Chronic inflammatory diseases, subclinical atherosclerosis, and cardiovascular diseases: Design, objectives, and baseline characteristics of a prospective case-cohort study ‒ ELSA-Brasil.

OBJECTIVES: This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. METHODS: A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. RESULTS: The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. CONCLUSIONS: The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.

Chronic inflammatory diseases, subclinical atherosclerosis, and cardiovascular diseases: Design, objectives, and baseline characteristics of a prospective case-cohort study ‒ ELSA-Brasil

Abstract Objectives This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. Methods A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. Results The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. Conclusions The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.

Ultrasound Core Laboratory for the Household Air Pollution Intervention Network Trial: Standardized Training and Image Management for Field Studies Using Portable Ultrasound in Fetal, Lung, and Vascular Evaluations.

Ultrasound Core Laboratories (UCL) are used in multicenter trials to assess imaging biomarkers to define robust phenotypes, to reduce imaging variability and to allow blinded independent review with the purpose of optimizing endpoint measurement precision. The Household Air Pollution Intervention Network, a multicountry randomized controlled trial (Guatemala, Peru, India and Rwanda), evaluates the effects of reducing household air pollution on health outcomes. Field studies using portable ultrasound evaluate fetal, lung and vascular imaging endpoints. The objective of this report is to describe administrative methods and training of a centralized clinical research UCL. A comprehensive administrative protocol and training curriculum included standard operating procedures, didactics, practical scanning and written/practical assessments of general ultrasound principles and specific imaging protocols. After initial online training, 18 sonographers (three or four per country and five from the UCL) participated in a 2 wk on-site training program. Written and practical testing evaluated ultrasound topic knowledge and scanning skills, and surveys evaluated the overall course. The UCL developed comprehensive standard operating procedures for image acquisition with a portable ultrasound system, digital image upload to cloud-based storage, off-line analysis and quality control. Pre- and post-training tests showed significant improvements (fetal ultrasound: 71% ± 13% vs. 93% ± 7%, p < 0.0001; vascular lung ultrasound: 60% ± 8% vs. 84% ± 10%, p < 0.0001). Qualitative and quantitative feedback showed high satisfaction with training (mean, 4.9 ± 0.1; scale: 1 = worst, 5 = best). The UCL oversees all stages: training, standardization, performance monitoring, image quality control and consistency of measurements. Sonographers who failed to meet minimum allowable performance were identified for retraining. In conclusion, a UCL was established to ensure accurate and reproducible ultrasound measurements in clinical research. Standardized operating procedures and training are aimed at reducing variability and enhancing measurement precision from study sites, representing a model for use of portable digital ultrasound for multicenter field studies.

Vascular Age as a Cardiovascular Risk Marker in Asymptomatic Patients with Type 2 Diabetes.

AIM: There is a wide variety of cardiovascular outcomes in patients with type 2 diabetes (T2DM), even in asymptomatic individuals. Carotid intima-media thickness (CIMT) is a marker of subclinical atherosclerosis and can be considered as a predictor of cardiovascular risk (CVR). The aim of this study was to evaluate the relationship between CIMT-determined vascular age (VA), CVR scores, and thyroid function in asymptomatic patients with T2DM. PATIENTS AND METHODS: Clinical laboratory and CIMT parameters were measured in 154 asymptomatic patients with T2DM. The Framingham risk score (FRS) was performed with chronological age (CA) and with VA. A multinomial logistic regression model was used to analyze variables related to CVR reclassification. RESULTS: The use of CIMT-determined VA led to the reclassification of 54 (35.52%) out of 152 asymptomatic T2DM patients, being 20 (37.03%) to a lower categorical risk and 34 (62.96%) to a higher categorical risk according to FRS. The variables that were associated to reclassification to a higher categorical risk were positive family history (FH) of premature coronary artery disease (p=0.046), FH of thyroid disease (p=0.010), use of statins (p=0.027), and free T4 levels (p=0.009). CONCLUSION: VA determined from CIMT allowed the reclassification of the CVR in asymptomatic T2DM patients. FH of premature CAD, FH of known thyroid disease, use of statins, and free T4 levels were associated to a reclassification into a higher risk category. The use of doppler to perform CIMT measure is currently more accessible, especially in a low-middle income country like Brazil. However, further prospective studies must be performed to establish the predictive values of CIMT on atherosclerosis and how thyroid function acts like cardiovascular risk marker on CVR scores.

