Effect of rosuvastatin and sevelamer on the progression of coronary artery calcification in chronic kidney disease: a pilot study.

INTRODUCTION: Coronary artery calcification (CAC) is highly prevalent among chronic kidney disease (CKD) patients and its strong association with mortality has been recognized early in the course of CKD. The aim of the present study was to test the effect of rosuvastatin and sevelamer hydrochloride on the progression of CAC in nondialyzed CKD patients. METHODS: An open-label, randomized and controlled pilot study was conducted including 117 CKD patients (62% men, 56.9 ± 11.2 years, eGFR 36 ± 16.5 ml/min). Patients were randomly assigned to rosuvastatin (n = 38; 10 mg/day), to sevelamer hydrochloride (n = 38; 2,400 mg/day) and to control (n = 41) groups. CAC (by multislice computed tomography) and biochemical analyses were performed at baseline and after 24 months. RESULTS: At baseline, CAC was observed in 55%, 58% and 61% of patients in the rosuvastatin, sevelamer hydrochloride and control groups, respectively (p = 0.87). Calcium score at baseline as well as its absolute and relative changes during 24 months were similar among the groups. Low density lipoprotein cholesterol (LDL-c) was higher and decreased significantly in the rosuvastatin group (p < 0.01). The analysis adjusting for LDL-c showed that the drug regimens were not associated with the progression of CAC (drug effect p = 0.85; time-effect p < 0.001; interaction p = 0.76). CONCLUSIONS: Treatment with rosuvastatin and sevelamer hydrochloride may not delay the progression of CAC in non-dialysis dependent CKD patients.

Effects of different degrees of insulin sensitivity on endothelial function in obese patients.

BACKGROUND: Obesity derived from intra-abdominal fat deposition tends to increase hormonal and cytokine production, thus worsening insulin sensitivity and leading to endothelial dysfunction. Hyperinsulinemia is considered an independent risk factor for ischemic heart disease and cause of endothelial dysfunction in healthy individuals. OBJECTIVE: To assess the impact of different degrees of insulin resistance, measured by HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), on endothelial function in obese, non-diabetic patients without prior history of cardiovascular events and different metabolic syndrome components. METHODS: Forty obese individuals were submitted to anthropometric measurements, BP measurements at office and ABPM and laboratory tests, in addition to non-invasive ultrasound assessment of endothelial function. Patients were divided into 3 groups according to the level of insulin resistance: patients with HOMA-IR values from 0.590 to 1.082 were assigned to Group 1 (n=13), from 1.083 to 1.410 to Group 2 (n=14) and from 1.610 to 2.510 to Group 3 (n=13). RESULTS: We found a significant difference in flow-mediated dilation in group 3 compared to group 1 (9.2 ± 7.0 vs 18.0 ± 7.5 %, p=0.006). There was a negative correlation between endothelial function and insulin, HOMA-IR and triglycerides. CONCLUSION: Our data suggest that mild changes in insulin resistance levels assessed by HOMA-IR may have an impact on vasodilatatory endothelial function in uncomplicated obese individuals with different cardiovascular risk factors.

Efeitos de diferentes graus de sensibilidade a insulina na função endotelial de pacientes obesos / Effects of different degrees of insulin sensitivity on endothelial function in obese patients / Efectos de diferentes grados de sensibilidad a la insulina en la función endotelial de pacientes obesos

FUNDAMENTO: A obesidade derivada da deposição de gordura intra-abdominal tende a aumentar a produção de hormônios e citoquinas, piorando a sensibilidade a insulina e levando a disfunção endotelial. A hiperinsulinemia é considerada um fator de risco independente para doença isquêmica cardíaca e é uma causa de disfunção endotelial em indivíduos saudáveis. OBJETIVO: Avaliar o impacto de diferentes graus de resistência a insulina, medida pelo HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), sobre a função endotelial de obesos, pacientes não diabéticos, sem história prévia de eventos cardiovasculares e diversos componentes da síndrome metabólica. MÉTODOS: Um total de 40 indivíduos obesos foi submetido a medidas antropométricas, pressão arterial de consultório, MAPA e exames laboratoriais, além de avaliação ultrassonográfica não invasiva da função endotelial. Os pacientes foram divididos em três grupos de acordo com o grau de resistência a insulina: pacientes com valores de HOMA-IR entre 0,590 e 1,082 foram incluídos no Grupo 1 (n = 13); entre 1,083 e 1,410 no Grupo 2 (n = 14); e entre 1,610 e 2,510 no Grupo 3 (n = 13). RESULTADOS: Encontramos uma diferença significativa na vasodilatação mediada por fluxo no Grupo 3 em relação ao Grupo 1 (9,2 ± 7,0 vs 18,0 ± 7,5 por cento, p = 0,006). Houve uma correlação negativa entre a função endotelial e insulina, HOMA-IR e triglicérides. CONCLUSÃO: Nosso estudo sugere que leves alterações nos níveis de resistência a insulina avaliada pelo HOMA-IR podem causar algum impacto sobre a função vasodilatadora do endotélio em indivíduos obesos não complicados com diferentes fatores de risco cardiovascular.

