Meike Coldewey

Johannes Gutenberg-Universität Mainz, Mayence, Rheinland-Pfalz, Germany

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Publications (15)44.44 Total impact

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    ABSTRACT: Background Right ventricular dysfunction (RVD) and cardiac troponin I (cTnI) are important tools for risk stratification in pulmonary embolism (PE). We investigate the association of RVD and cTnI in normotensive PE patients and calculate a cTnI cut-off level for predicting RVD and submassive PE. Methods Clinical, laboratory, radiological and echocardiagraphic data were analysed. Patients were categorised into groups with or without RVD and compared focussing on cTnI. Effectiveness of cTnI for predicting RVD and submassive PE was tested. Results One hundred twenty-nine normotensive PE patients, 71 with and 58 without RVD, were included. Patients with RVD were older (75.0 years (61.3/81.0) vs. 66.0 years (57.7/75.1), P = 0.019). cTnI (0.06 ng/ml (0.02/0.23) vs. 0.01 ng/ml (0.00/0.03), P P = 0.016) were higher in PE with RVD. cTnI was associated with RVD (OR 3.95; 95 % CI 1.95–8.02, p = 0.00014). AUC for cTnI diagnosing RVD was 0.79, and for submassive PE0.87. Cut-off values for cTnI predicting RVD and submassive PE were 0.01 ng/ml, with a negative predictive value of 73 %. cTnI was positively correlated with age, D-dimer and creatinine. Conclusions In normotensive PE patients, cTnI is helpful for risk stratification and excluding RVD. cTnI elevation is correlated with increasing age and reduced kidney function.
    Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 12/2014; · 1.41 Impact Factor
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    ABSTRACT: Pulmonary embolism (PE) is potentially life-threatening. Aim of this study was to identify genderspecific differences in acute PE and in risk stratification of hemodynamically stable PE patients.
    Deutsche medizinische Wochenschrift (1946). 11/2014; 139(46):2329-34.
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    ABSTRACT: Background Depressive symptoms have detrimental effects on quality of life and mortality. Poor adherence to treatment regimen is a potential mechanism for the increased risk for adverse medical events associated with depression. Regarding oral anticoagulation with vitamin K antagonists, adherence is crucial for the outcome. Little is known about the clinical relevance of current depressiveness for anticoagulation treatment.Objectives To examine the impact of current depressiveness on anticoagulation treatment in regular medical care.Patients/Methods We examined the association between clinically significant depressiveness as assessed by the Patient Health Questionnaire-2 ≥ 2 (PHQ-2 ≥ 2) with the percentage of time in the therapeutic range (TTR), self-rated compliance, several aspects of health literacy, anticoagulation side-effects and treatment satisfaction in a cross-sectional study of 1,790 oral anticoagulation outpatients.Results716 participants (40.0%) had clinically significant depressive symptoms. Depressed persons reported lower compliance with intake of prescribed medication and regular visits for control of anticoagulation, more unspecific side-effects (e.g. pruritus) and lower satisfaction with the anticoagulation treatment and their doctors’ expertise and empathy. Depressed as compared with non-depressed individuals had a lower TTR (-4.67, 95%CI -8.39 to -0.95). Increasing severity of depressiveness was related with decreasing TTR. However, depressiveness lost its significant impact on TTR after multivariable adjustment (-3.11, 95%CI -6.88 to 0.66).Conclusions Clinically significant depressiveness was highly prevalent and impaired several aspects of anticoagulation treatment. Depressiveness should be regarded as a clinically significant condition that needs to be addressed in the management of anticoagulation patients.This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 10/2014; · 6.08 Impact Factor
