Aktuelle Koronarstenttechnologie

2014

Environmental stressors and cardiovascular risk: Impact of environmental noise exposure on vascular oxidative stress and damage

2018

Epidemiological studies have demonstrated that traffic noise exposure is associated with cardiovascular diseases such as arterial hypertension, myocardial infarction and stroke. Persistent chronic noise exposure increases the risk of cardiovascular and metabolic diseases such as arterial hypertension, coronary artery disease, diabetes and stroke. Large epidemiological studies (reviewed in Munzel et al. Eur. Heart J. 2017, 38 (8):550–556) point towards a link between the incidence of ischemic heart diseases and exposure to noise, supporting its role as an independent cardiovascular risk factor. Recently, the underlying molecular mechanisms leading to noise-dependent adverse effects on the va…

Diabetes Mellitus and Its Impact on Patient-Profile and In-Hospital Outcomes in Peripheral Artery Disease

2021

Background: In patients with peripheral artery disease (PAD), the impact of diabetes mellitus (DM) on patient-profile and adverse in-hospital events is not well investigated. Methods: The German nationwide inpatient sample 2005–2019 was used for this analysis. Hospitalized PAD patients were stratified for DM and the influence of DM on patient-profile and adverse in-hospital events was investigated. Results: Our study comprised 2,654,871 hospitalizations (54.3% aged ≥70 years, 36.7% females) of patients with PAD in Germany 2005–2019. Among these, 864,691 (32.6%) patients had DM and 76,716 (2.9%) died during hospitalization. Diabetic PAD patients revealed an aggravated cardiovascular profile …

Atrial fibrillation is associated with cardiac hypoxia.

2008

BACKGROUND: Atrial fibrillation (AF), the most common human arrhythmia, is responsible for substantial morbidity and mortality and may be promoted by selective atrial ischemia and atrial fibrosis. Consequently, we investigated markers for hypoxia and angiogenesis in AF. METHODS: Right atrial appendages (n=158) were grouped according to heart rhythm [sinus rhythm (SR) or AF]. The degree of fibrosis and microvessel density of all patients were determined morphometrically using Sirius-Red- and CD34/CD105-stained sections, respectively. Next, sections (n=77) underwent immunostaining to detect hypoxia- and angiogenesis-related proteins [hypoxia-inducible factor (HIF)1 alpha, HIF2 alpha, vascular…

Domains of Physical Activity in Relation to Stiffness Index in the General Population.

2021

Background Regular exercise training represents an important modifier of arterial stiffness (AS). Therefore, sex‐specific relations between domains of physical activity (PA; commuting, domestic, and leisure‐time PA, including active sport and occupational PA) with AS were investigated. Methods and Results Stiffness index by digital photoplethysmography was investigated in 12 650 subjects from the GHS (Gutenberg Health Study). Self‐reported PA was evaluated by the “Short Questionnaire to Assess Health‐Enhancing Physical Activity” and reported as activity score peer week, being a combined measure of duration, frequency, and intensity of PA. Multivariable linear regression analysis demonstrat…

In-hospital outcomes of catheter-directed thrombolysis in patients with pulmonary embolism.

2020

AbstractAimsCatheter-directed treatment of acute pulmonary embolism (PE) is technically advancing. Recent guidelines acknowledge this treatment option for patients with overt or imminent haemodynamic decompensation, particularly when systemic thrombolysis is contraindicated. We investigated patients with PE who underwent catheter-directed thrombolysis (CDT) in the German nationwide inpatient cohort.Methods and resultsData from hospitalizations with PE (International Classification of Disease code I26) between 2005 and 2016 were collected by the Federal Office of Statistics in Germany. Patients with PE who underwent CDT (OPS 8-838.60 or OPS code 8-83b.j) were compared with patients receiving…

Endothelium- and nitric oxide-dependent vasorelaxing activities of gamma-butyrobetaine esters: possible link to the antiischemic activities of mildro…

2004

Mildronate [3-(2,2,2-trimethylhydrazine) propionate (THP)] is an antiischemic drug acting mainly via inhibition of fatty acid beta-oxidation. Some effects of the drug cannot be explained by the latter mechanism. We tested the eventual nitric oxide (NO) dependence of the mildronate action. Mildronate, gamma-butyrobetaine (GBB) and GBB methyl ester induced transient increases in nitric oxide (NO) concentrations in rat blood and myocardium. In vitro, these compounds neither modified the activities of purified neuronal and endothelial recombinant nitric oxide synthases (NOSs) nor were able to interact with their active site. GBB induced vasodilatation at high concentrations only (EC50 = 5 x 10(…

The impact of aircraft noise on vascular and cardiac function in relation to noise event number: a randomized trial

2020

Abstract Aims Nighttime aircraft noise exposure has been associated with increased risk of hypertension and myocardial infarction, mechanistically linked to sleep disturbance, stress, and endothelial dysfunction. It is unclear, whether the most widely used metric to determine noise exposure, equivalent continuous sound level (Leq), is an adequate indicator of the cardiovascular impact induced by different noise patterns. Methods and results In a randomized crossover study, we exposed 70 individuals with established cardiovascular disease or increased cardiovascular risk to two aircraft noise scenarios and one control scenario. Polygraphic recordings, echocardiography, and flow-mediated dila…

Impact of atrial fibrillation/flutter on the in-hospital mortality of ischemic stroke patients.

2020

Stroke is the second leading cause of death worldwide. Ischemic strokes, which are caused by atrial fibrillation/flutter (AF), may be more devastating than those that occur without AF.The purpose of this study was to investigate the impact of AF on adverse events in hospitalized ischemic stroke patients and to estimate the elevated impact of AF on the occurrence of these adverse events.The nationwide German inpatient sample of the years 2005-2015 was used for this analysis. Ischemic stroke patients were identified by ICD code I63 and stratified by AF. Logistic regression models were used to investigate the impact of AF on adverse in-hospital events and adjusted for age, sex, and comorbiditi…

Quadrivalvular non-bacterial thrombotic endocarditis in a patient with clear cell cervical cancer

2022

Non-bacterial thrombotic endocarditis (NBTE) is a rare finding, which is mostly associated with malignant diseases leading to hypercoagulability. We report the case of a severe quadruple valve non-bacterial thrombotic endocarditis in a patient with clear cell cervical cancer.

Disturbed Lipid Metabolism in Diabetic Patients with Manifest Coronary Artery Disease Is Associated with Enhanced Inflammation

2021

Background: Diabetic vasculopathy plays an important role in the pathophysiology of coronary artery disease (CAD) with oxidative stress as a strong mediator. This study aims to elucidate the underlying pathomechanisms of diabetic cardiac vasculopathy leading to coronary disease with an emphasis on the role of oxidative stress. Therefore, novel insights into antioxidant pathways might contribute to new strategies in the treatment and prevention of diabetic CAD. Methods: In 20 patients with insulin-dependent or non-insulin dependent diabetes mellitus (IDDM/NIDDM) and 39 non-diabetic (CTR) patients, myocardial markers of oxidative stress, vasoactive proteins, endothelial nitric oxide synthase …

Effects of Long-Term Nitroglycerin Treatment on Endothelial Nitric Oxide Synthase (NOS III) Gene Expression, NOS III–Mediated Superoxide Production, …

2000

Abstract —Long-term nitroglycerin (NTG) treatment has been shown to be associated with cross-tolerance to endothelium-dependent vasodilators. It may involve increased production of reactive oxygen species (such as superoxide, O 2 ·− ) that rapidly inactivate the nitric oxide (NO) released from the endothelial cells. It remains to be elucidated, however, whether long-term treatment with NTG alters the activity and expression of the endothelial NO synthase (NOS III) and whether this enzyme can contribute to O 2 ·− formation. We studied the influence of long-term NTG treatment on the expression of NOS III as assessed by RNase protection assay and Western blot. Tolerance was measured ex vivo i…

Type-D personality and depersonalization are associated with suicidal ideation in the German general population aged 35–74: Results from the Gutenber…

2009

Suicidal ideation (SID) is a major risk factor for suicide attempts. Mental disorders are among the strongest correlates of suicide, with depression and anxiety disorders playing a major role. The present study aims to investigate the contribution of under researched factors contributing to SID such as depersonalization, Type-D personality and cardiovascular risk factors.Factors associated with SID were investigated in a sample of N=5000 participants (aged 35-74 years) of the community-based survey "Gutenberg Heart Study". The factors were assessed by self-report instruments, computer-assisted interviews and medical examination.7.5% of the sample reported SID over the last 2 weeks. In the u…

1-Year Outcomes of Everolimus-Eluting Bioresorbable Scaffolds Versus Everolimus-Eluting Stents

2016

Abstract Objectives The purpose of this study was to compare the 1-year outcomes of the ABSORB everolimus-eluting bioresorbable scaffold (BRS) (Abbott Vascular, Santa Clara, California) and the XIENCE everolimus-eluting stent (EES) (Abbott Vascular) in patients undergoing percutaneous coronary intervention. Background Randomized studies of the ABSORB BRS have been performed in selected patient and lesion scenarios. The available registries of the ABSORB BRS reflect real-world practice more closely compared with randomized studies, but most of them are limited by the small sample size and the lack of comparative outcomes versus second-generation drug-eluting stents. Methods A total of 1,189 …

Auswirkungen von Umweltrisikofaktoren wie Lärm und Luftverschmutzung auf die psychische Gesundheit: Was wissen wir?

2020

ZusammenfassungImmer mehr Studien unterstreichen die Rolle von Lärm und Luftverschmutzung als bedeutsame Umweltrisikofaktoren. Ungeklärt ist, welche Einflüsse Lärm und Luftverschmutzung auf die psychische Gesundheit ausüben. Aktuelle Studienergebnisse zeigen, dass Umgebungslärm (vor allem Verkehrslärm) und verschiedene Bestandteile von Luftverschmutzung (vor allem Feinstaub) das Risiko für psychische Erkrankungen wie Depressionen, Angststörungen, Psychosen und Suizid erhöhen können. Pathophysiologische Mechanismen umfassen sowohl biologische (wie oxidativen Stress und Inflammation) als auch psychosoziale Faktoren (wie mentalen Stress). Umweltrisikofaktoren wie Lärm und Luftverschmutzung kön…

Making it More Sensitive

2011

About a decade ago, the prevailing wisdom was that conventional risk factors explained only approximately half of the risk for a myocardial infarction or stroke. Consequently, efforts to identify novel risk factors were undertaken to improve cardiovascular risk prediction. The hypothesis that inflammation is a central contributor to atherothrombosis has stimulated sustained efforts to characterize the specific molecules and pathways that may be involved and to identify biomarkers in humans that enable detection of underlying inflammatory activation to improve cardiovascular risk prediction. Ridker et al1 pioneered this work and reported that systemic low-grade inflammation assessed by measu…

Chest Pain Unit Network in Germany

2017

![Figure][1] ![Figure][1] The fundamental goal of a chest pain unit (CPU) is to streamline the differential diagnosis of acute or newly symptomatic chest pain of unclear origin. Data from the United States [(1)][2] and the United Kingdom [(2)][3] demonstrated the superiority of CPUs

Coagulation and inflammation in long‐term cancer survivors: results from the adult population

2018

Essentials The increase of cancer survival remains curtailed by cardiovascular mortality. We studied a large range of inflammatory and coagulation biomarkers in long-term cancer survivors. Cancer history has an important impact on mortality independent of cardiovascular risk factors. Fibrinogen and von Willebrand factor are potential biomarkers in survivors of increased mortality. Summary Background The advances in cancer treatment and detection of early cancer have resulted in a steady increase in the number of of cancer survivors over the years. However, because of the long-term toxic effects of chemotherapy and radiotherapy, the incidence of cardiovascular disease (CVD) is increasing in …

Telemedicine-Based Specialized Care Improves the Outcome of Anticoagulated Individuals with Venous Thromboembolism-Results from the thrombEVAL Study.

2020

Venous thromboembolism (VTE) is a life-threatening disease with risk of recurrence. Oral anticoagulation (OAC) with vitamin K antagonists (VKA) is effective to prevent thromboembolic recurrence. We aimed to investigate the quality of OAC of VTE patients in regular medical care (RMC) compared to a telemedicine-based coagulation service (CS). The thrombEVAL study (NCT01809015) is a prospective, multi-center study to investigate OAC treatment (recruitment: January 2011&ndash

Differential effects of organic nitrates on endothelial progenitor cells are determined by oxidative stress

2007

Determinants of arterial stiffness in pre- and postmenopausal women

2013

Centre procedural volume and adverse in‐hospital outcomes in patients undergoing percutaneous transvenous edge‐to‐edge mitral valve repair usingMitra…

2021

AIMS The number of transcatheter mitral valve repair (TMVr) procedures has increased substantially during the last years. A better understanding of the relationship between hospital volume of transcatheter transvenous mitral valve repairs using MitraClip® and patient outcomes may provide information for future policy decisions to improve patient management. METHODS AND RESULTS We analysed patient characteristics and in-hospital outcomes for all TMVr procedures using MitraClip® performed in Germany from 2011 to 2017. Hospitals were stratified according to centre volumes and patients were compared for baseline characteristics and adverse in-hospital events. Overall, 24 709 inpatients were tre…

Ambient Air Pollution and Atherosclerosis: Insights Into Dose, Time, and Mechanisms.

2021

Ambient air pollution due to particulate matter ≤2.5 μ is the leading environmental risk factor contributing to global mortality, with a preponderant majority of these deaths attributable to atherosclerotic cardiovascular disease (ASCVD) causes such as stroke and myocardial infarction. Epidemiological studies in humans have provided refined estimates of exposure risk, with evidence suggesting that risk association with particulate matter ≤2.5 levels and ASCVD continues at levels well below air quality guidelines in North America and Europe. Mechanistic studies in animals and humans have provided a framework of understanding of the duration and pathways by which air pollution exposure may pr…

Prevalence of Strabismus and Its Impact on Vision-Related Quality of Life

2020

Purpose This study investigates the prevalence of manifest strabismus and its subtypes in adulthood and analyzes the risk factors and its impact on vision-related quality of life (VRQoL). Design The Gutenberg Health Study (GHS) is a population-based, observational cohort study. A cross-sectional analysis of the baseline examination was conducted. Participants Participants aged 35 to 74 years were included (n = 15  010). Methods All participants were examined with a comprehensive ophthalmologic and general examination including the Hirschberg corneal reflex test to detect manifest strabismus. The following risk factors were analyzed: age, sex, socioeconomic status, birth weight, maternal age…

Is At Least One Vitamin Helping Our Vasculature?