BACKGROUND: Obesity derived from intra-abdominal fat deposition tends to increase hormonal and cytokine production, thus worsening insulin sensitivity and leading to endothelial dysfunction. Hyperinsulinemia is considered an independent risk factor for ischemic heart disease and cause of endothelial dysfunction in healthy individuals. OBJECTIVE: To assess the impact of different degrees of insulin resistance, measured by HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), on endothelial function in obese, non-diabetic patients without prior history of cardiovascular events and different metabolic syndrome components. METHODS: Forty obese individuals were submitted to anthropometric measurements, BP measurements at office and ABPM and laboratory tests, in addition to non-invasive ultrasound assessment of endothelial function. Patients were divided into 3 groups according to the level of insulin resistance: patients with HOMA-IR values from 0.590 to 1.082 were assigned to Group 1 (n=13), from 1.083 to 1.410 to Group 2 (n=14) and from 1.610 to 2.510 to Group 3 (n=13). RESULTS: We found a significant difference in flow-mediated dilation in group 3 compared to group 1 (9.2±7.0 vs 18.0±7.5 percent, p=0.006). There was a negative correlation between endothelial function and insulin, HOMA-IR and triglycerides. CONCLUSION: Our data suggest that mild changes in insulin resistance levels assessed by HOMA-IR may have an impact on vasodilatatory endothelial function in uncomplicated obese individuals with different cardiovascular risk factors.

FUNDAMENTO: La obesidad derivada del depósito de grasa intraabdominal tiende a aumentar la producción de hormonas y citocinas, empeorando la sensibilidad a la insulina y llevando a disfunción endotelial. La hiperinsulinemia es considerada un factor de riesgo independiente para enfermedad isquémica cardíaca y es una causa de disfunción endotelial en individuos sanos. OBJETIVO: Evaluar el impacto de diferentes grados de resistencia a la insulina, medida por el HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), sobre la función endotelial de obesos, pacientes no diabéticos, sin historia previa de eventos cardiovasculares y diversos componentes del síndrome metabólico. MÉTODOS: Un total de 40 individuos obesos fue sometido a medidas antropométricas, presión arterial de consultorio, MAPA y exámenes de laboratorio, además de evaluación ultrasonográfica no invasiva de la función endotelial. Los pacientes fueron divididos en tres grupos de acuerdo con el grado de resistencia a insulina: pacientes con valores de HOMA-IR entre 0,590 y 1,082 fueron incluidos en el Grupo 1 (n = 13); entre 1,083 y 1,410 en el Grupo 2 (n = 14); y entre 1,610 y 2,510 en el Grupo 3 (n = 13). RESULTADOS: Encontramos una diferencia significativa en la vasodilatación mediada por flujo en el Grupo 3 en relación al Grupo 1 (9,2 ± 7,0 vs 18,0 ± 7,5 por ciento, p = 0,006). Hubo una correlación negativa entre la función endotelial e insulina, HOMA-IR y triglicéridos. CONCLUSIÓN: Nuestro estudio sugiere que leves alteraciones en los niveles de resistencia a la insulina evaluada por el HOMA-IR pueden causar algún impacto sobre la función vasodilatadora del endotelio en individuos obesos no complicados con diferentes factores de riesgo cardiovascular.

Intima-media thickness is associated with inflammation and traditional cardiovascular risk factors in non-dialysis-dependent patients with chronic kidney disease.

