Débora Cristina Torres Valença’s research while affiliated with Rio de Janeiro State University and other places

Background This study aimed to evaluate whether soluble vascular cytoadhesive molecule-1 (sVCAM-1), intracellular cytoadhesive molecule-1 (sICAM-1), and endothelial function as assessed by EndoPat outweighed traditional risk factors for the presence of diabetic retinopathy (DR) in patients with type 1 diabetes (T1D). Methods Patients aged ≥ 12 years completed a clinical–epidemiological questionnaire. Fasting venous blood samples were obtained (lipid profile, glycemic control, and C-reactive protein levels). Vascular reactivity was assessed via peripheral arterial tonometry performed by supplying the reactive hyperemia index (RHI) through the EndoPAT device. sVCAM-1 and sICAM-1 levels were measured using multiplex assays. Results Data were obtained from 187 patients (51.3% female), aged 32 ± 13 years with a disease duration of 14 (6–15) years and mean hemoglobin A1c (HbA1c) of 9.1% ± 2.1%. After adjustments were made, age, HbA1c, arterial blood pressure, and use of drugs that could interfere with endothelial function were found to be associated with DR. No association was noted with sVCAM-1 and sICAM-1 levels and RHI. Conclusions In our sample, sVCAM-1, sICAM and EndoPAT did not outweigh the traditional DR risk factors, such as age, high HbA1c, arterial blood pressure, and use of drugs that could interfere with endothelial function and are significantly associated with DR. Further prospective studies should evaluate if markers of endothelial dysfunction could predict diabetes-related micro and macrovascular complications in T1D.

Introduction: Hypertension often clusters with other cardiovascular risk factors such as obesity, dyslipidemia and glucose intolerance. Weight loss can decrease Blood Pressure (BP) and improve cardiometabolic abnormalities. There is evidence that hypertension and obesity are associated with alterations in gut microbiome. Recent studies evaluating the effects of probiotics on BP, body weight, metabolic profile, inflammatory biomarkers, endothelial function and arterial stiffness found inconsistent results, probably due to the wide heterogeneity in trials design. To date, it is not known if probiotics can potentiate the effects of energy restriction in individuals with increased risk of metabolic, inflammatory and vascular abnormalities such as individuals presenting hypertension and obesity. Objective: To evaluate the effects of probiotics during energy restriction on BP, body adiposity (total, central and visceral), insulin resistance, lipid profile, microvascular reactivity and arterial stiffness in obese hypertensive subjects. Methods: This 12-week randomized, double-blind, controlled clinical trial with obese hypertensive adults, instructed to follow an energy-reduced diet (−800 Kcal/day) will be conducted at State University of Rio de Janeiro, Brazil. Probiotics and control groups will take one capsule/day containing nine freeze-dried probiotic strains and cellulose, respectively. At baseline and at the end of the study, participants will undergo nutritional, laboratory, BP and vascular evaluation. Nutritional assessment will include bioelectrical impedance analysis and dual energy X-ray absorptiometry. Laboratory parameters will include glucose, insulin, lipid profile, C-reactive protein, adiponectin, tumor necrosis factor alpha, interleukin-6 and lipopolysaccharide. Post-occlusive microvascular reactivity will be evaluated by laser speckle contrast imaging and oscillometric pulse wave analysis by Mobil-O-Graph.

Background: Observational studies have highlighted an association between serum uric acid (SUA) levels and cardiovascular risk factors. Despite the growing body of evidences, several studies were conducted in older individuals or in carriers of diseases susceptible to affect SUA levels and cardiometabolic risk markers. Objective: To evaluate the relationship of SUA with body adiposity, metabolic profile, oxidative stress, inflammatory biomarkers, blood pressure and endothelial function in healthy young and middle-aged adults. Methods: 149 Brazilian adults aged 20-55 years, both sexes, underwent evaluation of body adiposity, SUA, fasting glucose and insulin, lipid profile, malondialdehyde (MDA), high sensitivity C-reactive protein (hs-CRP), adiponectin, blood pressure and endothelial function. Endothelial function was assessed by the reactive hyperemia index (RHI) derived from peripheral arterial tonometry method. Participants were allocated in two groups according to SUA levels: control group (CG; n = 130; men ≤ 7 mg/dL, women ≤ 6 mg/dL) and hyperuricemia group (HG; n = 19; men > 7 mg/dL, women > 6 mg/dL). A P-value < 0.05 was considered statistically significant. Results: After adjustment for confounders, participants in HG compared with those in CG displayed higher body mass index (BMI): 34.15(33.36-37.19) vs.31.80 (26.26-34.42) kg/m2,p = 0.008, higher MDA: 4.67(4.03-5.30) vs. 3.53(3.10-4.07) ng/mL, p < 0.0001 and lower RHI: 1.68 ± 0.30 vs. 2.05 ± 0.46, p = 0.03). In correlation analysis adjusted for confounders, SUA was positively associated (p < 0.05) with BMI, waist circumference, LDL-cholesterol, triglycerides and MDA, and negatively associated (p < 0.05) with HDL-cholesterol, adiponectin and RHI. Conclusions: This study suggests that in healthy young and middle-aged adults higher SUA levels are associated with higher body adiposity, unfavorable lipid and inflammatory phenotype, higher oxidative stress and impaired endothelial function.

