Remodelado vascular excéntrico: su relación con trastornos metabólicos y el incremento de la masa corporal / Eccentric Vascular Remodeling: Its Relationship with Metabolic Disorders and Increased Body Mass

RESUMEN Introducción: Existe evidencia reciente que establecería a la hipoperfusión muscular como causa primaria de trastornos metabólicos en respuesta a la sobrealimentación. Esta concepción centrípeta del desarrollo de trastornos metabólicos podría implicar no solo alteraciones en la microvasculatura, sino también afectación en las arterias de conductancia. Objetivos: 1) Determinar la asociación entre diámetro basal de la arteria humeral (D-Hum) y la vasodilatación mediada por flujo (VDMF) 2) Analizar la asociación de ambos parámetros conforme aumenta de la masa corporal 3) Evaluar asociaciones entre el D-Hum/VDMF con componentes del síndrome metabólico (SM) 4) Evaluar la asociación independiente de ambas variables con el SM. Material y métodos: Se evaluaron 3493 pacientes. Se excluyeron pacientes < 18 y >80 años, con patología cardiovascular previa, insuficiencia renal crónica (IRC), colagenopatías, y tratados con estatinas. Se determinó presión arterial (PA), parámetros antropométricos y perfil metabólico, y se clasificó a los sujetos de acuerdo con la presencia de SM según AHA/NHLBI 2019. Se midieron D-Hum en mm y VDMF en %. Se analizó la asociación lineal entre D-Hum y VDMF y se analizaron ambas variables según decilos de índice de masa corporal (IMC). Se evaluaron asociaciones entre D-Hum/VDMF con la PA, glucemia (Glu), triglicéridos (TG) y colesterol de alta densidad (HDLc). Se realizaron dos regresiones logísticas con SM como variable dependiente y D-Hum o VDMF más edad, sexo, IMC y factores de riesgo coronario (FRC) como independientes. Resultados: Ingresaron 1995 pacientes (48,2 ± 11 años, 56 % hombres). El D-Hum y la VDMF presentaron una asociación inversa (r= -0,42; p < 0,0001). El D-Hum aumentó según decilos del IMC (p < 0,000001); la VDMF mostró relación inversa con los decilos crecientes de IMC (p < 0,000001). El D-Hum presentó correlación directa con PA, Glu y TG; e inversa con HDLc (p < 0,05 en todos los casos). La VDMF mostró correlación inversa con PA, Glu y TG; y directa con HDLc (p < 0,05 en todos los casos). El D-Hum se asoció en forma independiente con el SM ajustado por edad, sexo, IMC y FRC (OR 1,42, p = 0,0019), mientras que la VDMF no (OR 0,98, p = 0,217). Conclusión: El remodelado vascular excéntrico se asoció con un compromiso en la adaptación vascular ante aumentos en la demanda de flujo sanguíneo y con alteraciones metabólicas a lo largo del incremento de la masa corporal. Así, el compromiso dinámico de la vasculatura podría tener un rol determinante en el desarrollo de alteraciones metabólicas en forma sincrónica con la ganancia de peso.

ABSTRACT Background: Recent evidence would establish muscle hypoperfusion as the primary cause of metabolic disorders in response to overfeeding. This centripetal concept on the development of metabolic disorders could involve not only alterations in the microvasculature, but also affect the conductance arteries. Objectives: The aim of this study was 1) to determine the association between baseline brachial artery diameter (BAD) and flow-mediated vasodilation (FMVD), 2) To analyze the association of both parameters throughout the increase in body mass, 3) To evaluate associations between BAD/FMVD with components of the metabolic syndrome (MS) and 4) To evaluate the independent association of both variables with MS. Methods: A total of 3493 patients were evaluated. Patients <18 and >80 years old, those with previous cardiovascular disease, chronic kidney disease (CKD), collagenopathies, or treated with statins were excluded from the study. Blood pressure (BP), anthropometric parameters and metabolic profile were determined, and the subjects were classified according to the presence of MS conforming AHA/NHLBI 2019 criteria. BAD was measured in mm and FMVD as percentage. The linear association between BAD and FMVD was assessed, and both variables were analyzed according to deciles of body mass index (BMI). Associations between BAD/FMVD with BP, glucose (Glu), triglycerides (TG) and high-density cholesterol (HDL-C) levels were evaluated. Two logistic regression analyses were performed with MS as dependent variable and BAD or FMVD plus age, gender, BMI, and coronary risk factors (CRF) as independent variables. Results: A total of 1995 patients (48.2 ± 11 years, 56% men) were admitted in the study. An inverse correlation was found between BAD and FMVD (r= -0.42; p < 0.0001). BAD increased according to deciles of BMI (p < 0.000001), while FMVD showed an inverse relationship with increasing deciles of BMI (p < 0.000001). BAD exhibited a direct correlation with BP, Glu and TG; and an inverse relationship with HDL-C (p < 0.05 in all cases). FMVD presented an inverse correlation with BP, Glu and TG; and a direct correlation with HDL-C (p < 0.05 in all cases). BAD was independently associated with MS adjusted for age, gender, BMI and CRF (OR 1.42, p=0.0019), while FMVD was not (OR 0.98, p = 0.217). Conclusion: Eccentric vascular remodeling was associated with vascular adaptation to increased blood flow demand and with metabolic alterations throughout the increase in body mass. Thus, the dynamic compromise of vasculature could play a decisive role in the development of metabolic alterations occurring synchronously with weight gain.

