Peripheral microvascular dysfunction is also present in patients with ischemia and no obstructive coronary artery disease (INOCA).

BACKGROUND: In patients with ischemia and no obstructive coronary artery disease (INOCA), coronary microvascular dysfunction is associated with higher rate of major adverse cardiovascular events. OBJECTIVE: To demonstrate if microvascular dysfunction present in coronary microcirculation of patients with INOCA may be detected noninvasively in their peripheral circulation. METHODS: 25 patients with INOCA and 25 apparently healthy individuals (controls) were subjected to nailfold videocapillaroscopy (NVC) and venous occlusion plethysmography (VOP) to evaluate peripheral microvascular function and blood collection for biomarkers analysis, including soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelin-1 (ET-1) and C-reactive protein (CRP). RESULTS: Red blood cell velocity (RBCV) before and after ischemia (RBCVmax) were significantly lower in patients with INOCA (p = 0.0001). Time to reach maximal red blood cell velocity (TRBCVmax) was significantly longer in INOCA group (p = 0.0004). Concerning VOP, maximal blood flow (p = 0.004) and its relative increment were significantly lower in patients with INOCA (p = 0.0004). RBCVmax showed significant correlations with sVCAM-1 (r = -0.38, p < 0.05), ET-1 (r = -0.73, p < 0.05) and CRP (r = -0.33, p < 0.05). Relative increment of maximal post-ischemic blood flow was significantly correlated with sVCAM-1 (r = -0.42, p < 0.05) and ET-1 (r = -0.48, p < 0.05). CONCLUSIONS: The impairment of microvascular function present in coronary microcirculation of patients with INOCA can be also detected in peripheral microcirculation.

Acute Effects of Metformin and Vildagliptin after a Lipid-Rich Meal on Postprandial Microvascular Reactivity in Patients with Type 2 Diabetes and Obesity: A Randomized Trial.

BACKGROUND: Type 2 diabetes mellitus and obesity are both related to endothelial dysfunction. Postprandial lipemia is a cardiovascular risk. Notably, it is known that a high-fat diet may elicit microvascular dysfunction, even in healthy subjects. Since anti-diabetic drugs have different mechanisms of action and also distinct vascular benefits, we aimed to compare the results of two anti-diabetic drugs after the intake of a lipid-rich meal on microcirculation in patients with type 2 diabetes and obesity. In parallel, we also investigated the metabolic profile, oxidative stress, inflammation, plasma viscosity, and some gastrointestinal peptides. SUBJECTS/METHODS: We included 38 drug-naïve patients, all women aged between 19 and 50 years, with BMI ≥ 30 kg/m2. We performed endothelial measurements and collected samples before (fasting) and after the intake of a lipid-rich meal at 30, 60, 120, and 180 min. Patients were randomized to metformin or vildagliptin, given orally just before the meal. Endothelial function was assessed by videocapillaroscopy and laser-Doppler flowmetry to investigate microvascular reactivity. Besides, we also investigated plasma viscosity, inflammatory and oxidative stress biomarkers, gastrointestinal peptides, and metabolic profile in all time points. RESULTS: No differences at baseline were noted between groups. Vildagliptin increased glucagon-like peptide-1 compared to metformin. Paired comparisons showed that, during the postprandial period, vildagliptin significantly changed levels of insulin and glucagon-like peptide-1, and also the dipeptidyl peptidase-4 activity, while metformin had effects on plasma glucose solely. Metformin use during the test meal promoted an increase in functional capillary density, while vildagliptin kept non-nutritive microvascular blood flow and vasomotion unchanged. CONCLUSIONS: After the intake of a lipid-rich meal, the use of vildagliptin preserved postprandial non-nutritive microflow and vasomotion, while metformin increased capillary recruitment, suggesting protective and different mechanisms of action on microcirculation.

Nutrition Information in Oncology - Extending the Electronic Patient-Record Data Set.

