostic value of 12-months N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) levels on adverse cardiovascular events in patients with stable coronary heart disease. Methods NT-proBNP concentrations were measured at baseline and at 12-months follow-up in participants of cardiac rehabilitation (median follow-up 8.96 years). Cox-proportional hazards models evaluated the prognostic value of log-transformed NT-proBNP levels, and of 12-months NT-proBNP relative changes on adverse cardiovascular events adjusting for established risk factors measured at baseline. Results Among 798 participants (84.7% men, mean age 59 years) there were 114 adverse cardiovascular events. 12-months NT-proBNP levels were higher than baseline levels in 60 patients (7.5%) and numerically more strongly associated with the outcome in multivariable analysis (HR 1.65 [95% CI 1.33-2.05] vs. HR 1.41 [95% CI 1.12-1.78], with a net reclassification improvement (NRI) of 0.098 [95% CI 0.002-0.194] compared to NRI of 0.047 [95% CI -0.0004-0.133] for baseline NT-proBNP levels. A 12-month 10% increment of NTproBNP was associated with a HR of 1.35 [95% CI 1.12-1.63] for the onset of an adverse cardiovascular event. Subjects with a 12-month increment of NT-proBNP had a HR of 2.56 [95% CI 1.10-5.95] compared to those with the highest 12-months reduction. Conclusions Twelve-months NT-proBNP levels after an acute cardiovascular event are strongly associated with a subsequent event and may provide numerically better reclassification of patients at risk for an adverse cardiovascular event compared to NT-proBNP baseline levels after adjustment for established risk factors.
    Type of Publication: Journal article published
    PubMed ID: 25629613
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  • 2
    Keywords: TRIAL ; OUTCOMES ; METAANALYSIS ; GENETIC-VARIANTS ; ABCB1 ; TREATMENT PLATELET REACTIVITY ; PROTON-PUMP INHIBITORS ; CLOPIDOGREL THERAPY ; CYP2C19 GENOTYPE
    Abstract: Background: CYP2C19*2 polymorphism is related to metabolizer phenotypes resulting in reduced effectiveness in converting the antiplatelet drug clopidogrel to active drug. An association of the genotype itself with adverse outcomes is discussed. We investigated the prognostic value of carriage of the CYP2C19*2 allele in a high risk group of patients with prevalent coronary heart disease (CHD) at baseline during long-term follow-up under conditions of routine clinical care. Methods: In n=1050 patients with stable CHD at baseline genotyping of CYP2C19 allele *2 (rs4244285; 681G〉A) was performed. The Cox-proportional hazards model was employed to investigate the association of CYPC19*2 allele status with cardiovascular disease (CVD) events during eight year follow-up. The analysis was also performed in patients who did not take clopidogrel or ticlopidin. Results: Only the very few patients homozygous for a loss-of-function variant of CYP2C19, allele *2 (2.6%), had a statistically significantly higher incidence rate for secondary CVD events during long-term follow-up than wild-type carriers (50.8 versus 21.5 per 1000 patients years; rate for heterozygous carries 17.2 per 1000 patient years). The hazard ratio after adjustment for covariates compared to the wild-type carriers was 2.59 (95% confidence interval (CI) 1.27-5.28) and 0.80 (95% CI 0.52-1.23) for homozygous and heterozygous allele carriers, respectively. Conclusions: In this medium-size group of patients with stable CHD homozygous carriers of the loss-of-function allele CYP2C19*2 were at increased risk for subsequent CVD events during 8 year follow-up independent of other risk factors. As only few patients carried the homozygous loss-of-function variant and we found overall no evidence for improved clinical utility, a benefit of genotyping in this patient population seems unlikely.
    Type of Publication: Journal article published
    PubMed ID: 23981380
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