2014

See related article, pp 1290–1298 Cardiovascular risk factors such as diabetes mellitus, arterial hypertension, chronic smoking, and hypercholesterolemia are cardiovascular risk factors known to be associated with endothelial dysfunction, a condition that may predict long-term progression of atherosclerosis as well as cardiovascular event rates (for review, see Munzel et al1) Although the mechanisms underlying this phenomenon are complex and multifactorial, there is growing body of evidence that oxidative stress attributable to increased production of reactive oxygen–derived free radicals may play a pivotal role in this process.2 Increased superoxide production by enzyme systems such as the…

Inappropriate evaluation of methodology and biases by P. Morfeld and T.C. Erren.

2020

Venous thromboembolism in patients hospitalized for hip joint replacement surgery

2020

Venous thromboembolism (VTE) is a potentially life-threatening disease. Major transient risk factors include trauma, surgery, and immobilization. Patients undergoing hip joint replacement (HJR) are characterized by a high risk of postoperative VTE, but data on the time trends of VTE rates in this population are sparse.In an analysis of the German nationwide inpatient sample, we included all hospitalizations for elective primary HJR in Germany from 2005 to 2016. Time trends of the surgical procedure, overall death rates, and VTE rates were analysed, and predictors of VTE identified.Overall, 1,885,839 inpatients with elective primary HJR (59.1% women, 51.4% ≥70 years) were included in the ana…

The German CPU Registry: Comparison of troponin positive to troponin negative patients

2013

Lars S. Maier ⁎, Harald Darius , Evangelos Giannitsis , Raimund Erbel , Michael Haude , Christian Hamm , Gerd Hasenfuss , Gerd Heusch , Harald Mudra , Thomas Munzel , Claus Schmitt , Burghard Schumacher , Jochen Senges , Thomas Voigtlander , Jan B. Schuttert a a Dept. of Cardiology & Pneumology/Heart Centre, Georg-August-University, Gottingen, Germany b Dept. of Cardiology, Angiology & Intensive Care Medicine, Vivantes Hospital Neukolln, Berlin, Germany c Dept. of Cardiology, Angiology & Pneumology, Ruprecht-Karls-University, Heidelberg, Germany d Dept. of Cardiology, West-German Heart Centre, University of Essen, Germany e Dept. of Cardiology & Nephrology, Lukas Hospital, Neuss, Germany f …

A prospective cohort study to identify and evaluate endotypes of venous thromboembolism: Rationale and design of the Genotyping and Molecular Phenoty…

2019

Abstract Several clinical, genetic and acquired risk factors for venous thromboembolism (VTE) have been identified. However, the molecular pathophysiology and mechanisms of disease progression remain poorly understood. This is reflected by uncertainties regarding the primary and secondary prevention of VTE and the optimal duration of antithrombotic therapy. A growing body of literature points to clinically relevant differences between VTE phenotypes (e.g. deep vein thrombosis (DVT) versus pulmonary embolism (PE), unprovoked versus provoked VTE). Extensive links to cardiovascular, inflammatory and immune-related morbidities are testament to the complexity of the disease. The GMP-VTE project …

Comparison of Direct and Indirect Antioxidant Effects of Linagliptin (BI 1356, ONDERO) with other Gliptins – Evidence for Anti-inflammatory Propertie…

2010

Feasibility of a MPR-based 3DTEE guidance protocol for transcatheter direct mitral valve annuloplasty.

2020

Objectives Several interventional approaches have been established for the treatment of severe mitral regurgitation (MR) in patients at elevated risk for surgery. Direct annuloplasty is a relatively novel option in transcatheter mitral valve repair dedicated to reverse pathology in specific subsets of MR. With regard to echocardiographic guidance, this procedure presents with higher efforts in comparison with edge-to-edge therapy to enable safe and exact positioning of the device's anchors; evidence on optimal peri-interventional imaging is sparse. We tested a specific 3D-echo-guidance protocol implementing single-beat multiplanar reconstruction (MPR) and evaluated its feasibility. Methods …

The sodium-glucose co-transporter 2 inhibitor empagliflozin improves diabetes-induced vascular dysfunction in the streptozotocin diabetes rat model b…

2014

Objective In diabetes, vascular dysfunction is characterized by impaired endothelial function due to increased oxidative stress. Empagliflozin, as a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), offers a novel approach for the treatment of type 2 diabetes by enhancing urinary glucose excretion. The aim of the present study was to test whether treatment with empagliflozin improves endothelial dysfunction in type I diabetic rats via reduction of glucotoxicity and associated vascular oxidative stress. Methods Type I diabetes in Wistar rats was induced by an intravenous injection of streptozotocin (60 mg/kg). One week after injection empagliflozin (10 and 30 mg/kg/d) was adminis…

New Therapeutic Implications of Endothelial Nitric Oxide Synthase (eNOS) Function/Dysfunction in Cardiovascular Disease

2019

The Global Burden of Disease Study identified cardiovascular risk factors as leading causes of global deaths and life years lost. Endothelial dysfunction represents a pathomechanism that is associated with most of these risk factors and stressors, and represents an early (subclinical) marker/predictor of atherosclerosis. Oxidative stress is a trigger of endothelial dysfunction and it is a hall-mark of cardiovascular diseases and of the risk factors/stressors that are responsible for their initiation. Endothelial function is largely based on endothelial nitric oxide synthase (eNOS) function and activity. Likewise, oxidative stress can lead to the loss of eNOS activity or even “uncoupli…

Deep vein thrombus formation induced by flow reduction in mice is determined by venous side branches.

2013

Interaction between vascular wall abnormalities, inflammatory leukocytes, platelets, coagulation factors and hemorheology in the pathogenesis of deep vein thrombosis (DVT) is incompletely understood, requiring well defined animal models of human disease. METHODS AND RESULTS: We subjected male C57BL/6 mice to ligation of the inferior vena cava (IVC) as a flow reduction model to induce DVT. Thrombus size and weight were analyzed macroscopically and sonographically by B-mode, pulse wave (pw) Doppler and power Doppler imaging (PDI) using high frequency ultrasound. Thrombus size varied substantially between individual procedures and mice, irrespective of the flow reduction achieved by the ligatu…

Global health burden of PM2.5, black and organic carbon aerosols

2021

Diagnostic and prognostic performance of myeloperoxidase plasma levels compared with sensitive troponins in patients admitted with acute onset chest …

2012

Background— Activation of leukocytes with release of myeloperoxidase (MPO) has been linked to acute coronary disease. To date, studies investigating the diagnostic and prognostic performance of circulating MPO in patients with chest pain (CP) are mainly retrospective, of low size, and lack a cut-off value for MPO. Herein, we prospectively assess the diagnostic and prognostic properties of MPO compared with sensitive troponin I (sTNI) in patients admitted to the emergency room with CP. Methods and Results— One thousand, eight hundred and eighteen consecutive patients (mean age, 61.4±13.5 years; 33.6% female) admitted for CP underwent determination of MPO, sTnI, and B-natriuretic peptide pla…

Nebivolol inhibits superoxide formation by NADPH oxidase and endothelial dysfunction in angiotensin II-treated rats.

2006

Nebivolol is a β 1 -receptor antagonist with vasodilator and antioxidant properties. Because the vascular NADPH oxidase is an important superoxide source, we studied the effect of nebivolol on endothelial function and NADPH oxidase activity and expression in the well-characterized model of angiotensin II–induced hypertension. Angiotensin II infusion (1 mg/kg per day for 7 days) caused endothelial dysfunction in male Wistar rats and increased vascular superoxide as detected by lucigenin-derived chemiluminescence, as well as dihydroethidine staining. Vascular NADPH oxidase activity, as well as expression at the mRNA and protein level, were markedly upregulated, as well as NOS III uncoupled, …

Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction

2008

Endothelial dysfunction (ED) in the setting of cardiovascular risk factors such as hypercholesterolemia, hypertension, diabetes mellitus, chronic smoking as well as in patients with heart failure has been shown to be at least in part dependent on the production of reactive oxygen species (ROS) such as superoxide and the subsequent decrease in vascular bioavailability of nitric oxide (NO). Methods to quantify endothelial dysfunction include forearm plethysmography, flow-dependent dilation of the brachial artery, finger-pulse plethysmography, pulse curve analysis, and quantitative coronary angiography after intracoronary administration of the endothelium-dependent vasodilator acetylcholine. S…

Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension

2017

Multicellular interactions of platelets, leukocytes, and the blood vessel wall support coagulation and precipitate arterial and venous thrombosis. High levels of angiotensin II cause arterial hypertension by a complex vascular inflammatory pathway that requires leukocyte recruitment and reactive oxygen species production and is followed by vascular dysfunction. We delineate a previously undescribed, proinflammatory coagulation-vascular circuit that is a major regulator of vascular tone, blood pressure, and endothelial function. In mice with angiotensin II-induced hypertension, tissue factor was up-regulated, as was thrombin-dependent endothelial cell vascular cellular adhesion molecule 1 ex…

Different calculations of ankle-brachial index and their impact on cardiovascular risk prediction.

2008

Background— An ankle-brachial index (ABI; ratio of ankle and brachial systolic blood pressure) <0.9 indicates peripheral arterial disease (PAD) and is a strong predictor of cardiovascular events. The aim of the present study was to address the prognostic value of different methods of ABI calculation. Methods and Results— In 831 patients admitted with chest pain for diagnostic heart catheterization, blood pressure of both anterior and posterior tibial arteries was measured. ABI was calculated for each leg with the higher of the 2 ankle pressures (current definition of the American Heart Association) or with the lower of the 2 ankle pressures (modified definition) in relation to the highe…

Sex-specific differences in mortality and the obesity paradox of patients with myocardial infarction ages70 y.

2017

Abstract Objectives Recent studies suggest an obesity survival paradox in patients with acute myocardial infarction (MI). The aim of this study was to investigate the in-hospital mortality of patients aged ≥70 y with acute MI relative to sex and obesity. Methods We selected patients ≥70 y of age with a diagnosis of acute MI based on the International Classification of Diseases (ICD) code I21 in the nationwide database of the Federal Statistical Office of Germany in 2014. We stratified the patients for sex and obesity versus nonobesity, and obesity classes I, II, and III. We compared the in-hospital mortality of these groups. Results In 2014, 122 607 patients ≥70 y of age were diagnosed with…

Number of nitrate groups determines reactivity and potency of organic nitrates: a proof of concept study in ALDH-2−/− mice

2007

Background and purpose: Mitochondrial aldehyde dehydrogenase (ALDH-2) has been shown to provide a pathway for bioactivation of organic nitrates and to be prone to desensitization in response to highly potent, but not to less potent, nitrates. We therefore sought to support the hypothesis that bioactivation by ALDH-2 critically depends on the number of nitrate groups within the nitrovasodilator. Experimental approach: Nitrates with one (PEMN), two (PEDN; GDN), three (PETriN; glyceryl trinitrate, GTN) and four (pentaerithrityl tetranitrate, PETN) nitrate groups were investigated. Vasodilatory potency was measured in isometric tension studies using isolated aortic segments of wild type (WT) an…

Area at Risk and Viability after Myocardial Ischemia and Reperfusion Can Be Determined by Contrast-Enhanced Cardiac Magnetic Resonance Imaging

2008

<i>Background/Aims:</i> Clinical differentiation between infarcted and viable myocardium in the ischemic area at risk is controversial. We investigated the potential of contrast-enhanced cardiac magnetic resonance imaging (ceCMRI) in determining the area at risk 24 h after ischemia. <i>Methods:</i> Myocardial ischemia was induced by percutaneous coronary intervention of the left anterior descending coronary artery in pigs. Coronary occlusion time was 30 min in group A, which caused little myocardial infarction and 45 min in group B, which led to irreversible damage. 24 h after reperfusion ceCMRI was performed at 2 and 15 min after administration of gadolinium-diethyl…

Birthweight and its association with retinal vessel equivalents – Results from the population‐based German Gutenberg Health Study

2020

Comparison of DPP‐4 inhibition versus GLP‐1 analogue supplementation on survival and vascular complications in experimental sepsis (145.2)

2014

Background: Dipeptidyl peptidase [DPP]-4 inhibitors are a new class of drug for the treatment of hyperglycemia and recent studies revealed anti-inflammatory effects of these gliptins in experimenta...

Refined atrial fibrillation screening and cost-effectiveness in the German population

2021

ObjectiveLittle is known on optimal screening population for detecting new atrial fibrillation (AF) in the community. We describe characteristics and estimate cost-effectiveness for a single timepoint electrocardiographic screening.MethodsWe performed a 12-lead ECG in the German population-based Gutenberg Health Study between 2007 and 2012 (n=15 010), mean age 55±11 years, 51% men and collected more than 120 clinical and biomarker variables, including N-terminal pro B-type natriuretic peptide (Nt-proBNP), risk factors, disease symptoms and echocardiographic variables.ResultsOf 15 010 individuals, 466 (3.1%) had AF. New AF was found in 32 individuals, 0.2% of the total sample, 0.5% of indivi…

Survival Benefit of Obese Patients With Pulmonary Embolism.

2018

To investigate the impact of obesity and underweight on adverse in-hospital outcomes in pulmonary embolism (PE).Patients diagnosed as having PE based on International Statistical Classification of Diseases and Related Health Problems, 10th Revision, German Modification code I26 in the German nationwide inpatient database were stratified for obesity, underweight, and normal weight/overweight (reference group) and compared regarding adverse in-hospital outcomes.From January 1, 2011, through December 31, 2014, 345,831 inpatients (53.3% females) 18 years and older were included in this analysis; 8.6% were obese and 0.5% were underweight. Obese patients were younger (67.0 vs 73.0 years), were mo…

Takotsubo Syndrome: Impact of endothelial dysfunction and oxidative stress

2021

Takotsubo Syndrome (TTS) is characterized by a transient left ventricular dysfunction recovering spontaneously within days or weeks. Although the pathophysiology of TTS remains obscure, there is growing evidence suggesting TTS to be associated with increased production of reactive oxygen species (ROS), which may be involved in causing transient coronary and peripheral endothelial dysfunction leading to a transient impairment of myocardial contraction due to stunning (apical ballooning). Endothelial dysfunction is mainly caused by decreased vascular and myocardial nitric oxide bioavailability in response to increased ROS production. Accordingly, studies in humans and animal models demonstrat…

Regional and global contributions of air pollution to risk of death from COVID-19

2020

Abstract Aims The risk of mortality from the coronavirus disease that emerged in 2019 (COVID-19) is increased by comorbidity from cardiovascular and pulmonary diseases. Air pollution also causes excess mortality from these conditions. Analysis of the first severe acute respiratory syndrome coronavirus (SARS-CoV-1) outcomes in 2003, and preliminary investigations of those for SARS-CoV-2 since 2019, provide evidence that the incidence and severity are related to ambient air pollution. We estimated the fraction of COVID-19 mortality that is attributable to the long-term exposure to ambient fine particulate air pollution. Methods and results We characterized global exposure to fine particulates…

Impairment of the extrusion transporter for asymmetric dimethyl-L-arginine: a novel mechanism underlying vasospastic angina.

