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1.
Prog Cardiovasc Dis ; 68: 25-35, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34537204

RESUMO

BACKGROUND: The heart has the capacity to adapt to different demands. The pathophysiological mechanisms involved with sedentarism are not fundamentally the opposite of those related with physical activity and regular exercise. We investigated the impact of lower cardiorespiratory fitness (CRF) on heart's plasticity and function in a population-based setting. METHODS: We used data from 1165 participants (539 women; 46.3%) aged 21-81 years from two independent cohorts of the Study of Health in Pomerania (SHIP-2 and SHIP-TREND-0). We analyzed the cross-sectional associations of peak oxygen uptake (VO2peak), determined by symptom-limited cardiopulmonary exercise testing, with structural and functional left ventricular (LV) and left atrial (LA) parameters determined by magnetic resonance imaging (MRI) using multivariable- adjusted linear regression models. RESULTS: A 1 L/min lower VO2peak was associated with a 10.5 g (95% confidence interval: 8.00 to 12.9; p < 0.001) lower LV mass, a 14.8 mL (10.9 to 18.6; p < 0.001) lower LV end-diastolic volume, a 0.29 mm (0.19 to 0.40; p < 0.001) lower LV wall-thickness, a 8.85 mL/beat (6.53 to 11.2; p < 0.001) lower LV stroke volume, a 0.42 L/min (0.25 to 0.60; p < 0.001) lower LV cardiac output and a 7.51 mL (3.88 to 11.1; p < 0.001) lower LA end-diastolic volume. Moreover, there were no associations with a concentric or eccentric remodeling and LV and LA ejection fraction. CONCLUSIONS: Lower CRF was associated with a smaller heart, LV wall-thickness and mass, LV and LA stroke volume and cardiac output. Conversely, there was no association with LA and LV ejection fraction. Our cross-sectional observations are consistent with cardiac adaptations reflecting reduced volume loading demands of a sedentary lifestyle - "the sedentary's heart".

2.
Prog Cardiovasc Dis ; 68: 36-51, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34562438

RESUMO

BACKGROUND: The cardiac muscle has the ability to adapt to different loading conditions. We analyzed the associations of the age-related decreasing handgrip strength (HGS), a marker of muscular fitness, on cardiac structure and function in a community-based sample. METHODS: We performed cross-sectional analyses of 4646 subjects (2554 women; 55.0%) aged 20 to 93 years from two independent cohorts of the Study of Health in Pomerania (SHIP-2 and SHIP-TREND-0). We analyzed the associations of HGS with structural and functional left and right ventricular (LV and RV) and left atrial (LA) parameters as determined by echocardiography and magnetic resonance imaging (MRI) as well with log-transformed NT-proBNP values using multivariable-adjusted linear regression models. RESULTS: MRI data showed that a 1 kg lower HGS was associated with a 0.40 mL (95% confidence interval: 0.26 to 0.54; p < 0.001) lower LV end-diastolic volume, a 0.011 mm (0.005 to 0.018; p = 0.001) lower LV wall-thickness, a 0.59 g (0.43 to 0.75; p < 0.001) lower LV mass, a 0.58 mL/beat (0.43 to 0.74; p < 0.001) lower LV stroke volume, a 0.03 L/min (0.02 to 0.04; p < 0.001) lower LV cardiac output, a 0.48 mL (0.27 to 0.68; p < 0.001) lower LA end-diastolic volume, and a 1.02 mL (0.71 to 1.32) lower RV end-diastolic volume. Similar findings were observed for echocardiographic parameters. Moreover, lower HGS was associated with higher echocardiographic LV diastolic stiffness and NT-proBNP levels. CONCLUSIONS: In this large population-based sample, lower muscular fitness as assessed by HGS was associated with lower LV wall thickness and mass as well as with smaller chamber size, stroke volume and cardiac output of the LV, LA and RV. Moreover, HGS was inversely related to LV diastolic stiffness and NT-proBNP values. These outcomes might demonstrate the effects of an aging-related decrease in physical activity and lower muscular fitness on the heart - "the sedentary's heart".

