Endothelium-dependent Brachial Artery Research Articles

Abstract 17170: Association of Plasma Homocysteine Levels in Cancer Survivors - Data From Framingham Heart Study Offspring Cohort

Introduction: Cancer survivors experience a high prevalence of vascular remodeling from their anti-cancer therapies, which can lead to arterial stiffness. High plasma homocysteine (Hcy) is associated with increased cardiovascular disease risk via its role in decreasing nitric oxide bioavailability and impairing vascular function. However, there is limited work on its role in cancer survivorship. We, therefore, hypothesized that survivors of breast, gastrointestinal, and prostate cancer with elevated plasma Hcy values have higher arterial stiffness and lower endothelial function compared to those with low plasma Hcy. Methods: We evaluated cardiovascular disease-free cancer survivors in the Framingham Heart Study Offspring Cohort (n=196, 66±8 years old, 55.1% women, 26.4±1.2 years from cancer diagnosis, Range: [23.8 - 29.6 years]) with plasma Hcy measurements. The cohort median plasma Hcy was used to define low (<8.16 μmol/L) and high Hcy (≥8.16 μmol/L) groups. Arterial stiffness was assessed via carotid-femoral pulse wave velocity (cfPWV). Peripheral vascular endothelial function was assessed via endothelium-dependent brachial artery flow-mediated dilation (FMD). Differences in cfPWV, FMD, and cardiovascular risk factors were assessed via independent sample t-test or chi-square test. Differences in cfPWV and FMD were further assessed via one-way ANCOVA with age, sex, and cardiovascular medications included as covariates. Results: cfPWV was significantly higher in the high Hcy (9.9±1.5m/s) vs. low Hcy group (8.5±1.9m/s, p=0.005); however, there were no differences in FMD between groups (2.4±1.7 vs. 2.7±2.0%, p=0.42). After controlling for our covariates, cfPWV was still significantly higher in the high Hcy group (Mean[95% CI]): (9.8[9.0-10.61]) compared to the low Hcy group (8.5[8-9.1]) (p=0.015). Conclusions: Our findings suggest an association between elevated Hcy and an increase in arterial stiffness in cancer survivors. This supports the potential adverse consequences of vascular stiffening following cancer diagnosis and treatment which could have long-term cardiovascular health implications.

Relationship between the volume of perivascular adipose tissue and the vascular wall lesion

Aim. To study the relationship between the volume of perivascular adipose tissue (PVAT) and the vascular wall lesion.Material and methods. The study included 318 patients without cardiovascular disease (mean age, 63,5±13,7 years). Hypertension was detected in 268 (84,3%) patients. All patients underwent assessment of anthropometric characteristics, lipid profile, arterial wall stiffness with the estimation of cardio-ankle vascular index, intima-media thickness, brachial artery endothelial vasomotor function. Chest computed tomography was performed with the estimation of the volumes of PVAT and pericardial adipose tissue (PAT).Results. The volume of PVAT, on average, was 0,3 [0,2; 0,4] cm3 . The VAT volume was significantly higher in obese individuals when compared with patients with normal body weight: 0,4 [0,3; 0,5] vs 0,25 [0,2; 0,4] cm3 (p=0,0007). The VAT volume was higher in individuals with an increased CAVI level when compared with patients with normal CAVI values: 0,4 [0,3; 0,5] vs 0,3 [0,25; 0,3] (p=0,02). A significant correlation was found between the VAT volume and body mass index (r=0,27, p<0,005), waist circumference (r=0,41, p<0,005), CAVI (r=0,49, p<0,05), impaired endothelium-dependent brachial artery vasodilation (r=0,38, p<0,05). When performing multiple linear regression, a significant relationship of CAVI was found with age (β±SE, 0,51±0,15; p=0,002) and volume of PVAT (β±SE, 0,41±0,13; p=0,005).Conclusion. The results indicate the relationship of PVAT with visceral obesity and vascular wall stiffness parameters.

Increased circulating endothelial progenitor cells (EPCs) in prepubertal children born prematurely: a possible link between prematurity and cardiovascular risk.