Objectives: To find out an normality value for microvascular response (physiological and pharmacological) assessed through laser speckle contrast imaging (LSCI) based on Endo-PAT, which identifies the ones with Endothelial Dysfunction (ED) in patients with Type 1 Diabetes (T1D). Methods: Patients with T1D, aged ≥12years underwent a clinical-epidemiological questionnaire. Fasting blood samples were obtained (lipid profile, glycemic control and levels of C-reactive protein). Vascular reactivity was assessed in the forearm through the technique of LSCI at baseline, during post occlusive reactive hyperemia (PORH) and during iontophoresis of acetylcholine (ACh) and peripheral arterial tonometry was performed by supplying the RHI through Endo-PAT device. Results: 189 patients were evaluated, 97 women (51.3%) with T1D, aged 32±13years and with a disease duration of 16 (6-21) years and mean A1c of 9.2% (±2.2). Receiver Operating Characteristics curve (ROC) analysis according to RHI showed that the Area under curve (AUC) of ACh of 10,369 Laser Speckle Perfusion Unit (LSPU) presented sensitivity and specificity of 65% and 87,5%, respectively, (p=0.002) in those patients with T1D's duration <5years. Overall, no test of vascular reactivity was able to distinguish the ideal cuttoff based on RHI. Conclusion: In the present study, we could find an ideal cut off value of microcirculation assessment through endothelium-dependent vasodilation to ACh using LSCI according to Endo-PAT's score, only in those under 5years of disease duration. Further prospective studies shall be conducted to evaluate its predictive cardiovascular value.

Objective: To test whether laser speckle contrast imaging (LSCI) coupled with physiological post-occlusive reactive hyperemia (PORH) and pharmacological iontophoresis of acetylcholine (ACh) as local vasodilator stimuli could distinguish between cutaneous microvascular responses of Type 1 Diabetes (T1DM)'s patients with endothelial dysfunction and that of healthy controls. Methods: Patients with T1DM aged ≥12years completed a clinical-epidemiological questionnaire. Data detailing patients' such as daily insulin dose, duration of diabetes, and use of pharmaceuticals such as antihypertensive drugs and statins that could interfere with endothelial function were obtained. Vascular reactivity was assessed in the forearm by LSCI and PORH at baseline and during iontophoresis of ACh using increasing anodic currents of 30, 60, 90, 120, 150 and 180μA in 10second intervals. Results: This study included 50 patients with T1DM and 30 control subjects. The mean resting flux did not differ between patients and control subjects. T1DM patients exhibited endothelial dysfunction upon challenge with physiological or pharmacological stimuli. The microvascular response to both ACh and PORH (i.e., maximum response at peak and amplitude) were significantly reduced in patients with diabetes compared with control subjects (p<0.001). Conclusion: We demonstrated that endothelium-dependent skin microvascular vasodilator responses are significantly impaired in patients with T1DM compared to healthy subjects investigated using LSCI coupled with ACh iontophoresis and PORH. Additionally, we find that LSCI is a promising methodology for studying physiological vascular reactivity in T1DM.

