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1.
Am J Hypertens ; 27(10): 1301-7, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24610897

RESUMO

BACKGROUND: Low-grade chronic inflammation is a characteristic feature of obesity, the most important lifestyle risk factor for hypertension. Elevated plasma concentrations of the inflammatory biomarker C-reactive protein (CRP) are associated with an increased risk of hypertension, but elevated plasma CRP concentrations are also closely associated with obesity. It is uncertain whether CRP is directly involved in the pathogenesis of hypertension or is only a marker of other pathogenic processes closely related to obesity. METHODS: We studied 103 obese men (body mass index (BMI) ≥ 30.0 kg/m(2)); 63 of these men had 24-hour ambulatory blood pressure (ABP) ≥ 130/80 mm Hg and comprised the obese hypertensive (OHT) group. The 40 remaining obese men had 24-hour ABP < 130/80 mm Hg and comprised the obese normotensive (ONT) group. Our control group comprised 27 lean normotensive (LNT) men. All participants were medication-free. We measured plasma CRP concentrations with a high-sensitivity assay and determined body composition by dual energy x-ray absorptiometry scanning. RESULTS: There were no differences in anthropometric measures (BMI, waist circumference, or total fat mass percentage) between OHT and ONT groups (P ≥ 0.08). The obese groups had higher CRP concentrations than the LNT group (OHT: median = 2.30, interquartile range (IQR) = 1.10-4.10mg/L; ONT: median = 2.55, IQR = 1.25-4.80 mg/L; LNT: median = 0.60, IQR = 0.30-1.00 mg/L; P < 0.001), but there was no difference in CRP concentrations between OHT and ONT groups (P = 1.00). In the obese men, CRP was not correlated with either 24-hour systolic (r = 0.04; P = 0.71) or 24-hour diastolic ABP (r = -0.03; P = 0.78). CONCLUSIONS: Obese hypertensive men, matched for anthropometric measurements, have plasma CRP concentrations similar to those of obese normotensive men.


Assuntos
Proteína C-Reativa/metabolismo , Hipertensão/metabolismo , Obesidade/metabolismo , Adulto , Estudos de Casos e Controles , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Obesidade/complicações
2.
Am J Hypertens ; 27(4): 620-7, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24025723

RESUMO

BACKGROUND: Several studies have shown that obese persons have lower circulating natriuretic peptide (NP) concentrations. The cause of the relative NP deficiency seen in obese persons is poorly understood, although variation in body composition and metabolic abnormalities has been suggested to play a role. Thus, the aim of this study was to assess whether variation in circulating NP concentrations would be associated with differences in metabolic disturbances rather than with differences in body composition. METHODS: In 27 normal weight men (body mass index (BMI) = 20.0-24.9kg/m(2)) and 103 obese men (BMI ≥ 30kg/m(2)), we determined body composition (total, android, and gynoid fat mass) by dual energy x-ray absorptiometry scanning, and we measured fasting serum concentrations of midregional proatrial NP (MR-proANP) and insulin, as well as fasting plasma glucose concentrations. RESULTS: Mean weight ± SD was 74.9±6.7kg in the normal weight men and 106.1±10.8kg in obese men. Applying multiple regressions, adjusting for age and weight status (normal weight vs. obese), serum MR-proANP concentrations were significantly inversely associated with serum insulin concentrations (ß = -0.39; P < 0.0001) and plasma glucose concentrations (ß = -0.21; P = 0.02) but not with total (ß = 0.00), android (ß = -0.01), or gynoid (ß = 0.03) fat mass percentage (P > 0.76). No significant interaction effects between metabolic measurements or body composition measurements and weight status on MR-proANP concentrations were found (P > 0.08). CONCLUSIONS: In normal weight and obese men, lower circulating NP concentrations are associated with higher insulin and glucose concentrations and not with the proportion of total fat mass or the distribution of fat mass.


Assuntos
Fator Natriurético Atrial/sangue , Composição Corporal , Obesidade/metabolismo , Adulto , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Estudos Transversais , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue
3.
Clin Chem ; 59(11): 1621-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23842203

