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Conen D.,University of Basel | Adam M.,University of Basel | Adam M.,Swiss Tropical and Public Health Institute | Roche F.,Jean Monnet University | And 15 more authors.
Circulation | Year: 2012

Background-: Premature atrial contractions (PACs) are independent predictors of atrial fibrillation, stroke, and death. However, little is known about PAC frequency in the general population and its association with other cardiovascular risk factors. Methods and Results-: We performed a cross-sectional analysis among participants of the population-based Swiss cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA). 24-hour Holter electrocardiograms to assess PAC prevalence and frequency were performed in a random sample of 1742 participants aged >50 years. The median (interquartile range) number of PACs per hour was 0.8 (0.4-1.8), 1.1 (0.5-2.4), 1.4 (0.7-4.6), 2.3 (0.8-6.9), and 2.6 (1.2-6.5) among participants aged 50 to 55, 55 to 60, 60 to 65, 65 to 70, and ≥ 70 years, respectively (P<0.0001). Only 18 (1.0%) participants did not have at least 1 PAC during Holter monitoring. In multivariable negative binomial regression models, PAC frequency was significantly associated with age (risk ratio [RR] per SD 1.80; P<0.0001), height (RR per SD 1.52; P<0.0001), prevalent cardiovascular disease (RR 2.40; P<0.0001), log-transformed N-terminal pro B-type natriuretic peptides (RR per SD 1.27; P<0.0001), physical activity ≥2 hours per day (RR 0.69; P=0.002), and high-density lipoprotein cholesterol (RR per SD 0.80; P=0.0002). Hypertension and body mass index were not significantly related to PAC frequency. Conclusions-: To our knowledge, this is the first study to assess risk factors for PAC frequency in the general population aged ≥50 years. PACs are common, and their frequency is independently associated with age, height, history of cardiovascular disease, natriuretic peptide levels, physical activity, and high-density lipoprotein cholesterol. The underlying mechanisms of these relationships need to be addressed in future studies. © 2012 American Heart Association, Inc.


Lehmann N.,Institute for Medical Informatics | Schmermund A.,Cardioangiological Center Bethanien | Moebus S.,Institute for Medical Informatics | Stang A.,Martin Luther University of Halle Wittenberg | And 5 more authors.
Hypertension | Year: 2012

Prehypertension is a frequent condition and has been demonstrated to increase cardiovascular risk. However, the association with coronary atherosclerosis as part of target organ damage is not well understood. We investigated the cross-sectional relationship and longitudinal outcome between blood pressure categories and coronary artery calcification (CAC), quantified by electron beam computed tomography, in 4181 participants from the population-based Heinz Nixdorf Recall Study cohort. At baseline, we observed a continuous increase in calcium scores with increasing blood pressure categories. During a median follow-up period of 7.18 years, 115 primary end points (2.8%; fatal and nonfatal myocardial infarction) and 152 secondary end points (3.6%; stroke and coronary revascularization) occurred. We observed a continuous increase in age-and risk factor-adjusted secondary endpoints (hazard ratios [95% CI]) with increasing blood pressure categories (referent: normotension) in men: prehypertension, 1.80 (0.53-6.13); stage 1 hypertension, 2.27 (0.66-7.81); and stage 2 hypertension, 4.10 (1.27-13.24) and in women: prehypertension, 1.13 (0.34-3.74); stage 1 hypertension, 2.14 (0.67-6.85); and stage 2 hypertension, 3.33 (1.24-8.90), respectively, but not in primary endpoints. Cumulative event rates were determined by blood pressure categories and the CAC. In prehypertension, the adjusted hazard ratios for all of the events were, for CAC 1 to 99, 2.05 (0.80-5.23; P=0.13); 100 to 399, 3.12 (1.10-8.85; P=0.03); and ≥400, 7.72 (2.67-22.27; P=0.0002). Risk of myocardial infarction and stroke in hypertension but also in prehypertension depends on the degree of CAC. This marker of target-organ damage might be included, when lifestyle modification and pharmacotherapeutic effects in prehypertensive individuals are tested to avoid exposure to risk and increase benefit. © 2011 American Heart Association, Inc.