Introduction: Weight loss is one of the treatment options for obstructive sleep apnea (OSA) in patients with excess body adiposity. However, the effects of moderate energy restriction on OSA are not known. Objective: To evaluate the effects of moderate energy restriction on severity of OSA, blood pressure (BP), sympathetic activity, oxidative stress, inflammation, body adiposity, metabolic profile and endothelial function in obese patients with OSA. Methods: A 16-week randomized clinical trial, involving 21 obese subjects aged 20-55y with apnea/hipopnea index (AHI) ≥ 5 events/h. Subjects were randomized in 2 groups: 11 in energy restriction group (ERG) and 10 in control group (CG). ERG was instructed to follow an energy-restricted diet (-800 kcal/day) and CG was advised not to change food intake. At the beginning and at the end of the study, participants underwent evaluation of: OSA with Watch- PAT200® including the determination of OSA severity parameters, body adiposity, BP, plasma catecholamines, c-reactive protein (CRP), adiponectin, malondialdehyde, metabolism of glucose, lipid profile and endothelial function (Endo PAT 2000®). Results: ERG, compared to CG, presented significantly greater reduction in body weight (-5.6±1.8 vs. 0.4±1.2kg, p<0.001) and in all parameters of body adiposity; AHI (-7.2±2.8 vs. 0.1±1.9 events/h, p=0.04); number of O2 desaturation >4% (-33.7±15.6 vs. 1.8±7.9, p=0.04); plasma adrenaline (-12.7±3.0 vs. -1.3±3.9pg/mL, p=0.04); and significantly greater increase in minimum O2 saturation (4.6±1.6 vs. -0.6±1.4%, p=0.03). ERG showed greater decrease, however without statistical significance, in systolic BP (-4.2±1.9 vs. 2.3±1.4mmHg, p=0.05), insulin (-5.1±1.9 vs. -0.7±1.3μU/mL, p=0.07) and HOMA-IR (-1.2±0.5 vs. -0.08±0.3, p=0.09). During the study period, changes in body adiposity presented significant correlation with changes in parameters of OSA severity, BP, insulin, HOMA-IR, norepinephrine and adiponectin. Changes in parameters of OSA severity presented significant association with changes in CRP. Conclusions: This study suggests that in obese patients with OSA moderate energy restriction is able to reduce body adiposity, parameters of OSA severity and sympathetic nervous system activity.

Background: Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease (CVD). Several of the proposed mechanisms for the development of CVD in OSA are similar to those proposed for the increased risk of CVD in obesity, being difficult to determine the influence of OSA on these pathogenic mechanisms in obese individuals. Objectives: The purpose of this study was to evaluate the relationship of OSA with endothelial function, oxidative stress, inflammatory biomarkers, metabolic profile, sympathetic nervous system activity and blood pressure (BP) in obese individuals. Methods: In this cross-sectional study, were included 53 obese adults (28 women). Sleep study was performed with Watch-PAT200® and the diagnosis of OSA was made when apnea-hipopnea index (AHI) ≥5 events/h (n=33). All participants underwent evaluation of: body adiposity, BP, plasma catecholamines, high sensitivity C-reactive protein (hs-CRP), adiponectin, malondialdehyde, glucose, insulin, lipid profile and endothelial function (Endo-PAT 2000®). Results: Mean age (39.6 ± 1.5 vs. 32.5 ± 2.1y) and percentage of male participants (61% vs. 25%) were significantly higher in participants with OSA than in those without OSA (p=0.01). In univariate analysis participants with OSA compared with those without OSA exhibited higher values of neck circumference (40.98 ± 0.63 vs. 38.65 ± 0.75 cm, p=0.02), glucose (92.54 ± 1.97 vs. 80.2 ± 1.92 mg/dL, p=0.0001), noradrenaline (0.16±0.02 vs. 0.12±0.03 ng/mL, p=0.02) and systolic BP (126.05 ± 1.61 vs. 118.16 ± 1.86 mmHg, p=0.003). After adjustment for confounders, only glucose and hs-CRP were significantly higher in OSA patients. In correlation analysis, after controlling for confounders, AHI was associated with neck circumference (r=0.31,p=0.03) and hs-CRP (r=0.30,p=0.04), while minimum O2 saturation was associated with neck circumference (r=-0.31,p=0.03), insulin (r=-0.29,p=0.04) and HOMA-IR (r=-0.30,p=0.04). Conclusion: The present study suggests that in obese individuals OSA is associated with inflammation and worse glycemia; higher AHI correlates with increased central adiposity and inflammation; and lower oxygen saturation is related with insulin resistance.