Electronic health records (EHRs) present extensive patient information and may be used as a tool to improve health care. However, the oncology context presents a complex content that increases the difficulties of EHR application. This study aimed at developing openEHR-archetypes representing clinical concepts in cancer nutrition-care, as well as to develop an openEHR-template including the aforementioned archetypes. The study involved the following stages: 1) a thorough literature review, followed by an expert's (nutrition guideline authors) survey, aiming to identify the main statements of published clinical guidelines on nutrition in cancer patients that were not included on the Clinical Knowledge Manager (CKM) repository; 2) modelling of the archetypes using the Ocean Archetype Software and submission to the CKM repository; 3) creating an example template with Template Designer; and 4) automatic conversion of the openEHR-template into a readily usable EHR using VCIntegrator. The clinical concepts (among 17 clinical concepts not yet available in the CKM repository) chosen for further development were: body composition, diet plan, dietary nutrients, dietary supplements, dietary intake assessment, and Malnutrition Screening Tool (MST). So far, four archetypes were accepted for review in the CKM repository and a template was created and converted into an EHR. This study designed new openEHR-archetypes for nutrition management in cancer patients. These archetypes can be included in EHR. Future studies are needed to assess their applicability in other areas and their practical impact on data quality, system interoperability and, ultimately, on clinical practice and research.

Obesity blunts cephalic-phase microvascular responses to food.

Neurally mediated anticipatory responses, also named cephalic-phase responses, and microcirculatory regulation are two important mechanisms to maintain metabolic homeostasis. Altered cephalic-phase responses in obesity and its metabolic consequences have been proposed. There is, however, a lack of studies focusing on in vivo assessment of the microcirculation during this phase in patients with obesity. In this randomized controlled trial, we selected patients with obesity and healthy subjects after clinical and laboratory assessments. Those with obesity were randomized into two groups: experimental (cephalic-phase microvascular response stimulation - CP group, n = 13) and controls (n = 14). Healthy subjects (n = 17) were also included to form a CP control group. Skin microvascular assessment was used as a model of systemic microcirculation. Resting functional capillary density (FCD) and peak FCD during post-occlusive reactive hyperemia (PORH) were measured by dorsal finger videocapillaroscopy and expressed mainly capillary recruitment capacity. Resting red blood cell velocity (RBCV), peak RBCV during PORH (RBCVmax), and time taken to reach RBCVmax (TRBCVmax) were assessed by dynamic nailfold videocapillaroscopy and expressed the microhemodynamics. Patients with obesity (with or without stimulus) failed to show an increase on FCD during PORH post-stimulus (p = 0.221 and p = 0.307, respectively) depicting lack of capillary recruitment. In contrast, healthy subjects presented an increase in this microvascular outcome (p = 0.004). Changes in all variables of microhemodynamics occurred in both CP groups (healthy and those with obesity). During CP, we originally demonstrated an absence of capillary recruitment in subjects with obesity. These findings might contribute to the literature of microvascular impairment and metabolic conditions.

Can openEHR Represent the Clinical Concepts of an Obstetric-Specific EHR - ObsCare Software?

ObsCare is an obstetric-specific Electronic Health Record in use in nine Portuguese obstetric departments. Like other EHRs, it faces major challenges related to semantic interoperability and data quality. openEHR is proposed to address those needs. This study aimed to describe a summary representation of Obscare workflow and to validate whether archetypes in the openEHR Clinical Knowledge Manager repository can represent ObsCare clinical concepts. The study included the phases: a) ObsCare form selection; b) Description of the workflow care process; c) Detailed data extraction; and d) CKM models analysis. 379 variables were analyzed: 219 were fully represented in CKM repository; 99 were partially represented and needed archetype modification; and 61 were not represented and need new archetypes. To conclude, our study showed that the openEHR CKM repository requires further enhancements to be able to fully answer to the needs of an obstetric-specific EHR, the ObsCare software.

30-days effects of vildagliptin on vascular function, plasma viscosity, inflammation, oxidative stress, and intestinal peptides on drug-naïve women with diabetes and obesity: a randomized head-to-head metformin-controlled study.

BACKGROUND: Obesity is the main risk factor for diabetes and excessive visceral fat triggers low-grade inflammatory process, mediated by activation and release of cytokines and high flow of free fatty acids that contribute to insulin resistance, increased oxidative stress, and impaired endothelial function. Metformin and vildagliptin have known vasculoprotective actions, but the value of these drugs on drug-naïve diabetic patients during 30 days use warrants investigation. Our purpose was to observe their effects on endothelial function, oxidative stress, inflammatory biomarkers, and plasma viscosity. METHODS: 38 women with obesity and type 2 diabetes drug-naïve, aged between 19 and 50 years, BMI ≥ 30 kg/m2, were recruited and subjected to measurements of endothelial function, nutritive skin microvascular reactivity, plasma viscosity, inflammatory and oxidative stress biomarkers at baseline and randomized 1:1 to ingest metformin (850 mg twice/day) or vildagliptin (50 mg twice/day) during 30 days, and then, re-evaluated. RESULTS: No differences between groups were noticed at baseline. After treatment, vildagliptin promoted an improvement on endothelial-dependent and -independent vasodilatations, at arteriole level, while metformin resulted in improved nutritive microvascular reactivity, at the capillary level. Intragroup analysis showed that vildagliptin reduced insulin, C-peptide and oxidized LDL, and increased adiponectin and glucagon-like peptide-1 while metformin reduced weight, plasma glucose, total cholesterol, HDL-c, LDL-c, and dipeptidyl peptidase-4 activity, with an unexpected increase on tumor necrosis factor-α. No significant difference in plasma viscosity was noted. CONCLUSIONS: In the vascular beds investigated, both drugs used for only 30 days improved endothelial function, through distinct, and possibly, complementary mechanisms on drug-naïve diabetic women.Trial Registration ClinicalTrials.gov: NCT01827280.