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    ABSTRACT: The prevalence of pulmonary embolism (PE) increases progressively with age. Less data about the impact of increasing age on the severity of PE are available. The objectives of this study were to investigate the impact of increasing age on the severity of normotensive PE. Retrospective analysis of clinical, laboratory, radiological and echocardiagraphic data of normotensive patients with PE was performed. According to patients' age at the moment of acute PE event, the total number of 129 normotensive PE patients was subdivided into 4 age groups. In age groups 18-59, 60-69, 70-79 and 80-94 years were, respectively, a number of 30, 31, 33 and 35 patients included. Percentage of women in age groups increased with advanced age (P = 0.021). Systolic pulmonary artery pressure (PAP) (P < 0.0001) and frequency of incomplete or complete right bundle-branch block (RBBB) (P = 0.019), of right ventricular dysfunction (RVD) (P = 0.00031) and of submassive PE stadium with intermediate risk (P = 0.0016) increased significantly with growing age. Multivariable regression model confirmed an association between age and submassive PE [OR (per year) 1.04; 95 % CI, 1.02-1.07, P = 0.0020] as well as female gender and submassive PE (OR 2.45; 95 % CI, 1.10-5.50, P = 0.029) and tachycardia and submassive PE (OR 15.33; 95 % CI, 3.45-68.24, P = 0.00034). Advanced age, female gender and tachycardia are risk factors for a submassive PE with intermediate risk in normotensive PE patients. The percentage of PE patients with submassive PE, right ventricular overload, RVD, RBBB, elevated systolic PAP increases with advanced age.
    Heart and vessels. 06/2014;
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    ABSTRACT: Since decades, oral anticoagulation (OAC) with vitamin K antagonists (VKA) is an established therapy for both prevention and treatment of thromboembolism in daily clinical routine. Increasing life expectancy, demographic changes, and novel oral anticoagulants have led to an increasing complexity of medical therapy. However, data on quality and management of VKA therapy with phenprocoumon in current medical care are limited. Our aim is to investigate the quality of OAC with VKA in current health care and to evaluate the potential for improvements. The investigator-initiated thrombEVAL study programme comprises two cohorts of patients treated with vitamin K antagonists for oral anticoagulation therapy in real-life settings: a multicentre cohort of patients in regular medical care and a multilocal, single-centre cohort of patients in a telemedicine-based coagulation service. The study programme is expected to enrol a total number of approximately 2000 to 2500 patients. Both cohorts will build on a detailed clinical assessment of participants and anticoagulation therapy at study enrolment. Subsequently active and passive follow-up investigations are carried out to document and validate complications of the treatment. The primary short-term outcome is the distribution of time in therapeutic range; the primary long-term outcome comprises the composite of stroke, systemic embolism, myocardial infarction, major and clinically relevant bleeding, and death. The thrombEVAL project will provide a large prospective observational cohort of patients predominantly treated with phenprocoumon. It will evaluate the quality of oral anticoagulation in regular medical care and a telemedicine-based coagulation service.
    European Journal of Preventive Cardiology 03/2014; · 3.90 Impact Factor
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    ABSTRACT: Echocardiography for risk stratification in hemodynamically stable patients with pulmonary embolism (PE) is well-established. Right ventricular dysfunction (RVD) is associated with an elevated mortality and adverse outcome. The aim of our study was to compare RVD criteria and investigate the role of elevated systolic pulmonary artery pressure (sPAP) in the diagnosis of RVD. We retrospectively analyzed the echocardiographic and laboratory data of all hemodynamically stable patients with confirmed PE (2006-2011). The data were compared with three different definitions of RVD: Definition 1: RV dilatation, abnormal motion of interventricular septum, RV hypokinesis or tricuspid regurgitation. Definition 2: as with definition 1 but including elevated sPAP (>30mmHg). Definition 3: elevated sPAP (>30mmHg) as single RVD criterion. A total number of 129 patients (59.7% women, age 70.0years (60.7/81.0)) were included in this study. Median Troponin I level was measured as 0.02ng/ml (0/0.14); mean sPAP 33.9±18.5mmHg. The troponin cut-off levels for predicting a RVD of the 3 RVD definitions were in definition 1-3: >0.01ng/ml, >0.01ng/ml and >0.00ng/ml. Analysis of the ROC curve showed an AUC for RVD definitions 1-3: 0.790, 0.796 and 0.635. The combination of commonly used RVD criteria with added elevated sPAP improves the diagnosis of RVD in acute PE. Troponin I values of >0.01ng/ml in acute PE point to an RVD.
