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1.
Sci Rep ; 10(1): 9210, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32514044

RESUMO

Cerebral small vessel disease (CSVD) is a widespread condition associated to stroke, dementia and depression. To shed light on its opaque pathophysiology, we conducted a neuroimaging study aiming to assess the location of CSVD-induced damage in the human brain network. Structural connectomes of 930 subjects of the Hamburg City Health Study were reconstructed from diffusion weighted imaging. The connectome edges were partitioned into groups according to specific schemes: (1) connection to grey matter regions, (2) course and length of underlying streamlines. Peak-width of skeletonised mean diffusivity (PSMD) - a surrogate marker for CSVD - was related to each edge group's connectivity in a linear regression analysis allowing localisation of CSVD-induced effects. PSMD was associated with statistically significant decreases in connectivity of most investigated edge groups except those involved in connecting limbic, insular, temporal or cerebellar regions. Connectivity of interhemispheric and long intrahemispheric edges as well as edges connecting subcortical and frontal brain regions decreased most severely with increasing PSMD. In conclusion, MRI findings of CSVD are associated with widespread impairment of structural brain network connectivity, which supports the understanding of CSVD as a global brain disease. The pattern of regional preference might provide a link to clinical phenotypes of CSVD.

2.
Artigo em Alemão | MEDLINE | ID: mdl-32125462

RESUMO

BACKGROUND: Asthma is one of the most common chronic diseases in both children and adults. Asthma first occurring in adulthood (adult-onset asthma, AOA) is associated with poorer prognosis compared to childhood-onset asthma (COA), which urgently calls for more research in this area. The aim of this work was to analyze the data on asthma collected in the German National Cohort and compare it with the German Health Interview and Examination Survey for Adults (DEGS), in particular regarding AOA. MATERIAL AND METHODS: Our analysis was based on the dataset of the main questionnaire at mid-term of the German National Cohort baseline examination, comprising 101,723 participants. Variables considered in the analyses were self-reported diagnosis of asthma, age at first diagnosis, asthma treatment in the past 12 months, age, and sex. RESULTS: In the midterm dataset, 8.7% of women and 7.0% of men in the German National Cohort reported that they had ever been diagnosed with asthma. Approximately one third of participants with asthma received their initial diagnosis before their 18th birthday. COA affected 2.2% of women and 2.8% of men, whereas AOA affected 6.5% of women and 4.2% of men. During the previous 12 months, 33% of COA cases and 60% of AOA cases were medically treated. CONCLUSION: The proportion of persons affected by asthma in the German National Cohort, as well as observed patterns regarding age and gender, corresponds to other data sources such as DEGS. However, in our analysis, the proportion of individuals with AOA was higher than described in the literature. The increase in cumulative asthma diagnoses with age is markedly steeper in younger participants, indicating a rising trend over time.


Assuntos
Asma/diagnóstico , Adulto , Fatores Etários , Idade de Início , Asma/epidemiologia , Criança , Doença Crônica , Estudos de Coortes , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Inquéritos e Questionários
3.
Artigo em Alemão | MEDLINE | ID: mdl-32157352

RESUMO

BACKGROUND: Data on self-reported cardiovascular and metabolic diseases are available for the first 100,000 participants of the population-based German National Cohort (GNC, NAKO Gesundheitsstudie). OBJECTIVES: To describe assessment methods and the frequency of self-reported cardiovascular and metabolic diseases in the German National Cohort. MATERIALS AND METHODS: Using a computer-based, standardized personal interview, 101,806 participants (20-75 years, 46% men) from 18 nationwide study centres were asked to use a predefined list to report medical conditions ever diagnosed by a physician, including cardiovascular or metabolic diseases. For the latter, we calculated sex-stratified relative frequencies and compared these with reference data. RESULTS: With regard to cardiovascular diseases, 3.5% of men and 0.8% of women reported to have ever been diagnosed with a myocardial infarction, 4.8% and 1.5% with angina pectoris, 3.5% and 2.5% with heart failure, 10.1% and 10.4% with cardiac arrhythmia, 2.7% and 1.8% with claudicatio intermittens, and 34.6% and 27.0% with arterial hypertension. The frequencies of self-reported diagnosed metabolic diseases were 8.1% and 5.8% for diabetes mellitus, 28.6% and 24.5% for hyperlipidaemia, 7.9% and 2.4% for gout, and 10.1% and 34.3% for thyroid diseases. Observed disease frequencies were lower than reference data for Germany. CONCLUSIONS: In the German National Cohort, self-reported cardiovascular and metabolic diseases diagnosed by a physician are assessed from all participants, therefore representing a data source for future cardio-metabolic research in this cohort.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Metabólicas/epidemiologia , Estudos de Coortes , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Autorrelato , Inquéritos e Questionários
4.
Artigo em Alemão | MEDLINE | ID: mdl-32170398
5.
Artigo em Alemão | MEDLINE | ID: mdl-32185449

