Circulating dipeptidyl peptidase IV activity correlates with cardiac dysfunction in human and experimental heart failure.

BACKGROUND: The present study addresses the hypothesis that the activity of dipeptidyl peptidase IV (DPPIV), an enzyme that inactivates peptides that possess cardioprotective actions, correlates with adverse outcomes in heart failure (HF). The therapeutic potential of DPPIV inhibition in preventing cardiac dysfunction is also investigated. METHODS AND RESULTS: Measurements of DPPIV activity in blood samples obtained from 190 patients with HF and 42 controls demonstrated that patients with HF exhibited an increase of ≈130% in circulating DPPIV activity compared with healthy subjects. Furthermore, an inverse correlation was observed between serum DPPIV activity and left ventricular (LV) ejection fraction in patients with HF. Similarly, radiofrequency LV ablation-induced HF rats displayed higher DPPIV activity in the plasma (≈50%) and heart tissue (≈3.5-fold) compared with sham-operated rats. Moreover, positive correlations were observed between the plasma DPPIV activity and LV end-diastolic pressure and lung congestion. Two days after surgery, 1 group of LV ablation-induced HF rats was treated with the DPPIV inhibitor sitagliptin (40 mg/kg BID) for 6 weeks, whereas the remaining rats were administered water. Hemodynamic measurements demonstrated that radiofrequency LV-ablated rats treated with sitagliptin exhibited a significant attenuation of HF-related cardiac dysfunction, including LV end-diastolic pressure, systolic performance, and chamber stiffness. Sitagliptin treatment also attenuated cardiac remodeling and cardiomyocyte apoptosis and minimized pulmonary congestion. CONCLUSIONS: Collectively, the results presented herein associate circulating DPPIV activity with poorer cardiovascular outcomes in human and experimental HF. Moreover, the results demonstrate that long-term DPPIV inhibition mitigates the development and progression of HF in rats.

Myocyte diameter and fractional area of collagen are not associated with survival time of outpatients with idiopathic dilated cardiomyopathy: a study based on right ventricular endomyocardial biopsies.

Morphometric data obtained from the analysis of endomyocardial biopsy might be useful to evaluate prognosis of patients with dilated cardiomyopathy. We measured the myocyte diameter, its coefficient of variation and the fractional area of collagen in right ventricular endomyocardial biopsies of 35 outpatients with idiopathic dilated cardiomyopathy. None of the evaluated histological parameter was associated with the survival time of the patients (range: 2 to 5588; median: 706 days). Right ventricular endomyocardial biopsy should not be indicated to predict evolution or fatal outcome in patients with idiopathic dilated cardiomyopathy.

Perfil lipídico de indivíduos sem cardiopatia com sobrepeso e obesidade / Lipidic profile of individuals without cardiopathy with overweight and obesity

OBJETIVO: Avaliar o perfil lipídico de indivíduos com sobrepeso e obesidade submetidos à avaliação cardiológica e que não mostraram evidências de cardiopatia. MÉTODOS: Amostra com 684 indivíduos, 389 (56,9 por cento) mulheres e 295 (43,1 por cento) homens, com idade de 14 a 74 (média 40,6) anos, sem evidências de cardiopatia após avaliação clínica e análise do eletrocardiograma, radiografia do tórax, teste ergométrico em esteira e ecocardiograma bidimensional com Doppler. Foi estudado o perfil sérico de lípides e glicose quanto ao sexo e faixas do índice de massa corpórea (IMC) - eutróficos até 24,9 Kg/m², sobrepeso 25-29,9 Kg/m² e obesos > 30 Kg/m². RESULTADOS: Apresentaram diferença estatisticamente significativa entre os sexos (médias): glicose (mg/dL) de mulheres 90,21±23,13 e homens 95,28±28,64 (p<0.001); triglicérides (mg/dL) de mulheres 97,27±55,24 e homens 141,47±57,06 (p<0,001) e HDL-C (mg/dL) de mulheres 52,63±13,92 e homens 43±10,88 (p<0,001). O IMC médio das mulheres foi 26,15 e dos homens 26,33 (p=ns). Na análise por faixas de IMC houve diferença significativa entre os sexos (p=0,037). Na faixa de sobrepeso e obesidade, apenas as médias de triglicérides das mulheres mostraram diferença estatisticamente significativa: mulheres com sobrepeso 102,25±60,68 mg/dL e obesas 121,64±63,57 mg/dL (p=0,034). CONCLUSAO: Mulheres sem cardiopatia apresentaram níveis séricos de glicose, triglicérides e HDL-colesterol inferiores aos homens. Em ambos os sexos, as médias são menores na comparação entre eutróficos e com excesso de peso, e apenas as médias dos triglicérides das mulheres com sobrepeso e obesidade apresentou diferença significativamente estatística.