    Thrombosis Research 01/2014; · 3.13 Impact Factor
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    ABSTRACT: We report about a 56-year-old man with dyspnoea and leg pain diagnosed with Leriche syndrome and chronic heart failure caused by dilated cardiomyopathy (DCM) with acute cardiac decompensation. Optimising of chronic heart failure therapy with diuretic and antihypertensive drugs leaded to recompensation. A defibrillator was implanted, and afterwards surgical therapy of Leriche syndrome was planned.Leriche syndrome is an uncommon variant of atherosclerotic occlusive disease characterised by total occlusion in abdominal aorta and/or both iliac arteries. If aortic stenosis develops slowly, collateral vascular circulation can be found frequently. Typical symptoms are claudication, symptoms related to an arterial insufficiency of the lower extremities, erectile dysfunction and weight loss. Risk factors of Leriche syndrome are diabetes mellitus, hypertension, hyperlipaemia and smoking. Further it is often associated with chronic renal failure and coronary artery disease. Diagnosis is normally made by computed tomography (CT) or magnetic resonance imaging (MRI). Standard therapy is surgical revascularisation.DCM is a common cause of a congestive heart failure, which could be induced by coronary artery disease, hypertension, toxic, metabolic, inflammatory and infectious agents, and inherited gene defects.
    Wiener klinische Wochenschrift 12/2013; · 0.81 Impact Factor
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    ABSTRACT: Diabetes mellitus is a major risk factor for the development of cardiovascular disease and oxidative stress plays an important role in this process. Therefore, we investigated the effects of hyperglycemia on the formation of reactive oxygen species (ROS) and nitric oxide/cGMP signaling in two different endothelial cell cultures. Human umbilical vein endothelial cells (HUVEC) and EA.hy 926 cells showed increased oxidative stress and impaired NO-cGMP signaling in response to hyperglycemia. The major difference between the two different cell types was the dramatic decrease in viability in HUVEC whereas EA.hy cells showed rather increased growth under hyperglycemic conditions. Starvation led to an additional substantial decrease in viability and increased superoxide formation in HUVEC. Both endothelial cell types, HUVEC and EA.hy 926, may be used as models for vascular hyperglycemia. However, high growth medium should be used to avoid starvation-induced oxidative stress and cell death.
    Journal of diabetes and its complications 04/2012; 26(3):155-62. · 2.11 Impact Factor
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    ABSTRACT: Nitrate tolerance is likely attributable to an increased production of reactive oxygen species (ROS) leading to an inhibition of the mitochondrial aldehyde dehydrogenase (ALDH-2), representing the nitroglycerin (GTN) and pentaerythrityl tetranitrate (PETN) bioactivating enzyme, and to impaired nitric oxide bioactivity and signaling. We tested whether differences in their capacity to induce heme oxygenase-1 (HO-1) might explain why PETN and not GTN therapy is devoid of nitrate and cross-tolerance. Wistar rats were treated with PETN or GTN (10.5 or 6.6 microg/kg/min for 4 days). In contrast to GTN, PETN did not induce nitrate tolerance or cross-tolerance as assessed by isometric tension recordings in isolated aortic rings. Vascular protein and mRNA expression of HO-1 and ferritin were increased in response to PETN but not GTN. In contrast to GTN therapy, NO signaling, ROS formation, and the activity of ALDH-2 (as assessed by an high-performance liquid chromatography-based method) were not significantly influenced by PETN. Inhibition of HO-1 expression by apigenin induced "tolerance" to PETN whereas HO-1 gene induction by hemin prevented tolerance in GTN treated rats. HO-1 expression and activity appear to play a key role in the development of nitrate tolerance and might represent an intrinsic antioxidative mechanism of therapeutic interest.