RESUMO

BACKGROUND: Infectious diseases continue to play an important role for disease perception, health-economic considerations and public health in Germany. In recent years, infectious diseases have been linked to the development of non-communicable diseases. Analyses of the German National Cohort (GNC) may provide deeper insights into this issue and pave the way for new targeted approaches in disease prevention. OBJECTIVES: The aim was to describe the tools used to assess infectious diseases and to present initial data on infectious disease frequencies, as well as to relate the GNC assessment tools to data collection methods in other studies in Germany. METHODS: As part of the baseline examination, questions regarding infectious diseases were administered using both an interview and a self-administered touchscreen questionnaire. Data from the initial 101,787 GNC participants were analysed. RESULTS: In the interview, 0.2% (HIV/AIDS) to 8.6% (shingles) of respondents reported ever having a medical diagnosis of shingles, postherpetic neuralgia (in cases where shingles was reported), hepatitis B/C, HIV/AIDS, tuberculosis or sepsis if treated in hospital. In the questionnaire, 12% (cystitis) to 81% (upper respiratory tract infections) of respondents reported having experienced at least one occurrence of upper or lower respiratory tract infections, gastrointestinal infections, cystitis or fever within the past 12 months. OUTLOOK: The cross-sectional analyses of data and tools presented here - for example on determinants of susceptibility to self-reported infections - can be anticipated from the year 2021 onward. Beyond that, more extensive research into infectious disease epidemiology will follow, particularly once analyses of GNC biological materials have been performed.


Assuntos
Doenças Transmissíveis/epidemiologia , Estudos de Coortes , Estudos Transversais , Alemanha/epidemiologia , Humanos , Autorrelato , Inquéritos e Questionários
6.
Artigo em Alemão | MEDLINE | ID: mdl-32072217

RESUMO

Physical fitness is defined as an individual's ability to be physically active. The main components are cardiorespiratory fitness (CRF), muscle strength, and flexibility. Regardless of physical activity level, physical fitness is an important determinant of morbidity and mortality.The aim of the current study was to describe the physical fitness assessment methodology in the German National Cohort (NAKO) and to present initial descriptive results in a subsample of the cohort.In the NAKO, hand grip strength (GS) and CRF as physical fitness components were assessed at baseline using a hand dynamometer and a submaximal bicycle ergometer test, respectively. Maximum oxygen uptake (VO2max) was estimated as a result of the bicycle ergometer test. The results of a total of 99,068 GS measurements and 3094 CRF measurements are based on a data set at halftime of the NAKO baseline survey (age 20-73 years, 47% men).Males showed higher values of physical fitness compared to women (males: GS = 47.8 kg, VO2max = 36.4 ml·min-1 · kg-1; females: GS = 29.9 kg, VO2max = 32.3 ml · min-1 · kg-1). GS declined from the age of 50 onwards, whereas VO2max levels decreased continuously between the age groups of 20-29 and ≥60 years. GS and VO2max showed a linear positive association after adjustment for body weight (males ß = 0.21; females ß = 0.35).These results indicate that the physical fitness measured in the NAKO are comparable to other population-based studies. Future analyses in this study will focus on examining the independent relations of GS and CRF with risk of morbidity and mortality.