2012

Abstract A 37-year old male patient presented with frequent angina attacks (up to 40/day) largely resistant to classical vasodilator therapy. The patient showed severe coronary and peripheral endothelial dysfunction, increased platelet aggregation and increased platelet-derived superoxide production. The endothelial nitric oxide synthase (eNOS)-inhibitor N G -nitro- l -arginine methyl ester (L-NAME) reduced superoxide formation in platelets identifying “uncoupled” eNOS as a superoxide source. Oral l -arginine normalized coronary and peripheral endothelial dysfunction and reduced platelet aggregation and eNOS-derived superoxide production. Plasma concentrations of the endogenous NOS inhibito…

Dinitrosyl-iron triggers apoptosis in Jurkat cells despite overexpression of Bcl-2

2004

Cells expressing the cytokine-inducible NO synthase are known to trigger apoptosis in neighboring cells. Paramagnetic dinitrosyl nonheme iron complexes (DNIC) were found in tumor tissue about 40 years ago; however, the role of these NO(+)-bearing species is not completely understood. In the human Jurkat leukemia cell line, the application of the model complex DNIC-thiosulfate (50-200 microM) induced apoptosis (defined by phosphatidylserine externalization) in a concentration- and time-dependent manner. In Jurkat cells, the pan-caspase inhibitor, zVADfmk (50 microM), and/or stable transfection of antiapoptotic protein, Bcl-2, was unable to afford protection against DNIC-induced apoptosis. Th…

Vascular Dysfunction in Streptozotocin-Induced Experimental Diabetes Strictly Depends on Insulin Deficiency

2010

<i>Objective:</i> In previous studies we and others have shown that streptozotocin (STZ)-induced diabetes in rats is associated with vascular oxidative stress and dysfunction. In the present study, we sought to determine whether vascular dysfunction and oxidative stress strictly depend on insulin deficiency. <i>Methods:</i> The effects of insulin (2.5 U/day s.c., 2 weeks) therapy on vascular disorders in STZ-induced (60 mg/kg i.v., 8 weeks) diabetes mellitus (type I) were studied in Wistar rats. The contribution of NADPH oxidase to overall oxidative stress was investigated by in vivo (30 mg/kg/day s.c., 4 days) and in vitro treatment with apocynin. <i>Results:&…

Loss of life expectancy from air pollution compared to other risk factors: a worldwide perspective

2020

Abstract Aims Long-term exposure of humans to air pollution enhances the risk of cardiovascular and respiratory diseases. A novel Global Exposure Mortality Model (GEMM) has been derived from many cohort studies, providing much-improved coverage of the exposure to fine particulate matter (PM2.5). We applied the GEMM to assess excess mortality attributable to ambient air pollution on a global scale and compare to other risk factors. Methods and results We used a data-informed atmospheric model to calculate worldwide exposure to PM2.5 and ozone pollution, which was combined with the GEMM to estimate disease-specific excess mortality and loss of life expectancy (LLE) in 2015. Using this model, …

Impact of atrial fibrillation on in-hospital mortality of ischemic stroke patients and identification of promoting factors of atrial thrombi – Result…

2019

Abstract Ischemic stroke is one of the leading causes of death and disability. Atrial fibrillation (AF) is a well-recognized risk factor for ischemic stroke. We aimed to investigate the impact of AF on in-hospital mortality of ischemic stroke patients and to identify parameters associated with intra-cardiac thrombogenic material. Patients were selected by screening the nationwide sample for ischemic stroke by ICD-Code (I63), stratified for AF. In this cohort, the association between in-hospital deaths and AF was investigated. In a second study, we performed a retrospective analysis of patients who underwent transesophageal echocardiography (TEE) for various reasons, assigned these to 2 grou…

KCND3 is a novel susceptibility locus for early repolarization

2019

AbstractThe presence of an early repolarization pattern (ERP) on the surface electrocardiogram (ECG) is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait but molecular genetic determinants are unknown. We assessed the ERP in 12-lead ECGs of 39,456 individuals and conducted a two-stage meta-analysis of genome-wide association studies (GWAS). In the discovery phase, we included 2,181 cases and 23,641 controls from eight European ancestry studies and identified 19 genome-wide significant (p<5E-8) variants in the KCND3 (potassium voltage gated channel subfamily D member 3) gene with a p-value of 4.6E-10. …

Relations of Sex to Diagnosis and Outcomes in Acute Coronary Syndrome

2018

Background The atypical presentation of women with acute coronary syndrome ( ACS ) has been related to delayed diagnosis and treatment, which may explain worse outcome compared with men. Methods and Results We analyzed pooled data of 2520 patients of 2 prospective cohorts in terms of differences in presentation and management of women and men suggestive of ACS . Using logistic regression, we established 2 diagnostic models and tested their diagnostic performance in both sexes separately. Sex‐specific differences in management of patients with ACS were ascertained and a 2‐year follow‐up was performed. Women were older than men (median 67 versus 61 years, P =0.001), had more often dyspnea (2…

Multiple biomarkers and atrial fibrillation in the general population.

2014

BACKGROUND: Different biological pathways have been related to atrial fibrillation (AF). Novel biomarkers capturing inflammation, oxidative stress, and neurohumoral activation have not been investigated comprehensively in AF. METHODS AND RESULTS: In the population-based Gutenberg Health Study (n = 5000), mean age 56 ± 11 years, 51% males, we measured ten biomarkers representing inflammation (C-reactive protein, fibrinogen), cardiac and vascular function (midregional pro adrenomedullin [MR-proADM], midregional pro atrial natriuretic peptide [MR-proANP], N-terminal pro-B-type natriuretic peptide [Nt-proBNP], sensitive troponin I ultra [TnI ultra], copeptin, and C-terminal pro endothelin-1), a…

Sex-specific differences regarding seasonal variations of incidence and mortality in patients with myocardial infarction in Germany

2019

Seasonal variation regarding the incidence and the short-term mortality of acute myocardial infarction (MI) was frequently reported, but data about sex-specific differences are sparse.We analysed the impact of seasons and temperature on incidence and in-hospital mortality of patients with acute MI in Germany between 2005 and 2015.The nationwide sample comprised 3,008,188 hospitalizations of MI patients (2005-2015). The incidence was 334.7/100,000 citizens/year. Incidence inclined from 316.3 to 341.6/100,000 citizens/year (β 0.17 [0.10 to 0.24], P  0.001), while in-hospital mortality rate decreased from 14.1% to 11.3% (β -0.29 [-0.30 to -0.28], P  0.001). Overall, 377,028 (12.5%) patients di…

Transgastric imaging-The key to successful periprocedural TEE guiding for edge-to-edge repair of the tricuspid valve.

2021

Intraprocedural transesophageal echocardiography (TEE) guidance plays an essential role in transcatheter repair therapy of the tricuspid valve (TV). So far, several different imaging concepts are in use. We propose an imaging protocol that fully addresses the morphological complexity of the TV and further offers efficacious workarounds for the frequently occurring restrictions of TV imaging in edge-to-edge repair of the TV. As a tertiary referral center with a large experience of more than 250 cases of transcatheter edge-to-edge repair (TEER) of the TV performed at the Heart Valve Center in Mainz/Germany, we have constantly adapted our peri-interventional echocardiographic approach to accom…

Effect of tea consumption on oxidative stress and expression of DNA repair genes among metal press workers exposed to occupational noise

2020

Abstract Several studies have shown that tea consumption is associated with beneficial effects on human health, which is mainly explained by the antioxidant properties of tea. However, evidence on the effect of nutrition interventions on oxidative stress in an occupational setting is limited. Therefore, the present study aimed to investigate the effect of tea consumption on oxidative stress in noise-exposed metal press workers. The study sample comprised 24 metal press workers and 24 age-matched control subjects. Metal press workers were assigned to the intervention group consisting of a glass of jujube tea and a portion of raisins per day for 4 weeks. Full-shift noise dosimetry was perform…

Assessment of microRNAs in patients with unstable angina pectoris.

2014

Aims While cardiac troponin measurements have significantly improved the early diagnosis of myocardial infarction, the timely biomarker-based diagnosis of unstable angina pectoris (UAP) remains a major unmet clinical challenge. The aim of this study was to assess levels of circulating microRNAs (miRNAs) as possible novel biomarkers in patients with UAP. Methods and results A three-phase approach was conducted, comprising (i) profiling of miRNAs in patients with UAP and controls groups; (ii) replication of significant miRNAs in an independent patient cohort, (iii) validation of a multi-miRNAs panel in a third cohort. Out of 25 miRNAs selected for replication, 8 miRNAs remained significantly …

O44. Inhibition of CD98-associated amino acid transporters by dinitrosyl iron complexes

2008

Bioresorbable vascular scaffold use for coronary bifurcation lesions: A substudy from GHOST EU registry

2016

Objectives The aim of this study was to evaluate midterm outcomes of bioresorbable vascular scaffolds (BVS) implanted in bifurcation lesions. Background BVS have emerged as an alternative to conventional metallic drug-eluting stents for the treatment of coronary complex lesions. Methods Between November 2011 and January 2014, 1189 patients underwent percutaneous coronary intervention with BVS at 10 European centers (GHOST EU registry). Of these, 289 consecutive patients (302 bifurcation lesions) treated with either single-stenting (n = 260) or double-stenting (n = 42) were evaluated. Results True bifurcations were treated in 44.7%. Intravascular ultrasound and optical coherence tomography w…

Association of transcatheter direct mitral annuloplasty with acute anatomic, haemodynamic, and clinical outcomes in severe mitral valve regurgitation.

2020

Abstract Aims Several approaches for transcatheter mitral valve repair for functional mitral valve regurgitation are established. Interventional direct annuloplasty is a novel trans‐venous, trans‐septal approach. While feasibility was proven recently, knowledge on its influence on cardiac dimensions, pressures, biomarkers, and clinical outcomes is sparse. Methods and results Patients consecutively treated with direct annuloplasty‐only procedures between December 2015 and April 2018 were included in this monocentric analysis. Echocardiographic measurements, biomarker levels, clinical status [New York Heart Association (NYHA) class and 6 min walk test] were assessed at baseline, at discharge,…

eNOS Uncoupling in Cardiovascular Diseases - the Role of Oxidative Stress and Inflammation

2013

Many cardiovascular diseases and drug-induced complications are associated with - or even based on - an imbalance between the formation of reactive oxygen and nitrogen species (RONS) and antioxidant enzymes catalyzing the break-down of these harmful oxidants. According to the “kindling radical” hypothesis, the formation of RONS may trigger in certain conditions the activation of additional sources of RONS. According to recent reports, vascular dysfunction in general and cardiovascular complications such as hypertension, atherosclerosis and coronary artery diseases may be connected to inflammatory processes. The present review is focusing on the uncoupling of endothelial nitric oxide synthas…

Increased Circulating Levels of 3-Nitrotyrosine Autoantibodies

2012

3-nitrotyrosine formation is an oxidative protein modification that was first discovered in vivo in the early 1990s by Beckman and colleagues.1,2 The biological relevance of this process was extensively investigated in the subsequent years and further facilitated by the development of 3-nitrotyrosine–specific antibodies.3 Protein tyrosine nitration is mainly mediated by 3 biochemical processes (Figure): (1) by peroxynitrite (ONOO−) formation,4–6 the reaction product of nitric oxide (•NO) and superoxide (•O2−); (2) by a (myelo)peroxidase-catalyzed nitrogen dioxide radical (•NO2) formation from hydrogen peroxide and nitrite;7,8 and (3) by a nonspecific formation of the nitrogen dioxide radica…

Inflammation, atherosclerotic burden and cardiovascular prognosis.

2006

The aim of this study was to evaluate the impact of various inflammatory markers on atherosclerotic burden and cardiovascular prognosis.In a prospective study 720 patients preceding coronary angiography were enrolled. In all patients carotid and leg arteries were examined using sonographic methods and C-reactive protein, fibrinogen, interleukin-18 (IL-18) and interleukin-6 have been determined. Patients were compared with regard to atherosclerotic burden: no clinically significant stenosis (N=57, 7.9%), coronary artery disease only (N=362, 50.3%), coronary artery disease with peripheral atherosclerosis (=multi-vascular atherosclerosis, N=301, 41.8%).Follow-up data after a median of 6.5 year…

Die interdisziplinäre Notaufnahme im Zusammenspiel mit Chest Pain Units, Brustschmerzambulanzen und Cardiac Arrest Centern

2019

ZusammenfassungDie notfall- bzw. akutmedizinische Versorgung der Bevölkerung von Patienten gewinnt mehr und mehr an Bedeutung. In Deutschland stellen sich zum Beispiel pro Jahr hunderttausende Patienten mit Brustschmerzen in Notaufnahmen vor, wobei sich bei ca. 5 – 20% ein akutes Koronarsyndrom nachweisen lässt. Zudem werden pro Jahr 75 000 prähospitale Reanimationen durchgeführt, von denen mehr als 60% kardial bedingt sind. Die primäre Anlaufstelle dieser kardialen Patienten ist in der Regel eine Notaufnahme, die, wenn möglich, Strukturen vorhalten soll, um diese Patienten rasch und effizient zu diagnostizieren und zeitnah lebensrettende Maßnahmen einzuleiten. Gefordert werden heutzutage, …

Coronary Stent Strut Fractures: Classification, Prevalence and Clinical Associations

2021

Introduction. The frequency, characteristics and clinical implications of Strut fractures (SFs) remain incompletely understood. Methods and results. A total of 185 (160 patients) newer-generation drug-eluting stents (DES) were imaged. SFs were found in 21 DES (11.4%) and were classified in four patterns: one single stacked strut (41%)

Association of MR-proadrenomedullin with cardiovascular risk factors and subclinical cardiovascular disease.