    Arteriosclerosis Thrombosis and Vascular Biology 09/2007; 27(8):1729-35. · 6.34 Impact Factor
  • Vascular Pharmacology 09/2006; 45(3). · 3.21 Impact Factor
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    ABSTRACT: Nitric oxide (NO)-induced vasorelaxation involves activation of large conductance Ca2+-activated K+ channels (BK). A regulatory BKbeta1 subunit confers Ca2+, voltage, and NO/cGMP sensitivity to the BK channel. We investigated whether endothelial function and NO/cGMP signaling is affected by a deletion of the beta1-subunit. Vascular superoxide in BKbeta1-/- was measured using the fluorescent dye hydroethidine and lucigenin-enhanced chemiluminescence. Vascular NO formation was analyzed using electron paramagnetic resonance (EPR), expression of NADPH oxidase subunits, the endothelial NO synthase (eNOS), the soluble guanylyl cyclase (sGC), as well as the activity and expression of the cyclic GMP-dependent kinase I (cGK-I) were assessed by Western blotting technique. eNOS, sGC, cGK-I expression and acetylcholine-induced NO production were unaltered in Bkbeta1-/- animals, whereas endothelial function was impaired and the activity of the cGK-I was reduced. Vascular O2- and expression of the NADPH oxidase subunits p67phox and Nox1 were increased. Endothelial dysfunction was normalized by the NADPH oxidase inhibitor apocynin. Potassium chloride- and iberiotoxin-induced depolarization mimicked the effect of BKbeta1-deletion by increasing vascular O2- in an NADPH-dependent fashion. The deletion of BKbeta1 causes endothelial dysfunction by increasing O2- formation via increasing activity and expression of the vascular NADPH oxidase.
    Arteriosclerosis Thrombosis and Vascular Biology 09/2006; 26(8):1753-9. · 6.34 Impact Factor
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    ABSTRACT: The hemodynamic and anti-ischemic effects of nitroglycerin (GTN) are rapidly blunted as a result of the development of nitrate tolerance. Hydralazine has been shown to prevent tolerance in experimental and clinical studies, all of which may be at least in part secondary to antioxidant properties of this compound. The antioxidant effects of hydralazine were tested in cell free systems, cultured smooth muscle cells, isolated mitochondria, and isolated vessels. Inhibitory effects on the formation of superoxide and/or peroxynitrite formation were tested using lucigenin and L-012 enhanced chemiluminescence as well as DHE-fluorescence. The peroxynitrite scavenging properties were also assessed by inhibition of nitration of phenol. Prevention of impairment of NO downstream signaling and GTN bioactivation was determined by measurement of P-VASP (surrogate parameter for the activity of the cGMP-dependent kinase-I, cGK-I) and mitochondrial aldehyde dehydrogenase (ALDH-2) activity. Hydralazine dose-dependently decreased the chemiluminescence signal induced by peroxynitrite from SIN-1 and by superoxide from HX/XO in a cell free system, by superoxide in smooth muscle cells and mitochondria acutely challenged with GTN. Moreover, hydralazine inhibited the peroxynitrite-mediated nitration of phenols as well as proteins in smooth muscle cells in a dose-dependent fashion. Finally, hydralazine normalized impaired cGK-I activity as well as impaired vascular ALDH-2 activity. Our results indicate that hydralazine is a highly potent radical scavenger. Thus, the combination with isosorbide dinitrate (ISDN) will favorably influence the nitroso-redox balance in the cardiovascular system in patients with congestive heart failure and may explain at least in part the improvement of prognosis in patients with chronic congestive heart failure.