From ObsCare Software to an OpenEHR Platform: Modelling Obstetric Archetypes.

INTRODUCTION AND AIMS: Electronic health records (EHRs) are important tools to facilitate communication between care providers and to improve clinical research. In obstetrics they became essential. The ObsCare software was created to answer to the need for an EHR with specific obstetric features. The present study aimed to develop openEHR-archetypes capable of representing an ObsCare® EHR form and to create an openEHR-template using the developed archetypes. METHODS: The study was performed in four phases: 1) selection and description of the ObsCare form; 2) Clinical Knowledge Manager (CKM) analysis; 3) modelling of the archetypes; 4) creation and testing of the template. RESULTS: One openEHR-archetype - Newborn summary - was modelled to assemble the following three clinical concepts that were not represented in CKM: hours of life, "Examination of newborn movements" and "Examination of reflexes". Finally, an openEHR-template was built and automatically converted into an EHR by VCIntegrator. CONCLUSIONS: Considering the potential to improve clinical research, we believe that more obstetric-gynecologic clinical statements should be modelled into openEHR.

Organ dysfunction in cirrhosis: a mechanism involving the microcirculation.

INTRODUCTION: Microcirculation is essential for adequate tissue perfusion and organ function. Microcirculatory changes may occur in cirrhosis, inducing loss of multiorgan function. The aim was to evaluate preliver transplantation and postliver transplantation aspects of multiorgan function, microcirculation, inflammatory, and endothelial biomarkers and survival in a controlled study including cirrhotic outpatients. PATIENTS AND METHODS: We accessed functional capillary density (FCD) and red blood cell acceleration (RBCA) by nailfold videocapillaroscopy. Inflammatory and endothelial biomarkers [interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, endothelin-1, and tumor necrosis factor-α] were analyzed. Cerebral and renal functions were assessed to represent organ dysfunction and regression analyses were carried out. Receiver operating characteristic curves were constructed and survival Kaplan-Meier analysis was carried out. RESULTS: Fifty-four patients and 18 controls were included. Inflammatory and endothelial markers increased in advanced disease. FCD was reduced and RBCA was progressively lower according to disease severity. RBCA correlated inversely with inflammatory and endothelial biomarkers, and directly with renal function. The presence of hepatic encephalopathy correlated inversely with RBCA and directly with IL-6 and endothelin-1. In multivariate analysis, RBCA was an independent factor for organ dysfunction. The area under the receiver operating chartacteristic curve for IL-6 for survival was 0.74 (0.59-0.89), P=0.05. Transplant-free survival was 97.5% for values under 5.78 ng/ml (IL-6 best cutoff) and 83.9% above 5.78 ng/ml, log-rank=0.018. Eleven patients underwent transplantation, with an overall improvement in microcirculatory function. CONCLUSION: Our results suggest a mechanism of organ damage in cirrhosis, where microcirculatory dysfunction could be correlated to inflammatory and endothelial biomarkers, and loss of multiorgan function. IL-6 seems to be an important survival marker of inflammation. Liver transplantation improved microcirculatory dysfunction, corroborating this hypothesis.

Microcirculation and biomarkers in patients with resistant or mild-to-moderate hypertension: a cross-sectional study.