Endothelial progenitor cells (EPCs) ensure vascular integrity and neovascularization. No studies have investigated EPCs in preterm-born children beyond infancy. One hundred and thirty-six prepubertal children were enrolled: 63 preterm and 73 born at term (controls). Circulating CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs were measured in preterm-born children compared to controls. Body mass index (BMI), waist-to-hip ratio (WHR), neck circumference, systolic and diastolic blood pressure (SBP and DBP, respectively), fasting glucose, insulin, lipid profile, common carotid and abdominal aortic intima-media thickness (cIMT and aIMT, respectively), endothelium-dependent brachial artery flow-mediated dilation (FMD), and echocardiographic parameters were also assessed. Circulating CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs were significantly higher in preterm-born children compared to controls (p < 0.001 and p < 0.001, respectively). In total study population and in the preterm-born group, EPCs were significantly lower in children born to mothers with gestational diabetes compared to non-diabetic mothers. Prematurity was associated with higher WHR, neck circumference, SBP, DBP, cIMT, aIMT, mean pressure, and velocity of pulmonary artery; the peak velocity of the brachial artery was significantly lower in children born prematurely. In multiple regression analysis, preterm birth and maternal gestational diabetes were recognized as independent predictors of EPCs. Circulating EPCs were increased in prepubertal preterm-born children in comparison with peers born full-term. Maternal gestational diabetes was associated with a decrease in EPCs. Mounting evidence supports the adverse effect of prematurity on cardiovascular health. However, the underlying mechanisms that could lead to endothelial dysfunction in preterm-born individuals are not fully understood. Endothelial progenitor cells (EPCs) ensure vascular integrity, normal endothelial function and neovascularization. No studies have investigated the EPCs counts in peripheral blood beyond infancy in children born prematurely. Circulating EPCs were significantly higher in preterm-born prepubertal children compared to controls, thus indicating that prematurity is possibly associated with endothelial damage. In total study population and in the preterm-born group, maternal gestational diabetes was associated with decreased EPCs concentrations.

Drug Correction of Vascular Remodeling in Patients with Hypertension: Results of 52-Week Prospective Study ARTERIA-AG

Aim. To study the long-term dynamics of vascular remodeling in patients with hypertension and high and very high cardiovascular risk when statin is added to antihypertensive therapy with a fixed combination of calcium antagonist and angiotensin converting enzyme (ACE) inhibitor.Material and methods. Hypertensive patients (n=75) with high and very high cardiovascular risk (age 51.5 [44;58] years) were included in the study. Patients were randomized into two groups. The first group (n=36) received a fixed combination of amlodipine and lisinopril in starting dose of 5/10 mg/day. The second group (n=39) received the same antihypertensive therapy and additionally rosuvastatin (20 mg/day). The follow-up period was 52 weeks. The effect of therapy on the following parameters was evaluated: level of office and average daily blood pressure (BP), central BP in the aorta, augmentation index (AIx), pulse wave velocity (PWV), endothelium-dependent brachial artery vasodilation, carotid intima-media complex thickness, carotid arteries plaque height, and blood lipid profile indicators.Results. A significant decrease in office and average daily BP was found in both groups: from 171.5 (152;194)/104.5 (97;112) to 140.0 (129;154)/87.0 (83;95) mm Hg and from 142.1 (135;153)/86.7 (83;97) to 124.6 (119;133)/76.5 (73;80) mm Hg, respectively, in the 1st group; from 169.5 (160;190)/103.5 (95;109) to 135.0 (125;141)/83.0 (77;88) mm Hg and from 139.9 (136;152)/86.2 (80;92) to 125.1 (118;134)/74.0 (70;81) mm Hg, respectively, in the 2nd group (p&lt;0.001 for all changes). The frequency of reaching the target office BP level was higher in the 2nd group (p=0.031). Significant decrease in total cholesterol by 33.1% and low-density lipoprotein cholesterol by 50.0% was observed in the group 2. Central BP in the aorta decreased in both groups; the degree of central BP reduction did not differ significantly. AIx decreased from 36.5 (24;41)% to 25.0 (15;36)% (p=0.04) in the 1st group and from 36.0 (30;41)% to 24.0 (20;32)% in the 2nd group (p&lt;0.0001) with a more pronounced decrease in AIx after 24 weeks of therapy (-4.8% and -9.4%, respectively, p=0.036). This trend continued at the end of the observation (-6.4% and -10.8%, respectively, p=0.08). Carotid-femoral and carotid-radial PWV decreased only in the 2nd group from 9.5 (8.2;10.7) to 8.3 (7.6;8.9) m/s (p=0.003) and from 9,6 (8.5;10.6) to 8.4 (7.9;9.3) m/s (p=0.01), respectively. A significant decrease in the thickness of the intima-media from 1.08 (1.0;1.2) to 1.02 (0.9;1.1) cm (p&lt;0.0001) and the height of the plaque from 2.2 (2,2;1.7) to 2.1 (2.1;1.7) mm (p=0.001) was found in the 2nd group.Conclusion. Addition of rosuvastatin to the fixed combination of amlodipine and lisinopril in treatment of hypertensive patients with high and very high cardiovascular risk was accompanied by a more frequent (compared with amlodipine and lisinopril only) achievement of the target office BP level and more pronounced reduction in the following indicators: augmentation index, carotid-femoral and carotid-radial PWV, intima-media thickness, plaque height, total cholesterol and low density lipoprotein cholesterol blood levels.