High-sensitivity C-reactive protein concentration in a healthy Brazilian population.

BACKGROUND: The use of serum high-sensitivity C-reactive protein (hs-CRP) for cardiovascular risk profiling requires knowledge of the distribution in different populations. We studied serum hs-CRP in a healthy Brazilian population, with no evidence of heart disease, relative to gender and smoking status as well as other clinical and laboratory variables. METHODS: 684 healthy Brazilian individuals, aged 14-74 years (mean 40.6 years), 295 men (43.1%) and 389 women (56.9%), were enrolled between July 1998 and July 2001. The relationship between the log-transformed hs-CRP, stratified by gender and smoking status (non-smokers, smokers), and clinical and laboratory variables were analyzed using the Spearman correlation coefficient and multiple linear regression. RESULTS: In a multiple linear regression model age (beta=1.0069, p=0.03), body mass index (BMI) (beta=1.0093, p<0.01), total cholesterol/HDL cholesterol ratio (TC/HDL-C) (beta=1.1015, p<0.01) and heart rate (beta=1.0139, p<0.01) were independently correlated with hs-CRP. Stratification according to gender and smoking was able to disclose different interactions between these variables and hs-CRP. Variables significantly correlated in each stratum were as follows: in smoker men, age (beta=1.0236, p=0.04) and TC/HDL-C (beta=1.2065, p<0.01); in non-smoker men, BMI (beta=1.0786, p<0.01) and TC/HDL-C (beta=1.1397, p=0.01); in smoker women, BMI (beta=1.1006, p=0.03); and in non-smoker women, BMI (beta=1.0873, p<0.01), TC/HDL-C (beta=1.1405, p=0.01) and heart rate (beta=1.0165, p=0.02). CONCLUSIONS: The clinical and laboratory variables studied influenced the concentration of hs-CRP according to gender and smoking. In assessing the risk of cardiovascular events in relation to serum hs-CRP level, stratification by gender and smoking status is indicated.

The influence of tumor necrosis factor -308 and C-reactive protein G1059C gene variants on serum concentration of C-reactive protein: evidence for an age-dependent association.

BACKGROUND: C-reactive protein (CRP) synthesis and activity are modulated both by genetic and environmental factors. Data about the influence of genetic factors upon CRP concentration are sparse. We evaluated the hypothesis that allele variations in the genes encoding the CRP and TNF-alpha genes could modulate hs-CRP serum concentration in the general population. METHODS: Six hundred and eighty-four asymptomatic Brazilian individuals, selected between July 1998 and July 2001, 295 men (43.1%) and 389 women (56.9%) were studied. Laboratory assessment included: serum glucose, cholesterol, triglycerides, thyroid-stimulating hormone, uric acid and CRP measured by a high-sensitivity assay (hs-CRP). TNF -308 and CRP G1059C genotypes were obtained through PCR amplification and restriction enzyme digestion. RESULTS: Serum concentrations of hs-CRP were distributed into population quartiles. There was no significant difference of hs-CRP serum concentration regarding CRP gene G1059C polymorphism. However, there was a tendency for higher hs-CRP serum levels in individuals harboring the TNFA2 allele in quartile 4. In addition, ANOVA factorial modeling using log-transformed hs-CRP serum level as the dependent variable disclosed a significant association between hs-CRP and the TNFA2 allele following stratification for age quartiles (p=0.01). Finally, the presence of TNFA2 allele in this age group increased the odds of being in the fourth quartile of hs-CRP concentration (p<0.05, OR=5.1). CONCLUSION: These findings suggest an association between a functional genetic variant of the TNF-alpha gene and hs-CRP levels at particular age groups.