BACKGROUND: Mortality due to cardiovascular causes is high in chronic kidney disease (CKD). Intima-media thickness (IMT) and inflammation are early atherosclerosis markers, although data are lacking about their association in the CKD non-dialysis-dependent (CKD-NDD) population. The aim of the present study was to evaluate the association between IMT, inflammation and other cardiovascular risk factors in such patients. METHODS: CKD-NDD patients (n = 122) were subjected to measurements of carotid IMT and inflammatory marker levels in a cross-sectional study. RESULTS: Mean patient age was 55.2 +/- 11.3 years (61.5% males). Median C-reactive protein (CRP) was 0.28 mg/dl (0.03-14.2). The median interleukin (IL)-6 count was 4.75 pg/ml (0.7-243), the mean adiponectin was 27.8 +/- 7.3 ng/ml and the mean IMT was 0.61 +/- 0.19 mm. Four (3.3%) patients had IMT above the normal range. IMT was higher in males (p < 0.001), patients with estimated glomerular filtration rate <60 ml/min (p = 0.030), inflammation (p = 0.005) and higher IL-6 levels (p = 0.023). IMT was correlated with age (R = 0.538; p < 0.001), waist circumference (R = 0.235; p = 0.016), CRP (R = 0.191; p = 0.035) and systolic blood pressure (R = 0.181; p = 0.048). In a multiple regression analysis, the independent determinants of IMT were age (beta = 0.512; p < 0.001) and CRP levels (beta = 0.159; p = 0.041). CONCLUSION: The present study demonstrated that although the IMT values were within the normal range, there was a clear association of IMT with age, as well as with inflammation in an asymptomatic CKD-NDD population.

Pulse wave velocity--a useful tool for cardiovascular surveillance in pre-dialysis patients.

BACKGROUND: Cardiovascular mortality is high among patients with chronic kidney disease. Pulse wave velocity (PWV) is a simple method used for arterial distensibility evaluation. Few data are available concerning PWV in pre-dialysis patients. The aim of this study was to evaluate the association between PWV and cardiovascular disease in pre-dialysis. METHODS: One hundred and four patients were submitted to PWV analysis, coronary artery calcium (CAC) determination with a multi-slice CT scan of the coronary arteries, echocardiogram and a carotid intima-media thickness (IMT) evaluation, with a high resolution ultrasound. The demographic characteristics and laboratory tests results were studied. RESULTS: The mean age of those studied was 54.4 +/- 11.5 years, 60% were males and the mean creatinine clearance was 40 ml/min/1.73 m(2). The mean PWV was 12.2 +/- 3.4 m/s and it was significantly higher in males, diabetics, those with creatinine clearance <60 ml/min and proteinuria > or =1 g/24 h. PWV was correlated with systolic blood pressure, age, triglycerides, total cholesterol and 24 h proteinuria. In the multiple regression analysis, PWV was significantly associated with diabetes, age, systolic blood pressure and cholesterol. Fifty-eight patients (56%) presented coronary calcification and PWV correlated with coronary calcium score (R = 0.48; P < 0.001) and calcium volume (R = 0.50; P < 0.001). Moreover, PWV was higher in patients with coronary calcification (13.4 +/- 3.6 m/s vs 10.7 +/- 2.4 m/s; P < 0.001). The mean left ventricular mass index (LVMI) was 106 +/- 31 g/m(2) and 24% of patients had left ventricular hypertrophy, while 19 (18.3%) patients had left ventricular dysfunction. PVW was correlated with LVMI (R = 0.25; P = 0.01) while no association could be seen between PWV and the ejection fraction or left ventricular dysfunction. A correlation between the IMT and PWV was observed (R = 0.27; P = 0.005). In addition, those with a thicker IMT had a higher PWV (13.2 +/- 3.4 m/s vs 11. 2 +/- 3.2 m/s; P = 0.003). CONCLUSION: PWV is associated with cardiovascular disease in pre-dialysis patients and can be a useful tool to identify patients with increased cardiovascular risk.

Effects of low birth weight in 8- to 13-year-old children: implications in endothelial function and uric acid levels.