    Biochemical and Biophysical Research Communications 01/2006; 338(4):1865-74. · 2.28 Impact Factor
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    ABSTRACT: Nitroglycerin (GTN)-induced tolerance was reported to be associated with increased levels of reactive oxygen species (ROS) in mitochondria. In the present study, we further investigated the role of ROS for the development of nitrate tolerance by using heterozygous manganese superoxide dismutase knock-out mice (Mn-SOD+/-). Mn-SOD is acknowledged as a major sink for mitochondrial superoxide. Vasodilator potency of mouse aorta in response to acetylcholine and GTN was assessed by isometric tension studies. Mitochondrial ROS formation was detected by 8-amino-5-chloro-7-phenylpyrido[3,4-d]pyridazine-1,4-(2H,3H)dione sodium salt (L-012)-enhanced chemiluminescence and mitochondrial aldehyde dehydrogenase (ALDH-2) activity was determined by a high-performance liquid chromatography-based assay. Aortic rings from Mn-SOD+/- mice showed normal endothelial function and vasodilator responses to GTN. In contrast, preincubation of aorta with GTN or long-term GTN infusion caused a marked higher degree of tolerance as well as endothelial dysfunction in Mn-SOD+/- compared with wild type. Basal as well as GTN-stimulated ROS formation was significantly increased in isolated heart mitochondria from Mn-SOD+/- mice, correlating well with a marked decrease in ALDH-2 activity in response to in vitro and in vivo GTN treatment. The data presented indicate that deficiency in Mn-SOD leads to a higher degree of tolerance and endothelial dysfunction associated with increased mitochondrial ROS production in response to in vitro and in vivo GTN challenges. These data further point to a crucial role of ALDH-2 in mediating GTN bioactivation as well as development of GTN tolerance and underline the important contribution of ROS to these processes.
    Molecular Pharmacology 10/2005; 68(3):579-88. · 4.41 Impact Factor
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    ABSTRACT: Mitochondrial aldehyde dehydrogenase (ALDH-2) was recently identified to be essential for the bioactivation of glyceryl trinitrate (GTN). Here we assessed whether other organic nitrates are bioactivated by a similar mechanism. The ALDH-2 inhibitor benomyl reduced the vasodilator potency, but not the efficacy, of GTN, pentaerythritol tetranitrate (PETN), and pentaerythritol trinitrate in phenylephrine-constricted rat aorta, whereas vasodilator responses to isosorbide dinitrate, isosorbide-5-mononitrate, pentaerythritol dinitrate, pentaerythritol mononitrate, and the endothelium-dependent vasodilator acetylcholine were not affected. Likewise, benomyl decreased GTN- and PETN-elicited phosphorylation of the cGMP-activated protein kinase substrate vasodilator-stimulated phosphoprotein (VASP) but not that elicited by other nitrates. The vasodilator potency of organic nitrates correlated with their potency to inhibit ALDH-2 dehydrogenase activity in mitochondria from rat heart and increase mitochondrial superoxide formation, as detected by chemiluminescence. In contrast, mitochondrial ALDH-2 esterase activity was not affected by PETN and its metabolites, whereas it was inhibited by benomyl, GTN applied in vitro and in vivo, and some sulfhydryl oxidants. The bioactivation-related metabolism of GTN to glyceryl-1,2-dinitrate by isolated RAW macrophages was reduced by the ALDH-2 inhibitors benomyl and daidzin, as well as by GTN at concentrations >1 microM. We conclude that mitochondrial ALDH-2, specifically its esterase activity, is required for the bioactivation of the organic nitrates with high vasodilator potency, such as GTN and PETN, but not for the less potent nitrates. It is interesting that ALDH-2 esterase activity was inhibited by GTN only, not by the other nitrates tested. This difference might explain why GTN elicits mitochondrial superoxide formation and nitrate tolerance with the highest potency.
    Molecular Pharmacology 12/2004; 66(6):1372-82. · 4.41 Impact Factor