Preterm Birth as a Risk Factor for Metabolic Syndrome and Cardiovascular Disease in Adult Life: A Systematic Review and Meta-Analysis

To determine if preterm birth is associated with components of the metabolic syndrome in adult life. A structured literature search was performed using PubMed. All comparative studies reported metabolic and cardiovascular outcomes in adults (≥18years of age) born preterm (<37weeks of gestation) compared with adults born at term (37-42weeks of gestation) and published through March 2018 were included. The major outcomes assessed were body mass index, waist circumference, waist-to-hip ratio, fat mass, systolic blood pressure (SBP), diastolic blood pressure (DBP), 24-hour SBP, 24-hour DBP, endothelium-dependent brachial artery flow-mediated dilation, carotid intima-media thickness, pulse wave velocity, fasting glucose and insulin, Homeostasis Model Assessment-Estimated Insulin Resistance Index, and lipid profiles. Quality appraisal was performed using a modified version of the Newcastle-Ottawa scale. A meta-analysis was performed for comparable studies which reported sufficient data. Forty-three studies were included, including a combined total of 18 295 preterm and 294 063 term-born adults. Prematurity was associated with significantly higher fat mass (P=.03), SBP (P<.0001), DBP (P<.0001), 24-hour SBP (P<.001), and 24-hour DBP (P<.001). Furthermore, preterm-born adults presented higher values of fasting glucose (P=.01), insulin (P=.002), Homeostasis Model Assessment-Estimated Insulin Resistance Index (P=.05), and total cholesterol levels (P=.05) in comparison with adults born at term, in random effect models. No statistically significant difference was found between preterm and term-born adults for the other outcomes studied. Preterm birth is strongly associated with a number of components of the metabolic syndrome and cardiovascular disease in adult life.

Estimation of the influence of photobiomodulation on the endothelial function in patients with arterial hypertension under the conditions of hyperuricemia

Introduction. In 2015, the global prevalence of hypertension in the world was estimated at 1.13 billion. The European Association for the Treatment of Hypertension (ESH) updated its recommendations in 2018 and officially added to the already existing risk factors of hypertension hyperuricemia. In patients with comorbidity of hyperuricemia and hypertension, endothelial dysfunction is observed. The aim of the study is to establish correlation between uric acid level and pulse wave velocity, Tei index, endothelium-dependent vasodilation of the brachial artery and evaluate the effect of photobiomodulation on endothelial dysfunction in patients with hypertension. Materials and methods. The study included 102 patients with hypertension: 48 without hyperuricemia (group 1) and 54 with comorbidity of hypertension and hyperuricemia (group 2). Groups 1A and 2A received antihypertensive therapy. Groups 1B and 2B — antihypertensive therapy with a course of intravenous laser therapy with a wavelength of 635 nm, course 10 procedures. Endothelium-dependent vasodilation of the brachial artery was determined by a breakdown with reactive hyperemia. Tei index was calculated during echocardiography. The pulse wave velocity was measured with a SonoScape S6 Pro. Results. Antihypertensive therapy in group 1A reduced the rate of the pulse wave by 7.8 %. Antihypertensive therapy and intravenous laser therapy in Group 1 reduced uric acid by 5.7 %, pulse rate by 12.2 %, Tei index by 9.5 %, increased endothelium dependent vasodilation of the brachial artery by 19.1 % (p &lt; 0,05). Antihypertensive therapy in Group 2A reduced uric acid by 4.7 %, pulse rate by 8.5 % and increased endothelium-dependent brachial artery vasodilation by 31.7 %. Combined use of antihypertensive therapy and intravenous laser therapy in group 2B reduced uric acid by 19.2 %, pulse wave speed by 21.9 %, Tei index by 29.0 %, increased endothelium- dependent vasodilation of the brachial artery by 97.7 % &lt; 0.05). A correlation was established between uric acid level and endothelium dependent vasodilation of the brachial artery r = - 0.62 (p &lt; 0.001) and between uric acid level and pulse wave velocity r = + 0.68, uric acid level and systolic blood pressure (day ) r = + 0.48 (p &lt; 0.001), uric acid level and Tei index r = + 0.47 (p &lt; 0.05). Conclusion. Given the established negative correlation between the mean strength between uric acid level and endothelium-dependent vasodilation of the brachial artery, it is appropriate to use in clinical practice a combination of antihypertensive therapy with intravenous laser therapy, which significantly reduces the level of uterine fibrillation hypertension and in patients with comorbidity of hypertension and hyperuricemia.