Microcirculation influences peripheral vascular resistance and therefore contributes to arterial blood pressure. The aim of this study was to investigate the correlation between serum markers of inflammation and microcirculatory parameters observed by nailfold videocapillaroscopy (NVC) in patients with resistant (RH, 58 [50-63] years, n = 25) or mild-to-moderate hypertension (MMH, 56 [47-64] years, n = 25) compared to normotensive patients (control group (CG), 33 [27-52] years, n = 25). C-reactive protein (CRP), endothelin, adiponectin, I-CAM and V-CAM levels were obtained by laboratory analysis. Functional capillary density (FCD; the number of capillaries with flowing red blood cells by unit tissue area), capillary diameters, maximum red blood cell velocity (RBCVmax) during the reactive hyperemia response/RBCVbaseline after 1 min of arterial occlusion at the finger base and time to reach RBCVmax were determined by NVC. A sub-analysis was also conducted on hypertensive patients not taking statins, with controlled/uncontrolled blood pressure. The RH group showed lower RBCV and RBCVmax values and longer TRBCVmax compared to MMH and CG patients, with worse values in those with uncontrolled blood pressure. FCD and diameters showed no significant differences among the three groups, with higher CRP values in the RH and MMH groups. An increase in endothelin was observed only in patients not taking statins in both hypertensive groups. Patients with severe hypertension and uncontrolled blood pressure levels presented more pronounced microvascular dysfunction, as well as higher serum values for CRP and endothelin (without statin treatment), suggesting that the use of statins decreases endothelin release.

Challenges in Design and Creation of Genetic openEHR-Archetype.

Since the Human Genomic Project discovered the sequencing of human genome, the interest about genome content in clinical practice has increased. Genetic information has become a key point to understand diseases or improve treatments, for example, the nutrigenomic and nutrigenetics. However, the huge amount of data generated raises the need for Electronic Health Record (EHR) improvements as it becomes increasingly necessary that it includes more specific genetic information. Thus, we aim to propose standard genetic archetypes (in openEHR) and describe our main challenges in this context. We assessed 2 bibliographical databases (Pubmed and Web of science) to determine the main clinical statements needed to create the archetypes. The clinical statements were organized in archetype-concepts, and they were created in openEHR archetype editor. One archetype - genetic test results - was created from a set of genetic data and submitted to CKM repository for review. Based on the modeled archetypes, an openEHR template can be created from the proposed archetype, mainly in the nutrigenomic area, genetic labs and others related to genetic.

Short-term effects of low-dose estradiol on endothelial function and blood viscosity in nondiabetic postmenopausal overweight women: a double-blind, placebo-controlled study.

OBJECTIVE: The beneficial effects of estrogen on endothelial function depend on its integrity. This study evaluates the short-term effects of low-dose transdermal estradiol on endothelial function, insulin sensitivity, and blood viscosity in nondiabetic overweight/obese women. METHODS: Forty-four nondiabetic overweight/obese women with a history of recent menopause were randomly allocated, in a double-blind fashion, to receive transdermal estradiol (1 mg/d, n = 22) or placebo (n = 22). The following parameters were assessed: endothelial reactivity (venous occlusion plethysmography and nailfold videocapillaroscopy), plasma levels of soluble adhesion molecules, insulin sensitivity (homeostasis model assessment of insulin resistance and areas under the curve of insulin and glucose during an oral glucose tolerance test), and blood and plasma viscosity. Data were expressed as means ±â€ŠSD or medians [first to third quartiles]. RESULTS: Participants were aged 51.8 ±â€Š2.3 years with a body mass index of 31.5 ±â€Š2.5 kg/m and time since menopause was 3 [2-5] years. At baseline, no differences between the groups were observed; however, after 3 months of treatment, the following changes were observed in the estradiol group compared with the placebo group: a decrease in the forearm vascular resistance at baseline (36.37 [24.9-51.27] vs 51.3 [40.88-70.03] mm Hg/mL per min 100 mL tissue, P < 0.01) and during the postocclusive reactive hyperemia response (15.93 [11.32-22.29] vs 22.13 [16.46-29.7] mm Hg/mL per min 100 mL tissue, P < 0.01), and an increase in red blood cell velocity at rest (0.316 [0.309-0.326] vs 0.303 [0.293-0.308] mm/s, P < 0.001) and during postocclusive reactive hyperemia response (0.374 [0.353-0.376] vs 0.341 [0.333-0.355] mm/s, P < 0.001). Furthermore, blood viscosity was lower in the estradiol group than in the placebo group (3.57 ±â€Š0.12 vs 3.76 ±â€Š0.22 mPa.s; P < 0.01). CONCLUSIONS: Short-term use of low-dose transdermal estradiol in nondiabetic overweight/obese women with a history of recent menopause improved endothelial function and decreased blood viscosity compared with placebo.

