Endothelium-dependent Vasodilation Of Brachial Artery Research Articles

(198) MID-TERM DETERIORATION OF ENDOTHELIAL FUNCTION AND METABOLIC PARAMETERS FOLLOWING ONE-YEAR ANDROGEN DEPRIVATION THERAPY IN MEN WITH PROSTATE CANCER

Abstract Introduction Androgen deprivation therapy (ADT) is a standard treatment for advanced prostate cancer. Although ADT delays cancer progression and alleviates cancer-related symptoms, this treatment is related to metabolic derangement and increase of cardiovascular risk. Despite the well-established association between the levels of circulating testosterone and endothelial integrity, the short to mid-term effects of ADT on vascular endothelial function are not completely understood. Objective Our aim was to evaluate the impact on endothelial function after one year of ADT, through the analysis of vascular parameters of the brachial artery, and the measurement of serum inflammatory markers. We also investigated the effects of this treatment on body composition and metabolic parameters. Methods We prospectively evaluated men with moderate to high-risk prostate cancer treated with ADT from January 2022 to January 2024 at our institution. Smokers and those who stopped smoking less than five years ago, decompensated diabetics (glycated hemoglobin >9%) and those who had already had a cardiovascular event were excluded. Ultrasound was used to assess vascular diameter and flow-mediated (FMD) endothelium-dependent brachial artery vasodilation. Metabolic and inflammatory profile included serum measurement of total cholesterol and fractions, triglycerides, fasting glucose, glycated hemoglobin, basal insulin, C-reactive protein, and bioelectrical impedance assessment of body fat distribution. Individuals were evaluated prior to ADT with goserelin acetate 10.80 mg and after 3 and 12 months of therapy, for those who remained on ADT for this entire timeframe. Difference between groups was analyzed using anova test. Results 32 men were evaluated in two visits (baseline and 3 months). From the initial group of patients, 18 men were also evaluated in a third visit (12 months). The mean age was 69 years and prevalence of diabetes was 31,25%. There was no significant change in FMD after 12 months of ADT (p = 0.25). The baseline diameter of the brachial artery demonstrated significant worsening after one year of ADT (p = 0.004) (Fig. 1). With regard to the metabolic profile, ADT significantly increased insulin resistance: fasting insulin levels (p = 0.03) and homeostatic model assessment insulin resistance (p = 0.04) increased significantly after 12 months. Total cholesterol and triglyceride concentrations were higher after 12 months of ADT (p = 0.04 and p = 0.03, respectively) (Fig. 2). There was a significant decrease in HDL after 12 months of treatment (p < 0.0001). Abdominal circumference, weight and body fat percentage increased significantly after ADT (p = 0.01; p < 0.0001; p = 0.006; respectively). After one year, there was a significant increase in blood pressure, both systolic (p = 0.02) and diastolic (p = 0.003). Conclusions Although the present study did not demonstrate a significant change in brachial artery FMD, we found a significant worsening of blood pressure, arterial diameter and metabolic profile with ADT, especially an increase in insulin resistance, dyslipidemia and abdominal circumference, which represent well-established risk factors for cardiovascular events. Disclosure No.

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.