The effect of an apple polyphenol extract rich in epicatechin and flavan-3-ol oligomers on brachial artery flow-mediated vasodilatory function in volunteers with elevated blood pressure

BackgroundThe primary aim of this study was to test the hypothesis that an orally ingested apple polyphenol extract rich in epicatechin and flavan-3-ol oligomers improves endothelium-dependent brachial artery flow-mediated vasodilatation (FMD) in volunteers with borderline hypertension. The secondary aim of the study was to test whether the investigational product would improve endothelium-independent nitrate-mediated vasodilatation (NMD).MethodsThis was a single centre, repeated-dose, double-blind, placebo-controlled, crossover study in 60 otherwise healthy subjects (26 men, 34 women; aged 40-65 years) with borderline hypertension (blood pressure 130-139/85-89 mmHg) or unmedicated mild hypertension (blood pressure 140-165/90-95 mmHg). The subjects were randomised to receive placebo or the apple polyphenol extract to provide a daily dose of 100 mg epicatechin for 4 weeks, followed by a four to five-week wash-out period, and then 4 weeks intake of the product that they did not receive during the first treatment period. FMD and NMD of the left brachial artery were investigated with ultrasonography at the start and end of both treatment periods, and the per cent increase of the arterial diameter (FMD% and NMD%) was calculated.ResultsWith the apple extract treatment, a significant acute improvement was detected in the mean change of maximum FMD% at the first visit 1.16 (p = 0.04, 95% CI: 0.04; 2.28), last visit 1.37 (p = 0.02, 95% CI: 0.22; 2.52) and for both visits combined 1.29 (p < 0.01, 95% CI: 0.40; 2.18). However, such improvement was not statistically significant when apple extract was compared with placebo. The overall long-term effect of apple extract on FMD% was not different from placebo. No statistically significant differences between the apple extract and placebo treatments were observed for endothelium-independent NMD.ConclusionsA significant acute improvement in maximum FMD% with apple extract administration was found. However, superiority of apple extract over placebo was not statistically significant in our study subjects with borderline hypertension or mild hypertension. The study raised no safety concerns regarding the daily administration of an apple polyphenol extract rich in epicatechin.Trial registrationThe trial is registered at http://clinicaltrials.gov (identifier: NCT01690676). Registered 25th May 2012.

A Randomized Trial of Vitamin D Supplementation on Vascular Function in CKD

Vitamin D deficiency associates with mortality in patients with CKD, and vitamin D supplementation might mitigate cardiovascular disease risk in CKD. In this randomized, double-blind, placebo-controlled trial, we investigated the effect of cholecalciferol supplementation on vascular function in 120 patients of either sex, aged 18-70 years, with nondiabetic CKD stage 3-4 and vitamin D deficiency (serum 25-hydroxyvitamin D ≤20 ng/ml). We randomized patients using a 1:1 ratio to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in endothelium-dependent brachial artery flow-mediated dilation at 16 weeks. Secondary outcome measures included changes in pulse wave velocity and circulating biomarkers. Cholecalciferol supplementation significantly increased endothelium-dependent brachial artery flow-mediated dilation at 16 weeks, whereas placebo did not (between-group difference in mean change: 5.49%; 95% confidence interval, 4.34% to 6.64%; P<0.001). Intervention also led to significant favorable changes in pulse wave velocity and circulating IL-6 levels. Thus, in nondiabetic patients with stage 3-4 CKD and vitamin D deficiency, vitamin D supplementation may improve vascular function. This study is registered with the Clinical Trials Registry of India (no.: CTRI/2013/05/003648).

Hyperhomocysteinemia in patients with chronic kidney disease and its relationship with the functional status of the cardiovascular system