Dynamic nailfold videocapillaroscopy may be used for early detection of microvascular dysfunction in obesity.

OBJECTIVES: It has been hypothesized that obesity is the primary cause of microvascular dysfunction (MD), which could be a pathway to increase blood pressure and decrease insulin sensitivity. Due to the high prevalence of this metabolic disorder in the world today, the aim of this study was to investigate which is the most appropriate videocapillaroscopic method, between nailfold and dorsal finger, to assess microvascular function in obese patients since both techniques are non-invasive and could be used for early detection as well as for follow-up. METHODS: Eighteen lean [27.8±6.2years, body mass index (BMI) 21.8±1.8kg/m(2)] and nineteen obese (30.8±4.6years; BMI 32.3±1.5kg/m(2)) women participated in the study. Dynamic nailfold videocapillaroscopy assessed morphological (capillary diameters) and functional [functional capillary density (FCD); red blood cell velocity (RBCV) at baseline and peak and time (TRBCVmax) taken to reach it during the post-occlusive reactive hyperemia (PORH) response, after 1-min ischemia] parameters; while dorsal finger videocapillaroscopy assessed FCD at rest and capillary recruitment during PORH and post-venous occlusion. RESULTS: RBCV (0.32±0.01 vs. 0.30±0.01mm/s; p<0.0001) and RBCVmax (0.32±0.01 vs. 0.30±0.015mm/s; p=0.0020) were significantly higher in control subjects compared to the obese group. Moreover, TRBCVmax was prolonged in the obese group compared to control one (3.5±1.4 vs. 5.5±1.3s; p=0.0001). Multiple regression analysis showed that these variables were influenced by some others, especially those related to adiposity and metabolic disease. On the other hand, dorsal finger videocapillaroscopy did not show any significant differences between groups. CONCLUSION: Our results strongly suggest that microvascular dysfunction consequent to obesity could be better detected by dynamic nailfold videocapillaroscopy than by dorsal finger videocapillaroscopy.

Endothelial function and insulin resistance in early postmenopausal women with cardiovascular risk factors: importance of ESR1 and NOS3 polymorphisms.

Cardiovascular benefits from estradiol activation of nitric oxide endothelial production may depend on vascular wall and on estrogen receptor alpha (ESR1) and nitric oxide synthase (NOS3) polymorphisms. We have evaluated the microcirculation in vivo through nailfold videocapillaroscopy, before and after acute nasal estradiol administration at baseline and after increased sheer stress (postocclusive reactive hyperemia response) in 100 postmenopausal women, being 70 controls (healthy) and 30 simultaneously hypertensive and diabetic (HD), correlating their responses to PvuII and XbaI ESR1 polymorphisms and to VNTR, T-786C and G894T NOS3 variants. In HD women, C variant allele of ESR1 Pvull was associated to higher vasodilatation after estradiol (1.72 vs 1.64 mm/s, p = 0.01 compared to TT homozygotes) while G894T and T-786C NOS3 polymorphisms were connected to lower increment after shear stress (15% among wild type and 10% among variant alleles, p = 0.02 and 0.04). The G variant allele of ESR1 XbaI polymorphism was associated to higher HOMA-IR (3.54 vs. 1.64, p = 0.01) in HD and higher glucose levels in healthy women (91.8 vs. 87.1 mg/dl, p = 0.01), in which increased waist and HOMA-IR were also related to the G allele in NOS3 G894T (waist 93.5 vs 88.2 cm, p = 0.02; HOMA-IR 2.89 vs 1.48, p = 0.05). ESR1 Pvull, NOS3 G894T and T-786C polymorphism analysis may be considered in HD postmenopausal women for endothelial response prediction following estrogen therapy but were not discriminatory for endothelial response in healthy women. ESR1 XbaI and G894T NOS3 polymorphisms may be useful in accessing insulin resistance and type 2 diabetes risks in all women, even before menopause and occurrence of metabolic disease.

Obesity, metabolic syndrome, impaired fasting glucose, and microvascular dysfunction: a principal component analysis approach.