Assuntos
Teste de Esforço , Aptidão Física , Adulto , Feminino , Alemanha , Força da Mão , Humanos , Masculino , Oxigênio , Consumo de Oxigênio , Adulto Jovem
7.
Artigo em Alemão | MEDLINE | ID: mdl-32078705

RESUMO

BACKGROUND: A nationwide assessment of the respiratory status on the basis of standardized lung function measurements has so far not been available in Germany. The present work describes the lung function tests in the German National Cohort (GNC) and presents initial results based on the GNC Midterm Baseline Dataset. MATERIAL AND METHODS: The assessment of lung function in the GNC comprised spirometry (level 1) and the determination of exhaled nitric oxide (FeNO, level 2). Our quality assurance concept included regular training of lung function test procedures at various GNC sites, interim evaluations of test quality, as well as regular calibration/measurement checks of test equipment. For spirometry, we established a stepwise procedure for offline quality control based on raw flow volume curves. RESULTS: In the present dataset (n = 101,734), spirometry was available for 86,893 study participants and FeNO was available for 15,228 participants. The average (±SD) FEV1 Z score (according to GLI 2012) was -0.321 ± 1.047, the FVC Z score was -0.153 ± 0.941, and the FEV1/FVC Z score was -0.337 ± 0.901. The difference in FEV1/FVC between current smokers and never-smokers increased with age. The average FeNO was 14.2 ÷ 2.0 ppb. Current smoking reduced FeNO levels by 43%, whereas respiratory allergy increased FeNO levels by 16% in nonsmokers. DISCUSSION: The results of spirometry and the FeNO measurements are in the expected range with regard to their distributions and correlates. The GNC provides a valuable basis for future investigations of respiratory health and its determinants as well as research into the prevention of respiratory diseases in Germany.


Assuntos
Testes Respiratórios , Asma , Expiração , Alemanha , Humanos , Espirometria
8.
Artigo em Alemão | MEDLINE | ID: mdl-32047976

RESUMO

BACKGROUND: The German National Cohort (NAKO) is an interdisciplinary health study aimed at elucidating causes for common chronic diseases and detecting their preclinical stages. This article provides an overview of design, methods, participation in the examinations, and their quality assurance based on the midterm baseline dataset (MBD) of the recruitment. METHODS: More than 200,000 women and men aged 20-69 years derived from random samples of the German general population were recruited in 18 study centers (2014-2019). The data collection comprised physical examinations, standardized interviews and questionnaires, and the collection of biomedical samples for all participants (level 1). At least 20% of all participants received additional in-depth examinations (level 2), and 30,000 received whole-body magnet resonance imaging (MRI). Additional information will be collected through secondary data sources such as medical registries, health insurances, and pension funds. This overview is based on the MBD, which included 101,839 participants, of whom 11,371 received an MRI. RESULTS: The mean response proportion was 18%. The participation in the examinations was high with most of the modules performed by over 95%. Among MRI participants, 96% completed all 12 MRI sequences. More than 90% of the participants agreed to the use of complementary secondary and registry data. DISCUSSION: Individuals selected for the NAKO were willing to participate in all examinations despite the time-consuming program. The NAKO provides a central resource for population-based epidemiologic research and will contribute to developing innovative strategies for prevention, screening and prediction of chronic diseases.


Assuntos
Nível de Saúde , Inquéritos e Questionários , Adulto , Idoso , Doença Crônica , Estudos de Coortes , Estudos Epidemiológicos , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Adulto Jovem
9.
Eur J Epidemiol ; 35(2): 169-181, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31705407

RESUMO

The Hamburg City Health Study (HCHS) is a large, prospective, long-term, population-based cohort study and a unique research platform and network to obtain substantial knowledge about several important risk and prognostic factors in major chronic diseases. A random sample of 45,000 participants between 45 and 74 years of age from the general population of Hamburg, Germany, are taking part in an extensive baseline assessment at one dedicated study center. Participants undergo 13 validated and 5 novel examinations primarily targeting major organ system function and structures including extensive imaging examinations. The protocol includes validate self-reports via questionnaires regarding lifestyle and environmental conditions, dietary habits, physical condition and activity, sexual dysfunction, professional life, psychosocial context and burden, quality of life, digital media use, occupational, medical and family history as well as healthcare utilization. The assessment is completed by genomic and proteomic characterization. Beyond the identification of classical risk factors for major chronic diseases and survivorship, the core intention is to gather valid prevalence and incidence, and to develop complex models predicting health outcomes based on a multitude of examination data, imaging, biomarker, psychosocial and behavioral assessments. Participants at risk for coronary artery disease, atrial fibrillation, heart failure, stroke and dementia are invited for a visit to conduct an additional MRI examination of either heart or brain. Endpoint assessment of the overall sample will be completed through repeated follow-up examinations and surveys as well as related individual routine data from involved health and pension insurances. The study is targeting the complex relationship between biologic and psychosocial risk and resilience factors, chronic disease, health care use, survivorship and health as well as favorable and bad prognosis within a unique, large-scale long-term assessment with the perspective of further examinations after 6 years in a representative European metropolitan population.