Background: Obstructive sleep apnea (OSA) is considered an independent risk factor for cardiovascular disease and reported as the most common secondary cause of high blood pressure (BP) maintenance. Objective: To determine the prevalence of OSA and verify its association with endothelial function behavior and anthropometric parameters in patients with resistant hypertension (RHGroup) and BP controlled by medication (CHGroup). Methods: Cross-sectional study involving 40 hypertensive patients (20 in RHG and 20 in CHG), aged between 18 and 75 years. Endothelial function and OSA were assessed by peripheral arterial tonometry. BP was measured by oscillometric method on automatic device. Endothelial function was assessed by peripheral arterial tonometry (PAT) by EndoPAT2000 and the OSA diagnosis also through PAT, using the portable device WatchPAT200. Anthropometric evaluation was performed through measurements of waist (WaC), hip and neck circumference (NC), BMI, waist to height ratio (WHtR), and body composition assessed by BIA. Results: The prevalence of OSA in RHG was 85% (17 of 20)[apnea-hypopnea index = 12.39±1.89], and 80% (16 of 20) in CHG (AHI=20.74±4.69) and it was more frequent in men (93.7% [15 of 16] vs 75% [16 of 24]; p=0.0455, OR =3.86; 95% IC 0.99 to 5.09). Both groups presented similar anthropometric parameters values. Endothelial function evaluated by reactive hyperemia index was similar in both groups (RHG: 1.88±0.44 vs CHG: 2.03±0.43; p=0.47). Although we found differences in oxygen desaturation> 4% (RHG: 28.75 ± 5.08 vs CHG: 64.15 ± 16.97, p = 0.05), total sleep time (RHG: 307.2 ± 71.3 vs CHG: 323.3 ± 83.8 min) and minimum saturation (RHG: 87.8±3.8 vs CHG: 83.3±10.6%) was not different. In general, OSA was correlated with weight (r = 0.5135, p = 0.0007), BMI (r = 0.4146, p = 0.0078), WaC (r = 0, 4458, p = 0.005), NC (r = 0.3863, p = 0.01) and WHtR (r = 0.3907, p = 0.01) and independently associated with impairment of endothelial function (p = 0.0297, OR = 0.17, 95% CI 0.04 to 0.72). Conclusions: The findings of the present study show that the prevalence of OSA was similar in both groups and suggest that, in hypertensive subjects, OSA occurs more frequently in men, being associated with endothelial dysfunction and correlated positively with weight, BMI and WaC.

Background: Cardiovascular diseases are the leading cause of mortality in Western countries. Some studies have suggested that green tea has beneficial effects on different cardiovascular risk factors. However, others have failed to show such an association. Objective: To evaluate the effects of green tea on blood pressure, endothelial function, metabolic profile, inflammatory biomarkers and body adiposity in obese pre-hypertensive women. Methods: Crossover randomized controlled double-blinded trial. Twenty women with obesity and pre-hypertension, aged 28-59 years, with stable body weight were randomized to receive a daily supplement of 3 capsules that contained either 500mg of green tea extract (GTE) or a matching placebo for 4 weeks, with a washout period of 2 weeks between the treatments. Blood pressure was evaluated by ambulatory blood pressure monitoring (ABMP). Endothelial function was evaluated by peripheral arterial tonometry method, using Endo-PAT 2000®. The inflammatory status was assessed by interleukin 6, tumor necrosis factor alpha, vascular cell adhesion molecule, intercellular adhesion molecule, plasminogen activator inhibitor-1, vascular endothelial growth factor, E-selectin, adiponectin and C-reactive protein. Results: After administration of GTE compared with placebo there was a significant reduction in systolic blood pressure during 24h (pre 130.3±1.7 vs. post 127.0±2.0 mmHg; p= 0.02), daytime (pre 134.0±1.7 vs. post 130.7±2.0 mmHg; p= 0.04) and nighttime (pre 122.2±1.8 vs. post 118.4±2.2 mmHg; p= 0.02). After consumption of green tea, there was an increase, although not statistically significant, in reactive hyperemia index (pre 1.98±0.10 vs. post 2.22±0.14), besides reduction in the concentration of intercellular adhesion molecule (pre 91.8±8.0 vs. post 85.8±5.6 ng/ml) and vascular endothelial growth factor (pre 195.8±46.2 vs. post 158.6±38.7 pg/ml), however without statistical significance. The other variables did not change significantly after consumption of green tea. Conclusions: The findings of the present study suggest that green tea has a beneficial effect on blood pressure and possibly on endothelial function.