3.
Cardiovasc Diabetol ; 20(1): 168, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407812

RESUMO

BACKGROUND: Compared to individuals without type 2 diabetes mellitus, the relative increase in cardiovascular mortality is much higher in women than in men in individuals with type 2 diabetes mellitus. METHODS: We evaluated data from 7443 individuals (3792 women, 50.9%), aged 20 to 81 years, from two independent population-based investigations, SHIP-0 and MONICA/KORA S3. We analyzed the longitudinal sex-specific associations of lipoprotein(a) with cardiovascular mortality in individuals with and without type 2 diabetes mellitus using Cox regression. RESULTS: During a median follow-up of 20.5 years (136,802 person-years), 657 participants (404 men and 253 women) died of cardiovascular causes. Among individuals without type 2 diabetes mellitus, men had a significantly higher risk for cardiovascular mortality compared to women in unadjusted model and after adjustment. On the other hand, in participants with type 2 diabetes mellitus, the risk for cardiovascular mortality was not different between men and women in the unadjusted model and after adjustment for age, body mass index, low-density lipoprotein-cholesterol, fasting status and study sample (SHIP-0, MONICA/KORA S3). Further adjustment for lipoprotein(a) concentrations had no impact on the hazard ratio (HR) for cardiovascular mortality comparing men versus women in individuals without type 2 diabetes mellitus [HR: 1.94; 95% confidence interval (CI) 1.63 to 2.32; p < 0.001]. In individuals with type 2 diabetes mellitus, however, further adjustment for lipoprotein(a) led to an increased risk for cardiovascular mortality in men and a decreased risk in women resulting in a statistically significant difference between men and women (HR: 1.53; 95% CI 1.04 to 2.24; p = 0.029). CONCLUSIONS: Women are described to have a stronger relative increase in cardiovascular mortality than men when comparing individuals with and without type 2 diabetes mellitus. Higher lipoprotein(a) concentrations in women with type 2 diabetes mellitus than in men with type 2 diabetes mellitus might partially explain this finding.

5.
Cardiovasc Diabetol ; 18(1): 145, 2019 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684945

RESUMO

BACKGROUND: Mortality attributable to heart failure remains high. The prevalence of heart failure in patients with diabetes mellitus ranges from 19 to 26%. It is estimated that up to 21.1 million adults in the United States have diagnosed diabetes mellitus and around 80.8 million have impaired fasting glucose. We investigated the associations of fasting glucose (FG) and fasting insulin (FI), the homeostasis model assessment-insulin resistance index (HOMA-IR) and 2-h postload glucose (2HG) and insulin (2HI) with parameters of left ventricular geometry and function and arterial stiffness determined by magnetic resonance imaging in individuals without diagnosed type 2 diabetes. METHODS: Cross-sectional analyses of 1001 individuals (453 women, 45.3%), aged 21 to 80 years, from two independent population-based studies, the Study of Health in Pomerania (SHIP-TREND-0) and KORA FF4 Study. FG, FI, HOMA-IR, 2HG and 2HI, as well as glucose tolerance categories, were analyzed for associations with heart and arterial parameters using multivariable-adjusted linear regression models. RESULTS: In total, 390 individuals (39%) had prediabetes (isolated impaired fasting glucose, isolated glucose tolerance or both), and 49 (4.9%) were found to have unknown type 2 diabetes. In the multivariable-adjusted analysis, positive linear associations of FG, FI, HOMA-IR, 2HG and 2HI with arterial stiffness index and left ventricular wall-thickness and concentricity and inverse linear associations with left ventricular end-diastolic volume were observed. A 1 mmol/l higher FG was associated with a 1.18 ml/m2.7 (1.80 to 0.57; p < 0.001) lower left ventricular end-diastolic volume index, a 0.042 mm/m2.7 (0.014 to 0.070) higher left ventricular wall-thickness index, a 0.12 mmHg m2.7/ml (0.06 to 0.17; p < 0.001) greater arterial stiffness index and a 0.037 g/ml (0.018 to 0.056; p < 0.001) higher left ventricular concentricity. CONCLUSIONS: Our findings suggest that higher glucose levels in the prediabetic range and insulin resistance might lead to higher arterial stiffness and concentric remodeling of the heart.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Insulina/sangue , Estado Pré-Diabético/sangue , Rigidez Vascular , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Remodelação Ventricular , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Resistência à Insulina , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Medição de Risco , Fatores de Risco , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/epidemiologia , Adulto Jovem
6.
J Proteomics ; 209: 103508, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31476444