Low birth weight has been associated with an increased incidence of adult cardiovascular disease. Endothelial dysfunction and high levels of serum uric acid are associated with hypertension. In this study, we have determined whether uric acid is related to blood pressure and vascular function in children with low birth weight. We evaluated vascular function using high-resolution ultrasound, blood pressure, and uric acid levels in 78 children (35 girls, 43 boys, aged 8 to 13 years). Increasing levels of uric acid and systolic blood pressure were observed in children with low birth weight. Birth weight was inversely associated with both systolic blood pressure and uric acid; on the other hand, uric acid levels were directly correlated with systolic blood pressure in children of the entire cohort. Low birth weight was associated with reduced flow-mediated dilation (r=0.427, P<0.001). Because the children with low birth weight had elevated uric acid as well as higher systolic blood pressure levels, we evaluated the correlation between these variables. In the low birth weight group, multiple regression analysis revealed that uric acid (beta=-2.886; SE=1.393; P=0.040) had a graded inverse relationship with flow-mediated dilation, which was not affected in a model adjusting for race and gender. We conclude that children with a history of low birth weight show impaired endothelial function and increased blood pressure and uric acid levels. These findings may be early expressions of vascular compromise, contributing to susceptibility to disease in adult life.

[Endothelial function of normotensive adolescents with no risk factors for arterial hypertension]. / Função endotelial de adolescentes normotensos sem fatores de risco para hipertensão arterial.

OBJECTIVE: To define standards for normal endothelial function in adolescents by high-resolution ultrasound measurement of endothelium-dependent vascular dilatation. METHODS: This was a cross-sectional, descriptive, observational study and part of the thematic project "Clinical Study of Growth, Behavior, Arterial Hypertension, Obesity and Oral Health" (ECCCHOS) that was developed by the Discipline of Nutrition at the Universidade Federal de São Paulo. Thirty-one adolescents, eight male and twenty-three female, with no risk factors for systemic arterial hypertension were selected from 1,420 secondary school students. The students were daytime pupils at a school in the southeastern district of the city of São Paulo, the capital of São Paulo state, located in the Southeast region of Brazil. All results are presented in the form of means with standard deviations and percentiles. RESULTS: For male students, endothelium-dependant dilation 90 seconds after the cuff was released was 20.9+/-6.7% [mean +/-1 standard deviation] with a 10th percentile of 12.5 and for females these figures were 18.8+/-12.9% with a 10th percentile of 6.6%. Values for the whole group of subjects were 19.3+/-11.7% and 6.7%, respectively. CONCLUSION: Endothelium-dependant vascular dilation of 6.7%, after 90 seconds, which corresponds to the 10th percentile, can be considered the lower limit of normality for this age group. Knowledge of this limit is important for the diagnosis of endothelium dysfunction that appears before cardiovascular disease.

Função endotelial de adolescentes normotensos sem fatores de risco para hipertensão arterial / Endothelial function of normotensive adolescents with no risk factors for arterial hypertension

OBJETIVO: Definir padrões de normalidade da função endotelial de adolescentes através de avaliação ultra-sonográfica da dilatação vascular dependente do endotélio. MÉTODOS: Estudo descritivo observacional de corte transversal, parte do projeto temático "Estudos Clínicos de Crescimento, Comportamento, Hipertensão Arterial, Obesidade e Saúde Bucal", de sigla ECCCHOS, desenvolvido na Disciplina de Nutrologia da Universidade Federal de São Paulo - Escola Paulista de Medicina. Foram selecionados 31 adolescentes, sendo oito do sexo masculino e 23 do feminino, sem fatores de risco conhecidos para hipertensão arterial sistêmica, entre 1.420 alunos de uma escola de ensino médio da cidade de São Paulo, capital do estado de São Paulo, situado no Sudeste do Brasil. Para apresentação de todos os resultados, utilizaram-se as médias, desvios padrão e percentis. RESULTADOS: A dilatação vascular dependente do endotélio 90 segundos pós-liberação do manguito foi de 20,9±6,7 por cento [média mais ou menos 1 desvio padrão (DP)] e o 10° percentil ficou em 12,5 por cento no sexo masculino e de 18,8±12,9 por cento DP e o 10° percentil em 6,6 por cento no sexo feminino. Os valores no grupo todo foram de 19,3±11,7 por cento e 6,7 por cento, respectivamente. CONCLUSÃO: O 10° percentil (6,7 por cento) da curva de distribuição dos valores de dilatação vascular dependente do endotélio, em adolescentes do presente estudo, pode ser considerado como limite inferior da normalidade. O conhecimento desse limite é importante para o diagnóstico de disfunções endoteliais que aparecem antes das doenças cardiovasculares.