Heinz J.,Institute of Clinical Chemistry | Westphal S.,Institute of Clinical Chemistry | Borucki K.,Institute of Clinical Chemistry | Luley C.,Magdeburg University Hospital | Dierkes J.,Institute of Clinical Chemistry
Circulation | Year: 2010

Background-In observational studies, hyperhomocysteinemia has been found to be a risk factor for total mortality and cardiovascular events in patients with end-stage renal disease. These patients have grossly elevated homocysteine levels that can be lowered by supplementation with folic acid and vitamin B12. We conducted a randomized clinical trial with B vitamins to reduce homocysteine levels and therefore cardiovascular events and total mortality. Methods and Results-This randomized, double-blind multicenter study was conducted in 33 dialysis centers in north and east Germany between July 2002 and July 2008. We randomly assigned 650 patients with end-stage renal disease who were undergoing hemodialysis to 2 postdialysis treatments: 5 mg folic acid, 50 μg vitamin B12, and 20 mg vitamin B6 (active treatment) or 0.2 mg folic acid, 4 μg vitamin B12, and 1.0 mg vitamin B6 (placebo) given 3 times per week for an average of 2 years. The primary outcome was total mortality; the secondary outcome was fatal and nonfatal cardiovascular events. The primary outcome occurred in 102 patients (31%) receiving the active treatment and in 92 (28%) receiving placebo (hazard ratio, 1.13; 95% confidence interval, 0.85 to 1.50; P=0.51). The secondary outcome occurred in 83 patients (25%) receiving the active treatment and in 98 (30%) receiving placebo (hazard ratio, 0.80; 95% confidence interval, 0.60 to 1.07; P=0.13). Conclusions-Increased intake of folic acid, vitamin B12, and vitamin B6 did not reduce total mortality and had no significant effect on the risk of cardiovascular events in patients with end-stage renal disease. © 2010 American Heart Association, Inc.


Geisen U.,Institute of Clinical Chemistry | Zieger B.,Laboratory for Hemostaseology | Nakamura L.,Laboratory for Hemostaseology | Weis A.,Albert Ludwigs University of Freiburg | And 3 more authors.
Thrombosis Research | Year: 2014

Introduction Ristocetin cofactor activity of Von Willebrand factor (VWF:RCo) and the ratio VWF:RCo to its antigen VWF:Ag are used as routine screening to estimate VWF function and to detect types of Von Willebrand disease (VWD) caused by loss of high molecular weight multimers. However, the VWF:RCo test is prone to analytic imprecisions due to various reasons. We compared an assay for VWF activity (VWF:Ac) with VWF:RCo putting emphasis on the ratios to VWF:Ag. Materials and Methods We evaluated 942 samples from 432 patients and evaluated three groups in detail: normal patients (normal multimers, VWF:Ag and VWF:RCo > 0.5 U/ml, VWD type 1 excluded; n = 258), VWD type 1 (n = 76) and acquired Von Willebrand syndrome (AVWS, n = 326). In addition, 30 healthy subjects were analysed. Results VWF:Ac and VWF:RCo correlated well (Pearsońs r = 0.96, p < 0.01), so did their ratios to VWF:Ag (Pearsońs r = 0.82, p < 0.01). We calculated the normal range of VWF:Ac/VWF:Ag for healthy subjects as 0.8-1.16. In comparison, the reference range (mean ± 2std) derived from normal patient samples was 0.73-1.14. The corresponding ranges for VWF:RCo/VWF:Ag came to 0.74-1.23 (healthy) and 0.62-1.25 (normal patients). The ratios showed similar results regarding VWD type 1. The sensitivity for AVWS was higher with VWF:Ac/VWF:Ag than with VWF:RCo/VWF:Ag (97.5% versus 84.7%). Conclusions The data suggest that the results obtained with the VWF:Ac assay are comparable to that of the VWF:RCo assay. An AVWS was more reliably detected by VWF:Ac/VWF:Ag. We assume that the VWF:Ac assay could replace VWF:RCo for routine screening for AVWS, especially when prompt evaluation is required. © 2014 Elsevier Ltd.