STUDY OF VASCULAR ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Abstract. Currently, inflammatory bowel disease (IBD) is the most complex and not fully resolved problem in modern gastroenterology. IBD, with its two main subtypes, Crohn's disease (CD) and ulcerative colitis (UC), is a complex multifactorial pathology caused by external and internal factors, including host genetics, the immune system, environmental factors, and the gut microbiome. The possible involvement of endothelial dysfunction is also discussed. There is evidence that in diseases characterized by chronic systemic inflammation, it affects the properties of the arteries and causes both endothelial dysfunction and changes in arterial stiffness. The aim is to study the functional state of the vascular endothelium in patients with inflammatory bowel diseases. Material and methods. A total of 69 patients with IBD aged 18 to 70 years (44.0 ± 1.4 years) were examined. All patients were divided into 2 groups depending on the nosology. 1st group consisted of 45 patients with UC, among them 23 women (51.1 %) and 22 men (48.9 %), 2nd group – 24 patients with HC, of which 14 women (58.3 %) and 10 men (41.7 %). To assess endothelial function, the method for determining endothelium-dependent vasodilation of the brachial artery (BA) in a test with reactive hyperemia was used to assess the change in BA diameter (dPA), a ATL PHILIPS HDI 5000 SONOS CT ultrasound machine with a 7.5 MHz linear transducer was used. The endothelial function index was calculated as the difference between dPA after decompression and the initial value, expressed as a percentage. The content of a soluble vascular cell adhesion molecule 1 (VCAM-1) was determined in blood serum by an enzyme immunoassay using a test system («Bender MedSystems GmbH», Austria) using an enzyme immunoassay analyzer «Stat Fax 303 Plus» («Awareness Technology Inc.», USA). The number of desquamated endothelial cells in the peripheral blood was determined by the method of J. Hladovec. Results. In the study of endothelium-dependent vasodilation (EDVD) PA in a test with reactive hyperemia, dysfunctions of the vascular endothelium were found in 75.4 % of the examined patients. Changes in vascular endothelial function were found in 82.3 % of patients with UC and 62.5 % with CC, mainly due to endothelial dysfunction (ED). Significant differences were found between the indicators of the average increase in dPA in the test with reactive hyperemia with decreased endothelial function (DEF) and normal endothelial function (NEF), as well as with DEF and ED in patients with severe UC. ED was observed 5.2 times more often than NEF (c2 = 56.8; p < 0.001) and 2.6 times more often than PFE (c2 = 31.5; p < 0.001). With moderate severity of the disease, DEF and ED occurred with the same frequency and 2.2 times higher than the number of patients with NEF (c2 = 11.3; p = 0.0008), changes in endothelium-dependent vasodilation were accompanied by a significant increase in the VCAM-1 level in serum of all IBD patients, but the highest expression of VCAM-1 was observed in UC. At the same time, the concentration of VCAM-1 was inversely correlated with endothelium-dependent vasodilation of BA (r = - 0.54, p < 0.01), which is confirmed by the quantitative characteristics of the level of VCAM-1 in various states of the endothelium. The study of the content of circulating desquamated endothelial cells in the peripheral blood made it possible to establish an increase in their number by 5 times with ED – up to (15.5 ± 4.8) × 104/L (p < 0.05), 2 times with DEF – up to (5.7 ± 0.3) × 104/L (p < 0.001) versus (3.1 ± 0.4) × 104/L in the control group. An inverse correlation was found between the number of desquamated endothelial cells and endothelium-dependent BA vasodilation (r = - 0.59, p < 0.01). Conclusions. The results of a comprehensive study of the functional state of the vascular endothelium indicate that the course of IBD is accompanied by a syndrome of endothelial dysfunction (with a predominance of DE), which is characterized by a decrease in endothelium-dependent vasodilation of BA, an increase in the level of VCAM-1 and the content of circulating desquamated endothelial cells in the blood. Keywords: inflammatory bowel disease, Crohn's disease, ulcerative colitis, endothelial dysfunction.

Paraoxonase in women with hypertension of different reproductive age. Relationship with cardio-metabolic risk factors

Annotation. Paraoxonase is a high-density lipoprotein-associated pleiotropic enzyme able to detoxify proatherogenic compounds such as oxi-low-density-lipoproteins and homocysteine-thiolactone. Low paraoxonase activity is likely to be involved in the development of cardiovascular diseases. The aim of the study – to investigate the relationship between paraoxonase activity, structural and functional markers of the heart and blood vessels, cardio-metabolic risk factors in women with hypertension of different reproductive age. The study included 193 women aged 32-70 years (55.4±0.68 years) with essential stage II hypertension. The control group consisted of 46 healthy women. The arylesterase activity of paraoxonase (EC 3.1.1.2) in blood serum was determined by spectrophotometric method. Statistical processing of the obtained results was performed in the application package SPSS22 (© SPSS Inc.). The mean and standard error of the mean (M ± m) were calculated. Student's t-test was used. Pearson correlation analysis was performed at p <0.05. It was found that in women with hypertension there was a significant decrease (16%) in serum paraoxonase activity, compared with healthy women. Low paraoxonase activity was registered in 33.3% of premenopausal patients and 56.7% of postmenopausal patients (p˂0.05) and was associated with serum estradiol levels (r=0.33, 0.41, p<0.05). Low paraoxonase activity was associated with aberrant levels of lipids, homocysteine, obesity, metabolic syndrome, increased left ventricular mass index and carotid intima-media thickness, decreased brachial artery endothelium-dependent vasodilation. Thus, the decrease in serum paraoxonase activity in women with hypertension is related with the reproductive age of patients and the development of unfavorable metabolic, structural and functional changes in the heart and blood vessels.