Diagnostic value of attenuation measurements of the kidney on unenhanced helical CT of obstructive ureterolithiasis.

OBJECTIVE: The objective of this study was to assess the diagnostic value of attenuation measurements of the kidney on unenhanced helical CT in patients with obstructive ureterolithiasis. MATERIALS AND METHODS: Consecutive unenhanced helical CT scans of patients referred for acute unilateral renal colic were retrospectively reviewed. Patients with CT evidence of other urinary system diseases were excluded. Included scans (n = 145) were assessed for ureteral stone and secondary signs of obstruction such as unilateral collecting system or ureteral dilatation, perinephric stranding, and periureteral edema. Renal attenuation in Hounsfield units was measured in the upper, middle, and lower portions of the parenchyma, and a mean value was determined for each kidney. RESULTS: Ureteral stones were present in 76 patients. Renal attenuation on the side with lithiasis was lower than on the opposite kidney: 27.2 +/- 3.9 H vs 32.6 +/- 3.4 H (p < 0.001). Attenuation differences between kidneys were higher for patients with ureterolithiasis: 5.4 +/- 3.2 H (range, -3.3 to 13.0 H) versus 1.2 +/- 1.0 H (range, 0-4.7 H) (p < 0.001). An attenuation difference between kidneys greater than or equal to 5.0 H had 61% sensitivity, 100% specificity, 100% positive predictive value, 69% negative predictive value, and 79% accuracy for diagnosis of ureteral lithiasis. CONCLUSION: Attenuation difference between kidneys greater than or equal to 5.0 H was a valuable sign and had diagnostic performance similar to other secondary signs of obstructive ureterolithiasis. Furthermore, attenuation difference had the advantage of being an objective, measurement-based indicator.

Estudo ultra-sonográfico em joelhos de recém-nascidos normais / Ultrasonographic study of knees of normal newborns

Os autores apresentam análise ultra-sonográfica de 62 joelhos normais de 31 crianças recém-nascidas, todas com dois dias de idade, sendo 18 do sexo masculino e 13 do feminino. A avaliaçäo das dimensões da patela mostrou: espessura variando de 0,45cm a 0,75cm, com média de 0,57cm; comprimento de 1,00cm a 1,84cm, com média de 1,24cm; largura de 1,13cm a 1,80cm, com média de 1,39cm; faceta articular de 0,70cm a 1,00cm, com média de 0,86cm; comprimento do tendäo patelar de 1,44cm a 2,52cm, com média de 2,16cm. A altura patelar foi avaliada pelos índices de Blackburne-Peel (variaçäo de 0,73 a 1,42 e média de 0,99) e Insall-Salvati (variaçäo de 1,14 a 2,39 e média de 1,75). Avaliou-se ainda o ângulo do sulco intercondilar (AS), que apresentou valores semelhantes ao do adulto (variaçäo de 132º a 152° e média de 144°). Outros parâmetros, como largura do sulco intercondilar (LS), largura das epífises femoral e tibial e seus respectivos núcleos de crescimento ossificado, foram medidos. O ultra-som mostrou ser um bom método de avaliaçäo do joelho no recém-nascido

Is the number of microembolic signals related to neurologic outcome in coronary bypass surgery?

Coronary artery bypass surgery (CABG) without cardiopulmonary bypass (CPB) may potentially reduce the number of microembolic signals (MES) associated with aortic manipulation or generated by the pump circuit, resulting in a better neurologic outcome after surgery. Our aim was to compare the frequency of MES and neurologic complications in CABG with and without CPB. Twenty patients eligible to routine CABG without CPB were randomized to surgery with CPB and without CPB and continuously monitored by transcranial Doppler. Neurologic examination was performed in all patients before and after surgery. The two groups were similar with respect to demographics, risk factors, grade of aortic atheromatous disease and number of grafts. The frequency of MES in the nonCPB group was considerably lower than in CPB patients, however, we did not observe any change in the neurologic examination during the early postoperative period. Neurologic complications after CABG may be related to the size and composition of MES rather than to their absolute numbers. A large prospective multicentric randomized trial may help to elucidate this complex issue