Assuntos
Doença Crônica/epidemiologia , Idoso , Fibrilação Atrial , Estudos de Coortes , Doença da Artéria Coronariana , Feminino , Alemanha/epidemiologia , Insuficiência Cardíaca , Humanos , Incidência , Estilo de Vida , Imagem por Ressonância Magnética , Masculino , Transtornos Mentais , Pessoa de Meia-Idade , Neoplasias , Saúde Bucal , Vigilância da População , Prevalência , Estudos Prospectivos , Proteômica , Qualidade de Vida , Projetos de Pesquisa , Fatores de Risco , Acidente Vascular Cerebral , Inquéritos e Questionários
10.
J Cardiovasc Magn Reson ; 20(1): 68, 2018 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-30244673

RESUMO

BACKGROUND: The purpose of this work is to describe the objectives and design of cardiovascular magnetic resonance (CMR) imaging in the single center, prospective, population-based Hamburg City Health study (HCHS). The HCHS aims at improving risk stratification for coronary artery disease (CAD), atrial fibrillation (AF) and heart failure (HF). METHODS: The HCHS will finally include 45,000 inhabitants of the city of Hamburg (Germany) between 45 and 74 years who undergo an extensive cardiovascular evaluation and collection of biomaterials. Risk-scores for CAD, AF and HF are used to create enriched subpopulations who are invited for CMR. A total number of approximately 12,362 subjects will undergo CMR and incident CAD, AF and HF will be assessed after 6 years follow-up. The standard CMR protocol includes cine-CMR, T1 and T2 mapping, aortic/mitral valve flow measurements, Late gadolinium enhancement, angiographies and measurements of aortic distensibility. A stress-perfusion scan is added in individuals at risk for CAD. The workflow of CMR data acquisition and analyses was evaluated in a pilot cohort of 200 unselected subjects. RESULTS: The obtained CMR findings in the pilot cohort agree with current reference values and demonstrate the ability of the established workflow to accomplish the objectives of HCHS. CONCLUSIONS: CMR in HCHS promises novel insights into major cardiovascular diseases, their subclinical precursors and the prognostic value of novel imaging biomarkers. The HCHS database will facilitate combined analyses of imaging, clinical and molecular data ("Radiomics").


Assuntos
Fibrilação Atrial/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Insuficiência Cardíaca/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Projetos de Pesquisa , Idoso , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/fisiopatologia , Meios de Contraste/administração & dosagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/fisiopatologia , Feminino , Seguimentos , Alemanha/epidemiologia , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Masculino , Meglumina/administração & dosagem , Pessoa de Meia-Idade , Compostos Organometálicos/administração & dosagem , Projetos Piloto , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Tempo , Fluxo de Trabalho
11.
Biomolecules ; 8(3)2018 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-30029528

RESUMO

Bicuspid aortic valve (BAV) disease is the most common congenital malformation of the human heart with a prevalence of 1⁻2% in the general population. More than half of patients with a BAV present with a dilated proximal aorta (so-called bicuspid aortopathy) which is associated with an enhanced risk of life-threatening aortic complications. Up to now, the pathogenesis of bicuspid aortopathy as well as the risk stratification of aortic complications has not yet been sufficiently clarified. Recent findings have shown that bicuspid aortopathy features phenotypic heterogeneity. Two distinct valvulo-aortic phenotypes, the so-called root phenotype, as well as a dilation of the tubular ascending aorta, coincide with a significantly different risk for aortal complications. However, the phenotype-based classification that is only based on these two clinical forms is not sufficient to estimate the risk of aortal complications in a prognostically relevant way. Therefore, there is growing clinical interest to assess novel approaches in BAV research and to introduce circulating biomarkers as an elegant diagnostic tool to improve risk stratification in BAV aortopathy. A large scale epidemiological cohort study, ranking from apparently healthy individuals to disease patients, and comprehensive biobanks provide the opportunity to study BAV disease and its complications and to identify novel biomarkers for BAV aortopathy surveillance and prognosis. Firstly, the data indicate that several protein-based biomarkers and non-coding RNA molecules, in particular circulating microRNAs, can serve as relevant molecular biomarkers to predict the course of BAV-associated aortopathy. Here, we review the current literature and knowledge about BAV from a clinical point of view, and report about novel approaches in BAV biomarker research.


