Association of frailty with endothelial dysfunction and its possible impact on negative outcomes in Brazilian predialysis patients with chronic kidney disease.

BACKGROUND: Frailty is a state of physiological vulnerability common in the elderly. It is more predominant in patients with Chronic Kidney Disease in comparison to healthy subjects, which can also be diagnosed in non-elderly individuals and be associated with innumerous causes such as muscle strength, body composition and inflammation. The association between frailty and endothelial function, as well as the association between frailty and the combined outcome of mortality multiple cause and start of renal replace therapy were assessed. METHODS: In the initial analysis, sixty-one predialysis patients with Chronic Kidney Disease stages were evaluated and included in this study. Due to patient drop-out during follow-up, fifty-seven patients were subsequently re-evaluated 12 months later. The diagnosis of frailty was based on the Johansen et al. (J Am Soc Nephrol 18(11):2960-67, 2007) criteria. The groups were divided into Non-frail and Frail. Sociodemographic, inflammatory markers (IL-6, TNF-?, CRP-us), endothelial dysfunction (flow-mediated vasodilatation - FMD), body composition (DXA) and the 25-hidroxi-vitamin D parameters were analyzed. RESULTS: The average age of the patients used in the study was 64.9 ± 10.3 years old. The predominance of frailty was 42.6%, of which 46% were non-elderly. After some adjustments, frailty was associated with gender (OR = 11.32; IC 95% = 2.30 to 55.67), advanced age (OR = 4.07; IC 95% = 1.02 to 16.20), obesity (OR = 6.63; IC 95% = 0.82 to 11.44) and endothelial dysfunction (OR = 3.86; IC 95% = 1.00 to 14.88). The ratio of the incidence of frail subjects to the variable outcome was 2.5 (CI 95%, 1.04 to 6.50). CONCLUSIONS: Although an observational study does not allow one to determine the casual relation between frailty and endothelial dysfunction, we conclude that frailty was predominant in our sample of Brazilian patients with chronic kidney disease on predialysis, even in elderly individuals. This was linked to either worse endothelial function or mortality.

Pulmonary function and exercise tolerance are related to disease severity in pre-dialytic patients with chronic kidney disease: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) involves a progressive, irreversible loss of kidney function. While early-stage CKD patients may show changes in pulmonary function and lowered exercise tolerance, the role of the estimated glomerular filtration rate (eGFR) in these patterns remains unknown. The aim of this study was to investigated pulmonary function and exercise tolerance in pre-dialytic CKD patients. METHODS: A cross-sectional study was carried out with 38 adult volunteers divided into a control group (CG), consisting of 9 healthy adults, and 29 pre-dialytic CKD patients in stages 3 (G3), 4 (G4), and 5 (G5). All participants underwent spirometric and manovacuometric tests, a cardiopulmonary exercise test (CPET), a 6-minute walk test (6MWT), and laboratory tests. RESULTS: The significant differences was observed in maximal exercise tolerance, measured as peak oxygen consumption percentage (VO2peak) (mL/kg/min) (CG = 28.9 ± 7.8, G3 = 23.3 ± 5.6, G4 = 21.4 ± 5.2, G5 = 20.2 ± 6.9; p = 0.03), and submaximal exercise tolerance, measured by 6MWT (m) (CG = 627.6 ± 37.8, G3 = 577.4 ± 66.1, G4 = 542.7 ± 57.3, G5 = 531.5 ± 84.2, p = 0.01). The eGFR was associated with pulmonary function-forced expiratory volume in the first second percentage (FEV1) (%) (r = 0.34, p = 0.02) and maximum inspiratory pressure (PImax) (r = 0.41, p = 0.02) - and exercise tolerance - VO2peak (mL/kg/min) (r = 0.43, p = 0.01) and 6MWT distance (m) (r = 0.55, p < 0.01). CONCLUSION: Pre-dialytic CKD patients showed lower maximal and submaximal exercise tolerances than healthy individuals.

[Spironolactone reduces blood pressure and albuminuria of obese hypertensive patients with metabolic syndrome]. / Espironolactona reduz a pressão arterial e a albuminúria de hipertensos obesos com síndrome metabólica.