RESUMO

BACKGROUND: Plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict mortality in several clinical settings, but the long-term prognostic importance of suPAR in chest pain patients admitted on suspicion of non-ST-segment elevation acute coronary syndrome (NSTEACS) is uncertain. METHODS: suPAR concentrations were measured on admission in 449 consecutive chest pain patients in a single center between January 3, 2005, and February 14, 2006. Patients were followed for all-cause mortality from discharge until July 28, 2011. RESULTS: The diagnoses at discharge comprised high-risk NSTEACS [non-ST elevation myocardial infarction or unstable angina with electrocardiogram (ECG) abnormalities] in 77 patients (17.2%) and low-risk NSTEACS without evidence of myocardial ischemia in 257 (57.2%) of patients. Another 115 (25.6%) of patients received other diagnoses. During a median follow-up of 5.7 years (range, 0.01-6.6 years) there were 162 (36.1%) deaths. suPAR was predictive of mortality independent of age, sex, smoking, final diagnosis for the hospitalization, comorbidities (diabetes, hypertension, previous myocardial infarction, and heart failure), and variables measured on the day of admission (renal function, inflammatory markers, and markers of myocardial ischemia) with a hazard ratio (95% CI) of 1.93 (1.48-2.51) per SD increase in log-transformed suPAR, P < 0.0001. The use of suPAR improved the predictive accuracy of abnormal ECG findings and increased troponin concentrations regarding all-cause mortality (c statistics, 0.751-0.805; P < 0.0001). CONCLUSIONS: suPAR is a strong predictor of adverse long-term outcomes and improves risk stratification beyond traditional risk variables in chest pain patients admitted with suspected NSTEACS.


Assuntos
Angina Instável/diagnóstico , Dor no Peito/diagnóstico , Infarto do Miocárdio/diagnóstico , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Angina Instável/mortalidade , Angina Instável/fisiopatologia , Dor no Peito/mortalidade , Dor no Peito/fisiopatologia , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Troponina T/sangue
4.
Hypertension ; 62(1): 147-53, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23670298

RESUMO

Obesity is a strong risk factor for hypertension, but the mechanisms by which obesity leads to hypertension are incompletely understood. On this background, we assessed dietary sodium intake, serum levels of natriuretic peptides (NPs), and the activity of the renin-angiotensin system in 63 obese hypertensive men (obeseHT: body mass index, ≥30.0 kg/m(2); 24-hour ambulatory blood pressure, ≥130/80 mm Hg), in 40 obese normotensive men (obeseNT: body mass index, ≥30.0 kg/m(2); 24-hour ambulatory blood pressure, <130/80 mm Hg), and in 27 lean normotensive men (leanNT: body mass index, 20.0-24.9 kg/m(2); 24-hour ambulatory blood pressure, <130/80 mm Hg). All study subjects were medication free. As a surrogate estimate for dietary sodium intake, we measured sodium excretion in a 24-hour urine collection and we measured serum levels of midregional proatrial NP and plasma levels of renin and angiotensin II. The obese men had higher mean (±SD) urinary sodium excretion (obeseHT, 213.6±85.2 mmol; obeseNT, 233.0±70.0 mmol) than the lean normotensive men (leanNT, 155.5±51.7 mmol; P=0.003). ObeseHT had lower (median [interquartile range]) serum midregional proatrial NP levels (49.2 [37.3-64.7] pmol/L) than leanNT (69.3 [54.3-82.9] pmol/L; P=0.003), whereas obeseNT had midregional proatrial NP levels in between (54.1 [43.2-64.7] pmol/L); obeseNT had lower (median [interquartile range]) plasma levels of renin (5.0 [3.0-8.0] mIU/L versus 9.0 [4.0-18.0]) and angiotensin II (2.4 [1.5-3.5] pmol/L versus 4.2 [2.2-7.9]) than obeseHT (P≤0.049), whereas obeseHT had similar plasma levels of renin and angiotensin II as leanNT (P≥0.19). Thus, despite a high sodium intake and a high blood pressure, obese hypertensive men have a relative NP deficiency and an inadequate renin-angiotensin system suppression.


Assuntos
Angiotensina II/sangue , Fator Natriurético Atrial/deficiência , Hipertensão/sangue , Obesidade/sangue , Sistema Renina-Angiotensina/fisiologia , Renina/sangue , Adulto , Idoso , Fator Natriurético Atrial/sangue , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Composição Corporal , Seguimentos , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/fisiopatologia , Prognóstico
5.
Mol Genet Genomic Med ; 1(1): 54-65, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-24498601

RESUMO

Mitochondrial dysfunction is a characteristic of heart failure. Mutations in mitochondrial DNA, particularly in MT-CYB coding for cytochrome B in complex III (CIII), have been associated with isolated hypertrophic cardiomyopathy (HCM). We hypothesized that MT-CYB mutations might play an important causal or modifying role in HCM. The MT-CYB gene was sequenced from DNA isolated from blood from 91 Danish HCM probands. Nonsynonymous variants were analyzed by bioinformatics, molecular modeling and simulation. Two germline-inherited, putative disease-causing, nonsynonymous variants: m.15024G>A; p.C93Y and m.15482T>C; p.S246P were identified. Modeling showed that the p.C93Y mutation leads to disruption of the tertiary structure of Cytb by helix displacement, interfering with protein-heme interaction. The p.S246P mutation induces a diproline structure, which alters local secondary structure and induces a kink in the protein backbone, interfering with macromolecular interactions. These molecular effects are compatible with a leaky phenotype, that is, limited but progressive mitochondrial dysfunction. In conclusion, we find that rare, putative leaky mtDNA variants in MT-CYB can be identified in a cohort of HCM patients. We propose that further patients with HCM should be examined for mutations in MT-CYB in order to clarify the role of these variants.