Assessment of intima-media thickness of the carotid artery and intraluminal diameter of the brachial artery as cardiovascular risk markers in Brazilian adolescents with overweight or obesity.

Background The intima-media thickness of the carotid artery (cIMT) and endothelial dysfunction are associated with cardiovascular (CV) disease. Objectives To evaluate the correlation between cIMT, brachial intraluminal diameter and flow-mediated vasodilation on the reactive hyperemia phase in adolescents with obesity with predictors of CV risk. Methods Seventy-three pubertal patients with overweight or obesity were evaluated (45 girls) with a mean (standard deviation [SD]) age of 12.9 (2.5) years. Patients underwent anthropometric measurements and had the lipid profile, oral glucose tolerance test (oGTT) and serum intercellular adhesion molecule-1 (sICAM-1) levels analyzed. The ratios of the waist circumference (WC)/height (WHtR) and triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C), homeostatic model assessment of insulin resistance (HOMA-IR), the Matsuda index and insulin area under the curve (AUC) were calculated. All patients were evaluated for cIMT and arterial blood flow velocity of the brachial artery. Results 75.3% of the patients had high cIMT values. We found a positive correlation between WHtR and cIMT (r = 0.233; p = 0.050). There was a positive correlation between sICAM-1 and insulin AUC (r = 0.323; p = 0.012) and WHtR (r = 0.258; p = 0.047). Patients with abnormal arterial dilation had higher sICAM-1 values (p = 0.02) despite having smaller WHtR (p = 0.046). Conclusions These adolescents with obesity had high cIMT values. Insulin resistance was associated with sICAM-1. Endothelial dysfunction was positively correlated with sICAM-1. There is no consensus about what the best laboratorial approach to evaluate insulin resistance in adolescents is, and the cutoff values of each method are arbitrary. So, as we saw earlier, the association between anthropometric data (WHtR) and ultrasound findings could be useful to evaluate the CV risk of these adolescents with obesity, because of its practical, direct and low-cost value.

Carotid intima-media thickness and metabolic syndrome in a rural population: Results from the Baependi Heart Study.

BACKGROUND AND AIMS: Carotid intima-media thickness (cIMT) is a strong predictor of cardiovascular events and associated with metabolic syndrome (MetS). MetS is a cluster of cardiovascular risk factors, but the association structure between specific factors and disease development is not well-established in rural populations. We described the association structure between MetS factors and cIMT in a sample from rural Brazil. METHODS: We studied 1937 participants from the Baependi Heart Study who underwent carotid ultrasound exam. We used ATP-III-2001 for MetS definition and linear mixed-effects models, adjusting by the family structure, to assess independent associations between the cardiovascular risk factors which define MetS and cIMT. RESULTS: The sample's mean age was 46 ± 16y, 61% female, 73% white, mean body-mass-index 26±5 kg/m2, mean cIMT 0.53 ± 0.16 mm, with 35% of the sample classified with MetS. As expected, cIMT demonstrated a linear relationship with increasing age, and cIMT higher values were observed for MetS (0.58 ± 0.16 mm) compared to non-MetS (0.49 ± 0.14 mm). Considering models for cIMT with MetS and all of its factors, we found that blood pressure, glucose and obesity were independently associated with cIMT, but not HDL or triglycerides. CONCLUSIONS: cIMT showed a linear relationship with increasing age. Blood pressure, obesity, and glucose were independently associated with cIMT, but not HDL-cholesterol or triglycerides. In a rural population, hypertension, diabetes and obesity play a more important role than lipids in determining cIMT interindividual variability.