RESUMO

To identify potential biomarkers supporting better phenotyping and to improve understanding of the pathophysiology of dilated cardiomyopathy (DCM), this study comparatively analyzed plasma protein profiles of DCM patients and individuals with low normal and normal left ventricular ejection fraction (LVEF) by mass spectrometry. After plasma depletion using a MARS Hu-6 column, global proteome profiling was performed using a LTQ-Orbitrap Velos mass spectrometer. To compare and confirm results, two different discovery sets of samples were investigated. Differentially abundant proteins are involved in lipid metabolism, coagulation, and acute phase response. Serum paraoxonase 1 (PON1), cystatin C, lysozyme C, apolipoprotein A-II, and apolipoprotein M were validated by targeted protein analysis in a third independent patient cohort. Additionally, PON1 levels were also determined by an ELISA. These data highlight PON1 as a potential marker for differentiating DCM patients not only from patients with normal LVEF, but also from heart failure patients with preserved ejection fraction. The results highlight lipid metabolism and inflammation as the major pathways being altered in DCM patients in comparison to patients presenting with suspicious myocarditis to the hospital. SIGNIFICANCE: Several studies focused on the identification of heart failure (HF) associated protein signatures in blood plasma, but only few that are largely based on only small sample series considered specific HF pathologies. Therefore, we performed a comparative global blood plasma protein profiling of a larger sample of individuals with reduced left ventricular ejection fraction (LVEF) classified as dilated cardiomyopathy patients and individuals with normal LVEF but presenting with suspicious myocarditis. DCM patients displayed altered levels of proteins involved in lipid metabolism, coagulation, and acute phase response. The most reliable candidates, such as serum paraoxonase 1 (PON1), cystatin C, lysozyme C, apolipoprotein A-II, and apolipoprotein M were validated by targeted protein analysis in an independent patient cohort. PON1 levels were also determined by an ELISA. These data highlight PON1 as a potential marker for differentiating DCM patients not only from patients with normal LVEF, but also from heart failure patients with preserved ejection fraction.


Assuntos
Cardiomiopatia Dilatada/metabolismo , Perfilação da Expressão Gênica , Plasma/química , Proteínas de Fase Aguda , Arildialquilfosfatase/análise , Arildialquilfosfatase/sangue , Biomarcadores/sangue , Coagulação Sanguínea , Cardiomiopatia Dilatada/sangue , Feminino , Humanos , Inflamação , Metabolismo dos Lipídeos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Proteômica/métodos , Volume Sistólico
7.
J Cell Physiol ; 234(7): 10111-10122, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30575044

RESUMO

Resident cardiac progenitor cells (CPCs) have gained attention in cardiac regenerative medicine primarily due to their paracrine activity. In our current study we determined the role of pathological conditions such as heart failure on the autocrine-paracrine action of stem cell antigen-1 (Sca-1) expressing CPC. This comparative secretome profiling of Sca-1+ cells derived from transgenic heart failure (αMHC-cyclin-T1/Gαq overexpression [Cyc] cells) versus healthy (wild-type [Wt] cells) mice, achieved via mass-spectrometric quantification, enabled the identification of over 700 proteins. Our results demonstrate that the heart failure milieu caused a 2-fold enrichment of extracellular matrix proteins (ECM) like biglycan, versican, collagen XII, and angiogenic factors like heparan sulfate proteoglycan 2, plasminogen activator inhibitor 1 in the secretome. We further elucidated the direct influence of the secretome on the functional behavior of Sca-1 + cells via in vitro tube forming assay. Secreted factors present in the diseased milieu induced tube formation in Cyc cells (1.7-fold; p < 0.01) when compared with Wt cells after 24 hr of exposure. The presence of conditioned media moderately increased the proliferation of Cyc cells but had a more pronounced effect on Wt cells. Overall, these findings revealed global modifications in the secretory activity of adult Sca-1 + cells in the heart failure milieu. The secretion of ECM proteins and angiogenic factors, which are crucial for cardiac remodeling and recovery, was notably enriched in the supernatant of Cyc cells. Thus, during heart failure the microenvironment of Sca-1 + cells might favor angiogenesis and proliferation suggesting their potential to recover the damaged heart.