INTRODUCTION: In recent years, a role for aldosterone in pathophysiology of metabolic syndrome and hypertension in this syndrome has been suggested. However, the treatment with antagonists of mineralocorticoid receptor in these individuals has not properly addressed. OBJECTIVE: To evaluate the effects of mineralocorticoid receptor blockade on blood pressure, inflammatory, metabolic and renal parameters in non-diabetic hypertensive individuals with the metabolic syndrome. METHODS: Twenty nine patients with metabolic syndrome were enrolled in a prospective protocol that consisted of 2 periods: baseline (2 weeks) in which demographic data were obtained and antihypertensive medicines were withdrawn, and treatment period when the individuals were treated with spironolactone 25-50 mg once-a-day, for 16 weeks. In both periods, inflammatory, metabolic and renal parameters were assessed and the 24-hour ambulatory blood pressure monitorization was performed. RESULTS: After spironolactone treatment, 24 hour systolic and diastolic blood pressure decreased from 143.5 ± 15.17 mmHg to 133.2 ± 17.34 mmHg (p = 0.025) and from 85.2 ± 11.10 mmHg to 79.3 ± 11.78 mmHg (p = 0.026), respectively. HDL-cholesterol increased from 44.0 ± 8.67 mg/dl to 49.0 ± 6.75mg/dl (p = 0.000) and C-reactive protein decreased significantly from 6.3 ± 7.54 mg/l to 4.6 ± 6.3 mg/l (p = 0.009). Fasting plasma glucose, insulin, HOMA-IR and triglycerides did not change significantly after mineralocorticoid receptor blockade. Estimated glomerular filtration rate did not change whereas the logarithm of albuminuria decreased significantly from 2.5 ± 0.92 to 2.0 ± 0.9 (p = 0.028). CONCLUSION: In hypertensive subjects with MS the administration of spironolactone in monotherapy was effective for hypertension control, decreased urinary albumin excretion and increased HDL-cholester ol plasma.

Espironolactone improves flow-mediated vasodilatation in subjects with the metabolic syndrome.

INTRODUCTION: The role of aldosterone in the pathophysiology of the metabolic syndrome (MS)-related endothelial dysfunction has been the subject of recent research. OBJECTIVE: To evaluate the effects of aldosterone blockade on flow-mediated vasodilation (FMD) and on renal and metabolic parameters of patients with the MS. METHODS: 19 MS subjects underwent clinical examination, laboratory work-up (serum lipid profile, glucose and insulin; creatinine clearance; microalbuminuria investigation), ambulatory blood pressure monitoring (ABPM), and FMD analysis before and after 16 weeks of aldosterone blockade with spironolactone. RESULTS: After the treatment period, FMD increased from 7.6 ± 5.63% to 15.0 ± 6.10% (p < 0.001), associated with a non-significant decrease of blood pressure (from 142.2 ± 16.37 mmHg to 138.8 ± 16.67 mmHg, and from 84.3 ± 10.91 mmHg to 82.7 ± 9.90 mmHg, respectively). HDL-cholesterol significantly increased, microalbuminuria showed a decreasing trend and creatinine clearance did not change after treatment. CONCLUSION: Aldosterone blockade in patients with the MS improved FMD without interfering with metabolic and renal parameters.

Comparação entre métodos de avaliação da modulação vagal cardíaca / Comparison of assessment methods of cardiac vagal modulation