2012

Abstract Aims and background Midregional proadrenomedullin (MR-proADM) is a protein, which exerts various effects on the cardiovascular system. Recent studies underscored its prognostic implications in patients with acute dyspnea and cardiovascular diseases. Therefore, we aimed to determine the distribution of MR-proADM in the general population and to reveal potential associations of MR-proADM with cardiovascular risk factors and measures of subclinical cardiovascular disease. Methods and results MR-proADM plasma concentrations were determined in individuals of the population-based cohort of the Gutenberg Health Study ( N  = 5000) using a commercially available fluoroimmunoassay. Individua…

P6456Neopterin for risk stratification of patients with acute chest pain

2018

Predilation, sizing and post-dilation scoring in patients undergoing everolimus-eluting bioresorbable scaffold implantation for prediction of cardiac…

2017

Aims: The aim of the study was to develop a scoring model to evaluate the quality of bioresorbable vascular scaffold (BVS) implantation and determine the model's usefulness in predicting adverse cardiac events. Methods and results: The implantation technique and clinical outcomes of 1,736 lesions treated with BVS were analysed using the GHOST-EU registry. Predilation, scaffold sizing, and post-dilation (PSP) were scored according to the hazard model derived from the weight of these variables. The primary end-point was a one-year device-oriented composite endpoint (DoCE) composed of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularisation. Def…

Predictors of early scaffold thrombosis: results from the multicenter prospective German-Austrian ABSORB RegIstRy.

2018

BACKGROUND In randomized clinical trials, the risk of thrombotic events with the absorb bioresorbable vascular scaffold (BVS) was significantly higher than with metallic drug-eluting stents. We evaluated predictors of scaffold thrombosis in the large-scale, multicenter German-Austrian ABSORB RegIstRy. METHODS AND RESULTS 3178 patients with treatment of 4252 lesions using 5020 scaffolds were included. Follow-up rate at 6 months was 97.4%. Forty-five (1.42%) patients experienced definite/probable scaffold thrombosis during follow-up. Multiple regression analysis showed implantation of absorb BVS in bifurcation lesions [odds ratio (OR): 4.43; 95% confidence interval (CI): 1.69-11.59; P=0.0024]…

C4BPB/C4BPA is a new susceptibility locus for venous thrombosis with unknown protein S-independent mechanism: results from genome-wide association an…

2010

3 Figures. 2 Tables. The online version of this article contains a data supplement.

Primary Persistent Atrial Fibrillation: A Distinct Arrhythmia Subentity of an Ablation Population

2015

INTRODUCTION Persistent atrial fibrillation (persAF) can occur either as a sustained arrhythmia that has progressed from initially paroxysmal AF or as primary persAF without a history of any spontaneously terminated episode. There is a paucity of data differentiating between the 2 different persAF entities. Thus, we prospectively evaluated baseline characteristics, electrophysiological features, and ablation outcome in these 2 patient cohorts. METHODS AND RESULTS A total number of 154 consecutive persAF patients (63 ± 10 years, f = 42, longstanding persAF = 60) were characterized in terms of having primary persAF (P-persAF group) or persAF that secondarily progressed from paroxysmal AF (S-p…

Monitoring White Blood Cell Mitochondrial Aldehyde Dehydrogenase Activity: Implications for Nitrate Therapy in Humans

2009

Recent animal data suggest that reduced lipoic acid (LA) prevents oxidative inhibition of the nitrate bioactivating enzyme, the mitochondrial aldehyde dehydrogenase (ALDH-2), and that pentaerythritol tetranitrate (PETN) does not induce nitrate tolerance because of its intrinsic antioxidative properties, thereby preserving ALDH-2 activity. We sought to determine whether ALDH-2 activity in circulating white blood cells (WBCs) can be used to monitor nitrate tolerance and whether LA can prevent nitroglycerin tachyphylaxis in humans. Eight healthy male volunteers received, in randomized order, a single dose of glyceryl trinitrate (GTN; 0.8 mg), PETN (80 mg), or GTN plus LA (600 mg) orally. GTN (…

Obere gastrointestinale Blutung mit hämorrhagischem Schock am Ende einer Urlaubsreise: Präklinische und innerklinische Versorgung eines gastrointesti…

2014

ZusammenfassungNach der Rückkehr aus dem Urlaub wurde ein 55-jähriger Patient mit Teerstuhl und hämorrhagischem Schock im Zugabteil eines InterCity der Deutschen Bahn notfallmedizinisch versorgt und in ein Krankenhaus der Maximalversorgung eingeliefert. Hier erfolgte zunächst die weitere notfallmedizinische Behandlung, in deren Rahmen in der internistischen Notaufnahme in interdisziplinärer Zusammenarbeit eine Stabilisierung der Hämodynamik sowie die Sicherung der Atemwege und Atemfunktion erfolgten. Anschließend wurde eine Notfall-Endoskopie des oberen Gastrointestinaltrakts durchgeführt. Ursächlich für das hämorrhagische Schockgeschehen war eine arteriell spritzende, endoskopisch nicht zu…

The interaction between circadian rhythms of endothelial function: resting versus recruitable endothelial function

2013

Reduction of ICD Shock Burden by Eliminating Back-Up Pacing Induced Ventricular Tachyarrhythmias

2014

ICD Shock Reduction by Subthreshold Pacing Introduction Implantable cardioverter defibrillators (ICD) may have the capacity to provoke or worsen ventricular tachyarrhythmias (VT). It has been reported that ICD shocks by itself can increase mortality. This study aimed to determine the role of back-up pacing-induced VT (PIT) in the overall ICD shock burden by avoiding pause-related ventricular back-up pacing. Methods and Results A population of 550 single-chamber ICD patients was studied. Of them, 17 (3%, 69 ± 16 years, 14 male) patients had documented episodes of PIT. A total of 431 VT episodes were documented including 89 (21%) due to PIT. In 3 patients, VT events were exclusively PITs. Aft…

In vitro and in vivo characterization of a new organic nitrate hybrid drug covalently bound to pioglitazone.

2014

<b><i>Background/Aims:</i></b> Organic nitrates represent a group of nitrovasodilators that are clinically used for the treatment of ischemic heart disease. The new compound CLC-3000 is an aminoethyl nitrate (AEN) derivative of pioglitazone, a thiazolidinedione antidiabetic agent combining the peroxisome proliferator-activated receptor γ agonist activity of pioglitazone with the NO-donating activity of the nitrate moiety. <b><i>Methods:</i></b> In vitro and in vivo characterization was performed by isometric tension recording, platelet function, bleeding time and detection of oxidative stress. <b><i>Results:</i></…

Apple Watch detecting coronary ischaemia during chest pain episodes or an apple a day may keep myocardial infarction away

2020

Genome-Wide Haplotype Analysis of Cis Expression Quantitative Trait Loci in Monocytes

2013

In order to assess whether gene expression variability could be influenced by several SNPs acting in cis, either through additive or more complex haplotype effects, a systematic genome-wide search for cis haplotype expression quantitative trait loci (eQTL) was conducted in a sample of 758 individuals, part of the Cardiogenics Transcriptomic Study, for which genome-wide monocyte expression and GWAS data were available. 19,805 RNA probes were assessed for cis haplotypic regulation through investigation of ∼2,1×109 haplotypic combinations. 2,650 probes demonstrated haplotypic p-values >104-fold smaller than the best single SNP p-value. Replication of significant haplotype effects were tested f…

ADMA and arginine derivatives in relation to non-invasive vascular function in the general population.

2015

Nitric oxide produced from l-arginine is central to vascular homeostasis. Little is known about the relationship between arginine derivatives including asymmetric dimethylarginine (ADMA) and non-invasive vascular function measures in the general population.In 5000 individuals (median age 56; 25th/75th percentile: 46, 65; 49% women) taking part in the population-based Gutenberg Health Study (Mainz area, Germany), we measured the relationship between the arginine derivatives asymmetric dimethylarginine (ADMA), N-monomethyl l-arginine (NMMA), symmetric dimethylarginine (SDMA) and l-arginine with flow-mediated dilation (FMD) and peripheral arterial tonometry (PAT). Weak bivariate correlations w…

Non‐bacterial thrombotic endocarditis in a patient with pancreatic carcinoma

2021

Nonbacterial thrombotic endocarditis (NBTE) is a rare condition that most often accompanies a malignant disease and involves a hypercoagulable state. We report the incidental finding of a rare case of an NBTE affecting the tricuspid valve in a patient with metastatic pancreatic carcinoma complicated by severe venous and arterial thromboembolisms.

Association of Low Birth Weight With Altered Corneal Geometry and Axial Length in Adulthood in the German Gutenberg Health Study

2019

IMPORTANCE: Low birth weight is associated with altered ocular organ development in childhood, including the morphology of the eye. However, no population-based data exist about this association in adulthood. OBJECTIVE: To evaluate whether low birth weight has a long-term association with anterior segment anatomy and axial length in adulthood. DESIGN, SETTING, AND PARTICIPANTS: The Gutenberg Health Study is a population-based, observational cohort study in Germany. All participants underwent ocular biometry. Among the participants with follow-up and self-reported birth weight available, associations were assessed between low birth weight and anterior segment anatomy and axial length using m…

Time‐dependent induction of vascular oxidative stress, inflammation, endothelial dysfunction and high blood pressure by aircraft noise exposure in mi…

2020

Targeting vascular (endothelial) dysfunction

2016

Abstract Cardiovascular diseases are major contributors to global deaths and disability-adjusted life years, with hypertension a significant risk factor for all causes of death. The endothelium that lines the inner wall of the vasculature regulates essential haemostatic functions, such as vascular tone, circulation of blood cells, inflammation and platelet activity. Endothelial dysfunction is an early predictor of atherosclerosis and future cardiovascular events. We review the prognostic value of obtaining measurements of endothelial function, the clinical techniques for its determination, the mechanisms leading to endothelial dysfunction and the therapeutic treatment of endothelial dysfunc…

Bevölkerungsbezogene psychische Gesundheit als Schlüsselfaktor im Umgang mit COVID-19

2020

Zusammenfassung Ziel Das Ziel des Beitrages besteht darin, auf die bedeutsame Rolle der Prävention und Reduktion der psychischen Belastungen in der Allgemeinbevölkerung und in sensiblen Gruppen im Rahmen der Coronavirus-Krankheit-2019 (COVID-19) -Pandemie hinzuweisen. Methodik Der vorliegende Beitrag umfasst die Analyse und Bewertung von Studien und Empfehlungen von Organisationen wie der Weltgesundheitsorganisation (WHO), die die bevölkerungsbezogenen psychischen Auswirkungen von Epi-/Pandemien und deren Einfluss auf den weiteren Verlauf untersucht haben. Ergebnisse Angstbedingte Verhaltensweisen können sich negativ auf den Verlauf von Epidemien auswirken. Im Rahmen vergangener Ausbrüche v…

Local transient myocardial liposomal gene transfer of inducible nitric oxide synthase does not aggravate myocardial function and fibrosis and leads t…

2010

Microcirculation (2010) 17, 69–78. doi: 10.1111/j.1549-8719.2010.00002.x Abstract Background:  This study was designed to explore the effect of transient inducible nitric oxide synthase (iNOS) overexpression via cationic liposome-mediated gene transfer on cardiac function, fibrosis, and microvascular perfusion in a porcine model of chronic ischemia. Methods and Results:  Chronic myocardial ischemia was induced using a minimally invasive model in 23 landrace pigs. Upon demonstration of heart failure, 10 animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection and 13 animals received a sham procedure to serve as control. The efficacy of this iNOS-gene-…

Association of ocular, cardiovascular, morphometric and lifestyle parameters with retinal nerve fibre layer thickness.

2017

BACKGROUND Glaucoma is a neurodegenerative disease, leading to thinning of the retinal nerve fibre layer (RNFL). The exact influence of ocular, cardiovascular, morphometric, lifestyle and cognitive factors on RNFL thickness (RNFLT) is unknown and was analysed in a subgroup of the Gutenberg Health Study (GHS). METHODS Global peripapillary RNFLT was measured in 3224 eyes of 1973 subjects (49% female) using spectral-domain optical coherence tomography (SD-OCT). The association of age, sex, ocular, cardiovascular, morphometric, lifestyle and cognitive factors on RNFLT was analysed using Pearson correlation coefficient and fitting a linear mixed model. RESULTS In the univariable analysis highest…

Isolated Pulmonary Embolism Is Associated With a High Risk of Arterial Thrombotic Disease

2020

Background Isolated PE is associated with a higher burden of atherosclerotic disease than other manifestations of VTE. Research Question We hypothesized that the presence of isolated PE may signal a chronically elevated risk of arterial thrombotic disease. Study Design and Methods Data from the VTEval Study, a prospective cohort study enrolling individuals with clinical suspicion and imaging-based diagnosis or exclusion of VTE, were analyzed. Patients with PE received whole-leg ultrasonography to assess presence of DVT. Regularized logistic regression identified features that discriminate between isolated PE and other VTE phenotypes at clinical presentation. Survival analyses were performed…

Chronic occupational noise exposure: Effects on DNA damage, blood pressure, and serum biochemistry

2019

Abstract Noise levels experienced by industrial workers may cause both auditory and non-auditory harmful effects. We have studied the effects of chronic industrial noise exposure on DNA damage, blood pressure, and serum biochemistry in factory workers. Male workers (109 individuals) in three parts of a food factory in Shahroud, Iran were enrolled as the exposed group and male office workers (123 individuals) were the unexposed control group. Noise exposure was measured (dosimetry) and the comet assay was used to evaluate DNA damage in peripheral blood mononuclear cells. Glutathione peroxidase (GPx) and ceruloplasmin (Cp) levels were measured in serum samples. GPx levels, systolic and diasto…

Assessing Planning Ability Across the Adult Life Span in a Large Population-Representative Sample: Reliability Estimates and Normative Data for the T…

2019

AbstractObjectives:The Tower of London (TOL) test has probably become the most often used task to assess planning ability in clinical and experimental settings. Since its implementation, efforts were made to provide a task version with adequate psychometric properties, but extensive normative data are not publicly available until now. The computerized TOL-Freiburg Version (TOL-F) was developed based on theory-grounded task analyses, and its psychometric adequacy has been repeatedly demonstrated in several studies but often with small and selective samples.Method:In the present study, we now report reliability estimates and normative data for the TOL-F stratified for age, sex, and education …

Conversion of biliverdin to bilirubin by biliverdin reductase contributes to endothelial cell protection by heme oxygenase-1—evidence for direct and …

2009

Heme oxygenase-1 (HO-1) is highly protective in various pathophysiological states such as cardiovascular and neurodegenerative diseases. HO-1-derived bilirubin is an efficient scavenger of reactive oxygen and nitrogen species (RONS). It remains to determine whether conversion of biliverdin to bilirubin is an essential step for HO-1-conferred protection of endothelial cells. RONS scavenging activities of biliverdin versus bilirubin were assessed by different RONS generating systems and detection techniques. We also silenced the biliverdin reductase (BVR) or HO-1 gene in cultured primary human endothelial cells (HUVECs) and measured the effect on RONS formation upon stimulation with lipopolys…

Normalization of endothelial dysfunction and vascular oxidative stress by chronic atorvastatin treatment in a rat model of streptozotocin-induced dia…

2006

Exploiting the Pleiotropic Antioxidant Effects of Established Drugs in Cardiovascular Disease.