Assuntos
Insuficiência Cardíaca/metabolismo , Coração , Células-Tronco/metabolismo , Animais , Proliferação de Células/fisiologia , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Neovascularização Fisiológica/fisiologia , Proteoma
8.
Circ Cardiovasc Imaging ; 10(3): e005544, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28298284

RESUMO

BACKGROUND: The different effects of total body weight (TBW), fat-free mass (FFM), and fat mass (FM) on left ventricular (LV) geometry and function are complex. We investigated the associations of changes over time in TBW, FM, and FFM with changes in LV geometry and function. METHODS AND RESULTS: We analyzed data from 1189 subjects (694 women), aged 44 to 86 years, from the baseline and the 5-year follow-up examination of the population-based SHIP (Study of Health in Pomerania). TBW was measured, and FFM and FM were calculated based on height-weight models derived from bioelectrical impedance studies. Echocardiographic measurements of LV geometry and function were performed according to the guidelines of the American Society of Echocardiography. Changes in body composition measures were associated with changes in LV geometry and function by multivariable-adjusted linear regression models. A 1-kg increase/decrease in TBW or FM was associated, respectively, with an increase/decrease of 0.89 g or 1.84 g in LV mass, whereas there was no such association on changes in FFM. Moreover, an increase in FM was associated with LV concentric remodeling and impairment of systolic and diastolic function parameters, whereas an increase in FFM was associated with LV eccentric remodeling and improved systolic and diastolic functional variables. CONCLUSIONS: Our findings indicate that changes in LV morphology and function depend on the type of body mass composition. Prospective data need to address whether specific changes in body composition over time may affect the risk for heart dysfunction more precisely than the change in TBW.


Assuntos
Adiposidade , Hipertrofia Ventricular Esquerda/fisiopatologia , Contração Miocárdica , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Remodelação Ventricular , Ganho de Peso , Perda de Peso , Adulto , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia , Feminino , Alemanha/epidemiologia , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/epidemiologia , Modelos Lineares , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/epidemiologia
9.
Atherosclerosis ; 245: 123-31, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26722832

RESUMO

BACKGROUND: Hepatic steatosis (HS) affects up to 35% of adults in the general population. Atrial fibrillation (AF) is the most prevalent sustained arrhythmia and has a substantial impact on healthcare costs. We analyzed cross-sectional associations of HS and serum liver enzyme levels with prevalent AF in a general population sample. METHODS: We analyzed data from 3090 women and men, aged 20-81 years, from the population-based Study of Health in Pomerania. HS was determined by ultrasonography. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltranspeptidase (GGT) were measured photometrically. AF was determined by automatic electrocardiographic analysis software. RESULTS: The prevalences of HS and AF were 30.3% and 1.49%, respectively. ALT, AST and GGT showed a positive linear association with the risk of prevalent AF, after multivariable adjustment. The adjusted odds ratios for AF per 1-standard deviation increment in log-transformed serum liver enzyme levels were 1.65 (95% confidence interval [CI]: 1.16 to 2.35; p = 0.006) for ALT, 1.47 (95%CI: 1.07 to 2.02; p = 0.017) for AST and 2.17 (95%CI: 1.64 to 2.87; p < 0.001) for GGT. In contrast, ultrasonographic HS was not associated with AF. CONCLUSIONS: Our findings indicate that moderately elevated serum liver enzymes, but not sonographic liver hyperechogenicity, were associated with increased AF prevalence in the general adult population. The hepatic release of increased levels of serum liver enzymes might be accompanied by higher levels of pro-inflammatory, pro-coagulant and pro-fibronogenic mediators that might lead to structural and electrical remodeling of the atrium resulting in the development and persistence of AF.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Fibrilação Atrial/epidemiologia , Fígado Gorduroso/epidemiologia , Nível de Saúde , gama-Glutamiltransferase/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/enzimologia , Estudos Transversais , Fígado Gorduroso/complicações , Fígado Gorduroso/enzimologia , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Fatores de Risco , Adulto Jovem
10.
Arterioscler Thromb Vasc Biol ; 35(5): 1265-70, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25767276