The Evaluation of Flow-Mediated Vasodilation in the Brachial Artery Correlates With Endothelial Dysfunction Evaluated by Nitric Oxide Synthase Metabolites in Marfan Syndrome Patients.

Marfan syndrome (MS) is of the most common connective tissue disorders. Although most patients have mutations in the fibrillin-1 gene (FBN1) and more than 1,700 mutations have been described, there are no mutations in less than 10% of patients. Aortic dilation is the most important complication; it involves chronic inflammatory processes and endothelial dysfunction. Prospective study from March 2015 to January 2017, in a cohort of 32 patients of MS confirmed by Ghent criteria and 35 controls of both genders, with a median age of 26 years (18-56). Patients had no comorbidities such as diabetes, hypertension, and/or neoplasms. They were not being treated with statin, NSAIDs, calcium antagonists, oral nitrates, and/or beta-blockers during 7 days prior to the study and patients with smoking history in the last 4 years. Controls were matched by age and gender. We analyzed endothelial dysfunction by flow-mediated vasodilation in the brachial artery, determining the maximum peak flow in the reactive hyperemia phase with a Philips Envisor device with Doppler capability. Its correlation with serum levels of biological markers that could participate in endothelial dysfunction pathways such as NO3-/NO2- ratio, NO2- , citrulline, TNFα, IL-1, IL-6, IL-10, IL-8, osteopontin, ICAM, VCAM, and NO3-/NO2- was determined. Endothelial dysfunction was found in 21 MS patients (65%). The aortic annulus (AAo) was of 27 mm (22-40) and 24 mm (22-30) (p = 0.04) in MS patients with and without dysfunction. The level of NO3-/NO2- ratio, was of 108.95 ± 12.05 nM/ml in controls vs. 170.04 ± 18.76 nM/ml in MS (p = 0.002), NO2- was of 33.78 ± 3.41 vs. 43.95 ± 2.59 nM/ml (p = 0.03), citrulline 62.65 ± 3.46 vs. 72.81 ± 4.35 µMol/ml (p = 0.06). VCAM median was 39 pg/ml (0-86) vs. 32 pg/ml (11-66) (p = 0.03), respectively. The correlation of VCAM with triglycerides (TG) was of 0.62 (p = 0.005). There were no differences in TNFα, IL-1, IL-6, IL-8, IL-10, and osteopontin. MS endothelial dysfunction is related to aortic diameters, and increased levels of VCAM, L-citrulline and NO3-/NO2- ratio, NO2- . VCAM-1 has a significant correlation with TG and could play a significant role in endothelial dysfunction.

Flow mediated vasodilation compared with carotid intima media thickness in the evaluation of early cardiovascular damage in menopausal women and the influence of biological and psychosocial factors.