2015

Cardiovascular disease is a leading cause of death and reduced quality of life worldwide. Arterial vessels are a primary target for endothelial dysfunction and atherosclerosis, which is accompanied or even driven by increased oxidative stress. Recent research in this field identified different sources of reactive oxygen and nitrogen species contributing to the pathogenesis of endothelial dysfunction. According to lessons from the past, improvement of endothelial function and prevention of cardiovascular disease by systemic, unspecific, oral antioxidant therapy are obviously too simplistic an approach. Source- and cell organelle-specific antioxidants as well as activators of intrinsic antiox…

Coronary artery disease: seeing or foreseeing?

2013

This editorial refers to ‘Discordance between Framingham Risk Score and atherosclerotic plaque burden’, by A. Pen et al., doi:10.1093/eurheartj/ehs473 The prevention of cardiovascular disease (CVD) has been a major priority and challenge for policy-makers and healthcare workers for at least five decades. In this ‘co-ordinated set of actions, at public and individual level, aimed at eradicating, eliminating, or minimizing the impact of CVDs and their related disability’,1 the capacity to predict the presence of coronary atherosclerosis obviously plays a central role. Studies show that the combination of a few major risk factors is an easily accessible proxy for risk stratification: the Europ…

Reversal of Endothelial Nitric Oxide Synthase Uncoupling and Up-Regulation of Endothelial Nitric Oxide Synthase Expression Lowers Blood Pressure in H…

2006

Objectives We sought to examine the hypothesis that a pharmacologic up-regulation of endothelial nitric oxide synthase (eNOS) combined with a reversal of eNOS uncoupling provides a protective effect against cardiovascular disease. Background Many cardiovascular diseases are associated with oxidant stress involving protein kinase C (PKC) and uncoupling of eNOS. Methods Messenger ribonucleic acid (mRNA) expression was analyzed with RNase protection assay or quantitative real-time polymerase chain reaction, vascular nitric oxide (NO) with spin trapping, and reactive oxygen species (ROS) with dihydroethidium fluorescence. Results Aortas of spontaneously hypertensive rats (SHR) showed an elevate…

Anti-oxidative effects in response to pentaerithrityl tetranitrate (PETN) treatment are mediated by heme oxygenase-1 and ferritin induction and preve…

2006

Pathogenic lipid‐binding antiphospholipid antibodies are associated with severity of COVID‐19

2021

Abstract Background Coronavirus disease 19 (COVID‐19)–associated coagulopathy is a hallmark of disease severity and poor prognosis. The key manifestations of this prothrombotic syndrome—microvascular thrombosis, stroke, and venous and pulmonary clots—are also observed in severe and catastrophic antiphospholipid syndrome. Antiphospholipid antibodies (aPL) are detectable in COVID‐19 patients, but their association with the clinical course of COVID‐19 remains unproven. Objectives To analyze the presence and relevance of lipid‐binding aPL in hospitalized COVID‐19 patients. Methods Two cohorts of 53 and 121 patients from a single center hospitalized for PCR‐proven severe acute respiratory syndro…

Depression and disease severity as correlates of everyday physical activity in heart transplant candidates

2010

Summary It is unclear to what extent patients awaiting heart transplantation (HTx) engage in physical activities. We examined the everyday physical activity and its associations with depressive symptoms and disease severity in 318 patients newly registered for HTx in the multi-site study ‘Waiting for a New Heart’ (aged 53.5 ± 11.4 years, 18% female patients). Participants completed questionnaires assessing depressive symptomatology and physical activity (number of physical activities, caloric expenditure associated with each activity), and estimated the distance they were able to walk without a break. Medical parameters at the time of listing [e.g. peak oxygen consumption (peakVO2); the Ger…

Sex-specific and age-related seasonal variations regarding incidence and in-hospital mortality of pulmonary embolism in Germany

2020

Background Studies have reported seasonal variations regarding the incidence and the short-term mortality of pulmonary embolism (PE). The aim of this study was to identify sex-specific and age-related differences in seasonal patterns regarding hospitalisations and mortality of PE patients. Methods We analysed the impact of seasons on incidence and in-hospital mortality of male and female hospitalised PE patients in Germany (2005–2015) based on the German nationwide inpatient sample. Results The German nationwide inpatient sample comprised 885 806 hospitalisations due to PE (2005–2015). Seasonal variations of both incidence (p=0.021) and in-hospital mortality (p<0.001) were of significant ma…

Nitroglycerin-induced endothelial dysfunction and tolerance involve adverse phosphorylation and S-glutathionylation of endothelial nitric oxide synth…

2011

Continuous administration of nitroglycerin (GTN) causes tolerance and endothelial dysfunction by inducing reactive oxygen species (ROS) production from various enzymatic sources, such as mitochondria, NADPH oxidase, and an uncoupled endothelial nitric oxide synthase (eNOS). In the present study, we tested the effects of type 1 angiotensin (AT(1))-receptor blockade with telmisartan on GTN-induced endothelial dysfunction in particular on eNOS phosphorylation and S-glutathionylation sites and the eNOS cofactor synthesizing enzyme GTP-cyclohydrolase I.Wistar rats were treated with telmisartan (2.7 or 8 mg/kg per day PO for 10 days) and with GTN (50 mg/kg per day SC for 3 days). Aortic eNOS phos…

Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dys…

2008

AimsImbalance between pro- and antioxidant species (e.g. during aging) plays a crucial role for vascular function and is associated with oxidative gene regulation and modification. Vascular aging is associated with progressive deterioration of vascular homeostasis leading to reduced relaxation, hypertrophy, and a higher risk of thrombotic events. These effects can be explained by a reduction in free bioavailable nitric oxide that is inactivated by an age-dependent increase in superoxide formation. In the present study, mitochondria as a source of reactive oxygen species (ROS) and the contribution of manganese superoxide dismutase (MnSOD, SOD-2) and aldehyde dehydrogenase (ALDH-2) were inves…

Development of an Analytical Assay for Electrochemical Detection and Quantification of Protein-Bound 3-Nitrotyrosine in Biological Samples and Compar…

2020

Reactive oxygen and nitrogen species (RONS) cause oxidative damage, which is associated with endothelial dysfunction and cardiovascular disease, but may also contribute to redox signaling. Therefore, their precise detection is important for the evaluation of disease mechanisms. Here, we compared three different methods for the detection of 3-nitrotyrosine (3-NT), a marker of nitro-oxidative stress, in biological samples. Nitrated proteins were generated by incubation with peroxynitrite or 3-morpholino sydnonimine (Sin-1) and subjected to total hydrolysis using pronase, a mixture of different proteases. The 3-NT was then separated by high performance liquid chromatography (HPLC) and quantifi…

PO-58 - Cardiovascular risk profile in survivors of adult cancer - results from the general population study.

2016

The advancements in cancer treatment and detection of early cancer have resulted in steady increase of adult cancer survivors over the years. However, due to the long term toxic effects of chemotherapy and radiotherapy, the incidence of cardiovascular diseases (CVD) is increasing in survivors. Identifying risk factors and interventions to reduce the excess burden of CVD in this vulnerable population is urgently needed.To investigate the cardiovascular risk factors (CVRFs), inflammation and coagulation profile in cancer survivors from a large population-based study.Presence of CVRFs and laboratory markers have been compared in individuals with (n=1,359) and without (n=13,626) history of canc…

Guideline-adherence regarding critical time intervals in the German Chest Pain Unit registry

2020

Background: Since 2008, the German Cardiac Society certified 256 Chest Pain Units (CPUs). Little is known about adherence to recommended performance measures in patients with suspected acute coronary syndrome (ACS) presenting to CPUs. We investigated guideline-adherence regarding critical time intervals and selected performance measures in German Chest Pain Units. Methods: From 2008 to 2014, 23,804 consecutive patients with suspected ACS were prospectively enrolled in the Chest Pain Unit registry of the German Cardiac Society. Results: Median time from symptom onset to first medical contact was 2 h in patients with ST-elevation myocardial infarction (STEMI) and 4 h in patients with unstable…

Inflammatory pathways in patients with heart failure and preserved ejection fraction.

2008

Immune activation is well established in patients with chronic heart failure and reduced ejection fraction (HF and reduced EF) and is associated with an impaired prognosis. Patients with heart failure and preserved ejection fraction (HF and preserved EF) have an impaired prognosis as well. It is not known whether they have signs of immune activation.We studied patients with HF and preserved EF (n=17, NYHA II [n=7]/III [n=10]) and patients with HF and reduced EF (n=17 NYHA II [n=1]/III [n=16]) and 20 controls. Echocardiography demonstrated preserved ejection fraction (LVEF 59+/-9%), but LV hypertrophy in patients with preserved EF as compared with patients with reduced EF (LVEF 23+/-5%). We …

Management of Pulmonary Embolism: Results from the German Chest Pain Unit Registry.

2020

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Since 2008, specialized chest pain units (CPUs) were implemented across Germany ensuring structured diagnostics in acute chest pain. This study aims to analyze the management of pulmonary embolism (PE) patients in such certified CPUs. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Data were retrieved from 13,902 patients enrolled in the German CPU registry and analyzed for the diagnosis of PE including patient characteristics, critical time intervals, diagnostic workup, treatment, and prognosis. PE patients were compared to the overall CPU patient cohort. Only patients with a complete 3-month follow-up were included. &lt;b&gt;&lt;i&gt;Resu…

AT1-receptor blockade by telmisartan upregulates GTP-cyclohydrolase I and protects eNOS in diabetic rats.

2008

Several enzymatic sources of reactive oxygen species (ROS) were described as potential reasons of eNOS uncoupling in diabetes mellitus. In the present study, we investigated the effects of AT1-receptor blockade with chronic telmisartan (25 mg/kg/day, 6.5 weeks) therapy on expression of the BH4-synthesizing enzyme GTP-cyclohydrolase I (GCH-I), eNOS uncoupling, and endothelial dysfunction in streptozotocin (STZ, 60 mg/kg iv, 7 weeks)-induced diabetes mellitus (type I). Telmisartan therapy did not modify blood glucose and body weight. Aortas from diabetic animals had vascular dysfunction as revealed by isometric tension studies (acetylcholine and nitroglycerin potency). Vascular and cardiac RO…

Value of color doppler jet area for grading regurgitation severity in patients with secondary mitral regurgitation - better than its reputation?

2013

GDF-15 predicts cardiovascular events in acute chest pain patients

2017

Background Treatment of patients presenting with possible acute myocardial infarction (AMI) is based on timely diagnosis and proper risk stratification aided by biomarkers. We aimed at evaluating the predictive value of GDF-15 in patients presenting with symptoms suggestive of AMI. Methods Consecutive patients presenting with suspected AMI were enrolled in three study centers. Cardiovascular events were assessed during a follow-up period of 6 months with a combined endpoint of death or MI. Results From the 1818 enrolled patients (m/f = 1208/610), 413 (22.7%) had an acute MI and 63 patients reached the combined endpoint. Patients with MI and patients with adverse outcome had higher GDF-15 le…

Impact of symptomatic atherosclerosis in patients with pulmonary embolism

2019

Atherosclerosis is associated with increased cardiovascular mortality. Associations between venous thromboembolism and atherosclerosis were recently reported. We aimed to investigate the impact of symptomatic atherosclerosis on adverse outcomes in patients with pulmonary embolism (PE) and to identify significant differences among patients with PE stratified by symptomatic atherosclerosis.Patients were selected by screening the nationwide inpatients sample for PE (ICD-code I26) stratified by symptomatic atherosclerosis (composite of coronary artery disease [ICD-code I25], myocardial infarction [ICD-code I21], ischemic stroke [ICD-code I63], and/or atherosclerotic arterial diseases [ICD-code …

ADMA, subclinical changes and atrial fibrillation in the general population.

2015

Abstract Background Pathways of oxidative stress, nitric oxide bioavailability and l-arginine derivatives are hypothesized to be related to atrial fibrillation (AF). Circulating methylated l-arginine metabolites can be assessed in the general population and may show an association with AF. Methods We determined l-arginine and its metabolites asymmetric dimethylarginine (ADMA), l-N ω -monomethylarginine (NMMA) and symmetric dimethylarginine (SDMA) in the population-based Gutenberg Health Study (n=5000), mean age 55±11years, 51% men, in association with clinical variables of AF such as electrocardiographic and echocardiographic measures and manifest AF. Results Individuals with AF (N=161), 71…

COX-2, Another Important Player in the Nitric Oxide–Endothelin Cross-Talk

2006

See related article, pages 1439–1445 Traditionally, the role of the endothelium was thought to be primarily that of a selective barrier to the diffusion of macromolecules from the vessel lumen to the interstitial space. During the past 20 years, numerous additional roles for the endothelium have been defined such as regulation of vascular tone, modulation of inflammation, promotion as well as inhibition of vascular growth, and modulation of platelet aggregation and coagulation. Endothelial dysfunction is a characteristic feature of patients with cardiovascular risk factors such as hypercholesterolemia, hypertension, diabetes mellitus, and chronic smoking. More recent studies indicate that i…

Oxidative stress and endothelial dysfunction: therapeutic implications.

2011

In a previous issue of Annals of Medicine, we presented evidence in support of the concept that an abnormally increased production of reactive oxygen species plays a central role in the genesis and progression of cardiovascular disease. While a number of preclinical lines of evidence support this concept, and despite the results of many studies suggesting a beneficial impact of antioxidant drugs on endothelial function, large clinical trials have failed to demonstrate a benefit of antioxidants on cardiovascular outcomes. Studies exploring the possibility that classical antioxidants such as vitamin C, vitamin E, selenium, or folic acid may improve the prognosis of patients with cardiac disea…

Low Homoarginine Levels in the Prognosis of Patients With Acute Chest Pain.