Assuntos
Doenças da Aorta/diagnóstico , Valva Aórtica/anormalidades , Biomarcadores/sangue , Doenças das Valvas Cardíacas/patologia , MicroRNAs/sangue , Doenças da Aorta/genética , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Valva Aórtica/patologia , Diagnóstico Precoce , Humanos , Fenótipo , Vigilância da População , Prognóstico
12.
Thorac Cardiovasc Surg ; 66(4): 278-286, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-27148933

RESUMO

Traditional risk stratification model of bicuspid aortic valve (BAV) aortopathy is based on measurement of maximal cross-sectional aortic diameter, definition of proximal aortic shape, and aortic stiffness/elasticity parameters. However, conventional imaging-based criteria are unable to provide reliable information regarding the risk stratification in BAV aortopathy, especially considering the heterogeneous nature of BAV disease. Given those limitations of conventional imaging, there is a growing clinical interest to use circulating biomarkers in the screening process for thoracic aortic aneurysms as well as in the risk-assessment algorithms. We aimed to systematically review currently available biomarkers, which may be of value to predict the natural evolution of aortopathy in individuals with BAV.


Assuntos
Aorta/metabolismo , Aneurisma Aórtico/sangue , Valva Aórtica/anormalidades , Biomarcadores/sangue , Doenças das Valvas Cardíacas/complicações , Aorta/diagnóstico por imagem , Aorta/cirurgia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/etiologia , Aneurisma Aórtico/cirurgia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Implante de Prótese Vascular , Tomada de Decisão Clínica , Dilatação Patológica , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca , Humanos , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco
13.
Clin Chem ; 63(12): 1877-1885, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28904053

RESUMO

BACKGROUND: High blood pressure (BP) is associated with an increased rate of cardiovascular events and mortality. Cardiovascular biomarkers are able to predict long-term risk in the general population, particularly in diseased cohorts. We undertook an investigation of the effect of 2 different antihypertensive treatments on cardiovascular biomarkers in a randomized trial. METHODS: The TEAMSTA study included 481 hypertensive patients. They were randomized to either 80-mg telmisartan + 5-mg amlodipine (TA) or 40-mg olmesartan + 12.5-mg hydrochlorothiazide (OH). The trial was performed as a prospective, randomized, double-blinded, controlled, single-center study. We measured BP, high-sensitivity cardiac troponin I (hs-cTnI), high-sensitivity cardiac troponin T (hs-cTnT), B-type natriuretic peptide (BNP), and N-terminal-pro-BNP (NT-proBNP) before randomization and after 6 months. RESULTS: Individuals were randomized into 2 groups: 230 individuals to the OH-group and 251 to the TA-group. After 6 months of treatment, a reduction in BP (systolic/diastolic) was seen, from 135.2/85.2 mmHg to 122.5/75.7 mmHg with similar effects in both groups. hs-cTnT concentrations were measureable in 26.2% of the study population, while hs-cTnI was detected in 98.3%. hs-cTnI concentrations were significantly reduced from 4.6 to 4.2 ng/L in the overall population, from 4.7 to 4.4 ng/L in the OH-group, and from 4.6 to 4.0 ng/L in the TA-group (all P < 0.001). No significant changes of hs-cTnT were observed. BNP and NT-proBNP concentrations decreased from 15.0 to 12.4 ng/L (P < 0.001) and from 64.8 to 53.3 ng/L (P < 0.001), respectively, after 6 months. CONCLUSIONS: The reduction in BP was associated with a decrease of high-sensitivity troponin I, BNP, and NT-proBNP concentrations, which might represent a cardiovascular risk reduction. CLINICAL TRIAL REGISTRATION: EudraCT 2009-017010-68.


Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Benzimidazóis/uso terapêutico , Benzoatos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Imidazóis/uso terapêutico , Tetrazóis/uso terapêutico , Idoso , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Telmisartan , Resultado do Tratamento , Troponina I/sangue , Troponina T/sangue
14.
Hypertension ; 70(4): 743-750, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28784648

RESUMO

Hypertension represents a major cardiovascular risk factor. The pathophysiology of increased blood pressure (BP) is not yet completely understood. Transcriptome profiling offers possibilities to uncover genetics effects on BP. Based on 2 populations including 2549 individuals, a meta-analyses of monocytic transcriptome-wide profiles were performed to identify transcripts associated with BP. Replication was performed in 2 independent studies of whole-blood transcriptome data including 1990 individuals. For identified candidate genes, a direct link between long-term changes in BP and gene expression over time and by treatment with BP-lowering therapy was assessed. The predictive value of protein levels encoded by candidate genes for subsequent cardiovascular disease was investigated. Eight transcripts (CRIP1, MYADM, TIPARP, TSC22D3, CEBPA, F12, LMNA, and TPPP3) were identified jointly accounting for up to 13% (95% confidence interval, 8.7-16.2) of BP variability. Changes in CRIP1, MYADM, TIPARP, LMNA, TSC22D3, CEBPA, and TPPP3 expression associated with BP changes-among these, CRIP1 gene expression was additionally correlated to measures of cardiac hypertrophy. Assessment of circulating CRIP1 (cystein-rich protein 1) levels as biomarkers showed a strong association with increased risk for incident stroke (hazard ratio, 1.06; 95% confidence interval, 1.03-1.09; P=5.0×10-5). Our comprehensive analysis of global gene expression highlights 8 novel transcripts significantly associated with BP, providing a link between gene expression and BP. Translational approaches further established evidence for the potential use of CRIP1 as emerging disease-related biomarker.


Assuntos
Proteínas de Transporte/genética , Hipertensão , Proteínas com Domínio LIM/genética , Acidente Vascular Cerebral , Adulto , Pressão Sanguínea/genética , Determinação da Pressão Arterial/métodos , Determinação da Pressão Arterial/estatística & dados numéricos , Proteínas Estimuladoras de Ligação a CCAAT/genética , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/diagnóstico , Hipertensão/genética , Masculino , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina/genética , Poli(ADP-Ribose) Polimerases/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Fatores de Transcrição/genética
15.
Echocardiography ; 34(6): 919-927, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28317170

RESUMO

Right heart dysfunction has been found to be a strong prognostic factor predicting adverse outcome in various cardiopulmonary diseases. Conventional echocardiographic measurements can be limited by geometrical assumptions and impaired reproducibility. Speckle tracking-derived strain provides a robust quantification of right ventricular function. It explicitly evaluates myocardial deformation, as opposed to tissue Doppler-derived strain, which is computed from tissue velocity gradients. Right ventricular longitudinal strain provides a sensitive tool for detecting right ventricular dysfunction, even at subclinical levels. Moreover, the longitudinal strain can be applied for prognostic stratification of patients with pulmonary hypertension, pulmonary embolism, and congestive heart failure. Speckle tracking-derived right atrial strain, right ventricular longitudinal strain-derived mechanical dyssynchrony, and three-dimensional echocardiography-derived strain are emerging imaging parameters and methods. Their application in research is paving the way for their clinical use.


Assuntos
Ecocardiografia/métodos , Disfunção Ventricular Direita/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Reprodutibilidade dos Testes , Disfunção Ventricular Direita/fisiopatologia
16.
Br J Clin Pharmacol ; 82(6): 1477-1485, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27434056

RESUMO

AIMS: Low blood concentrations of the naturally occurring amino acid L-homoarginine (L-hArg) are related to impaired cardiovascular outcome and mortality in humans and animals. L-hArg is a weak substrate of nitric oxide synthase and an inhibitor of arginases in vitro. The aim of our study was to obtain kinetic and dynamic data after oral L-hArg supplementation. METHODS: In a double-blind, randomized, placebo-controlled crossover study, 20 young volunteers received 125 mg L-hArg once daily for 4 weeks. Kinetic parameters (Cmax , Tmax and AUC0-24h ) were calculated after ingestion of single and multiple doses of oral supplementation as primary endpoint. Secondary endpoints that were evaluated were routine laboratory, L-arginine, asymmetric dimethylarginine (ADMA), pulse wave velocity (PWV), augmentation index (AIx), flow-mediated vasodilatation (FMD), corticospinal excitability, i.e. motor threshold (MT), and cortical excitability, i.e. intracortical inhibition (ICI) and facilitation (ICF). RESULTS: One hour after ingestion (Tmax ), L-hArg increased the baseline L-hArg plasma concentration (2.87 ± 0.91 µmol l-1 , mean ± SD) by 8.74 ± 4.46 [95% confidence intervals 6.65; 10.9] and 17.3 ± 4.97 [14.9; 19.6] µmol l-1 (Cmax ), after single and multiple doses, respectively. Once-only and 4 weeks of supplementation resulted in AUCs0-24h of 63.5 ± 28.8 [50.0; 76.9] and 225 ± 78.5 [188; 2624] µmol l-1 *h, for single and multiple doses, respectively. Routine laboratory parameters, L-arginine, ADMA, PWV, AIx, FMD, MT, ICI and ICF did not change by L-hArg supplementation compared to baseline. CONCLUSION: Once daily orally applied 125 mg L-hArg raises plasma L-hArg four- and sevenfold after single dose and 4 weeks of supplementation, respectively, and is safe and well tolerated in young volunteers.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Homoarginina/sangue , Administração Oral , Adulto , Área Sob a Curva , Estudos Cross-Over , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Voluntários Saudáveis , Homoarginina/administração & dosagem , Homoarginina/efeitos adversos , Humanos , Masculino , Adulto Jovem
17.
Int J Cardiol ; 192: 33-9, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-25985013