BACKGROUND: We aimed to evaluate the multivariate association between functional microvascular variables and clinical-laboratorial-anthropometrical measurements. METHODS: Data from 189 female subjects (34.0 ± 15.5 years, 30.5 ± 7.1 kg/m2), who were non-smokers, non-regular drug users, without a history of diabetes and/or hypertension, were analyzed by principal component analysis (PCA). PCA is a classical multivariate exploratory tool because it highlights common variation between variables allowing inferences about possible biological meaning of associations between them, without pre-establishing cause-effect relationships. In total, 15 variables were used for PCA: body mass index (BMI), waist circumference, systolic and diastolic blood pressure (BP), fasting plasma glucose, levels of total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG), insulin, C-reactive protein (CRP), and functional microvascular variables measured by nailfold videocapillaroscopy. Nailfold videocapillaroscopy was used for direct visualization of nutritive capillaries, assessing functional capillary density, red blood cell velocity (RBCV) at rest and peak after 1 min of arterial occlusion (RBCV(max)), and the time taken to reach RBCV(max) (TRBCV(max)). RESULTS: A total of 35% of subjects had metabolic syndrome, 77% were overweight/obese, and 9.5% had impaired fasting glucose. PCA was able to recognize that functional microvascular variables and clinical-laboratorial-anthropometrical measurements had a similar variation. The first five principal components explained most of the intrinsic variation of the data. For example, principal component 1 was associated with BMI, waist circumference, systolic BP, diastolic BP, insulin, TG, CRP, and TRBCV(max) varying in the same way. Principal component 1 also showed a strong association among HDL-c, RBCV, and RBCV(max), but in the opposite way. Principal component 3 was associated only with microvascular variables in the same way (functional capillary density, RBCV and RBCV(max)). Fasting plasma glucose appeared to be related to principal component 4 and did not show any association with microvascular reactivity. CONCLUSIONS: In non-diabetic female subjects, a multivariate scenario of associations between classic clinical variables strictly related to obesity and metabolic syndrome suggests a significant relationship between these diseases and microvascular reactivity.

Early postmenopausal women with cardiovascular risk factors improve microvascular dysfunction after acute estradiol administration.

OBJECTIVE: This study aimed to compare endothelial microcirculatory function in hypertensive and diabetic (HD) and healthy postmenopausal women before and after nasal application of 17ß-estradiol. METHODS: Seventy-one women aged 42 to 59 years within 10 years of menopause, divided into HD (n = 31) and similar-age healthy (n = 40) women were evaluated noninvasively through nailfold videocapillaroscopy before and 1 hour after estradiol, measuring basal (RBCV) and maximum (RBCVmax) red blood cell velocity after 1 minute of arterial occlusion, representing baseline and endothelial-mediated vasodilation, and time to reach RBCVmax (TRBCVmax), representing microvascular compliance/stiffness. RESULTS: Hot flashes did not differ from or affect microvascular results. Before estradiol, HD showed lower RBCV (1.495 ± 0.20 vs 1.52 ± 0.10 mm/s, P = 0.019), borderline lower RBCVmax (1.655 ± 0.09 vs 1.706 ± 0.10 mm/s, P = 0.054), and shorter TRBCVmax (7.94 ± 1.44 vs 8.8 ± 2.03 s, P = 0.011) compared with healthy women. After estradiol, RBCV and RBCVmax increased, and TRBCVmax decreased in both groups (P = 0.0001 for all). HD women showed a higher RBCV increment (14.6% ± 2% vs 11.1 ± 1.4%, P = 0.021) associated with a smaller TRBCVmax reduction (23.6% ± 2% vs 31% ± 2%, P = 0.045). Changes in RBCVmax did not differ between HD (11.6% ± 1%) and healthy (8.3% ± 1.3%, P = 0.1) women. RBCV, RBCVmax, and TRBCVmax absolute values after estradiol were similar between groups. Past oral contraceptive exposure (P = 0.035) and cigarette smoking (P = 0.047) influenced healthy women's microvascular responses to estradiol, whereas triglyceride levels impaired HD vasodilation (P = 0.028). CONCLUSIONS: Before estradiol, HD presented impaired microvascular dilation and compliance compared with control women of similar age. After estradiol, HD recovered microvascular endothelial-mediated dilation, reaching similar absolute values, but the smaller reduction in TRBCVmax suggests irreversible microvascular stiffness.

Novel findings in the cephalic phase of digestion: a role for microcirculation?

