ABSTRACT
RESUMO Objetivo: Investigar se a hiperemia reativa correlaciona-se com marcadores de disfunção endotelial e pode ser utilizada para identificar sepse na doença crítica. Métodos: Trata-se de estudo prospectivo em uma coorte de pacientes críticos. A disfunção endotelial foi avaliada quando da admissão, por meio da quantificação de hiperemia por tonometria arterial periférica e níveis plasmáticos de endotelina 1, E-selectina solúvel, endocana e sindecano 1. Os pacientes sépticos foram comparados com pacientes sem evidência de infecção. Resultados: Cinquenta e oito pacientes sépticos foram comparados com 28 controle. O logaritmo natural da tonometria arterial periférica teve correlação negativa com comorbidades cardiovasculares, severidade da doença e níveis plasmáticos de E-selectina solúvel (p = 0,024) e sindecano 1 (p < 0,001). O logaritmo natural da tonometria arterial periférica foi mais baixo nos pacientes sépticos quando comparado com os de pacientes controle (0,53 ± 0,48 versus 0,69 ± 0,42, respectivamente) e, quando ajustado à idade, o modelo multivariado predisse que cada 0,1 de diminuição em unidades de logaritmo natural da tonometria arterial periférica levou a aumento de 14,6% na probabilidade de infecção. Conclusão: A hiperemia reativa avaliada por tonometria arterial periférica tem estreita relação com E-selectina solúvel e sindecano 1, o que sugere associação entre ativação endotelial, degradação de glicocálix e reatividade vascular. A hiperemia reativa por tonometria arterial periférica parece estar comprometida em pacientes críticos, especialmente os com sepse.
Abstract Objective: To investigate whether reactive hyperemia measured by peripheral arterial tonometry correlates with markers of endothelial dysfunction and may be used to identify sepsis in critical illness. Methods: A prospective study was performed using a cohort of critically ill patients. Endothelial dysfunction was assessed on admission by quantifying reactive hyperemia-peripheral arterial tonometry and plasma levels of endothelin-1, soluble E-selectin, endocan and syndecan-1. Septic patients were compared to patients without evidence of infection. Results: Fifty-eight septic patients were compared to 28 controls. The natural logarithm of reactive hyperemia-peripheral arterial tonometry was negatively correlated with cardiovascular comorbidities, disease severity and plasma levels of soluble E-selectin (p = 0.024) and syndecan-1 (p < 0.001). The natural logarithm of reactive hyperemia-peripheral arterial tonometry was lower in septic patients than in controls (0.53 ± 0.48 versus 0.69 ± 0.42, respectively). When adjusted for age, the multivariable model predicted that each 0.1-unit decrease in natural logarithm of reactive hyperemia-peripheral arterial tonometry increased the odds for infection by 14.6%. m. Conclusion: Reactive hyperemia-peripheral arterial tonometry is closely related to soluble E-selectin and syndecan-1, suggesting an association between endothelial activation, glycocalyx degradation and vascular reactivity. Reactive hyperemia-peripheral arterial tonometry appears to be compromised in critically ill patients, especially those with sepsis.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Sepsis/diagnosis , Glycocalyx/metabolism , Hyperemia/etiology , Severity of Illness Index , Endothelium, Vascular/physiopathology , Biomarkers/blood , Prospective Studies , Cohort Studies , Critical Illness , Sepsis/blood , E-Selectin/metabolism , Syndecan-1/metabolism , Intensive Care Units , ManometryABSTRACT
El sobrepeso infantil se asocia a sobrepeso/obesidad en la edad adulta y constituye un factor de riesgo de diabetes y enfermedad cardiovascular. La disfunción endotelial es la etapa inicial de ateroesclerosis y precede a las evidencias anatómicas más tempranas de la misma. Este proceso está regulado por moléculas de adhesión localizadas en la superficie de leucocitos y células endoteliales y que tendrían un papel importante en la predicción de los eventos cardiovasculares. Entre estas moléculas, la E-Selectina (E-S) es una glicoproteína que se expresa exclusivamente en las células endoteliales activadas, en respuesta a citoquinas inflamatorias. Se ha sugerido que niveles aumentados de forma solubles de E-Selectina (sE-S) podrían ser marcadores específicos del endotelio vascular dañado. El objetivo de este trabajo fue determinar los niveles plasmáticos de sE-S en niños y adolescentes con sobrepeso y su relación con variables antropométricas y bioquímicas. Se estudiaron 40 niños con sobrepeso, de edades comprendidas entre 7 y 14 años y 20 niños controles de edad y sexo semejantes. Se consideró criterio de inclusión un IMC ≥ al percentilo 85 y menor al percentilo 95 para edad y sexo. Se determinó circunferencia de cintura (CC), IMC, estadio de Tanner y presión arterial. En ambos grupos se analizó: glucemia en ayunas, insulina plasmática, fibrinógeno (Fg), proteína C reactiva ultrasensible (uPCR), sE-S en plasma y perfil lipídico. Los datos se expresaron como mediana y rango intercuartil, empleándose el coeficiente de Spearman para las correlaciones entre variables. En los sujetos con sobrepeso fueron mayores los niveles de sE-S [72,0 (50,5-92,5) vs. 24,0(18,5-35,0) ng/ml; p = 0,0001], uPCR [1,9 (0,8-4,4) vs. 0,3 (0,2-1,1) mg/l; p = 0,001], Fg [350 (315-460) mg/dl vs. 247 (235-265) mg/dl; p = 0,0001]. También resultaron elevados los valores de insulina y triglicéridos. La sE-S se correlacionó con CC (r = 0,40; p = 0,02), uPCR (r = 0,58; p = 0,0001) y Fg (r = 0,50; p = 0,004). Estos resultados sugieren la presencia de activación endotelial y estado proinflamatorio en la población estudiada, destacándose la importancia del control del peso en los niños con el fin de reducir el riesgo cardiovascular en la adultez. Los autores declaran no poseer conflictos de interés.