RESUMO

OBJECTIVE: In developed countries, sclerotic and calcific degeneration of the aortic valve is a common disorder showing pathophysiologic similarities with atherothrombotic coronary disease. Light to moderate alcohol consumption has been associated with a lower risk for atherothrombotic coronary disease and mortality. Whether alcohol consumption affects the development of aortic valve sclerosis (AVS) is not well known. In the present study, we aim to analyze the cross-sectional association between average daily alcohol consumption and AVS in the general population. APPROACH AND RESULTS: We analyzed cross-sectional data from 2022 men and women, aged 45 to 81 years, from the population-based Study of Health in Pomerania. We used a computer-assisted interview that included beverage-specific questions about quantity and frequency of alcohol over the last 30 days to calculate the average quantity of alcohol consumption (in grams of ethanol per day). AVS was ascertained by echocardiography. The prevalence of AVS was 32.3%. Average daily alcohol intake displayed a J-type relation with AVS (fully adjusted P value: 0.005). Compared with individuals with an average consumption of 10 g of alcohol per day, multivariable-adjusted odds ratios were 1.60 (95% confidence interval, 1.19-2.14) among current abstainers and 1.56 (95% confidence interval, 1.01-2.41) among individuals with an average consumption of 60 g per day. CONCLUSIONS: Our findings indicate that light to moderate alcohol consumption was associated with a lower odd of having AVS. Prospective data need to address whether alcohol consumption and related changes over time in several biological markers affect the progression of AVS.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/patologia , Valva Aórtica/patologia , Calcinose/epidemiologia , Calcinose/patologia , Placa Aterosclerótica/epidemiologia , Placa Aterosclerótica/patologia , Distribuição por Idade , Idoso , Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Estudos Transversais , Ecocardiografia Doppler , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Medição de Risco , Distribuição por Sexo
11.
Cell Signal ; 27(7): 1286-96, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25817266

RESUMO

Although the apelin/APJ system is abundantly expressed in vascular endothelial cells (EC), it has not yet been considered to be regulated by fluid flow. The aim of this study was to explore the influence of shear stress on the expression of apelin/APJ in human EC. Therefore, gene and protein expression were assessed after flow exposure; cell supernatants were collected for measurements of NO and apelin; APJ or apelin knockdown were performed using siRNA. Our data show that gene and protein expression of apelin and APJ are modulated by fluid flow depending on the magnitude of shear stress. Moreover, apelin-12 activated NO production via PI3K/Akt signaling in human EC. In contrast, apelin-13 additionally activated Erk1/2 phosphorylation and enhanced EC proliferation. Knockdown of APJ inhibited phosphorylation of PI3K and impaired flow-induced eNOS and PECAM-1 expression. Knockdown of apelin had no influence on flow-induced APJ and PECAM-1 expression, but derogated eNOS expression under static and flow conditions. The present study reveals a flow-mediated adjustment of the apelin/APJ system in human EC in which APJ expression is induced by shear stress independently of its ligand. Furthermore, apelin-12 signaling is an essential regulatory element in endothelial NO synthesis.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Apelina , Linhagem Celular , Ensaio de Imunoadsorção Enzimática , Células Endoteliais da Veia Umbilical Humana , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Acoplados a Proteínas G/genética , Resistência ao Cisalhamento , Transdução de Sinais/efeitos dos fármacos
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