Achados ecocardiográficos em pacientes com suspeita diagnóstica de endocardite infecciosa / Echocardiographic findings in patients with suspected infective endocarditis

OBJETIVO: Avaliar os achados ecocardiográficos em pacientes com suspeita diagnóstica de endocardite infecciosa. MÉTODOS: Foram submetidos à investigação ecocardiográfica transtorácica e transesofágica 262 pacientes com suspeita diagnóstica de endocardite infecciosa. Analisadas imagens de vegetações, abscessos valvares e insuficiência periprotética aguda e avaliada a correlação com dados clínicos, laboratoriais, categoria diagnóstica e a evolução hospitalar. RESULTADOS: O diagnóstico de endocardite foi categorizado como definido em 127 (47,8 por cento) episódios, possível em 81 (30,4 por cento) e rejeitado em 58 (21,8 por cento). Nos pacientes com o diagnóstico definido, foram identificadas 135 imagens de vegetações, 37 de abscesso e 6 de insuficiência periprotética. Vegetações foram mais freqüentes em pacientes com endocardite por estreptococos do grupo viridans e enterococos (p=0,02) e com duração dos sintomas < 10 dias (p= 0,001); abscesso mais freqüente em pacientes com duração dos sintomas < 10 dias (p= 0,001) e insuficiência periprotética associada à maior necessidade de tratamento cirúrgico (p=0,001). Nos pacientes com o diagnóstico possível de endocardite, foram identificadas 8 imagens ecocardiográficas consideradas compatíveis com vegetações e, nos pacientes com diagnóstico de endocardite rejeitado, não foram demonstradas vegetações, abscessos valvares e insuficiência periprotética. CONCLUSAO: Nossos achados ecocardiográficos variaram de acordo com a categoria diagnóstica. A contribuição tanto para o diagnóstico quanto para a avaliação prognóstica deve levar em consideração a probabilidade pré-teste do diagnóstico de endocardite infecciosa.

Ambulatory blood pressure monitoring of patients with heart failure: a new prognosis marker

OBJECTIVE: To evaluate the relationship between 24-hour ambulatory arterial blood pressure monitoring and the prognosis of patients with advanced congestive heart failure. METHODS: We studied 38 patients with NYHA functional class IV congestive heart failure, and analyzed left ventricular ejection fraction, diastolic diameter, and ambulatory blood pressure monitoring data. RESULTS: Twelve deaths occurred. Left ventricular ejection fraction (35.2Ý7.3 percent) and diastolic diameter (72.2Ý7.8mm) were not correlated with the survival. The mean 24-hour (SBP24), waking (SBPw), and sleeping (SBPs) systolic pressures of the living patients were higher than those of the deceased patients and were significant for predicting survival. Patients with mean SBP24, SBPv, and SBPs > or = 105mmHg had longer survival (p=0.002, p=0.01 and p=0.0007, respectively). Patients with diastolic blood pressure sleep decrements (dip) and patients with mean blood pressure dip <=6mmHg had longer survival (p=0.04 and p=0.01, respectively). In the multivariate analysis, SBPs was the only variable with an odds ratio of 7.61 (CI: 1.56; 3704) (p=0.01). Patients with mean SBP<105mmHg were 7.6 times more likely to die than those with SBP > or = 105 mmHg CONCLUSION: Ambulatory blood pressure monitoring appears to be a useful method for evaluating patients with congestive heart failure

Tamponamento cardíaco fatal em portadora de lupus eritematoso sistêmico associado com vasculite semelhante a poliarterite nodosa / Fatal cardiac tamponade in systemic lupus erythematosus associated with vasculitis similar to polyarteritis nodosa

Mulher de 32 anos de idade apresentou lupus eritematoso sistêmico fatal em decorrência de tamponamento cardíaco por derrame pericárdico de instalaçäo rápida. A necrópsia revelou tamponamento cardíaco, achados de lupus eritematoso sistêmico e presença de vasculite semelhante a poliarterite nodosa näo diagnosticada previamente

We report the case of a 21 year-old woman who developed systemic lupus erythematosus and fatal cardiac tamponade. Necropsy examination revealed cardiac tamponade as well as other findings of SLE and an unsuspected vasculitis similar to polyarteritis nodosa