RESUMO

OBJECTIVES: Galectin-3 is an emerging biomarker playing an important, complex role in intracellular pathways of cardiovascular diseases and heart failure. We aimed therefore to investigate the predictive value of galectin-3 for incident cardiovascular disease and heart failure. METHODS: Galectin-3 levels were measured in 8444 participants of the general population-based FINRISK 1997 cohort. Cox proportional hazards regression analyses, adjusting for traditional Framingham risk factors, prevalent valvular heart disease, eGFR (estimated glomerular filtration rate) as well as NT-proBNP, were used to examine the predictive power of galectin-3. Measurements of discrimination and reclassification using 10-fold cross-validation were performed to control for over-optimism. Cardiovascular death (CD), all-cause mortality, myocardial infarction (MI), ischemic stroke (hemorrhagic strokes were excluded) and heart failure (HF) were used as endpoints. RESULTS: During the follow-up of up to 15 years there were in total 1136 deaths from any cause, 383 cardiac deaths, 359 myocardial infarctions, 401 ischemic strokes and 641 cases of incident heart failure. Hazard ratios (HR) were statistically significant for all-cause mortality (1.12, p < 0.001), cardiac death (1.15, p = 0.033) and heart failure (1.10, p = 0.049). Statistical significance was lost when analyzing by gender except for all-cause mortality. No significant improvements were observed in model discrimination or overall reclassification upon inclusion of galectin-3. Compared to NT-proBNP, the predictive power of galectin-3 was weaker but both remained significant, independently of each other. CONCLUSION: Galectin-3 levels were predictive for future cardiovascular events but improvements in discrimination and reclassifications were modest.


Assuntos
Doenças Cardiovasculares/diagnóstico , Galectina 3/sangue , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sistema de Registros
18.
Heart ; 100(21): 1715-21, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25080471

RESUMO

OBJECTIVES: We hypothesised that soluble ST2 (sST2) levels can identify people with elevated risk of subsequent cardiovascular disease (CVD) and add to existing risk prediction algorithms. BACKGROUND: ST2 is a receptor for the inflammatory cytokine IL33. Increased sST2 levels have been associated with heart failure and death in acute myocardial infarction patients and in the general population. METHODS: We measured high-sensitivity sST2 in 8444 men and women (25-74 years) from the FINRISK97 prospective population cohort. Cox proportional hazards modelling evaluated the ability of sST2 to predict fatal and non-fatal heart failure, CVD (coronary heart disease, stroke), diabetes, and death over 15 years follow-up. Discrimination and reclassification statistics for 10-year absolute risks compared the ability of sST2 to improve upon Framingham risk factors (FRF), N-terminal pro-brain natriuretic peptide (NT-proBNP), renal function (eGFR) and prevalent valvular heart disease (VHD). RESULTS: sST2 showed suggestive but non-significant associations with heart failure {(HR per 1 SD of log sST2 1.06; 95% CI 0.96 to 1.17 (562 events))}, and with CVD (1.01 95% CI 0.94 to 1.08) (914 events) after adjustment for FRF, NT-proBNP, eGFR and VHD. sST2 significantly predicted death from all causes following similar adjustment ({HR 1.09 (95% CI 1.01 to 1.19) (974 events))}. No improvement in the c-index was observed for models adding sST2 to the risk factors. CONCLUSIONS: In a healthy general population from Finland, sST2 did not improve long-term prediction of cardiovascular events including heart failure or all-cause mortality.