The Impact of Being Born Preterm or Small for Gestational Age on Early Vascular Aging in Adolescents.

OBJECTIVE: To assess the impact of being born preterm or small for gestational age (SGA) on early vascular aging (EVA) in a cohort of healthy Tyrolean adolescents. STUDY DESIGN: This study is part of an ongoing clinical trial, EVA Tyrol, a regional cohort study being conducted in western Austria. EVA was assessed in adolescents (mean age, 16 years) by means of carotid-femoral pulse wave velocity (PWV), carotid intima-media thickness (cIMT), and blood pressure measurements. Adolescents were grouped as either term or preterm. Subsequently, being born SGA was taken into consideration in subgroup analysis. Complete data on gestational age and birth weight were available for 930 adolescents. RESULTS: Systolic blood pressure and diastolic blood pressure were significantly higher in the preterm (mean gestational age, 34.8 ± 2.3 weeks) and appropriate for gestational age (AGA) group than in the term and AGA group (P < .05). This finding remained significant in linear regression analysis after adjustment for covariables in all models. PWV was significantly higher in the term-SGA group than in the term-AGA group (6.67 ± 1.73 m/s vs 6.07 ± 1.09 m/s; P < .05). In the linear regression analysis, this finding remained significant in all models. There were no differences in cIMT between study groups. CONCLUSION: Being born preterm or SGA might render persons susceptible to EVA. Long-term follow-up of preterm and SGA individuals is warranted to confirm these results.

Higher D-lactate levels are associated with higher prevalence of small dense low-density lipoprotein in obese adolescents.

BACKGROUND: Childhood obesity is associated with insulin resistance (IR), increased levels of small dense low-density lipoprotein (sd-LDL) as well as with augmented hepatic de novo lipogenesis, which implies increased triose phosphate fluxes that may lead to increased methylglyoxal (MG) and its catabolic end product D-lactate. We hypothesized that obese adolescents have increased D-lactate serum levels associated with high incidence of sd-LDL. METHODS: This is a cross-sectional study where the anthropometric characteristics, atherogenic dyslipidemia complex, sd-LDL (Lipoprint, Quantimetrix) and D-lactate (kinetic enzymatic analysis) were explored in 30 lean vs. 30 obese adolescents (16 females and 14 males per group) without metabolic syndrome (MetS). Endothelial function by flow-mediated dilation (FMD, by ultrasound) and arterial lesion by carotid intima media thickness (CIMT, by ultrasound) were also measured. RESULTS: The mean age of participants was 16.8 ± 1.4 years. Obese adolescents had a body mass index of 32.7 ± 3.8 vs. 21.8 ± 2.1 in lean participants. The obesity group showed higher D-lactate levels: 6.2 ± 3.0 vs. 4.5 ± 2.5 µmol/L, higher levels of insulin: 15 (9.6-23.5) vs. 7.9 (6.5-10.5) µIU/mL; triglyceride (TG): 1.46 (1.1-1.8) vs. 0.84 (0.6-1.2) mmol/L; non-high-density lipoprotein-cholesterol (NON-HDL-C): 2.8 ± 0.9 vs. 2.3 ± 0.7 mmol/L; total cholesterol (TC)/HDL-C) index: 2.9 ± 0.7 vs. 2.4 ± 0.5; TG/HDL-C index: 2.2 (1.5-2.8) vs. 1.1 (0.8-1.8); %LDL-3: 4.2 ± 4.07 vs. 1.9 ± 2.7; smaller LDL size: 270.6 ± 3 vs. 272.2 ± 1.1 Å. D-lactate correlated positively with LDL-2: r = 0.44 and LDL-3 (sd-LDL): r = 0.49 and negatively with large LDL-1: r = -0.48 and LDL size: r = -0.46; (p<0.05, p<0.01, p<0.001 and p<0.0001, respectively). Obese adolescents showed higher CIMT: 0.51 ± 0.08 vs. 0.46 ± 0.08 mm and lower FMD: 20.3% ± 6.7% vs. 26.0% ± 9.3%. CONCLUSIONS: Obese adolescents display subclinical signs of IR and endothelial dysfunction. Higher serum sd-LDL levels correlated positively with D-lactate levels. These findings suggest an association between atherogenic dyslipoproteinemia and whole body MG fluxes already detectable in apparently healthy obese adolescents.