Significance of the Interrelations of Cardiovascular Diseases with Anaerobic Bacteria of Subgingival Biofilm

Objective: The study of subgingival biofilm composition in patients with ischemic heart disease and concomitant periodontitis. Study design: For the study, 45 patients with moderate chronic periodontitis were examined. They were divided into three groups. Group 1 included 15 patients with acute myocardial infarction, Group 2–15 included patients with exertional angina (pectoris) and Group 3–15 included patients without cardiovascular diseases. Dental and cardiological health condition was determined, a biochemical blood test was conducted, brachial artery endothelium-dependent vasodilation was measured, and periodontopathogenic bacteria DNA in subgingival biofilm was detected. Results: Frequency of P. gingivalis, T. forsythia, and A. actinomycetemcomitans detection in Group 1 was significantly higher than in Group 3. In patients of Group 1 and Group 2 subgingival biofilm contained P. gingivalis two times more often (p = 0.027), while P. intermedia – four times less often (p = 0.006) than in Group 3. Presence of P. gingivalis and A. actinomycetemcomitans was related to periodontal destruction level. Brachial artery endothelium-dependent vasodilation moderately correlated with patient’s cardiological condition (r = 0.3284), biochemical markers of atherosclerosis (r = 0.6465), and frequency of P. intermedia detection in periodontal pockets (r = 0.3828). Values of brachial artery endothelium-dependent vasodilation in Group 1 and Group 2 were statistically significantly lower than in Group 3 (p < 0.05). Conclusions: A reliable relationship between parodontopathogenic bacteria colonization and development of acute myocardial infarction was established. In all patients with chronic periodontitis, endothelial dysfunction was observed, but brachial artery endothelium-dependent vasodilation was significantly lower in patients with concomitant cardiovascular diseases, which could be used for pathology prognosis

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.

Dynamics of clinical and laboratory parameters in patients with coronary heart disease in combination with type 2 diabetes mellitus and their effect on the structural and functional state of the heart and blood vessels in various cases of chronic heart fa

The aim: determination of the characteristics of the dynamics of clinical, laboratory and ultrasound parameters in patients with ischemic heart disease in combination with type 2 diabetes mellitus with various types of heart failureMaterial and methods. After the course of therapy, 100 men with CHF were examined in the hospital against the background of the combined course of IHD and type 2 diabetes with LV EF ≥ 50%, CHF of the II functional class, with glomerular filtration rate ≥ 50 ml / min / 1.73 m2, NT-proBNP ≥ 125 pg / ml.Patients were divided into groups depending on the nature of the course of heart failure: group I (n = 66) - patients with a stable course, group II (n = 34) - patients with an unfavourable course. Patients of group II, in turn, were divided into three subgroups depending on the nature of the adverse course: CHF: IIa (n = 7) - who died during the year of observation, IIb (n = 13) - with a decrease in LV EF, II in ( n = 14) with a violation of the state of diastolic function of the heart at the end of the observation period.An analysis of complaints, cardiological history, objective research was conducted, the level of NT-proBNP, total cholesterol), high-density lipoproteins, low-density lipoproteins and triglycerides were studied, and the atherogenic coefficient was calculated, glycosylated haemoglobin (HbA1c) was examined, serum glucose, insulin level, insulin resistance index (HOMA) were calculated.Transthoracic echocardiography (echocardiography) was performed, and endothelium-dependent brachial artery vasodilation (EDD) was examined.The Mann-Whitney U test was used to determine the differences between independent samples. The frequency of symptoms in groups was compared using the χ2 criterion. One-way analysis of variance was performed using the non-parametric Kruskal-Wallis test.Results. Adverse course of CHF in patients with CHD and type 2 diabetes, which progressed and ended in death, was associated with a significantly older age of men, with a longer history of CHD and type 2 diabetes, decreased tolerance for exercise, high levels of AH which is arguably a potential cause of CHF. I degree of diastolic dysfunction, despite the fact that the size of the left atrium did not go beyond normal, was noted in all patients, but the average size was significantly larger in the dead. Significantly fewer of these patients had LV EDV, indicating greater disruption of LV diastolic filling processes.Patients with a decrease in LV systolic function after 12 months of follow-up were characterized by a significant decrease in LV EF medians (by 21.5%) and test distance with a 6-minute walk (by 4.1%), while there was a tendency to increase endothelial dysfunction in the form of a decrease in the median EDD of the brachial arteries. Significant positive dynamics of the medians of all indicators of carbohydrate metabolism showed good control of the carbohydrate profile. Medians of lipid metabolism parameters did not experience significant dynamics, but tended to positive changes. The median NT-proBNP blood level was significantly reduced by 14%. A decrease in systolic function of the heart was associated with a tendency to increase the diastolic size of the left atrium and a significant increase in LV ESV.Conclusions. Two-thirds of CHD patients with CHF with preserved LV EF of the heart in combination with type 2 diabetes receiving pathogenetic complex therapy have a stable course of CHF observed during the year, which is characterized by improvement of the clinical and laboratory status of patients and parameters of the structural and functional state of the heart and vessels.An unfavourable course of heart failure during the year against the background of pathogenetic complex treatment in patients with CHD in combination with type 2 diabetes is accompanied by a decrease in systolic and / or diastolic LV heart function, exercise tolerance with a simultaneous absence of worsening dyslipidaemia and dysglycemia.In patients with CHD in combination with type 2 diabetes and retained LV EF, fasting glycemia and HbAc1 levels significantly affect the state of LV systolic and diastolic function, which indicates the important role of concomitant type 2 diabetes in heart remodelling in this category of patients

