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

RBCV₁ and RBCV₁ increment in HD women according to <i>NOS3 T-786C and G894T</i> genotypes.

<p>Data are presented as Whiskers plot. Comparison between groups was made by Mann Whitney test. RBCV₁: Red blood cells velocity (mm/s). RBCV₁ increment: Red blood cells velocity increment (%) after 1 min ischemia and subsequent reactive hyperemia response upon occlusion release. A, C, and E, RBCV₁ and <i>VNTR</i>, <i>-786C</i>, and <i>G894T</i> genotypes, respectively. B, D, and F, RBCV₁ increment and <i>VNTR</i>, <b><i>-</i></b><i>786C</i>, and <i>G894T</i> genotypes, respectively.</p

Clinical and laboratory data in HD and healthy women.

<p>Reference values: HOMA-IR, 2.1 T 0.7; Triglycerides, <150 mg/dl; HDL cholesterol, >50 mg/dl; hS C-reactive protein, <0.3 mg/dl; Estradiol, <44 pg/ml (post menopause without HT);</p><p>Oxidized LDL, <0.5 nmol/mg ApoPt.</p><p>BMI, body mass index; HOMA-IR, homeostasis model assessment of insulin resistance; RBCV₁: red blood cell velocity before estradiol: RBCV_max1: peak red blood cell velocity before estradiol: RBCV₁ increment: % of RBCV_max1 increase in relation to RBCV₁; TRBCV_max1: time to reach peak red blood cell velocity before estradiol; RBCV₂: red blood cell velocity after estradiol: RBCV_max2: peak red blood cell velocity after estradiol: RBCV₂ increment: % of RBCV_max2 increase in relation to RBCV₂: TRBCV_max2: time to reach peak red blood cell velocity after estradiol. Comparison between groups was performed by Mann Whitney test.</p

RBCV₂ and RBCV₂ increment in HD women according to <i>ESR1 PvuII</i> and <i>Xbal</i> genotypes.

<p>Data are presented as Whiskers plot. Comparison between groups was made by Mann Whitney test. RBCV₂: Red blood cells velocity (mm/s) after estrogen administration. RBCV₂ increment: Red blood cells velocity increment (%) after 1 min ischemia and subsequent reactive hyperemia response upon occlusion release after estrogen administration. A and C, RBCV₂ and <i>PvuII</i> and <i>Xbal</i> genotypes, respectively. B and D, RBCV₂ increment and <i>PvuII</i> and <i>Xbal</i> genotypes, respectively.</p

Frequencies of <i>ESR1</i> and <i>NOS3</i> polymorphisms in HD and healthy women.

<p>Comparison between genotypes was performed by Fisher’s exact test.</p

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-na&iuml;ve patients, all women aged between 19 and 50 years, with BMI &ge; 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

Seroprevalence of SARS-CoV-2 and assessment of epidemiologic determinants in Portuguese municipal workers

ObjectivesTo assess the seroprevalence of SARS-CoV-2 antibodies in municipal employees of Northern Portugal during the first pandemic wave (May–June 2020) and its association with potentially related risk factors for infection.Material and MethodsThe authors assessed municipal employees of 2 cities in Northern Portugal, in whom serological tests to SARS-CoV-2 and an epidemiological survey were applied. The authors assessed the proportion of individuals presenting IgM and/or IgG antibodies to SARS-CoV-2, and evaluated the association between having positive serological test results, epidemiologic variables and clinical presentations. Reported symptoms were evaluated on their sensitivity, specificity, and predictive values.ResultsThe authors assessed 1696 employees, of whom 22.0% were firefighters, 10.4% were police officers, 10.3% were maintenance workers, and 8.1% were administrative assistants. The seroprevalence of SARS-CoV-2 infection was 2.9% (95% CI: 2.1–3.7%). Administrative assistants comprised the professional group with highest seroprevalence of SARS-CoV-2 (OR = 1.9 in the comparison with other occupational groups, 95% CI: 0.8–4.3, p = 0.126). The seroprevalence of SARS-CoV-2 infection among those who were in direct contact with COVID-19 patients in their professional activity was 3.9%, compared to 2.7% among those who were not in direct contact with such patients (OR = 1.5, 95% CI: 0.8–2.8, p = 0.222). The highest risk of infection was associated with the presence of a confirmed SARS-CoV-2 infection in the household (OR = 17.4, 95% CI: 8.3–36.8, p < 0.001). Living with a healthcare professional was not associated with a higher risk of infection (OR = 1.0, 95% CI: 0.4–2.5, p = 0.934). Anosmia/dysgeusia was the symptom with the highest positive predictive value (52.2%, 95% CI: 31.8–72.6, p < 0.001) and specificity (99.3%, 95% CI: 98.9–99.7, p < 0.001), while cough was the most prevalent symptom among SARS-CoV-2 seropositive participants (36%).ConclusionsThe authors observed a SARS-CoV-2 seroprevalence of 2.9% among assessed municipal employees. Anosmia/dysgeusia was the COVID-19 symptom which displayed the highest positive predictive value and specificity