Brosche T.,Friedrich - Alexander - University, Erlangen - Nuremberg | Bertsch T.,Institute of Clinical Chemistry | Sieber C.C.,Friedrich - Alexander - University, Erlangen - Nuremberg | Hoffmann U.,University of Heidelberg
Archives of Gerontology and Geriatrics | Year: 2013

Severe sepsis is reportedly accompanied by oxidative stress with a depletion of antioxidant defense. We estimated plasmalogen vinyl ether bond (PVEB) levels in blood plasma of 20 elderly patients with initial severe sepsis, serving as a sensitive surrogate marker of oxidative stress, and compared them with standard markers, i.e., Acute Physiology and Chronic Health Evaluation (APACHE) II score, C-reactive protein (CRP), creatinine, white blood cell and platelet counts. Patients were included in the study and then blood samples were taken within 24h of the onset of symptoms of severe sepsis. Twenty sex- and age-matched, healthy individuals were included in the study as controls. We measured plasmalogen-derived hexadecanal dimethyl acetal (16:0 DMA) in isolated phospholipids from EDTA-plasma using gas chromatography. We found a 55% lower concentration of 16:0 DMA, corresponding to lower levels of PVEB in the patients' plasma compared to the controls (0.26±0.15 vs 0.58±0.13g/100g; p<0.001). In all patients' and non-survivors' samples the 16:0 DMA levels correlated negatively with plasma CRP values (RS=-0.48 and RS=-0.70, respectively; p<0.05), but not with APACHE II scores or other markers. The observed lower baseline content of PVEB may indicate oxidative stress contributing to the sequlae of sepsis, but did not correlate with the outcome or the severity of illness. Serial measurements are needed to validate PVEB as a marker in sepsis. © 2013 Elsevier Ireland Ltd.


Behnes M.,University of Heidelberg | Bertsch T.,Institute of Clinical Chemistry | Hoffmann U.,University of Heidelberg
Critical Care | Year: 2013

The multicenter study conducted by Lorente and coworkers - published in the previous issue of Critical Care - suggests that levels of tissue inhibitor of metalloproteinase (TIMP)-1 in association with the 372 T/C genetic polymorphism of TIMP-1 are promising markers to predict the clinical outcome of septic patients. TIMPs bind to active matrix metalloproteinases and, amongst other effects, inhibit their proteolytic activity of the extracellular matrix. Previous clinical studies showed increased plasma levels of TIMP-1 in nonsurvivors of sepsis, and showed associations between the 372 T/C genetic polymorphism of TIMP-1 and increased risk of developing certain diseases. In recent years, there has been great interest in understanding whether genetic determinants of the host response to systemic infections are associated with poor outcome. Furthermore, the pharmacogenomics of sepsis may allow us to target immune-modulating therapies. Measurement of TIMP-1 protein levels and TIMP-1 polymorphism 372 T/C in the intensive care setting could therefore be an attractive noninvasive tool to determine the outcome of septic patients, and might help to select patients potentially benefitting from a target-specific immune-modulatory therapy directed to matrix metalloproteinase/TIMP homeostasis. © 2013 BioMed Central Ltd.


Finsterer J.,Krankenanstalt Rudolfstiftung | Kovacs G.G.,Medical University of Vienna | Ahting U.,Institute of Clinical Chemistry
Neurology International | Year: 2013

Mitochondrial DNA depletion syndrome (MDS) is usually a severe disorder of infancy or childhood, due to a reduced copy number of mtDNA molecules. MDS with only mild, nonspecific clinical manifestations and onset in adulthood has not been reported. A 47-year-old Caucasian female with short stature and a history of migraine, endometriosis, Crohn's disease, C-cell carcinoma of the thyroid gland, and a family history positive for mitochondrial disorder (2 sisters, aunt, niece), developed day-time sleepiness, exercise intolerance, and myalgias in the lower-limb muscles since age 46y. She slept 9-10 hours during the night and 2 hours after lunch daily. Clinical exam revealed sore neck muscles, bilateral ptosis, and reduced Achilles tendon reflexes exclusively. Blood tests revealed hyperlipidemia exclusively. Nerve conduction studies, needle electromyography, and cerebral and spinal magnetic resonance imaging were noninformative. Muscle biopsy revealed detached lobulated fibers with subsarcolemmal accentuation of the NADH and SDH staining. Realtime polymerase chain reaction revealed depletion of the mtDNA down to 9% of normal. MDS may be associated with a mild phenotype in adults and may not significantly progress during the first year after onset. In an adult with hypersomnia, severe tiredness, exercise intolerance, and a family history positive for mitochondrial disorder, a MDS should be considered. © J. Finsterer et al., 2013 Licensee PAGEPress, Italy.