FUNDAMENTO: Diversos métodos têm sido utilizados para avaliar a modulação vagal cardíaca; entretanto, há lacunas quanto a associação e acurácia desses métodos. OBJETIVO: Investigar a associação entre três métodos válidos, reprodutíveis e comumente utilizados para avaliação da modulação vagal cardíaca, e comparar as suas acurácias. MÉTODOS: Trinta homens saudáveis (23 ± 4 anos) e 15 homens com coronariopatia (61 ± 10 anos) foram avaliados em ordem contrabalanceada pela Variabilidade da Frequência Cardíaca (VFC; variáveis: domínio do tempo = pNN50, DPNN e RMSSD, domínio da frequência = AF ms² e AF u.n.), Arritmia Sinusal Respiratória (ASR) e Teste de Exercício de 4 segundos (T4s). RESULTADOS: Indivíduos saudáveis apresentaram maior modulação vagal nos três métodos (p < 0,05). No grupo saudável houve correlação (p < 0,05) entre os resultados da VFC (pNN50 e DPNN) e da ASR, mas não houve correlação entre o T4s e os outros dois métodos estudados. No grupo com coronariopatia houve correlação entre os resultados da VFC (pNN50, DPNN, RMSSD, AF ms² e AF u.n.) e da ASR. Em adição, houve correlação entre o T4s e a ASR. Por fim, os métodos ASR e T4s apresentaram tamanho do efeito mais preciso e melhor acurácia (p < 0,05) comparados à VFC. CONCLUSÃO: A VFC e a ASR geraram resultados parcialmente redundantes em indivíduos saudáveis e em pacientes com coronariopatia, enquanto o T4s gerou resultados complementares a VFC e ASR em indivíduos saudáveis. Além disso, os métodos ASR e T4s foram mais precisos para discriminar a modulação vagal cardíaca entre indivíduos saudáveis e pacientes com coronariopatia comparados à VFC.

BACKGROUND: Several methods have been used to assess cardiac vagal modulation, but there are gaps regarding the association and accuracy of these methods. OBJECTIVE: To investigate the association between three valid, reproducible and commonly methods used to assess cardiac vagal modulation and compare their accuracies. METHODS: Thirty healthy men (23 ± 4 years) and 15 men with coronary artery disease (61 ± 10 years) were evaluated in counterbalanced design by Heart Rate Variability (HRV; variables: the time domain = pNN50, SDNN and RMSSD, the frequency domain HF = ms² and HF n.u.), Respiratory Sinus Arrhythmia (RSA) and 4-second Exercise Test (T4s). Thirty healthy men (23 ± 4 years) and 15 men with coronary artery disease (61 ± 10 years) were evaluated in counterbalanced order by Heart Rate Variability (HRV; variables: the time domain = pNN50, SDNN and RMSSD, the frequency domain HF = ms² and HF n.u.), Respiratory Sinus Arrhythmia (RSA) and 4-second Exercise Test (T4s). RESULTS: Healthy subjects had higher vagal modulation by the three methods (p <0.05). There was a correlation in the healthy group (p <0.05) between the results of HRV (SDNN and pNN50 and RSA, but there was no correlation between the T4s and the other two methods. In the group with coronary artery disease, there was a correlation between the results of HRV (pNN50, SDNN, RMSSD, HF ms² and HF n.u.) and RSA. In addition, there was a correlation between the RSA and T4s. Finally, the T4s and RSA methods presented more accurate effect size and better accuracy (p <0.05), when compared to the HRV. CONCLUSION: HRV and RSA generated partially redundant results in healthy subjects and in patients with coronary artery disease, while the T4s generated results that were complementary to HRV and RSA in healthy subjects. In addition, RSA and T4s methods were more accurate when discriminating cardiac vagal modulation between healthy subjects and patients with coronary artery disease, when compared to HRV.

Espironolactona melhora a vasodilatação fluxo mediada em indivíduos com síndrome metabólica / Espironolactone improves flow-mediated vasodilatation in subjects with the metabolic syndrome

INTRODUÇÃO: O papel da aldosterona na fisiopatologia da disfunção endotelial relacionada à síndrome metabólica (SM) tem sido objeto de estudos. OBJETIVO: Avaliar o bloqueio da aldosterona sobre a vasodilatação fluxo mediada (VDFM) e sobre parâmetros renais e metabólicos em indivíduos com SM. MÉTODOS: Dezenove indivíduos com SM foram submetidos a exame clínico; exames complementares: glicose, insulina, lipidograma, depuração da creatinina, microalbuminúria e a monitorização ambulatorial da pressão arterial (MAPA) e análise da VDFM antes e após 16 semanas do uso de espironolactona. RESULTADOS: Após o tratamento, observou-se aumento da VDFM, de 7,6 ± 5,63 por cento para 15,0 ± 6,10 por cento (p < 0,001), com redução não significante da pressão sistólica e diastólica (142,2 ± 16,37 mmHg para 138,8 ± 16,67 mmHg e 84,3 ± 10,91 mmHg para 82,7 ± 9,90 mmHg, respectivamente). O colesterol HDL (High-density lipoprotein - lipoproteína de alta densidade) aumento de modo significante, a microalbuminúria apresentou tendência à redução, enquanto a depuração da creatinina não variou significativamente com o tratamento. CONCLUSÃO: O bloqueio da aldosterona em pacientes com SM melhorou a VDFM, sem induzir alterações no perfil metabólico e em parâmetros renais.