Childhood overweight is associated to overweight/obesity adulthood and it is a risk factor for diabetes and cardiovascular disease. Endothelial dysfunction is the initial stage of atherosclerosis and precedes earliest anatomical evidence thereof. This process is regulated by adhesión molecules located on the surface of leucocytes and endothelial cells and would have an important role in the prediction of cardiovascular events. Between these molecules, E-selectin (E-S) is a glycoprotein that is express exclusively on activated endothelial cells in response to inflammatory cytokines. It has suggested that increases of soluble form of E-S (sE-S) could be an specific marker of damaged vascular endhotelium. The aim of this study was determine plasma levels of sE-S in overweight children and its relationship with anthropometric and biochemical variables. Forty overweight children aged between 7 to 14 years, and 20 control children of similar age and sex, were studied. Inclusión criteria was a BMI ≥ 85th percentile and below 95th percentile, for age and sex. Waist circunference (WC), BMI, Tanner stage and blood pressure were determined. In both groups fasting blood glucose and insulin, fibrinogen (Fg), high sensitivity C-reactive protein (hsCRP), sE-S and lipid profile were analyzed. The data were analyzed with the SPSS 15.0 program for Windows, expressed as the median and interquartile range. The Spearman's coefficient were used to measure correlations between the studied variables. Overweight subjects presented higher levels of sE-S [72.0 (50.5-92.5) vs. 24.0 (18.5-5,0) ng/ml, p = 0.0001], hsCPR [1.9 (0.8-4.4) vs. 0.3 (0.2-1.1) mg/l, p = 0.001], Fg [350 (315-460) vs. 247 (235-265) mg/dl, p = 0.0001]. Also insulin and triglycerides values were elevated. sE-S was correlated positivily with WC (r = 0.40, p = 002), hs PCR (r = 0.58, p = 0.0001) and Fg (r = 0.50, p = 0.004). These results suggest the presence of endothelial activation and a proinflammatory state in the studied population, and highlight the importance of weight control in children to reduce cardiovascular risk in adulthood. The authors do not have conflicts of interest.
ABSTRACT
El estado de hiperglucemia crónica en los pacientes diabéticos produce una agresión al endotelio vascular, conduciendo al desarrollo prematuro de ateroesclerosis. El objetivo de este trabajo fue determinar niveles de E-selectina soluble (sE-S) en una población infanto-juvenil con diabetes tipo1 (DT1) y su relación con el control glucémico y el perfil lipídico. Se estudiaron 30 pacientes con DT1 (16 mujeres y 14 varones), de edades comprendidas entre 6 y 15 años, comparados con 20 sujetos controles. Se determinaron: sE-S, glucemia en ayunas, hemoglobina glicosilada (HbA1c), colesterol total (CT), HDL-C, LDL-C, no HDL-C y triglicéridos (TG). Los niveles de sE-S fueron 66% más altos en los diabéticos que en los sujetos controles (p = 0.0001). Los pacientes fueron agrupados en: diabéticos con buen control glucémico (DBCG, HbA1c < 8%) y diabéticos con pobre control glucémico (DPCG, HbA1c > 8%). La concentración de sE-S en DPCG y en DBCG fue: 111.3 ± 40.5 vs. 68.0 ± 11.3 ng/ml, respectivamente p = 0.02. En los diabéticos la incidencia de valores no deseables en el perfil lipídico fue: CT: 50%; HDL-C 14%; LDL-C 52%, no HDL-C 26.7% y TG 14%. La sE-S se correlacionó mejor con HbA1c (r = 0.53, p = 0.0001) que con la glucemia en ayunas (r = 0.36, p = 0.008) y CT (r = 0.36, p = 0.009). De los resultados obtenidos se sugiere que la sE-S es un marcador temprano de disfunción endotelial y de probable riesgo de aterosclerosis en pacientes infanto-juveniles con DT1.
The chronic hyperglycemic state in diabetic patients produces an aggression to the vascular endothelium leading to a premature development of atherosclerosis. The objective of this paper was to determine the soluble E-selectin (sE-S) levels in children with type 1 diabetes (DT1) and its relationship with glycemic control and lipid profile. Thirty patients with DT1, (16 girls and 14 boys), age between 6 and 15 years were studied, whose data were compared with 20 control subjects. In both groups sE-S was determined as well as fasting glycemia, glycosylated hemoglobin (HbA1c), total cholesterol (TC), HDL-C, LDL-C, non-HDL-C and triglycerides (TG). sE-S values were 66% higher in diabetics than in control subjects (p = 0.001). Patients were grouped in: good glycemic control diabetics (GGCD, HbA1c < 8%) and poor glycemic control diabetics (PGCD, HbA1c > 8%). sE-S concentratios were in PGCD an GGCD respectively. 111.3 ± 40.5 vs 68.0 ± 11.3 ng/ml, p = 0.02. In the diabetic group, the incidence of non desirable values in the lipid profile parameters were: TC 50%; HDL-C 14%; LDL-C 52%, non-HDL-C 26.7% and TG 14%. sE-S values were better correlated with HbA1c (r = 0.53, p = 0.0001) than fasting glycemia (r = 0.36, p = 0.008), and CT (r = 0.36, p = 0.009). These results suggest that sE-S is an early marker of endothelial dysfunction and a probable risk marker of atherosclerosis in children with DT1.