Von Sarnowski B.,Institute of Clinical Chemistry | Ludemann J.,University of Greifswald | Volzke H.,University of Greifswald | Dorr M.,University of Greifswald | And 2 more authors.
Stroke | Year: 2010

Background And Purpose-: Cross-sectional studies describe a positive association between common carotid artery intima-media thickness (CCA-IMT) and carotid plaques (CP). However, longitudinal data on the predictive value of CCA-IMT for occurrence of CP are limited. Therefore, the role of increasing CCA-IMT in the atherosclerotic process is still discussed controversially. Methods-: We investigated the predictive value of CCA-IMT and the Framingham risk score (FRS) for incident CP formation in a population-based longitudinal study of 1922 subjects aged 45 to 81 years who underwent ultrasonography of both carotid arteries and received vascular risk factor assessment at baseline and after 5 years. CP was defined as any protruding focal thickening of the intima-media complex. Incident CP formation during follow-up was defined as the appearance of at least 1 CP in a previously plaque-free arterial segment (right and left common, internal, and external carotid arteries and carotid bifurcation). Results-: Among the 636 subjects without CP at baseline, 418 (66%) had at least 1 incident CP during follow-up. In a multivariable negative binominal regression model adjusted for age, gender, and the FRS, the number of arterial segments affected by incident CP was 1.53-fold higher (CI, 1.12-2.07; P<0.01) for subjects in the highest quartile of the overall CCA-IMT distribution compared to those in the lowest quartile. Conclusions-: Both CCA-IMT and FRS independently predict incident CP formation. The risk of CP formation may actually be underestimated in subjects with low FRS and high IMT. © 2010 American Heart Association, Inc.


Herbst A.,Ludwig Maximilians University of Munich | Rahmig K.,Ludwig Maximilians University of Munich | Stieber P.,Institute of Clinical Chemistry | Philipp A.,Ludwig Maximilians University of Munich | And 6 more authors.
American Journal of Gastroenterology | Year: 2011

Objectives: Colorectal cancer is the third most common cancer and a major cause of cancer-related deaths. Early detection of colonic lesions can reduce the incidence and mortality of colorectal cancer. Colonoscopy is the screening test for colorectal cancer with the highest efficacy, but its acceptance in the general public is rather low. To identify suitable tumor-derived markers that could detect colorectal cancer in blood samples, we analyzed the methylation status of a panel of genes in sera of affected patients. Methods: Using methylation-specific quantitative PCR, we analyzed the methylation of ten marker genes in sera of healthy individuals and patients with colorectal cancer. Results: Only HLTF, HPP1/TPEF, and NEUROG1 DNA methylation was detectable in at least 50% of patients with colorectal cancers. Whereas HLTF and HPP1/TPEF preferentially detected advanced and metastasized colorectal cancers, NEUROG1 methylation was detectable in UICC stages I-IV at a similar rate. Compared with other methylation markers, such as ALX4, SEPT9, and vimentin, NEUROG1 shows a higher sensitivity for colorectal cancer at UICC stages I and II. At a specificity of 91%, NEUROG1 reached a sensitivity of 61% (confidence interval, 50.4-70.6%) for the detection of colorectal cancers. Furthermore, detection of NEUROG1 methylation was independent of age and gender. Conclusions: Methylation of the NEUROG1 gene is frequently found in sera of patients with colorectal cancers independent of tumor stage. The quantitative detection of NEUROG1 DNA methylation in serum is a suitable approach for the non-invasive screening for asymptomatic colorectal cancer. © 2011 by the American College of Gastroenterology.


Arneth B.M.,Institute of Clinical Chemistry
Journal of Neuroimmunology | Year: 2010

The influence of the immune system was originally thought to be harmful regarding injuries and infarctions of the brain. Recently, there has been increasing evidence for the protective, positive effects of cells of the immune system on brain tissue. From an evolutionary biology standpoint, this hypothesis is more compelling than viewing the immune system only as a harmful influence. Herein we emphasize how physiological activation of immune cells following tissue damage and/or by infarcts of brain tissue can lead to an activation of T-lymphocytes. These activated T-lymphocytes are then regarded to perform several protective effects. © 2010 Elsevier B.V.

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