6.
Am J Cardiol ; 110(12): 1756-63, 2012 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-22981263

RESUMO

The plasma level of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is an independent predictor of cardiovascular disease and all-cause mortality in healthy subjects. The prognostic capability of suPAR, its temporal course, and its relation to plasma C-reactive protein (CRP) in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous intervention (PCI) is unknown. Therefore, the plasma suPAR and CRP levels were measured in 296 consecutive patients with ST-segment elevation myocardial infarction admitted for primary PCI at baseline and every 6 to 8 hours thereafter until the cardiac biomarker levels had peaked. The end points were all-cause mortality and fatal or nonfatal recurrent myocardial infarction (MI). During a median follow-up period of 5.75 years, 69 deaths and 48 nonfatal and 14 fatal recurrent MIs occurred. All-cause mortality increased significantly from 8.1% to 41.5% across increasing quartiles of suPAR levels at the end of follow-up (log-rank p <0.0001). After adjustment for other independent prognostic factors, a highly significant increase was seen in all-cause mortality (hazard ratio 1.45, 95% confidence interval, 1.19 to 1.76; p <0.001) and recurrent MI (hazard ratio 1.53, 95% confidence interval 1.16 to 2.01; p <0.01) for each standard deviation increment of suPAR levels). In contrast to plasma CRP, the suPAR levels remained stable after primary PCI. Furthermore, CRP did not predict mortality or reinfarction after adjustment for age and gender (p = 0.34). In conclusion, suPAR is a stable plasma biomarker after ST-segment elevation myocardial infarction treated with primary PCI that predicts all-cause mortality and recurrent MI.


Assuntos
Infarto do Miocárdio/sangue , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/efeitos adversos , Prognóstico , Modelos de Riscos Proporcionais , Recidiva , Análise de Sobrevida
7.
Cardiovasc Res ; 89(4): 786-93, 2011 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-21051419

RESUMO

AIMS: Atrial fibrillation (AF) is the most frequent arrhythmia. Screening of SCN5A-the gene encoding the α-subunit of the cardiac sodium channel-has indicated that disturbances of the sodium current may play a central role in the mechanism of lone AF. We tested the hypothesis that lone AF in young patients is associated with genetic mutations in SCN3B and SCN4B, the genes encoding the two ß-subunits of the cardiac sodium channel. METHODS AND RESULTS: In 192 unrelated lone AF patients, the entire coding sequence and splice junctions of SCN3B and SCN4B were bidirectionally sequenced. Three non-synonymous mutations were found in SCN3B (R6K, L10P, and M161T). Two mutations were novel (R6K and M161T). None of the mutations were present in the control group (n = 432 alleles), nor have any been previously reported in conjunction with AF. All SCN3B mutations affected residues that are evolutionarily conserved across species. Electrophysiological studies on the SCN3B mutation were carried out and all three SCN3B mutations caused a functionally reduced sodium channel current. One synonymous variant was found in SCN4B. CONCLUSION: In 192 young lone AF patients, we found three patients with suspected disease-causing non-synonymous mutations in SCN3B, indicating that mutations in this gene contribute to the mechanism of lone AF. The three mutations in SCN3B were investigated electrophysiologically and all led to loss of function in the sodium current, supporting the hypothesis that decreased sodium current enhances AF susceptibility.