The cephalic phase of digestion (CPD) has been extensively investigated in terms of digestion and metabolism. Nevertheless, microcirculatory changes required to prepare peripheral tissues in order to dispose nutrients have never been assessed. In this study, microvascular function has been evaluated to determine its behavior and potential association to hormonal secretions during CPD. Thirty-nine healthy male subjects, 23.4 ± 0.5 years (mean ± SD) and BMI of 23.3 ± 2.3 kg/m(2), were randomized into receiving cognitive-sensorial stimuli to elicit CPD (CPD group, n=20) or not (control group, n=19), after a 12-h overnight fast. Main outcomes were differences in resting and peak functional capillary density (FCD, cap/mm(2)); resting red blood cell velocity (RBCV), peak RBCV (RBCV(max)) and time taken to reach it (TRBCV(max)); peak flow and vasomotion, before and after CPD and their associations with insulin and/or pancreatic polypeptide (PP). In the CPD group, basal FCD (24.9 ± 7.6 to 28.3 ± 8.1, p=0.005), peak FCD (27.8 ± 6.3 to 32.6 ± 7.1, p=0.002), RBCV (0.306 ± 0.031 to 0.330 ± 0.027 mm/s, p=0.005), RBCV(max) (0.336 ± 0.029 to 0.398 ± 0.292 mm/s, p=0.005) and peak flow (23.5 ± 14.3 to 26.9 ± 15.8 PU, p<0.01) increased while TRBCV(max) decreased (4.9 ± 1.5 to 3.5 ± 1.2s, p=0.01). No significant changes could be detected in the control group. Groups have not presented differences for insulin, but PP significantly increased in the CPD group and was positively associated to basal FCD increase (rho=0.527, p=0.03). In conclusion, neurally-mediated anticipatory responses of digestion elicited functional capillary recruitment associated to PP in healthy men, suggesting a precocious role for microcirculation in the physiology of digestion and nutrient homeostasis.

Brazil nuts intake improves lipid profile, oxidative stress and microvascular function in obese adolescents: a randomized controlled trial.

BACKGROUND: Obesity is a chronic disease associated to an inflammatory process resulting in oxidative stress that leads to morpho-functional microvascular damage that could be improved by some dietary interventions. In this study, the intake of Brazil nuts (Bertholletia excelsa), composed of bioactive substances like selenium, α- e γ- tocopherol, folate and polyunsaturated fatty acids, have been investigated on antioxidant capacity, lipid and metabolic profiles and nutritive skin microcirculation in obese adolescents. METHODS: Obese female adolescents (n = 17), 15.4 ± 2.0 years and BMI of 35.6 ± 3.3 kg/m2, were randomized 1:1 in two groups with the diet supplemented either with Brazil nuts [BNG, n = 08, 15-25 g/day (equivalent to 3 to 5 units/day)] or placebo [PG (lactose), n = 09, one capsule/day] and followed for 16 weeks. Anthropometry, metabolic-lipid profiles, oxidative stress and morphological (capillary diameters) and functional [functional capillary density, red blood cell velocity (RBCV) at baseline and peak (RBCVmax) and time (TRBCVmax) to reach it during post-occlusive reactive hyperemia, after 1 min arterial occlusion] microvascular variables were assessed by nailfold videocapillaroscopy at baseline (T0) and after intervention (T1). RESULTS: T0 characteristics were similar between groups. At T1, BNG (intra-group variation) had increased selenium levels (p = 0.02), RBCV (p = 0.03) and RBCVmax (p = 0.03) and reduced total (TC) (p = 0.02) and LDL-cholesterol (p = 0.02). Compared to PG, Brazil nuts intake reduced TC (p = 0.003), triglycerides (p = 0.05) and LDL-ox (p = 0.02) and increased RBCV (p = 0.03). CONCLUSION: Brazil nuts intake improved the lipid profile and microvascular function in obese adolescents, possibly due to its high level of unsaturated fatty acids and bioactive substances. TRIAL REGISTRATION: Clinical Trials.gov NCT00937599.

Waist circumference leads to prolonged microvascular reactive hyperemia response in young overweight/obese women.

OBJECTIVES: Previous data in our laboratory have shown microvascular dysfunction in normoglycaemic subjects with metabolic syndrome (MS). In a step further, we have investigated which clinical parameters related or not to MS would elicit microvascular dysfunction and the need of diagnosing MS for the establishment of microcirculatory impairment in overweight/obese women. METHODS: Nineteen lean [23.6±3.1years, body mass index (BMI) 21.9±1.8kg/m(2)] and 59 overweight/obese [24.6±3.7years; BMI 34.4±5.9kg/m(2)] sedentary non-smoking women, divided in overweight/obese without (MS negative, n=36) and obese with MS (MS positive, n=23) were evaluated. Blood biochemistry, HOMA-IR index and anthropometric variables were determined. Morphological (capillary diameters) and functional [functional capillary density, red blood cell velocity (RBCV) at baseline and peak and time (TRBCV(max)) to reach it during post-occlusive reactive hyperemia after 1min ischemia] microcirculatory variables were examined by nailfold videocapillaroscopy. RESULTS: Compared to controls, overweight/obese MS negative and obese MS positive presented longer TRBCV(max); the presence of two MS components was sufficient to prolong it and the MS diagnosis did not add any significant impairment to the microcirculation. Among clinical parameters investigated, a direct relationship between TRBCV(max) and waist circumference and insulin concentrations was found. CONCLUSION: Our results have shown that microvascular dysfunction is independent of metabolic syndrome diagnosis and could be predicted by the waist circumference on young overweight/obese women, reinforcing the relationship between obesity-related microvascular/metabolic disturbances.