BACKGROUND: Women after menopause increase risk for cardiovascular disease and several factors may be related. The purpose was to study biological and psychosocial factors associated with early cardiovascular damage in pre- and postmenopausal women, assessed with carotid intima-media thickness vs flow-mediated dilatation. METHODS: Women 45 to 57 years old were grouped in the pre- (n = 60), early (n = 58) and late post-menopause (n = 59). Anthropometric, metabolic and hormonal data were registered, as well as measures of depression, anxiety, submission, perceived stress, and sleep alterations. Heart Rate Variability was recorded to obtain the information regarding sympathovagal balance. Carotid intima-media thickness and flow-mediated dilatation were assessed by ultrasound. Two-way ANOVA and multiple regression model were used. RESULTS: At late postmenopause, the carotid intima-media was thicker (p < 0.001) and flow-mediated dilatation decreased (p < 0.001). Carotid intima-media thickness was associated positively with age (p < 0.001), submission score (p = 0.029), follicle stimulating hormone levels (p < 0.001), and body mass index (p = 0.009). Flow-mediated dilatation was associated only with age (p < 0.001). Regarding heart rate variability, the time domain pNN50 measurement was higher in premenopausal women (p = 0.001), Low Frequency (LF) was higher in the two groups of postmenopausal (p = 0.001) and High Frequency (HF) higher in the early postmenopausal women (p = 0.042). CONCLUSIONS: Under our conditions carotid intima-media thickness had higher predictive value for early cardiovascular damage at menopause. The finding of the association of the submission score, indicates de influence of stress on vascular damage.

Endothelial dysfunction assessment by flow-mediated dilation in a high-altitude population.

INTRODUCTION: Endothelial function at high altitude has been measured only in populations that are genetically adapted to chronic hypoxia. The objective of this study was to evaluate endothelial dysfunction (ED) in a nongenetically adapted high-altitude population of the Andes mountains, in Huancayo, Peru (3,250 meters above sea level). METHODS: Participants included 61 patients: 28 cases and 33 controls. The cases were subjects with hypertension, diabetes mellitus, obesity, or a history of stroke or coronary artery disease. Flow-mediated vasodilation (FMD) of the brachial artery was measured in the supine position, at noon, after 5 minutes of resting. The brachial artery was identified above the elbow. Its basal diameter was measured during diastole, and FMD was tested after 5 minutes of forearm ischemia. Intima-media complex in the right carotid artery was also determined. An increase in the artery's baseline diameter <10% indicated a positive test. Endothelium-independent vasodilation was evaluated with sublingual nitrate administration. The intima-media complex in the right carotid artery was also measured. RESULTS: 100% of diabetics had ED; ED was also found in 68.8% of obese individuals, 55% of hypertensive patients, and 46.5% of controls. Age, height, body mass index, and waist diameter were higher in the cases as compared with the controls. A total of 57.9% (n=11) of the cases and 45.2% (n=19) of the controls presented ED. Patients without ED had a mean increase in brachial artery diameter of 23.16%, while in those with ED it was only 3.84%. Individuals with diabetes or hypertension had a greater thickness of the carotid artery intima media layer (1.092 versus 0.664 cm) (p=0.037). A positive test for ED was associated with a greater basal diameter of the brachial artery (4.66±0.62 versus 4.23±0.59 cm) (p=0.02). A total of 7 patients presented paradoxical response, developing posthyperemia vasoconstriction. DISCUSSION: The proportion of ED was high among controls and among patients with risk factors. Controls showed better FMD profiles than subjects studied in Tibet and the Himalayas.

Effect of ezetimibe plus pravastatin on endothelial dysfunction in patients with systemic lupus erythematosus.

BACKGROUND: Patients with systemic lupus erythematosus (SLE) have a higher risk for cardiovascular disease (CVD), not fully explained by the conventional risk factors. These patients have endothelial dysfunction (ED) as an early process of atherosclerosis, which can be reversed with therapy. OBJECTIVE: To determine the effect of ezetimibe plus pravastatin on endothelial function in patients with SLE after 12 months of treatment. PATIENTS AND METHODS: An open study, before and after, which assessed the effect of ezetimibe plus pravastatin treatment, was performed. Twenty two patients (21 women and one man) with diagnosis of SLE were studied, with a mean age 40 ± 5 years. Endothelial dysfunction was evaluated using vascular ultrasound of the brachial artery in order to measure the flow-mediated vasodilation (FMV) basal and after 12 months of treatment with pravastatin 40 mg/day plus ezetimibe 10 mg/day. In addition, a lipid profile: total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and serum C-reactive protein (CRP), was done. RESULTS: We found a basal FMV of 7.58% and 18.22% after 12 months of treatment, with an improvement of 10.64 points 95% CI (7.58-13.58), p < 0.001. TC decreased from 201.3 ± 58.9 mg/dL to 158.06 ± 50.13 mg/dL (p < 0.01); LDL-C from 125.78 ± 44.4 mg/dL to 78.8 ± 32.9 mg/dL (p < 0.001); HDL-C increased from 49.0 ± 16.8 mg/dL to 52.2 ± 13.8 mg/dL (p = 0.077). The basal and final concentrations of CRP were 4.49 and 2.8, respectively, with a mean decrease of 2.11 mg/dL, 95% CI (0.908-3.32), p < 0.002. Both drugs were well tolerated. CONCLUSION: Ezetimibe plus pravastatin significantly improved FMV in patients with SLE, decreasing ED and the lipid profile. This treatment ameliorated an early process of atherosclerosis and a risk factor for CVD.