Correlation between serum 25-hydroxyvitamin D levels and carotid intima-media thickness in a Brazilian population descended from African slaves

Hypovitaminosis D has been identified as a possible new cardiovascular risk factor. However, the results of studies correlating serum vitamin D levels with markers of subclinical atherosclerosis have been conflicting. The aim of this study was to correlate serum levels of 25-hydroxyvitamin D [25(OH)D] with carotid intima-media thickness (C-IMT) and conventional cardiovascular risk factors in Afro-descendants. A cross-sectional analysis was performed on a sample of 382 individuals from a cohort of descendants of African slaves, inhabitants of "Quilombola" communities, with a mean age of 57.79 ±15.3 years, 54.5% of whom were women. Socio-demographic and clinical data were collected and biochemical tests were performed, including serum levels of 25(OH)D by electrochemiluminescence and urinary albumin excretion, evaluated by the albumin/creatinine ratio (ACR) in a spot urine sample. All participants underwent high-resolution ultrasonography for C-IMT measurement. Hypovitaminosis D was defined as serum 25(OH)D levels <30 ng/mL. The mean serum 25(OH)D levels were 50.4±13.5 ng/mL, with a low prevalence of hypovitaminosis D (4.86%). By simple linear correlation, a significant inverse association between 25(OH)D levels and C-IMT (r=-0.174, P=0.001) was observed. However, after multiple linear regression analysis, the significance of the association between serum levels of 25(OH)D and C-IMT measurement was lost (β=-0.039, P=0.318) and only male gender, age, smoking, systolic blood pressure, glucose and low density lipoprotein (LDL)-cholesterol remained significantly associated with C-IMT. Levels of 25(OH)D were independently and positively associated with HDL-cholesterol and inversely associated with age and ACR. In conclusion, no independent association between 25(OH)D levels and C-IMT was observed in this population. On the other hand, there was an inverse association with albuminuria, a marker of endothelial lesion.

Circulating E-selectin levels and insulin resistance are associated with early stages of atherosclerosis in nonfunctional adrenal incidentaloma

Objective To evaluate circulating E-selectin levels in patients with nonfunctional adrenal incidentaloma (NFA) in relation to insulin resistance and early atherosclerosis.Subjects and methods A total of 40 patients with NFA (mean [SD] age: 55.6 [10.7] years; 70% were females) and 35 controls (mean [SD] age: 51.5 [8.1] years; 71.4% were females) selected from age-, gender- and body mass index (BMI)- matched healthy subjects were enrolled. Serum hsCRP, lipid profile, insulin levels and the homeostasis model assessment of insulin resistance (HOMA-IR) were evaluated. High-resolution B-mode ultrasonography was performed. Serum levels of E-selectin were evaluated by enzyme-linked immunosorbent assay.Results Patients with NFA had significantly higher values for E-selectin (14.9 (4.8) vs. 12.2 (4.1) ng/mL, p < 0.01) and CIMT (0.6 (0.1) vs. 0.5 (0.1) mm, p < 0.05) than controls. Serum E-selectin levels showed a statistically significant association with hsCRP (r = 0.751, p < 0.001), HOMA-IR (r = 0.575, p < 0.001) and CIMT (r = 0.762, p < 0.001). CIMT (Carotid intima media thickness) was increased in patients with NFA patients with NFA were more insulin resistant than controls and statistically significant relationship was found between size of tumor and HOMA-IR (r = 0.361, p < 0.001).Conclusion In conclusion, based on significantly higher values for E-selectin, CIMT and HOMA-IR in patients with NFA than controls along with significant correlation of E-selectin levels to CIMT, HOMA-IR and hs-CRP, our findings seems to indicate an increased risk of early atherosclerosis and impaired endothelial function in NFA patients, particularly in case of insulin resistance.