INTRODUCTION: The role of aldosterone in the pathophysiology of the metabolic syndrome (MS)-related endothelial dysfunction has been the subject of recent research. OBJECTIVE: To evaluate the effects of aldosterone blockade on flow-mediated vasodilation (FMD) and on renal and metabolic parameters of patients with the MS. METHODS: 19 MS subjects underwent clinical examination, laboratory work-up (serum lipid profile, glucose and insulin; creatinine clearance; microalbuminuria investigation), ambulatory blood pressure monitoring (ABPM), and FMD analysis before and after 16 weeks of aldosterone blockade with spironolactone. RESULTS: After the treatment period, FMD increased from 7.6 ± 5.63 percent to 15.0 ± 6.10 percent (p < 0.001), associated with a non-significant decrease of blood pressure (from 142.2 ± 16.37 mmHg to 138.8 ± 16.67 mmHg, and from 84.3 ± 10.91 mmHg to 82.7 ± 9.90 mmHg, respectively). HDL-cholesterol significantly increased, microalbuminuria showed a decreasing trend and creatinine clearance did not change after treatment. CONCLUSION: Aldosterone blockade in patients with the MS improved FMD without interfering with metabolic and renal parameters.

Comparison of assessment methods of cardiac vagal modulation.

BACKGROUND: Several methods have been used to assess cardiac vagal modulation, but there are gaps regarding the association and accuracy of these methods. OBJECTIVE: To investigate the association between three valid, reproducible and commonly methods used to assess cardiac vagal modulation and compare their accuracies. METHODS: Thirty healthy men (23 ± 4 years) and 15 men with coronary artery disease (61 ± 10 years) were evaluated in counterbalanced design by Heart Rate Variability (HRV; variables: the time domain = pNN50, SDNN and RMSSD, the frequency domain HF = ms² and HF n.u.), Respiratory Sinus Arrhythmia (RSA) and 4-second Exercise Test (T4s). Thirty healthy men (23 ± 4 years) and 15 men with coronary artery disease (61 ± 10 years) were evaluated in counterbalanced order by Heart Rate Variability (HRV; variables: the time domain = pNN50, SDNN and RMSSD, the frequency domain HF = ms² and HF n.u.), Respiratory Sinus Arrhythmia (RSA) and 4-second Exercise Test (T4s). RESULTS: Healthy subjects had higher vagal modulation by the three methods (p <0.05). There was a correlation in the healthy group (p <0.05) between the results of HRV (SDNN and pNN50 and RSA, but there was no correlation between the T4s and the other two methods. In the group with coronary artery disease, there was a correlation between the results of HRV (pNN50, SDNN, RMSSD, HF ms² and HF n.u.) and RSA. In addition, there was a correlation between the RSA and T4s. Finally, the T4s and RSA methods presented more accurate effect size and better accuracy (p <0.05), when compared to the HRV. CONCLUSION: HRV and RSA generated partially redundant results in healthy subjects and in patients with coronary artery disease, while the T4s generated results that were complementary to HRV and RSA in healthy subjects. In addition, RSA and T4s methods were more accurate when discriminating cardiac vagal modulation between healthy subjects and patients with coronary artery disease, when compared to HRV.

Polar S810 como recurso alternativo ao eletrocardiograma no teste de exercício de 4 segundos / Polar S810 as an alternative resource to the use of the electrocardiogram in the 4-second exercise test