2016

Background The endogenous amino acid homoarginine predicts mortality in cerebro‐ and cardiovascular disease. The objective was to explore whether homoarginine is associated with atrial fibrillation ( AF ) and outcome in patients with acute chest pain. Methods and Results One thousand six hundred forty‐nine patients with acute chest pain were consecutively enrolled in this study, of whom 589 were diagnosed acute coronary syndrome ( ACS ). On admission, plasma concentrations of homoarginine as well as brain natriuretic peptide ( BNP ), and high‐sensitivity assayed troponin I (hsTnI) were determined along with electrocardiography ( ECG ) variables. During a median follow‐up of 183 days, 60 ma…

Resistin, acute coronary syndrome and prognosis results from the AtheroGene study

2006

Resistin, an adipocyte and macrophage derived cytokine, causes insulin resistance and glucose intolerance. We investigated the impact of resistin as a diagnostic marker in patients with acute coronary syndrome and its prognostic value for future cardiovascular events.Resistin levels were determined in 1153 patients with stable angina (SAP), 380 patients with unstable angina, 278 patients with non-ST-elevation myocardial infarction (NSTEMI) and 111 patients with ST-elevation myocardial infarction (STEMI). All patients have been followed up for a median follow-up of 2.6 years. During follow-up, 70 patients died from cardiovascular causes.Compared to SAP, resistin levels (5.1 ng/mL in SAP) wer…

AT1-receptor blockade with irbesartan improves peripheral but not coronary endothelial dysfunction in patients with stable coronary artery disease

2007

Activation of the renin-angiotensin-aldosterone system plays an important role in the pathogenesis of endothelial dysfunction and atherosclerosis. Studies evaluating the effect of AT1-receptor blockers on endothelial dysfunction in patients with coronary artery disease (CAD) revealed mixed results. Studies addressing the effects of AT1-receptor blockers on the coronary and peripheral function in the same study population, are still lacking. We therefore aimed to test the effects of long-term therapy with the AT1-receptor blocker irbesartan (IRB) on both, the coronary and peripheral endothelial function in patients with CAD. Seventy-two patients with CAD were randomly assigned to double-blin…

Up in the air: links between the environment and cardiovascular disease

2019

Short‐term e‐cigarette vapor exposure causes vascular oxidative stress and dysfunction ‐ evidence for a close connection to brain damage and a key ro…

2020

Psoriasis and Its Impact on In-Hospital Outcome in Patients Hospitalized with Acute Kidney Injury

2020

Background: Psoriasis is a chronic inflammatory disease which affects the body far beyond the skin. Whereas there is solid evidence that chronic skin inflammation in psoriasis drives cardiovascular disease, the impact on renal impairment and acute kidney injury (AKI) is still unclear. We aimed to analyze the impact of psoriasis on the in-hospital outcome of patients hospitalized with AKI. Methods: In this retrospective database study, we investigated data on characteristics, comorbidities, and in-hospital outcomes for all hospitalized patients with AKI stratified for concomitant psoriasis, which were collected by the Federal Office of Statistics in Germany between 2005 and 2016. Results: Am…

Mean Platelet Volume and Arterial Stiffness - Clinical Relationship and Common Genetic Variability

2017

AbstractVessel wall stiffening is an important clinical parameter, but it is unknown whether platelets, key elements in the pathogenesis of arterial thrombosis, are associated with arterial stiffness. The present studies sought to determine whether mean platelet volume (MPV), a potential marker of platelet activation, is linked to vascular elasticity as assessed by the augmentation index (AIx), in 15,010 individuals from the population-based Gutenberg Health Study. Multivariable analysis showed that MPV in both males (β 0.776; 95thCI [0.250;1.16]; p = 0.0024) and females (β 0.881[0.328;1.43]; p = 0.0018) is strongly associated with AIx. Individuals with MPV and AIx above the sex-specific me…

Comparison of risk assessment strategies for not-high-risk pulmonary embolism

2015

We compared the prognostic performance of the 2014 European Society of Cardiology (ESC) risk stratification algorithm with the previous 2008 ESC algorithm, the Bova score and the modified FAST score (based on a positive heart-type fatty acid-binding protein (H-FABP) test, syncope and tachycardia, modified using high-sensitivity troponin T instead of H-FABP) in 388 normotensive pulmonary embolism patients included in a single-centre cohort study.Overall, 25 patients (6.4%) had an adverse 30-day outcome. Regardless of the score or algorithm used, the rate of an adverse outcome was highest in the intermediate-high-risk classes, while all patients classified as low-risk had a favourable outcome…

Mitochondrial oxidative stress and nitrate tolerance – comparison of nitroglycerin and pentaerithrityl tetranitrate in Mn-SOD+/- mice

2006

Abstract Background Chronic therapy with nitroglycerin (GTN) results in a rapid development of nitrate tolerance which is associated with an increased production of reactive oxygen species (ROS). According to recent studies, mitochondrial ROS formation and oxidative inactivation of the organic nitrate bioactivating enzyme mitochondrial aldehyde dehydrogenase (ALDH-2) play an important role for the development of nitrate and cross-tolerance. Methods Tolerance was induced by infusion of wild type (WT) and heterozygous manganese superoxide dismutase mice (Mn-SOD+/-) with ethanolic solution of GTN (12.5 μg/min/kg for 4 d). For comparison, the tolerance-free pentaerithrityl tetranitrate (PETN, 1…

Cardiac biomarkers and arterial stiffening: data from the Gutenberg Health study

2013

Peripheral artery disease, redox signaling, oxidative stress – Basic and clinical aspects

2017

Reactive oxygen and nitrogen species (ROS and RNS, e.g. H2O2, nitric oxide) confer redox regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. At higher concentrations, ROS and RNS lead to oxidative stress and oxidative damage of biomolecules (e.g. via formation of peroxynitrite, fenton chemistry). Peripheral artery disease (PAD) is characterized by severe ischemic conditions in the periphery leading to intermittent claudication and critical limb ischemia (end stage). It is well known that redox biology and oxidative stress play an important role in this setting. We here discuss the major pathways of oxidative stress and re…

Disturbed glucose metabolism and left ventricular geometry in the general population – results from the Gutenberg health study

2020

Abstract Background Prediabetes and type 2 diabetes mellitus (T2DM) have been demonstrated to alter left ventricular geometry and promote left ventricular (LV) hypertrophy (LVH). However, the impact of impaired glucose metabolism on cardiac structure is still not completely understood and controversially discussed. Purpose To investigate the impact of prediabetes and T2DM on left ventricular geometry and their potential interaction with LVH in the prediction of survival. Methods Data from the Gutenberg Health Study (N=15,010) – a population-based study with highly standardized phenotyping – were analysed. Information was obtained from computer-assisted personal interviews, medical-technical…

Disturbed Glucose Metabolism and Left Ventricular Geometry in the General Population

2021

Background: This study sought to investigate the prevalence and clinical outcome of left ventricular (LV) geometry in prediabetes and type 2 diabetes mellitus (T2DM) and the impact of glucose metabolism on the incidence of left ventricular hypertrophy (LVH). Methods: 15,010 subjects (35–74 years) of the population-based Gutenberg Health Study were categorized into euglycemia, prediabetes, and T2DM according to clinical and metabolic (HbA1c) information. Clinical outcome was assessed via structured follow-up. Results: The study comprised 12,121 individuals with euglycemia (81.6%), 1415 with prediabetes (9.5%), and 1316 with T2DM (8.9%). Prevalence of LVH increased from euglycemia (10.2%) ove…

Glutathione Peroxidase-1 Deficiency Potentiates Dysregulatory Modifications of Endothelial Nitric Oxide Synthase and Vascular Dysfunction in Aging

2014

Recently, we demonstrated that gene ablation of mitochondrial manganese superoxide dismutase and aldehyde dehydrogenase-2 markedly contributed to age-related vascular dysfunction and mitochondrial oxidative stress. The present study has sought to investigate the extent of vascular dysfunction and oxidant formation in glutathione peroxidase-1–deficient ( GPx-1 −/− ) mice during the aging process with special emphasis on dysregulation (uncoupling) of the endothelial NO synthase. GPx-1 −/− mice on a C57 black 6 (C57BL/6) background at 2, 6, and 12 months of age were used. Vascular function was significantly impaired in 12-month-old GPx-1 −/− -mice as compared with age-matched controls. Oxidan…

The relationship of ocular geometry with refractive error in normal and low birth weight adults

2020

Purpose Low birth weight (BW) individuals have an increased risk for myopic refractive error. However, it is unclear which ocular geometric alterations lead to an increase in myopic refractive error. This study aims to evaluate the impact of ocular biometry in interaction with BW on refractive error. Methods Participants of the prospective, observational, population-based Gutenberg Health Study (GHS) with self-reported BW aged 40–80 years and objective refraction and optical biometry were included. Linear regression analyses were conducted to evaluate associations between spherical equivalent with corneal power, anterior chamber depth, lens thickness and axial length and its interaction wit…

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness…

2011

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions a…

Exacerbation of adverse cardiovascular effects of aircraft noise in an animal model of arterial hypertension

2020

Arterial hypertension is the most important risk factor for the development of cardiovascular disease. Recently, aircraft noise has been shown to be associated with elevated blood pressure, endothelial dysfunction, and oxidative stress. Here, we investigated the potential exacerbated cardiovascular effects of aircraft noise in combination with experimental arterial hypertension. C57BL/6J mice were infused with 0.5 mg/kg/d of angiotensin II for 7 days, exposed to aircraft noise for 7 days at a maximum sound pressure level of 85 dB(A) and a mean sound pressure level of 72 dB(A), or subjected to both stressors. Noise and angiotensin II increased blood pressure, endothelial dysfunction, oxidati…

Redox regulation of cardiovascular inflammation – Immunomodulatory function of mitochondrial and Nox-derived reactive oxygen and nitrogen species

2017

Oxidative stress is a major hallmark of cardiovascular diseases although a causal link was so far not proven by large clinical trials. However, there is a close association between oxidative stress and inflammation and increasing evidence for a causal role of (low-grade) inflammation for the onset and progression of cardiovascular diseases, which may serve as the missing link between oxidative stress and cardiovascular morbidity and mortality. With the present review we would like to highlight the multiple redox regulated pathways in inflammation, discuss the sources of reactive oxygen and nitrogen species that are of interest for these processes and finally discuss the importance of angiot…

Psoriasis and its impact on the clinical outcome of patients with pulmonary embolism

2021

Abstract Background Venous thromboembolism (VTE) is common and associated with high morbidity and mortality. Although chronic inflammation was not categorized as a traditional risk factor for VTE, chronic inflammation might increase the risk to develop VTE events. While studies confirmed an increased cardiovascular morbidity and mortality in psoriatic patients, data regarding the influence of psoriasis on patients' cardiovascular profile and on prognosis of patients with pulmonary embolism (PE) are sparse. Purpose We aimed to investigate the impact of psoriasis on prognosis of PE patients. Methods Hospitalized PE patients were stratified for psoriasis and the impact of psoriasis on outcome …

Clinical impact of diabetes mellitus in patients hospitalized for myocardial infarction

2020

Abstract Background Diabetes mellitus (DM) represents a major cardiovascular risk factor for coronary artery disease and myocardial infarction (MI). Purpose We aimed to assess in-hospital events and time trends in MI patients with and without DM between 2005 and 2016 in Germany. Methods The nationwide German inpatient sample 2005–2016 was used for statistical analysis (source: Research Data Center (RDC) of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005–2016, own calculations). Hospitalized MI patients were stratified for the presence of DM and the impact of DM on in-hospital events was investigated. Results A total of 3,307,703 patients…

Trends in thrombolytic treatment and outcomes of acute pulmonary embolism in Germany.

2019

Abstract Aims Pulmonary embolism (PE) is the third most common cardiovascular cause of death; systemic thrombolysis is potentially lifesaving treatment in patients presenting with haemodynamic instability. We investigated trends in the use of systemic thrombolysis and the outcome of patients with acute PE. Methods and results We analysed data on the characteristics, comorbidities, treatment, and in-hospital outcome of 885 806 PE patients in Germany between 2005 and 2015. Incidence of acute PE was 99/100 000 population/year and increased from 85/100 000 in 2005 to 109/100 000 in 2015 [β 0.32 (0.26–0.38), P &amp;lt; 0.001]. During the same period, in-hospital case fatality rates decreased fro…

Serial assessments of microvascular obstruction by contrast-enhanced magnetic resonance predict contractile recovery and clinical outcome after reper…

2015

AIMS The purpose of the study was to investigate, using cardiac magnetic resonance (CMR), the presence and time course of microvascular obstruction (MO) in patients with acute myocardial infarction (AMI), and to test its relationship with cardiac remodeling and clinical outcomes. METHODS AND RESULTS 53 patients with AMI and successful percutaneous reperfusion underwent CMR examination at four separate timepoints: within the first 48 hours, at 10 days, at six and twelve months after infarction. MO was quantified immediately (early imaging) and 10 minutes (late imaging) after contrast administration in each session. The extent of MO decreased from early to late imaging at both the first and t…

Differential VASP phosphorylation controls remodeling of the actin cytoskeleton

2009

Proteins of the Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) family link signal transduction pathways to actin cytoskeleton dynamics. VASP is substrate of cAMP-dependent, cGMP-dependent and AMP-activated protein kinases that primarily phosphorylate the sites S157, S239 and T278, respectively. Here, we systematically analyzed functions of VASP phosphorylation patterns for actin assembly and subcellular targeting in vivo and compared the phosphorylation effects of Ena/VASP family members. Methods used were the reconstitution of VASP-null cells with `locked' phosphomimetic VASP mutants, actin polymerization of VASP mutants in vitro and in living cells, site-specific kinase-mediated…

Inflammation in right ventricular dysfunction due to thromboembolic pulmonary hypertension

2009

Activation of the immune system is well established in patients with chronic heart failure (CHF) and impaired left ventricular function. High levels of pro-inflammatory cytokines are associated with a poor prognosis. Chronic thromboembolic pulmonary hypertension (CTEPH) frequently leads to impaired right ventricular function. It is not known whether such patients display chronic immune activation as well.We studied 49 patients with CTEPH (50±2 years, right ventricular ejection fraction [RVEF] 29±2%, left ventricular ejection fraction [LVEF] 51±3%, mean±SEM) and compared their results with 17 patients with CHF (71±2 years, LVEF 23±1%) and 34 age-matched control subjects (age 57±2 years). We …

The Choice of the Filtering Method in Microarrays Affects the Inference Regarding Dosage Compensation of the Active X-Chromosome

2011

BackgroundThe hypothesis of dosage compensation of genes of the X chromosome, supported by previous microarray studies, was recently challenged by RNA-sequencing data. It was suggested that microarray studies were biased toward an over-estimation of X-linked expression levels as a consequence of the filtering of genes below the detection threshold of microarrays.Methodology/principal findingsTo investigate this hypothesis, we used microarray expression data from circulating monocytes in 1,467 individuals. In total, 25,349 and 1,156 probes were unambiguously assigned to autosomes and the X chromosome, respectively. Globally, there was a clear shift of X-linked expressions toward lower levels…

Syncope in the German Nationwide inpatient sample – Syncope in atrial fibrillation/flutter is related to pulmonary embolism and is accompanied by hig…

2019

Syncope is a common phenomenon in the general population. Although most of the causes are of benign origin, some comorbidities are accompanied by high mortality. We aimed to compare the in-hospital mortality of patients with syncope related to different comorbities and investigate the impact of syncope in patients with atrial fibrillation/flutter (AF).The nationwide inpatient sample of Germany of the years 2011-2014 was used for this analysis. Patients with syncope (ICD-code R55) were stratified by presence of selected comorbidities. Additionally, AF patients with and without syncope were compared. Incidence of syncope and in-hospital mortality were calculated. Syncope as a predictor of adv…

Invasive treatment of NSTEMI patients in German Chest Pain Units - Evidence for a treatment paradox.