Chronic kidney disease (CKD) is an important medical, social and economic problem nowadays. Patients with CKD are known to have an increased risk of development and progression of cardiovascular diseases. However, the causes and pathogenesis of cardiovascular complications are not well understood. One of the recently recognized “non-traditional” risk factors for the increased development of cardiovascular pathology in severe stages of CKD is hyperhomocysteinemia (HHC). The article presents the results of study of HHC frequency in patients with different stages of CKD as well as the relationship between HHC and endothelial dysfunction and structural-functional status of the heart. The study involved 148 persons with different stages of CKD who underwent immunoenzyme determination of total plasma homocysteine (HC), echocardiography, carotid ultrasonograghy, endothelial function was assessed as well. It was found that among the patients with CKD, 26 (21.1%) had normal and 34 (27.7%) had subnormal HC levels, mild HHC was observed in 30 (24.4%) and moderate HHC – in 33 (26.8%) cases, i.e. the total number of patients with elevated HC level was 88.9%. It should be noted that no patients with normal HC level were found among those with stage four CKD as well as in dialysis patients. The increase of blood plasma HC level was actually proportional to the severity of renal failure, which in its turn led to the shift in the number of cases towards higher rank indices of HHC level. In particular, while there were no patients with HHC among those with CKD-I, more than 50% of such patients were found in the group with CKD-V. Reduced myocardial contractility and echocardiographic markers of left ventricular hypertrophy in patients with CKD were found to be closely associated with HC concentrations in blood plasma. The data presented clearly demonstrate strong inverse correlation between endothelial dysfunction indices and HC level. So, the endothelium-dependent brachial artery vasodilation in patients with CKD-IV was lower by 3.8 and 1.5 times compared with control group and CKD-III group, respectively, and endothelium-independent vasodilation of the brachial artery – by 2.4 and 1.9 times, respectively. Correlation analysis also confirmed that impaired endothelium-dependent and endothelium-independent dilation with high statistical significance inversely correlated with the level of HC in blood plasma. Thus, the population of patients with CKD is characterized by high HHC frequency, which is closely associated with cardiovascular disorders (endothelial dysfunction, structural and functional remodelling of the myocardium) and can be an important risk factor for the development of vascular lesions. We believe that adequate correction of HHC, including administration of folic acid preparations could reduce the progression of vascular lesions in patients with CKD.

Usefulness of Brachial Artery Flow-Mediated Dilation to Predict Long-Term Cardiovascular Events in Subjects Without Heart Disease

Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. To determine the long-term association of brachial artery flow-mediated dilation (FMD) and adverse cardiovascular (CV) events in healthy subjects, we prospectively assessed brachial FMD in 618 consecutive healthy subjects with no apparent heart disease, 387 men (63%), and mean age 54 ± 11 years. After overnight fasting and discontinuation of all medications for ≥12 hours, FMD was assessed using high-resolution linear array ultrasound. Subjects were divided into 2 groups: FMD ≤11.3% (n = 309) and >11.3% (n = 309), where 11.3% is the median FMD, and were comparable regarding CV risk factors, lipoproteins, fasting glucose, C-reactive protein, concomitant medications, and Framingham 10-year risk score. In a mean clinical follow-up of 4.6 ± 1.8 years, the composite CV events (all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions) were significantly more common in subjects with FMD ≤11.3% rather than >11.3% (15.2% vs 1.2%, p = 0.0001, respectively). Univariate analysis demonstrated that the median FMD significantly predicted CV events (odds ratio 2.78, 95% CI 1.35 to 5.71, p <0.001). Multivariate analysis, controlling for traditional CV risk factors, demonstrated that median FMD was the best independent predictor of long-term CV adverse events (odds ratio 2.93, 95% CI 1.28 to 6.68, p <0.001). In conclusion, brachial artery median FMD independently predicts long-term adverse CV events in healthy subjects with no apparent heart disease in addition to those derived from traditional risk factor assessment.

Hypoadiponectinemia and aldosterone excess are associated with lack of blood pressure control in subjects with resistant hypertension

Obesity, arterial stiffness and high aldosterone levels can interact to cause resistant hypertension (RHTN). Lower adiponectin (APN) levels may be significantly associated with hypertension. However, the importance of hypoadiponectinemia as a complicating factor in the lack of blood pressure (BP) control in individuals with RHTN has not been demonstrated. Ninety-six RHTN patients were classified into uncontrolled (UCRHTN, n = 44) and controlled (CRHTN, n = 52) subgroups. Their APN and aldosterone levels, office and ambulatory BP (ABPM) measurements, endothelium-dependent brachial artery responses (flow-mediated dilation (FMD)), left ventricular mass index (LVMI) and pulse wave velocity (PWV) were evaluated. The UCRHTN subgroup had increased aldosterone levels, as well as higher LVMI and PWV. In addition, lower APN levels and impaired FMD response were found in this subgroup. The brachial and ABPM pulse pressures were inversely associated with the APN levels (r = -0.45, P = 0.002; r = -0.33, P = 0.03, respectively), as were the aldosterone levels and the PWV (r = -0.38, P = 0.01; r = -0.36, P = 0.02, respectively) in UCRHTN patients. The PWV was only significantly influenced by the APN level in the UCRHTN subgroup in the multivariate regression analysis. None of the correlations mentioned above were observed in the CRHTN subgroup. Hypoadiponectinemia and high aldosterone levels may therefore be implicated in resistance to antihypertensive therapy related to arterial stiffness.