FUNDAMENTO: O teste de exercício de 4 segundos (T4s) avalia o tônus vagal cardíaco durante o transiente inicial da frequência cardíaca (FC), em exercício dinâmico súbito, por meio da identificação do índice vagal cardíaco (IVC) obtido a partir do eletrocardiograma (ECG). OBJETIVO: Testar a utilização do monitor de frequência cardíaca (MFC) Polar S810 como recurso alternativo ao ECG na aplicação do T4s. MÉTODOS: Neste trabalho, 49 indivíduos do sexo masculino (25 ± 20 anos, 176 ± 12 cm, 74 ± 6 kg) realizaram o T4s. Os intervalos RR foram registrados simultaneamente por ECG e MFC. Calcularam-se média e desvio padrão do último intervalo RR do período pré-exercício ou o primeiro do período de exercício, aquele que for mais longo (RRB), do mais curto intervalo RR do período de exercício (RRC) e do IVC obtidos por ECG e MFC. Utilizou-se o teste t de Student para amostras dependentes (p < 0,05) para testar a significância das diferenças entre as médias. Para identificar a concordância entre o ECG e o MFC, utilizou-se a regressão linear, com cálculo do coeficiente de correlação de Pearson e a estratégia proposta por Bland e Altman. RESULTADOS: A regressão linear apresentou r² de 0,9999 para o RRB, 0,9997 para o RRC e 0,9996 para o IVC. A estratégia de Bland e Altman apresentou desvio padrão de 0,92 ms para o RRB, 0,86 ms para o RRC e 0,002 para o IVC. CONCLUSÃO: O MFC Polar S810 se mostrou eficiente na aplicação do T4s quando comparado ao ECG.

BACKGROUND: The 4-second exercise test (T4s) evaluates the cardiac vagal tone during the initial heart rate (HR) transient at sudden dynamic exercise, through the identification of the cardiac vagal index (CVI) obtained from the electrocardiogram (ECG). OBJECTIVE: To evaluate the use of the Polar S810 heart rate monitor (HRM) as an alternative resource to the use of the electrocardiogram in the 4-second exercise test. METHODS: In this study, 49 male individuals (25 ± 20 years, 176 ±12 cm, 74 ± 6 kg) underwent the 4-second exercise test. The RR intervals were recorded simultaneously by ECG and HRM. We calculated the mean and the standard deviation of the last RR interval of the pre-exercise period, or of the first RR interval of the exercise period, whichever was longer (RRB), of the shortest RR interval of the exercise period (RRC), and of the CVI obtained by ECG and HRM. We used the Student t-test for dependent samples (p < 0.05) to test the significance of the differences between means. To identify the correlation between the ECG and the HRM, we used the linear regression to calculate the Pearson's correlation coefficient and the strategy proposed by Bland and Altman. RESULTS: Linear regression showed r² of 0.9999 for RRB, 0.9997 for RRC, and 0.9996 for CVI. Bland e Altman strategy presented standard deviation of 0.92 ms for RRB, 0.86 ms for RRC, and 0.002 for CVI. CONCLUSION: Polar S810 HRM was more efficient in the application of T4s compared to the ECG.

[Polar S810 as an alternative resource to the use of the electrocardiogram in the 4-second exercise test]. / Polar S810 como recurso alternativo ao eletrocardiograma no teste de exercício de 4 segundos.

BACKGROUND: The 4-second exercise test (T4s) evaluates the cardiac vagal tone during the initial heart rate (HR) transient at sudden dynamic exercise, through the identification of the cardiac vagal index (CVI) obtained from the electrocardiogram (ECG). OBJECTIVE: To evaluate the use of the Polar S810 heart rate monitor (HRM) as an alternative resource to the use of the electrocardiogram in the 4-second exercise test. METHODS: In this study, 49 male individuals (25 +/- 20 years, 176 +/-12 cm, 74 +/- 6 kg) underwent the 4-second exercise test. The RR intervals were recorded simultaneously by ECG and HRM. We calculated the mean and the standard deviation of the last RR interval of the pre-exercise period, or of the first RR interval of the exercise period, whichever was longer (RRB), of the shortest RR interval of the exercise period (RRC), and of the CVI obtained by ECG and HRM. We used the Student t-test for dependent samples (p < or 0.05) to test the significance of the differences between means. To identify the correlation between the ECG and the HRM, we used the linear regression to calculate the Pearson's correlation coefficient and the strategy proposed by Bland and Altman. RESULTS: Linear regression showed r(2) of 0.9999 for RRB, 0.9997 for RRC, and 0.9996 for CVI. Bland e Altman strategy presented standard deviation of 0.92 ms for RRB, 0.86 ms for RRC, and 0.002 for CVI. CONCLUSION: Polar S810 HRM was more efficient in the application of T4s compared to the ECG.