Endothelial-mediated microcirculatory responses to an acute estradiol test are influenced by time since menopause, cumulative hormone exposure, and vasomotor symptoms.

OBJECTIVE: The aim of this study was to determine which factors could influence microcirculatory responses to an acute estradiol test during postmenopause. METHODS: Dynamic nailfold videocapillaroscopy was performed in 68 healthy 34- to 70-year-old postmenopausal women before and 1 hour after administration of 300 mug nasal estradiol. Red blood cell velocity (RBCV; mm/s) at rest and after the release of 60-second arterial occlusion (RBCVmax; mm/s) and time to reach it (TRBCVmax; s) were correlated to clinical and laboratory data. RESULTS: After estradiol administration, RBCV and RBCVmax increased by 13.4% and 9.4%, respectively, and TRBCVmax decreased by 29.1% (P = 0.0001 for all). These changes were not associated to the women's age but rather to time since menopause (P = 0.04; r = 0.245) and previous duration of hormone therapy (P = 0.03; r = 0.324). Past users of oral contraceptives presented higher velocities but smaller increases compared with never users (12.4% vs 17.7%, P = 0.022, for RBCV and 8.4% vs 13.7%, P = 0.028, for RBCVmax), and triglyceride levels were negatively associated to velocity increases (P = 0.05 and r = -0.243 for RBCV and P = 0.03 and r = -0.261 for RBCVmax) after estradiol administration. Previous smokers showed a smaller reduction in TRBCVmax, associated directly to total estimated number of smoked cigarettes (P = 0.03; r = -0.468). The reduction in TRBCVmax was also inversely related to the intensity of current vasomotor symptoms (P = 0.04; r = -0.252). CONCLUSIONS: Changes in RBCVs and TRBCVmax after estradiol administration indicate an increase in endothelial-dependent vasodilatation and vascular elasticity, respectively. Moreover, maintenance of endothelial responsiveness depends on cumulative exposure to sex steroids, duration of hormone deprivation, and triglyceride levels. Past smoking and current vasomotor symptoms could be associated to microvascular wall stiffness/elasticity.

Microcirculatory function in postmenopausal women: role of aging, hormonal exposure and metabolic syndrome.

Menopausal hormone therapy (HT) has shown conflicting cardiovascular endpoints, depending on the women studied. The endothelium is the main site for sex steroids cardiovascular action. To assess the influence of age, previous hormonal exposure and of metabolic syndrome (MS) on microcirculatory function, we studied 68 normotensive non-diabetic postmenopausal women, 34-70 years old, by dynamic nailfold videocapillaroscopy evaluating red blood cell velocity (RBCV) at baseline and during the reactive hyperemia response after 1 min ischemia (RBCV(max)) and time taken to reach it (TRBCV(max)). There was an inverse correlation between RBCV and RBCV(max), versus age (p=0.02 for both) and time since menopause (TSM, p=0.01 and p=0.03, respectively). Women who used oral contraceptives in the past showed higher RBCV (1.51+/-0.10 vs. 1.43+/-0.09 mm/s, p=0.01) and RBCV(max) (1.70+/-0.11 vs. 1.63+/-0.07 mm/s, p=0.03) compared to never user ones. A longer time after menopause without HT was associated to lower RBCV(max) (p=0.05). Women with MS had longer TRBCV(max) (9.85+/-1.77 vs. 8.47+/-1.71 s, p=0.02), as well as those with higher hematocrit, hemoglobin and leukocyte counts (p=0.03, p=0.01 and p=0.03, respectively) and lower HDL (p=0.03). In conclusion, in postmenopausal women of low cardiovascular risk, advanced age, longer TSM, longer time after menopause without HT and MS were associated to microcirculatory function impairment, whereas past use of oral contraceptives seemed to have a protective effect.