Tratamento de restrição e indução do movimento na reabilitação funcional de pacientes pós acidente vascular encefálico: uma revisão bibliográfica / A review about the effectiveness of the constraint induced movement therapy in rehabilitation of patients after stroke

INTRODUÇÃO: O Acidente Vascular Encefálico (AVE) é uma das doenças mais incidentes da hipermodernidade, que resulta em múltiplas sequelas. Uma das mais importantes refere-se à função motora do membro superior afetado que, em geral, é mais lenta que a do membro inferior e não acontece de forma adequada. A Terapia de Restrição e Indução do Movimento (TRIM) tem sido considerada uma técnica de reabilitação da função motora da extremidade hemiparética, capaz de promover melhora funcional deste membro. OBJETIVO: O objetivo deste estudo é realizar uma pesquisa bibliográfica para avaliar a eficácia da TRIM em pacientes acometidos por AVE. Material e Método: o presente estudo é uma revisão bibliográfica de artigos indexados na base de dados PubMed, publicados de janeiro de 2000 a dezembro de 2007, em inglês e português. Na estratégia de busca foram utilizados os unitermos: "cerebrovascular accident", "stroke", "CIMT", "constraint induced movement therapy". RESULTADOS E DISCUSSÃO: de modo geral, as pesquisas demonstram que a TRIM é uma técnica alternativa no campo de reabilitação funcional do membro superior parético, promovendo reorganização cortical, superação do "não uso aprendido" e melhora na quantidade e qualidade de movimentos, e que este efeito é transferido para o dia-a-dia do paciente durante suas atividades de rotina. CONCLUSÃO: a TRIM é um produto do advento científico da fisioterapia que traz benefícios funcionais para os pacientes que se submetem a ela. Porém, faz-se necessário investigar mais detalhadamente essa técnica a fim de reduzir as complicações psicológicas advindas deste tratamento, maximizando, assim, a funcionalidade do membro superior acometido.

INTRODUCTION: The cerebrovascular accident is one of the most incident disease of the modernity, that results in multiple sequels. One of the most important sequel is the impairment of the motor function of the affected upper limb and, usually, the rehabilitation is slower than the lower limb and, often, it does not happen in adequate form. The Constraint Induced Movement Therapy (CIMT) have been considered a rehabilitation technique for the affected upper limb and it’s able to promote the functional recovery of the hemiparetic arm. OBJECTIVE: the aim of this study is conducting a literature search to assess the effectiveness of the CIMT in patients after stroke. Materials and Method: this study is a literature review of articles indexed in the database PubMed, published from 2000 to 2007, in English and Portuguese. In the search strategy was used the following key-words: “cerebrovascular accident”, “stroke”, “constraint induced movement therapy” and “CIMT”. RESULTS AND DISCUSSION: in general, the researches shows that the CIMT is an alternative technique in the field of functional rehabilitation of the paretic arm, promoting cortical reorganization, overcoming of the “learned non-use”, improving the quality of movement and increasing amount of use and, these improvements are transferred to the daily life activities of the patient. CONCLUSION: CIMT is a product of the scientific advent of the physiotherapy that brings functional benefits for the patients after stroke. However, it’s necessary more investigation about this technique to reduce the psychological complications resulting from the treatment, thus maximizing the functionality of the affected upper limb.