Changes in endothelial function and depression scores are associated following long-term dietary intervention: A secondary analysis

ObjectiveCross-sectional studies show associations between depression and endothelial function (as measured by endothelium-dependent brachial artery flow-mediated dilatation [FMD]); but it is not known whether changes in these parameters are associated following dietary management. We have previously reported that compared with consumption of a high-carbohydrate (HC) diet, despite comparable weight loss, a very low-carbohydrate (LC diet) impaired FMD and increased depression. The purpose of this study was to conduct a secondary analysis to examine whether there was an association between changes in FMD and depression. MethodsForty-seven overweight men and women (body mass index 26–43 kg/m2 and ages 24–64 y) completed a 12-mo randomized controlled trial during which participants consumed either an energy-restricted, isocaloric LC or HC diet. Weight, body composition, Homeostasis Assessment of Insulin Resistance (HOMA), depression (Beck Depression Inventory [BDI]), Anxiety (Spielberger State-Trait Anxiety Inventory [STAI]) and FMD were assessed before and after the intervention. This secondary analysis focused on multiple regression analysis of these parameters. ResultsChanges in BDI were independently predicted by changes in FMD (β = −0.356; P = 0.026) but not by diet intervention assignment or changes in weight or HOMA. No variables were significant predictors of the change in STAI. ConclusionsOver time, impairments in FMD were independently associated with increased depression, independent of diet composition, or changes in weight and insulin resistance. This data supports a mechanistic association between depression and endothelial function, which may influence long-term health.

Endothelium-dependent vascular tone regulation mechanisms in patients with ischemic stroke

Aim. To study the role of nitroxidergic reactions of the circulatory system in the development of ischemic stroke. Methods. 51 patients (both males and females) with the diagnosis of ischemic stroke were examined. All patients were distributed to 3 groups according to the severity of neurological deficit. All patients underwent brain computed tomography or magnetic resonance imaging. Cerebral blood flow was examined by extra and transcranial ultrasonic dopplerography. Central hemodynamics was evaluated by echocardiography. General clinical examination, neurological and neuroophthalmological examinations were also performed. Vasomotor endothelial function was assessed using a 7 MHz linear transducer on the ultrasound unit «Medison SonoAce X8». The level of nitric oxide was assessed using its stable metabolites, nitrite and nitrate definition in serum. Neurological status was assessed according to the USA National Institutes of Health Stroke Scale. Results. Disorders of nitroxidergic mechanisms of blood vessels regulation were observed in patients with ischemic stroke. Endothelium-dependent brachial artery dilation disorders and nitric oxide persistent metabolites level decrease were related to the severity of the disease and the neurological deficit degree. Conclusion. The study of endothelium-dependent vascular tone regulation mechanisms revealed that these mechanisms are involved in the pathogenesis of ischemic stroke; the study of these mechanisms can be used to clarify the severity of neurological deficit, and possible prognosis.

Effects of Combined Glucose and Fat Load on Endothelium-Dependent Brachial Artery Vasodilatation in Hypertensive Patients

IntroductionThis study investigated the effects of combined glucose and fat load on glucose and lipid metabolism, as well as on vascular endothelial function, in hypertensive patients. Methods and ResultsA total of 98 hypertensive patients were randomly divided into 3 groups that received an oral fat tolerance test (OFTT), an oral glucose tolerance test (OGTT) or a combined oral glucose and fat tolerance test (OGFTT). Endothelium-dependent flow-mediated brachial artery dilation (FMD) was measured by vascular ultrasound and was used as an indicator of vascular endothelial function. There were no significant differences in demographics or clinical characteristics among the 3 groups before the study. Immediately after the OGFTT, the serum triglyceride levels and the area under the curve for serum glucose in the OGFTT group were not significantly different from those in the other 2 groups. However, the 1-hour FMD in the OGFTT group was significantly reduced compared with that of the OGTT group (5.45±0.75 versus 9.46±1.32, P<0.05), and the 4-hour FMD in the OGFTT group was also significantly reduced compared with the OFTT group (8.56±1.09 versus 9.76±2.00, P<0.05). ConclusionA combined glucose and fat load has a cumulative effect on vascular endothelial dysfunction in hypertensive patients.