2018

Background: Patients with non ST-segment elevation myocardial infarction (NSTEMI) represent the largest fraction of patients with acute coronary syndrome in German Chest Pain units. Recent evidence on early vs. selective percutaneous coronary intervention (PCI) is ambiguous with respect to effects on mortality, myocardial infarction (MI) and recurrent angina. With the present study we sought to investigate the prognostic impact of PCI and its timing in German Chest Pain Unit (CPU) NSTEMI patients. Methods and results: Data from 1549 patients whose leading diagnosis was NSTEMI were retrieved from the German CPU registry for the interval between 3/2010 and 3/2014. Follow-up was available at m…

Regulation of NADPH oxidase-mediated superoxide production by acetylation and deacetylation

2021

Oral treatment of apolipoprotein E-knockout (ApoE-KO) mice with the putative sirtuin 1 (SIRT1) activator resveratrol led to a reduction of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in the heart. In contrast, the SIRT1 inhibitor EX527 enhanced the superoxide production in isolated human polymorphonuclear granulocytes. In human monocytic THP-1 cells, phorbol ester-stimulated superoxide production was enhanced by inhibitors of histone deacetylases (HDACs; including quisinostat, trichostatin A (TSA), PCI34051, and tubastatin A) and decreased by inhibitors of histone acetyltransferases [such as garcinol, curcumin, and histone acetyltransferase (HAT) Inhibitor II]. Thes…

Extensive characterization of the human DDAH1 transgenic mice

2009

Abstract Purpose of the research Overexpression of the human dimethylarginine dimethylaminohydrolase type 1 (hDDAH1) gene was reported to have beneficial cardiovascular effects in mice. To date, it is unclear whether these effects are related to enhanced metabolic clearance of asymmetric dimethylarginine (ADMA) and l - N G -mono-methyl- l -arginine ( l -NMMA) or increased DDAH1 expression and activity in cardiovascular tissues of hDDAH1 transgenic mice. Principal results DDAH activity (DDAH1 + DDAH2) was found to be markedly increased in aortic and heart tissues but unaltered in liver and kidney tissues of hDDAH1 transgenic as compared to wild-type (WT) mice. In WT mice, DDAH activity was m…

Cystatin C and cardiovascular mortality in patients with coronary artery disease and normal or mildly reduced kidney function: results from the Ather…

2009

Aims Chronic kidney disease is associated with increased risk of cardiovascular disease. Cystatin C is a promising marker to reliably mirror renal function. The role of cystatin C in patients with coronary artery disease (CAD) and normal or mildly reduced kidney function is the subject of current investigation. Methods and results In 2162 patients, over the whole spectrum of CAD, baseline cystatin C concentrations were measured. Patients with an estimated glomerular filtration rate of ≤60 mL/min per 1.73 m2 ( n = 295) were excluded. In patients with complete follow-up information ( n = 1827), 66 cardiovascular deaths were registered during a median follow-up of 3.65 years. Logarithmically t…

B-type natriuretic peptide as a marker for sepsis-induced myocardial depression in intensive care patients.

2008

In early stages of septic shock, impaired myocardial function plays an important prognostic role. In this context, B-type natriuretic peptide (BNP) has been shown to be a neurohumoral marker for left ventricular dysfunction, because myocardial strain and ischemia both increase BNP concentration. The present study was designed to test if BNP allows for identification of patients at risk for developing sepsis-induced myocardial depression and if an increased concentration of BNP is associated with an adverse outcome in patients with septic shock.In a prospective study, 93 patients with septic shock were divided into one group with normal ventricular function (left ventricular ejection fractio…

The Oxidative Stress Concept of Nitrate Tolerance and the Antioxidant Properties of Hydralazine

2005

The hemodynamic and anti-ischemic effects of nitroglycerin (NTG) are rapidly blunted as a result of the development of nitrate tolerance. With initiation of NTG therapy, it is possible to detect neurohormonal activation and intravascular volume expansion. These so-called pseudotolerance mechanisms may compromise the vasodilatory effects of NTG. Long-term nitrate treatment also is associated with decreased vascular responsiveness caused by changes in intrinsic mechanisms of the tolerant vasculature itself. According to the oxidative stress concept, increased vascular superoxide (O 2 − ) production and an increased sensitivity to vasoconstrictors secondary to activation of protein kinase C co…

Interferon- and ribavirin-free therapy with new direct acting antivirals (DAA) for chronic hepatitis C improves vascular endothelial function.

2018

Abstract Introduction Chronic Hepatitis C virus infection (HCV) is associated with extrahepatic manifestations and an increased prevalence in cardiovascular disease. New direct acting antivirals (DAA) have revolutionized HCV treatment with high rates of sustained virological response (SVR). Recently it was demonstrated, that SVR reduces morbidity and overall mortality more than can be solely explained by hepatic effects, suggesting that treatment with DAA also affects cardiovascular disease. The aim of this pilot study was to identify possible underlying mechanisms behind the HCV-associated cardiovascular mortality reported by others. Methods and results 20 HCV patients (10 genotype GT1, 10…

Prognostic value of plasma tissue factor and tissue factor pathway inhibitor for cardiovascular death in patients with coronary artery disease: the A…

2007

Summary. Background: Tissue factor (TF) and its specific inhibitor, tissue factor pathway inhibitor (TFPI), are important contributors to the initiation of the coagulation process. Objectives: To compare plasma levels of soluble TF (sTF) and free-TFPI (f-TFPI) between patients with stable angina pectoris (SAP) and acute coronary syndrome (ACS) and to assess the impact of the two variables on long-term prognosis. Patients/methods: Patients with SAPs (n = 1146) and acute coronary syndrome (n = 523) from the AtheroGene study were included and followed for 2.3 years. Because of the strong impact of unfractionated heparin (UFH) on f-TFPI levels, but not on sTF levels, patients having received UF…

Prevalence of corneal arcus and associated factors in a German population-Results from the Gutenberg Health Study.

2021

Purpose We aimed to determine the prevalence of corneal arcus and to identify associated factors in the general population of Germany. Methods The Gutenberg Health Study (GHS) is a population-based cohort study in Germany, which includes an ophthalmological assessment. Refraction, distance-corrected visual acuity, non-contact tonometry and anterior segment imaging were performed for the five-year follow-up examination. Anterior segment photographs were graded for the presence of corneal arcus. Prevalence estimates were computed, and multivariable logistic regression analysis was applied to determine associated factors for corneal arcus including sex, age, spherical equivalent, central corn…

Impact of chronic obstructive pulmonary disease on the outcomes of patients with peripheral artery disease.

2019

Peripheral artery disease (PAD) and chronic obstructive pulmonary disease (COPD) are both related with high in-hospital mortality. We aimed to investigate the impact of COPD on the in-hospital outcomes in PAD.PAD patients were selected based on ICD-code I70.2 of the German nationwide database, stratified for COPD and compared regarding adverse in-hospital outcomes.Between 01/2005-12/2015, 5,611,827 inpatients (64.8% males) were diagnosed with PAD; of those, 13.6% were coded additionally with COPD. Overall, 277,894 PAD patients (5.0%) died during in-hospital course. Prevalence of cardiovascular diseases as well as cancer (12.1% vs. 7.0%, P  0.001) was higher in PAD patients with COPD compare…

5-Year Experience of In-Hospital Outcomes After Percutaneous Left Atrial Appendage Closure in Germany

2019

The aim of this study was to evaluate 5-year in-hospital trends and safety outcomes of left atrial appendage (LAA) closure in the German nationwide inpatient sample.The safety and efficacy of percutaneous LAA closure have been demonstrated in randomized trials and prospective cohort studies, but results from large samples are missing.Data on patient characteristics and in-hospital safety outcomes for all percutaneous LAA closures performed in Germany between 2011 and 2015 were analyzed. Overall, 15,895 inpatients were included.The annual number of LAA occlusions increased from 1,347 in 2011 to 4,932 in 2015 (β = 1.00; 95% confidence interval [CI]: 0.95 to 1.01; p 0.001), with a nonsignifica…

Activated thrombin activatable fibrinolysis inhibitor levels are associated with the risk of cardiovascular death in patients with coronary artery di…

2008

Summary. Background: Thrombin activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis. Results on the association between TAFI levels and the risk of coronary artery disease (CAD) are inconsistent. Objectives: We investigated the association between TAFI levels and the risk of cardiovascular events in CAD. Patients/Methods: 1668 individuals with angiographically proven CAD at baseline were followed for a median of 2.3 years, as part of the prospective AtheroGene cohort. Fifty-six deaths from cardiovascular (CV) causes and 35 non-fatal CV events were observed. Results: At baseline, three TAFI measurements were available: one evaluating the total amount of TAFI (t-TAFI), one measuri…

Molecular Mechanisms of the Crosstalk Between Mitochondria and NADPH Oxidase Through Reactive Oxygen Species—Studies in White Blood Cells and in Anim…

2014

Aims: Oxidative stress is involved in the development of cardiovascular disease. There is a growing body of evidence for a crosstalk between different enzymatic sources of oxidative stress. With the present study, we sought to determine the underlying crosstalk mechanisms, the role of the mitochondrial permeability transition pore (mPTP), and its link to endothelial dysfunction. Results: NADPH oxidase (Nox) activation (oxidative burst and translocation of cytosolic Nox subunits) was observed in response to mitochondrial reactive oxygen species (mtROS) formation in human leukocytes. In vitro, mtROS-induced Nox activation was prevented by inhibitors of the mPTP, protein kinase C, tyrosine kin…

Management of Oral Anti-Coagulation in Patients with Heart Failure-Insights from the ThrombEVAL Study

2018

AbstractPatients with heart failure (HF) are frequently anti-coagulated with vitamin K-antagonists (VKAs). The use of long-acting VKA may be preferable for HF patients due to higher stability of plasma concentrations. However, evidence on phenprocoumon-based oral anti-coagulation (OAC) therapy in HF is scarce. The aim of this study was to assess the impact of the presence of HF on quality of phenprocoumon-based OAC and the subsequent clinical outcome. Quality of OAC therapy and the incidence of adverse events were analysed in a cohort of regular care (n = 2,011) from the multi-centre thrombEVAL study program (NCT01809015) stratified by the presence of HF. To assess the modifiability of outc…

Estimation of Values below the Limit of Detection of a Contemporary Sensitive Troponin I Assay Improves Diagnosis of Acute Myocardial Infarction

2015

Abstract BACKGROUND The limit of detection (LoD) is the minimal amount of a substance that can be consistently detected. In the diagnosis of acute myocardial infarction (AMI) many patients present with troponin concentrations below the LoD of contemporary sensitive cardiac troponin I (cs-cTnI) assays. These censored values below the LoD influence the diagnostic performance of these assays compared to highly sensitive cTnI (hs-cTnI) assays. Therefore we assessed the impact of a new approach for interpolation of the left-censored data of a cs-cTnI assay in the evaluation of patients with suspected AMI. METHODS Our posthoc analysis used a real world cohort of 1818 patients with suspected MI. D…

Interferon-γ Induces Chronic Active Myocarditis and Cardiomyopathy in Transgenic Mice

2007

Chronic heart failure is associated with an activation of the immune system characterized among other factors by the cardiac synthesis and serum expression of proinflammatory cytokines. There is unequivocal clinical and experimental evidence that the cytokine tumor necrosis factor-alpha is involved in the development of chronic heart failure, but a putative cardiotoxic potential of the proinflammatory cytokine interferon (IFN)-gamma remains primarily unknown. To investigate this issue we analyzed the cardiac phenotype of SAP-IFN-gamma transgenic mice, which constitutively express IFN-gamma in their livers and hence exhibit high circulating serum levels of this cytokine. SAP-IFN-gamma mice s…

Advanced Protocol for Three-Dimensional Transesophageal Echocardiography Guidance Implementing Real-Time Multiplanar Reconstruction for Transcatheter…

2019

Transcatheter direct annuloplasty has been introduced as a novel interventional treatment option for severe mitral valve regurgitation. Until now, only one direct annuloplasty device (Edwards Cardioband) has been commercially available, being implanted in more than 250 patients worldwide. Yet this procedure poses greater challenges regarding optimal fluoroscopic and echocardiographic guidance compared with edge-to-edge repair: correct localization and orientation of the anchors upon penetration into the fibrous mitral annulus tissue and the basal left ventricular myocardium are preconditions for an optimal result and essential to avoid damage of the neighboring structures (atrioventricular …

Prognostic information of glycogen phosphorylase isoenzyme BB in patients with suspected acute coronary syndrome.