Assuntos
Fibrilação Atrial/etiologia , Fibrilação Atrial/genética , Mutação , Canais de Sódio/genética , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase , Subunidades Proteicas , Subunidade beta-3 do Canal de Sódio Disparado por Voltagem
8.
Echocardiography ; 27(9): 1031-7, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21039809

RESUMO

BACKGROUND: Mitral regurgitation (MR) secondary to ischemic heart disease (IHD) increases during exercise. We tested the hypothesis that the same is also true for MR due to mitral valve prolapse (MVP). METHODS: Consecutive patients with asymptomatic MR of varying severity underwent exercise test on a supine bicycle with workload up to a maximum of 100 W. Echocardiographic measurements were performed at rest and at peak exercise. The study was designed to detect an effective regurgitant orifice (ERO) change of at least 10 mm² during exercise. RESULTS: Twenty-six patients (21 male, age 56 ± 12 years (mean ± SD)) were included. Patients had an ERO of 35 ± 23 mm² (mean ± SD) and regurgitation volume of 48 ± 38 mL (mean ± SD). In these patients, ERO remained unchanged (an increase of 2 ± 15 mm² during exercise, P = 0.6). The regurgitation volume (RVol) decreased with 11 ± 16 mL (mean ± SD), P = 0.003. When calculated for 1 minute, RVol increased during exercise (P = 0.01), but in relation to the total cardiac output it decreased significantly (P = 0.02). CONCLUSION: Exercise does not increase the severity of MR due to MVP, in contrast to MR secondary to IHD. Different disease mechanisms behind these two types of MR could explain this difference.


Assuntos
Teste de Esforço , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Prolapso da Valva Mitral/diagnóstico por imagem , Prolapso da Valva Mitral/fisiopatologia , Esforço Físico , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/etiologia , Prolapso da Valva Mitral/complicações
9.
BMC Med Genet ; 11: 117, 2010 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-20670400

RESUMO

BACKGROUND: It is believed that hereditary hemochromatosis (HH) might play a role in cardiac disease (heart failure (HF) and ischemia). Mutations within several genes are HH-associated, the most common being the HFE gene. In a large cohort of HF patients, we sought to determine the etiological role and the prognostic significance of HFE genotypes. METHODS: We studied 667 HF patients (72.7% men) with depressed systolic function, enrolled in a multicentre trial with a follow-up period of up to 5 years. All were genotyped for the known HFE variants C282Y, H63D and S65C. RESULTS: The genotype and allele frequencies in the HF group were similar to the frequencies determined in the general Danish population. In multivariable analysis mortality was not predicted by C282Y-carrier status (HR 1.2, 95% CI: 0.8-1.7); H63D-carrier status (HR 1.0, 95% CI: 0.7-1.3); nor S65C-carrier status (HR 1.2, 95% CI: 0.7-2.0). We identified 27 (4.1%) homozygous or compound heterozygous carriers of HFE variants. None of these carriers had a clinical presentation suggesting hemochromatosis, but hemoglobin and ferritin levels were higher than in the rest of the cohort. Furthermore, a trend towards reduced mortality was seen in this group in univariate analyses (HR 0.4, 95% CI: 0.2-0.9, p = 0.03), but not in multivariate (HR 0.5, 95% CI: 0.2-1.2). CONCLUSION: HFE genotypes do not seem to be a significant contributor to the etiology of heart failure in Denmark. HFE variants do not affect mortality in HF.


Assuntos
Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/genética , Antígenos de Histocompatibilidade Classe I/genética , Proteínas de Membrana/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Insuficiência Cardíaca/mortalidade , Hemocromatose/genética , Proteína da Hemocromatose , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico
11.
Eur J Radiol ; 72(1): 92-7, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18687544

RESUMO

BACKGROUND: Multidetector computed tomography (MDCT) of the heart provides both anatomical and functional information. The objective of this study was to evaluate the accuracy of quantitative assessment of left ventricular contractile function in relation to two-dimensional transthoracic echocardiography (TTE). MATERIALS AND METHODS: Sixty-four patients with known or suspected coronary artery disease underwent ECG-gated 64-slice MDCT and TTE. Regional left ventricular contractile function was measured by percent systolic wall thickening (SWT) in 16 myocardial segments using MDCT, and compared with visual evaluation of wall motion score (WMS) by TTE. Global SWT by MDCT was calculated as the mean SWT of all myocardial segments and compared with wall motion index (WMI) by TTE. RESULTS: Eight hundred and eleven segments (81%) were classified as normokinetic, 142 (14%) as hypokinetic, 41 (4%) as akinetic and 5 (0.5%) as dyskinetic by TTE. A significant inverse linear trend was found between regional SWT by MDCT and WMS by TTE (p<0.001). Sensitivity and specificity for the identification of regional abnormalities of contractile function were 76% and 78%, respectively. A linear correlation between global SWT by MDCT and WMI by TTE was found (r=-0.8, p<0.001). Sensitivity and specificity for the identification of WMI>1.5 using global SWT was 91% and 94%, respectively. CONCLUSION: Quantification of systolic wall thickening by MDCT provides functional information, which is well correlated to visual assessment of global left ventricular contractile function by TTE.


Assuntos
Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Imageamento Tridimensional/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intensificação de Imagem Radiográfica/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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