Flow-Mediated Vasodilation Is Not Attenuated in Hypertensive Pregnancies Despite Biochemical Signs of Inflammation

Background. Our objective was to evaluate endothelial function and markers of inflammation during and after pregnancy in normal pregnancies compared to pregnancies complicated with hypertension or preeclampsia (PE). Methods and Results. We measured endothelium-dependent brachial artery flow-mediated vasodilation (FMD) and high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) in 32 women with normal pregnancy and in 28 women whose pregnancy was complicated with hypertensive disorder in the second half of pregnancy and minimum 3-month postpartum. Enhancement of endothelial function was greater in hypertensive than normal pregnancies, the mean FMD% being 11.0% versus 8.8% during pregnancy (P = 0.194) and 8.0% versus 7.9% postpartum (P = 0.978). Concentrations of markers of inflammation were markedly increased in pregnant hypertensive group compared to those after delivery (hsCRP 4.5 versus 0.80 mg/L, P = 0.023, IL-6 2.1 versus 1.2 pg/mL, P = 0.006; TNF-α 1.9 versus 1.5 pg/mL, P = 0.030). There were no statistically significant associations between the markers of inflammation and FMD. Conclusions. Brachial artery FMD was not attenuated in the third trimester hypertensive pregnancies compared to normal pregnancies, whereas circulating concentrations of hsCRP and IL-6 and TNF-α reacted to hypertensive complications.

Endogenous testosterone and brachial artery endothelial function in middle-aged men with symptoms of late-onset hypogonadism

In aging men, serum endogenous testosterone is inversely associated with common carotid intima-media thickness (IMT) and directly with beneficial plasma lipid levels; however, the relationship to endothelial function is poorly characterized. We examined the association between serum testosterone and endothelium-dependent brachial artery flow-mediated dilatation (FMD) in middle-aged to elderly men. A group of 83 men aged 40–69 years (mean 55.9 ± 7.5 [SD]) with andropausal symptoms were studied. We measured their serum lipids, testosterone, luteinizing hormone, mean carotid IMT and brachial artery FMD by high resolution B-mode ultrasound. Brachial FMD correlated inversely with vessel diameter (r = −0.38, p = 0.0004), alcohol consumption (r = −0.22, p = 0.047) and serum testosterone (r = −0.27, p = 0.01), but not with luteinizing hormone. In multivariate analysis, FMD was explained by testosterone (β = −0.17, p = 0.0226), high density lipoprotein cholesterol (β = 4.17, p = 0.0312) and vessel diameter (β = −4.37, p < 0.0001) when adjusted for age, body mass index, triglycerides, blood pressure, carotid IMT, smoking, alcohol consumption, cardiovascular diseases and use of lipid lowering medication (HMG-CoA reductase inhibitors). In middle-aged to elderly men, there is an inverse correlation between serum testosterone and brachial FMD. These data suggest that testosterone may have an adverse effect on systemic endothelial function.

Effects of a combined glucose and fat load on endothelium-dependent brachial artery vasodilatation in hypertensive patients

Background and aimsThe aim of this study was to investigate the effects of a combined glucose and fat load on glucose and lipid metabolism and vascular endothelial function in hypertensive...

The effect of pitavastatin calcium on endothelial dysfunction induced by hypercholesterolemia

Objective:To investigate whether endothelial function can be improved by the treatment of pitavastatin calcium via its antioxidant properties in hypercholesteremia patients.Methods:Forty patients with hypercholesteremia were randomized to receive pitavastatin calcium 1 or 2 mg/day for 8 weeks. Among them, four people were lost in the follow-up period. Before and after treatment, clinical and biochemical characteristics, markers of oxidative stress (plasma 8-iso-prostaglandin F2α and serum gp91phox) were determined and concomitantly endothelium-dependent brachial artery flow-mediated dilation (FMD) was measured by ultrasound examination. Thirty healthy subjects were chosen as controls.Results:For individuals with hypercholesteremia, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and serum gp91phox were significantly increased (p < 0.001 for all) and plasma 8-iso-prostaglandinF2α (8-iso-PGF2α) was significantly higher (p < 0.05), while FMD was obviously impaired (p < 0.001). Total cholesterol, LDL-C and serum gp91phox were significantly reduced (p < 0.001 for all), plasma 8-iso-PGF2α was lower and FMD was significantly improved after pitavastatin calcium treatment compared with those before treatment in any group (p < 0.05 for both). However, there was no significant difference between the 1-mg and 2-mg pitavastatin calcium groups post-therapy.Conclusions:Endothelial dysfunction induced by hypercholesteremia can be ameliorated by pitavastatin calcium treatment, which occurs in part through its antioxidative properties.