Vasodilatación mediada por flujo en niños con sobrepeso / Flow mediated vasodilation in overweight children

Introducción: El conocimiento actual sugiere que la enfermedad cardiovascular se origina y progresa desde la infancia y la adolescencia. La disfunción endotelial es un evento temprano y crucial en la aterosclerosis. Pacientes y Método: Estudio prospectivo que comparó la vasodilatación mediada por flujo (VMF) en niños con sobrepeso y niños de peso normal. Para medir la VMF se utilizó transductor adecuado de ultrasonido y el método estándar. Resultados: Ochenta y dos niños fueron incluidos; 49 eran casos (sobrepeso) y 33 controles. Los valores de VMF oscilaron entre -6 y 56% (promedio 11,1%) en niños con sobrepeso y de 0 a 29,6% (promedio 16,6%) en niños control (p < 0,05). Se presentó vasoconstricción paradójica en el 34,7% de los niños con sobrepeso y en ninguno de los controles (p < 0,05). Se encontró una asociación significativa entre vasoconstricción paradójica con obesidad central e hipertensión. Conclusión: Los resultados de este estudio muestran que la VMF es menor en niños con sobrepeso en comparación con los niños eutróficos, por lo que es más probable que exista disfunción endotelial en ellos.

Introduction: Present knowledge suggests that cardiovascular disease originates and progresses from childhood and adolescence. Endothelial dysfunction is an early and crucial event in atherosclerosis. Patients and Method: Prospective study that compares Flow Mediated Vasodilation (FMV) in children with overweight (OWC) and normal weight children. An ultrasound transducer a standard method were used to measure FMD. Results: The study included 82 children, of whom 49 were cases (OWC) and 33 controls. FMV values ranged from -6 to 56% (x = 11.1%) in OW, and from 0 to 29.6% (x = 16.6%) in control children (P<.005). Paradoxical vasoconstriction was found in 34.7% in OWC as compared to nil in controls (P<.005). A significant association was found between vasoconstriction and central obesity and hypertension. Conclusion: The results of this study show that FMV is lower in obese compared to normal children; thus they are more likely to have endothelial dysfunction.

[Flow mediated vasodilation in overweight children]. / Vasodilatación mediada por flujo en niños con sobrepeso.

INTRODUCTION: Present knowledge suggests that cardiovascular disease originates and progresses from childhood and adolescence. Endothelial dysfunction is an early and crucial event in atherosclerosis. PATIENTS AND METHOD: Prospective study that compares Flow Mediated Vasodilation (FMV) in children with overweight (OWC) and normal weight children. An ultrasound transducer a standard method were used to measure FMD. RESULTS: The study included 82 children, of whom 49 were cases (OWC) and 33 controls. FMV values ranged from -6 to 56% (x=11.1%) in OW, and from 0 to 29.6% (x=16.6%) in control children (P<.005). Paradoxical vasoconstriction was found in 34.7% in OWC as compared to nil in controls (P<.005). A significant association was found between vasoconstriction and central obesity and hypertension. CONCLUSION: The results of this study show that FMV is lower in obese compared to normal children; thus they are more likely to have endothelial dysfunction.

C-reactive protein is not correlated with endothelial dysfunction in overweight and obese women.