Assuntos
Doenças Cardiovasculares/mortalidade , Previsões , Vigilância da População/métodos , Receptores de Superfície Celular/sangue , Medição de Risco , Adulto , Distribuição por Idade , Idoso , Doenças Cardiovasculares/sangue , Feminino , Finlândia , Seguimentos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/epidemiologia , Humanos , Incidência , Proteína 1 Semelhante a Receptor de Interleucina-1 , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Precursores de Proteínas , Fatores de Risco , Distribuição por Sexo , Taxa de Sobrevida/tendências
19.
Atherosclerosis ; 228(2): 451-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23562132

RESUMO

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. Individuals were enrolled between April 2007 and October 2008. Subclinical cardiovascular disease was assessed using echocardiographic and functional measures of myocardial and vascular function. The mean age of the study population was 55.5 ± 10.9 years. In the overall population we determined a median MR-proADM plasma concentration of 0.44 nmol/L in men and women. MR-proADM concentrations were elevated in individuals with hypertension, diabetes, dyslipidemia, known cardiovascular disease, heart failure, peripheral artery disease, atrial fibrillation, and history of myocardial infarction and stroke. In men, we observed a positive association of MR-proADM with reduced ejection fraction, intraventricular septal diameter, wall thickness, and echocardiographic measures of diastolic dysfunction. CONCLUSIONS: In this study, we present age-dependent reference values for MR-proADM in a representative population sample. Elevated MR-proADM plasma concentrations were strongly associated with classical cardiovascular risk factors and manifest cardiovascular diseases. Furthermore, we revealed a gender-specific association with echocardiographic measures of hypertension. MR-proADM seems to be a promising prognostic biomarker for subclinical and manifest cardiovascular disease.


Assuntos
Adrenomedulina/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Fragmentos de Peptídeos/sangue , Precursores de Proteínas/sangue , Adulto , Fatores Etários , Idoso , Doenças Assintomáticas , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Ecocardiografia , Feminino , Fluorimunoensaio , Alemanha/epidemiologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Regulação para Cima
20.
Clin Res Cardiol ; 102(7): 495-503, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23519584

RESUMO

BACKGROUND: Severity of coronary artery disease (CAD) is related to cardiovascular outcome. We aimed to assess the long-term follow-up depending on Synergy between percutaneous coronary intervention with Taxus and cardiac surgery (SYNTAX) and Gensini score for prognosis. Both scores increase with complexity and thus reflect risk of cardiovascular events. METHODS AND RESULTS: We determined complexity and extent of CAD by the SYNTAX and Gensini score in the AtheroGene cohort (N = 1,974, with 22.6 % women). The endpoint was non-fatal myocardial infarction (N = 132) and cardiovascular death (N = 159) over a median follow-up of 5.4 (Q1: 5.23/Q3: 5.57) years up to 8 years maximum (follow-up rate 99.4%). For SYNTAX score, the following distribution was used: low (≤22, N = 1,404), medium (23-32, N = 314), high score (>32, N = 256). Gensini score was split into thirds. Cox regression analysis showed a hazard ratio (HR) of 1.5 (95% confidence interval 1.16-1.95; p = 0.0024) for the log transformed SYNTAX score in a fully adjusted model and a HR of 1.41 (95% CI 1.13-1.77; p = 0.0025) for the Gensini score. The SYNTAX score alone had a C-index of 0.62, whereas adding clinical variables increased the C-index to 0.67. Similar results were obtained for the Gensini score. Regarding the SYNTAX score using net reclassification index, discrimination of events and non-events was enhanced by 37.2% in a model of clinical variables and biomarkers and by 31.8% for the Gensini score. CONCLUSION: The SYNTAX and Gensini score in combination with clinical variables could be used to predict the cardiovascular prognosis during a long-term follow-up of up to 8 years in CAD patients.


Assuntos
Angiografia Coronária/métodos , Doença da Artéria Coronariana/fisiopatologia , Intervenção Coronária Percutânea/métodos , Idoso , Estudos de Coortes , Doença da Artéria Coronariana/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Prognóstico , Modelos de Riscos Proporcionais , Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo
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