Periodontal treatment effects on endothelial function and cardiovascular disease biomarkers in subjects with chronic periodontitis: protocol for a randomized clinical trial

BackgroundPeriodontal disease (PD) is an infectious clinical entity characterized by the destruction of supporting tissues of the teeth as the result of a chronic inflammatory response in a susceptible host. It has been proposed that PD as subclinical infection may contribute to the etiology and to the pathogenesis of several systemic diseases including Atherosclerosis. A number of epidemiological studies link periodontal disease/edentulism as independent risk factor for acute myocardial infarction, peripheral vascular disease, and cerebrovascular disease. Moreover, new randomized controlled clinical trials have shown an improvement on cardiovascular surrogate markers (endothelial function, sICAM, hsPCR level, fibrinogen) after periodontal treatment. Nonetheless, such trials are still limited in terms of external validity, periodontal treatment strategies, CONSORT-based design and results consistency/extrapolation. The current study is designed to evaluate if periodontal treatment with scaling and root planning plus local delivered chlorhexidine improves endothelial function and other biomarkers of cardiovascular disease in subjects with moderate to severe periodontitis.Methods/DesignThis randomized, single-blind clinical trial will be performed at two health centers and will include two periodontal treatment strategies. After medical/periodontal screening, a baseline endothelium-dependent brachial artery flow-mediated dilatation (FMD) and other systemic surrogate markers will be obtained from all recruited subjects. Patients then will be randomized to receive either supragingival/subgingival plaque cleaning and calculus removal plus chlorhexidine (treatment group) or supragingival plaque removal only (control group). A second and third FMD will be obtained after 24 hours and 12 weeks in both treatment arms. Each group will consist of 49 patients (n = 98) and all patients will be followed-up for secondary outcomes and will be monitored through a coordinating center. The primary outcomes are FMD differences baseline, 24 hours and 3 months after treatment. The secondary outcomes are differences in C-reactive protein (hs-CRP), glucose serum levels, blood lipid profile, and HOMA index.DiscussionThis RCT is expected to provide more evidence on the effects of different periodontal treatment modalities on FMD values, as well as to correlate such findings with different surrogate markers of systemic inflammation with cardiovascular effects.Trial registration numberClinicalTrials.gov Identifier: NCT00681564.

CARDIOVASCULAR PREDICTORS OF RENAL DYSFUNCTION IN ELDERLY HYPERTENSIVE PATIENTS: PP.30.194

Objective: To investigate the incidence and cardiovascular predictors of mild renal dysfunction in elderly patients with essential arterial hypertension (AH). Design and Method: 276 hypertensive patients (108 of those were male) at the mean age of 73.0 ± 7.3 years were examined. The following renal dysfunction indicators were stated: slight plasma creatinine increase 115–133 μmol/l in men or 107–124 μmol/l in women, microalbuminuria (MAU) by urine albumin-creatinine ratio >=2.5 mg/mmol in men or >=3.5 mg/mmol in women and creatinine clearance by Cockroft-Gault formula (CC) <60 ml/min/1.73 m2. The overt renal impairment was diagnosed in patients with plasma creatinine >133 μmol/l in men or >124 μmol/l in women. The 24-h ABPM was carried out. We studied AH risk factors such as serum lipids, smoking, waist circumference and AH target organs (heart and vessels) damage signs: echocardiographic left ventricular mass and ejection fraction (EF), 6-minute walk distance (6MWD), carotid intima-media thickness (IMT), ankle-brachial index, endothelium-dependent brachial artery dilatation test, carotid-femoral pulse wave velocity (PWV). The relations between above-mentioned parameters and renal dysfunction indicators were estimated by multiple logistic regression analysis. Results: Plasma creatinine level averaged 91.4(77–104) μmol/l, CC – 56.0(49–66) ml/min/1.73 m2, urine albumin-creatinine ratio – 0.9(0.2–2.4) mg/mmol. Slight plasma creatinine increase was found in 37 patients (13.4%), MAU – in 52 (18.8%), CC<60 ml/min/1.73 m2 – in 170 (61.6%), renal impairment - in 12 (4.3%). Regression analysis showed that hypercreatininemia was interrelated with male sex and waist circumference (R2=0.13, predictive value of the model is 81.8%). The level of LDL-cholesterol, waist circumference, IMT, systolic blood pressure hypotension load and EF were associated with MAU presence (R2 = 0.34, predictive value 83.0%). Markers of low CC were represented by waist size, PWV and 6MWD (R2 = 0.30, predictive value 68.7%). Conclusions: Elderly hypertensive patients most frequently (61.6%) display a moderate decline of creatinine clearance. The complex of cardiovascular, hemodynamic and metabolic predictors for different variants of hypertensive nephropathy was revealed. Appropriate logistic regression equations were created.