BACKGROUND: Obesity is a complex and multifactorial disease, has an inflammatory pattern and is associated with higher cardiometabolic risk. There are recent reports associating an elevated C-Reactive Protein (CRP) with a microscopic endothelial dysfunction. The objective is to evaluate if there is an association between serum levels of CRP and endothelial function in women with overweight/obesity, as well as the correlation between CRP and anthropometric variables. METHODS: This is a cross-sectional study that analyzed secondary data from patients treated in an institution of tertiary education, as part of the weight excess and cardiometabolic disease survey. The study included patients with overweight/obesity who had CRP and endothelial function tests already made and inserted into the survey database. The endothelial function was evaluated by: reactive hyperemia test (endothelium-dependent vasodilation). All tests were recorded and later analyzed by the same echocardiographer who performed the examination. Statistical analyses were realized in the Statistical Package for the Social Sciences (SPSS) version 14. It was considered statistically significant a P value < 0.05. RESULTS: This study included 47, nonsmoker women. with a BMI of 32.37 ± 5.06 kg/m(2), median of CRP of 2.59 mg/L and flow-mediated dilation (FMD) of 8.75% ± 5.22%. There was no correlation between CRP and endothelial dysfunction in this population (rs = 0.08, P = 0.64). No correlation was observed between CRP and BMI. There were no differences of endothelial dysfunction variables and CRP in groups in use or not of medications (Hypolipidemic, antihypertensives and hypoglycemic agents). CONCLUSION: There was no association between CRP and FMD and this can suggest that it is possible that the level of eNOS dysfunction associated with increased CRP is not enough to lead to macroscopic changes and harm vasodilation.

Valor prognóstico da função endotelial em portadores de aterosclerose: revisão sistemática / Prognostic value of endothelial function in patients with atherosclerosis: systematic review

A Vasodilatação Mediada por Fluxo (VMF) da artéria braquial, por meio da ultrassonografia, é um método de avaliação da função endotelial que pode oferecer informações fisiopatológicas, diagnósticas e prognósticas. A realização dessa revisão sistemática objetivou avaliar o nível de evidência na literatura a respeito da capacidade preditora da função endotelial, medida pela VMF da artéria braquial, por meio da ultrassonografia, quanto a eventos cardiovasculares, em indivíduos portadores de aterosclerose. Foram realizadas buscas nas bases de dados MEDLINE, SCIELO e LILACS e selecionados estudos de coorte prospectivos, em seres humanos, que analisaram o valor prognóstico da função endotelial medida pela VMF da artéria braquial, em populações portadoras de doença aterosclerótica, periférica ou coronariana. Trabalhos com evidentes vieses metodológicos foram excluídos. A seleção final constituiu-se de 15 estudos. Dos 13 estudos que, na análise univariada, mostraram significância estatística do método da VMF na predição de eventos cardiovasculares, 12 deles demonstraram sua capacidade preditora independente, em análise multivariada. Em nenhum dos trabalhos foi descrito valor prognóstico incremental em relação a modelos preditores tradicionais, como escore de Framingham. Resultados de três trabalhos sugerem que o método agrega valor prognóstico a marcadores isolados como: Índice Tornozelo-Braquial (ITB), diabetes e Proteína C Reativa (PCR) de alta sensibilidade. Em conclusão, a VMF da artéria braquial prediz risco cardiovascular, porém não é estabelecido seu valor preditor incremental a modelos prognósticos clínicos, não havendo, até o momento, evidências sólidas que amparem seu uso na rotina clínica para predição de risco cardiovascular.

Analysis of flow-mediated vasodilation (FMV) of the brachial artery by use of ultrasound allows assessing endothelial function, and provides pathophysiological, diagnostic and prognostic information. This systematic review was aimed at assessing the literature level of evidence of the predictive capacity of endothelial function, measured through brachial artery FMV by use of ultrasound, regarding cardiovascular events in individuals with atherosclerosis. The MEDLINE, SCIELO and LILACS databases were searched, and prospective cohort studies on human beings about the prognostic value of endothelial function, measured by use of brachial artery FMV in individuals with peripheral or coronary atherosclerosis, were selected. Studies with clear methodological biases were excluded. The final selection consisted of 15 studies. Of the 13 studies that on univariate analysis showed statistical significance of the FMV method to predict cardiovascular events, 12 showed independent predictive capacity on multivariate analysis. None of the studies reviewed described the incremental predictive value of FMV to the traditional predictive models, such as the Framingham score. Results of three studies have suggested that the method adds prognostic value to isolated markers such as ankle-brachial index (ABI), diabetes, and high-sensitivity C-reactive protein (hsCRP). In conclusion, brachial artery FMV predicts cardiovascular risk, but its incremental predictive value to clinical prognostic models has not been established. In addition, solid evidence supporting its use in routine clinical practice to predict cardiovascular risk still lacks.