2012

Early and adequate risk stratification is essential in patients with suspected acute coronary syndrome (ACS). The aim of the present study was to investigate whether glycogen phosphorylase BB (GPBB) could add prognostic information in the context of contemporary sensitive troponin I determination and B-type natriuretic peptide (BNP). Patients with suspected ACS were consecutively enrolled at 3 German study centers from January 2007 through December 2008. Troponin I, GPBB, and BNP were determined at admission. Follow-up information on the combined end point of death, myocardial infarction, revascularization, and hospitalization owing to a cardiovascular cause was obtained 6 months after enro…

Response to Letter Regarding Article, “Different Calculations of Ankle Brachial Index and Their Impact on Cardiovascular Risk Prediction”

2009

We thank Jaquinandi et al for their interest in our publication. We want to stress that the patient population of the AtheroGene study is not comparable with the patient populations reported in the articles from Lee et al and Kreitner et al, which included only patients with known advanced peripheral arterial disease.1,2 The AtheroGene study includes primarily patients with coronary artery disease, no patient had rest pain or peripheral ulcers and only 52 patients (6.3%) had intermittent claudication.3 In addition, …

Heparin–polynitroxides: Synthesis and preliminary evaluation as cardiovascular EPR/MR imaging probes and extracellular space-targeted antioxidants

2011

We report here the synthesis of heparin-polynitroxide derivatives (HPNs) in which nitroxide moieties are linked either to uronic acid or glycosamine residues of the heparin macromolecule. HPNs have low anticoagulant activity, possess superoxide scavenging properties, bind to the vascular endothelium/extra-cellular matrix and can be detected by EPR and MRI techniques. As the vascular wall-targeted redox-active paramagnetic compounds, HPNs may have both diagnostic (molecular MRI) and therapeutic (ecSOD mimics) applications.

Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.

2009

Context Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. Objective To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. Design, Setting, and Participants Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nuc…

Cyclooxygenase 2-selective and nonselective nonsteroidal anti-inflammatory drugs induce oxidative stress by up-regulating vascular NADPH oxidases.

2008

Cyclooxygenase 2-selective inhibitors (coxibs) and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increase in cardiovascular events. The current study was designed to test the effect of coxibs and nonselective NSAIDs on vascular superoxide and nitric oxide (NO) production. mRNA expression of endothelial NO synthase (eNOS) and of the vascular NADPH oxidases was studied in spontaneously hypertensive rats (SHR) and in human endothelial cells. The expression of Nox1, Nox2, Nox4, and p22phox was increased markedly by the nonselective NSAIDs diclofenac or naproxen and moderately by rofecoxib or celecoxib in the aorta and heart of SHR. The up-regulation of NADPH …

Contribution of airborne desert dust to air quality and cardiopulmonary disease

2019

Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression.

2012

We aimed to assess whether pri-miRNA SNPs (miSNPs) could influence monocyte gene expression, either through marginal association or by interacting with polymorphisms located in 3'UTR regions (3utrSNPs). We then conducted a genome-wide search for marginal miSNPs effects and pairwise miSNPs × 3utrSNPs interactions in a sample of 1,467 individuals for which genome-wide monocyte expression and genotype data were available. Statistical associations that survived multiple testing correction were tested for replication in an independent sample of 758 individuals with both monocyte gene expression and genotype data. In both studies, the hsa-mir-1279 rs1463335 was found to modulate in cis the expres…

Cardiac Troponins for the Diagnosis of Acute Myocardial Infarction in Chronic Kidney Disease

2018

Background Patients with chronic kidney disease ( CKD ) are at high risk of myocardial infarction. Cardiac troponins are the biomarkers of choice for the diagnosis of acute myocardial infarction ( AMI ) without ST ‐segment elevation ( NSTE ). In patients with CKD , troponin levels are often chronically elevated, which reduces their diagnostic utility when NSTE ‐ AMI is suspected. The aim of this study was to derive a diagnostic algorithm for serial troponin measurements in patients with CKD and suspected NSTE ‐ AMI . Methods and Results Two cohorts, 1494 patients from a prospective cohort study with high‐sensitivity troponin I (hs‐ cTnI ) measurements and 7059 cases from a clinical registr…

The German CPU Registry: Dyspnea independently predicts negative short-term outcome in patients admitted to German Chest Pain Units.

2015

While dyspnea is a common symptom in patients admitted to Chest Pain Units (CPUs) little is known about the impact of dyspnea on their outcome. The purpose of this study was to evaluate the impact of dyspnea on the short-term outcome of CPU patients.We analyzed data from a total of 9169 patients admitted to one of the 38 participating CPUs in this registry between December 2008 and January 2013. Only patients who underwent coronary angiography for suspected ACS were included. 2601 patients (28.4%) presented with dyspnea.Patients with dyspnea at admission were older and frequently had a wide range of comorbidities compared to patients without dyspnea. Heart failure symptoms in particular wer…

Glucagon-like peptide-1 receptor signalling reduces microvascular thrombosis, nitro-oxidative stress and platelet activation in endotoxaemic mice

2016

Background and purpose Excessive inflammation in sepsis causes microvascular thrombosis and thrombocytopenia associated with organ dysfunction and high mortality. The present studies aimed to investigate whether inhibition of dipeptidyl peptidase-4 (DPP-4) and supplementation with glucagon-like peptide-1 (GLP-1) receptor agonists improved endotoxaemia-associated microvascular thrombosis via immunomodulatory effects. Experimental approach Endotoxaemia was induced in C57BL/6J mice by a single injection of LPS (17.5 mg kg-1 for survival and 10 mg kg-1 for all other studies). For survival studies, treatment was started 6 h after LPS injection. For all other studies, drugs were injected 48 h bef…

Effects of oral niacin on endothelial dysfunction in patients with coronary artery disease: Results of the randomized, double-blind, placebo-controll…

2009

High-density-lipoproteins-cholesterol (HDL-C) is invertedly related to the incidence of cardiovascular events. Recent studies suggest that HDL-C directly improves endothelial function. Nicotinic acid (niacin) effectively raises serum HDL-C. We therefore hypothesized that treatment with niacin improves endothelial dysfunction in patients with coronary artery disease (CAD). One hundred seven patients with CAD were randomly assigned to double-blinded treatment for 12 weeks with extended-release (ER)-niacin 1000 mg/day (N) or placebo (C), respectively. Flow-mediated dilation (FMD) of the brachial artery, nitroglycerin-mediated endothelium-independent dilation (NMD) and serum lipid concentration…

Differential effects of diabetes on the expression of the gp91phox homologues nox1 and nox4.

2004

The nox2-dependent NADPH oxidase was shown to be a major superoxide source in vascular disease, including diabetes. Smooth muscle cells of large arteries lack the phagocytic gp91phox subunit of the enzyme; however, two homologues have been identified in these cells, nox1 and nox4. It remained to be established whether also increases in protein levels of the nonphagocytic NADPH oxidase contribute to increased superoxide formation in diabetic vessels. To investigate changes in the expression of these homologues, we measured their expression in aortic vessels of type I diabetic rats. Eight weeks after streptozotocin treatment, we found a doubling in nox1 protein expression, while the expressio…

The SGLT2 inhibitor empagliflozin improves the primary diabetic complications in ZDF rats

2017

Hyperglycemia associated with inflammation and oxidative stress is a major cause of vascular dysfunction and cardiovascular disease in diabetes. Recent data reports that a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), empagliflozin (Jardiance®), ameliorates glucotoxicity via excretion of excess glucose in urine (glucosuria) and significantly improves cardiovascular mortality in type 2 diabetes mellitus (T2DM). The overarching hypothesis is that hyperglycemia and glucotoxicity are upstream of all other complications seen in diabetes. The aim of this study was to investigate effects of empagliflozin on glucotoxicity, β-cell function, inflammation, oxidative stress and endothel…

In-hospital outcomes of catheter-directed thrombolysis in patients with pulmonary embolism

2020

Abstract Background and purpose Catheter-directed treatment of acute pulmonary embolism (PE) is technically advancing. Recent guidelines acknowledge this treatment option for patients with overt or imminent haemodynamic decompensation, particularly when systemic thrombolysis is contraindicated or has failed. We investigated baseline characteristics and in-hospital outcomes of patients with PE who underwent catheter-directed thrombolysis (CDT) in the German nationwide inpatient cohort. Methods Data from hospitalizations with PE between 2005 and 2016 were collected by the Federal Office of Statistics (Statistisches Bundesamt) in Germany and included in this analysis. Patients with PE who unde…

Explaining the phenomenon of nitrate tolerance.

2005

During the last century, nitroglycerin has been the most commonly used antiischemic and antianginal agent. Unfortunately, after continuous application, its therapeutic efficacy rapidly vanishes. Neurohormonal activation of vasoconstrictor signals and intravascular volume expansion constitute early counter-regulatory responses (pseudotolerance), whereas long-term treatment induces intrinsic vascular changes, eg, a loss of nitrovasodilator-responsiveness (vascular tolerance). This is caused by increased vascular superoxide production and a supersensitivity to vasoconstrictors secondary to a tonic activation of protein kinase C. NADPH oxidase(s) and uncoupled endothelial nitric oxide synthase …

Comparative impact of multiple biomarkers and N-terminal pro-brain natriuretic peptide in the context of conventional risk factors for the prediction…

2006

Background— Individual markers of inflammation may add incremental predictive value in the context of conventionally available risk factors. We evaluated the ability of 9 inflammatory biomarkers, microalbuminuria, and N-terminal pro-brain natriuretic peptide (Nt-proBNP) to improve cardiovascular risk prediction beyond that obtained from traditional risk factors in a secondary-prevention population. Methods and Results— We measured biomarkers representing the acute-phase reaction (C-reactive protein, fibrinogen, and interleukin-6), proinflammatory pathways (soluble tumor necrosis factor receptor-1 and -2, soluble interleukin-1 receptor antagonist, and interleukin-18), endothelial activation…

TCT-419 Usefulness of a scoring system for predicting adverse cardiovascular events in patients undergoing everolimus-eluting bioresorbable scaffolds…

2016

Gene therapy with iNOS enhances regional contractility and reduces delayed contrast enhancement in a model of postischemic congestive heart failure

2012

Aims: The purpose of this study was to evaluate the effect of transient local myocardial gene transfer of iNOS on cardiac function in a large mammal animal model of heart failure induced by chronic ischemia. Methods: Chronic myocardial ischemia was induced using a minimally invasive model in 16 landrace pigs. Upon demonstration of heart failure, eight animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection; eight animals received a sham procedure to serve as control. Results: The transmurality of late enhancement (control: 46.4%, iNOS: 35.9%; p < 0.05) was significantly decreased in the ischemic area in the iNOS-treated group. Wall thickness at end-…

Temporal Trends in the Prevalence of Infective Endocarditis in Germany Between 2005 and 2014

2016

Infective endocarditis (IE) is a potentially life-threatening disease. Little is known about temporal trends in its prevalence in Germany. In 2009, recommendations for antibiotic prophylaxis were deescalated in the revised European Society of Cardiology guideline to include only patients at high risk of IE. We selected patients with the discharge diagnosis of IE based on the International Classification of Diseases code I33 in the nationwide database of the Federal Statistical Office of Germany. We identified 94,364 patients with a diagnosis of IE from January 2005 to December 2014. Mean prevalence was 11.6 per 100,000 citizens per year in this 10-year-period. The annual IE prevalence showe…

Impact of pulmonary embolism on in-hospital mortality of patients with ischemic stroke

2020

Pulmonary embolism (PE) is a frequent complication in immobile stroke patients and an important cause of death in stroke patients. We aimed to investigate predictors of PE and the impact of PE on survival of ischemic stroke patients.Patients were selected by screening the German nationwide inpatient sample (2005-2017) for ischemic stroke (ICD-code I63) and stratified for occurrence of PE (ICD-code I26). Impact of PE on mortality and predictors for PE in ischemic stroke patients were analysed.Overall, 2,914,546 patients were hospitalized due to ischemic stroke (50.5% females; 69.3% aged ≥70 years) in Germany 2005-2017. Among these, 0.4% had PE and 7.2% died during hospitalization. In-hospita…

Evaluation of the short- and long-term safety and therapy outcomes of the everolimus-eluting bioresorbable vascular scaffold system in patients with …

2015

Abstract Background Third-generation drug-eluting metal stents are the gold standard for treatment of coronary artery disease. The permanent metallic caging of the vessel, however, can result in limited vasomotion, chronic inflammation, and late expansive remodeling, conditions that can lead to late and very late stent thrombosis. The development of bioresorbable scaffolds (BRSs) promises advantages over metal stents due to complete biodegradation within 2–4 years. Theoretically, since vessel scaffolding is temporary and no permanent implant remains in the vessel, BRSs, as opposed to metal stents, once degraded would no longer be potential triggers for stent-related adverse events or side e…

Epidemiologic Analysis of Asteroid Hyalosis and Associations: The Gutenberg Health Study

2021

Thrombin generation in cardiovascular disease and mortality – results from the Gutenberg Health Study

2020

Thrombin generation may be a potential tool to improve risk stratification for cardiovascular diseases. The aim of this study was to explore the relation between thrombin generation and cardiovascular risk factors, cardiovascular diseases, and total mortality. For this study, 5,000 subjects from the population-based Gutenberg Health Study were analyzed in a highly standardized setting. Thrombin generation was assessed by the Calibrated Automated Thrombogram method at 1 and 5 pM tissue factor triggers in platelet-poor plasma. Lag time, endogenous thrombin potential, and peak height were derived from the thrombin generation curve. Sex-specific multivariable linear regression analysis adjusted…

Abstract 13257: FEV1 and FVC predict Mortality in Individuals Without Manifest Lung Disease Independent of Cardiac Performance - Results From the Pop…

2015

Background: Pulmonary disease has consistently been related to increased mortality. We investigated central spirometry variables in relation to total mortality in individuals from the general population without diagnosed lung disease also accounting for cardiac function. Methods: In 15,010 individuals from the general population (mean age 55±11 years, age range 35-74 years, 50.5% men) in the Gutenberg Health Study we performed spirometry and multimodal transthoracic echocardiography. The biomarkers N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and high-sensitive troponin I (TnI) were measured in the first 5000 individuals using commercially available assays. Multivariable Cox regre…

Is oxidative stress a therapeutic target in cardiovascular disease?

2010

An abnormal production of reactive oxygen species (ROS) and the subsequent decrease in vascular bioavailability of nitric oxide (NO) have long been proposed to be the common pathogenetic mechanism of the endothelial dysfunction, resulting from diverse cardiovascular risk factors such as hypercholesterolaemia, diabetes mellitus, chronic smoking, metabolic syndrome, and hypertension. Superoxide produced by the nicotinamide dinucleotide phosphate (NADPH) oxidase, mitochondrial sources, or the xanthine oxidase may react with NO, thereby resulting in excessive formation of peroxynitrite, a reactive nitrogen species that has been demonstrated to accelerate the atherosclerotic process by causing d…