P3460Structural and functional changes of vascular wall in women of perimenopausal period with long-term menopausal hormone therapy

Abstract Introduction Features of changes in the vascular wall in women of the menopausal period are not sufficiently illuminated. Most of the studies evaluating the effect of menopausal hormonal therapy (MHT) on the structural and functional state of the vascular wall were limited to the time frame from several months to 1–3 years, which distinguishes them from our study. Purpose To evaluate structural and functional changes in the vascular wall in women of early postmenopausal period with prolonged use of low doses of MHT 1 mg of 17β-estradiol (E2) and 2 mg drospirenone (DRSP). Methods The study included 162 women in the early postmenopausal period with climacteric syndrome were divided into 2 groups: the main group of 84 women assigned MHT 1 mg E2 /2 mg DRSP, control group of 78 women who did not receive MHT. Duration of follow-up 5,2 (4,8; 5,7) years. Explored pulse wave velocity (PWV). Bbrachial blood pressure was measured non-invasively over the 24 h with an electronic, oscillometric, automated device (BPLab) with the assessment of 24-h central arterial pressure (CAP), aortic augmentation index (AIx), arterial stiffness index (ASI); ambulatory arterial stiffness index (AASI). Endothelium-dependent vasodilation (EDV) of the brachial artery was evaluated. Results In women of the main group PWV made up 7.19±1.7 m/s initial and 7.53±1.3 m/s to the end of the study (p&gt;0.05); in the control group - 7,21±1.8 m/s and 7.95±1.9 m/s (p&lt;0.001). In the women of the main group by the end of the study a decrease in the CAP was noted from 38.4±6.2 to 35.3±4.1 mm Hg. (p&lt;0.001), in the women of the control group there were no changes of 41.4±9.6 and 40.9±9.8 mm Hg. (p&lt;0.001 between women of both groups at the end of the study). In women of the control group, a significant increase in AIx was found from 31.0 (20.0; 35.0)% initially to 33.0 (29.0; 37.0)% by the end of the study (p&lt;0.05) and no changes in women of the main group – 27.0 (20.0; 35.0)% and 28.0 (20.0; 33.0)%. Multidirectional changes ASI were revealed: a decrease in women of the main group from 132.0 (121.0; 142.0) to 127.0 (115.5; 137.0) cu and an increase from 133.0 (111.0; 155.0) to 148.0 (134.2; 171.0) cu in women of the control group (p&lt;0.01 between women of both groups at the end of the study). By the end of the study, there was a decrease in AASI in women of the main group from 0.379 (0.320; 0.463) to 0.264 (0.203; 0.329) cu (p&lt;0.001) and the absence of changes AASI value in women of the control group – 0.360 (0.283; 0.471) and 0.370 (0.310; 0.476) cu. In women of the main group, an increase in the brachial artery EDV was found from 8.6±7.4% initially to 11.1±6.8% by the end of the study (p&lt;0.05) and no change in women in the control group −7.3±5.6% and 6.2±5.0%. Conclusion In women in early postmenopause with prolonged MHT of 1 mg E2/2 mg DRSP positive changes in the structural and functional state of the vascular wall were established.

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.

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.

PROGNOSTIC VALUE OF ENDOTHELIAL DYSFUNCTION IN CORONARY AND BRACHIAL ARTERIES, AND COMMON RISK FACTORS IN DEVELOPMENT OF CARDIOVASCULAR COMPLICATIONS IN PATIENTS WITH MICROVASCULAR ANGINA

Aim. To study prognostical significance of vasomotor disorder of coronary and brachial arteries, and traditional risk factors in development of cardiovascular complications in patients with microvascular angina (MVA) and cardial syndrome X; a retrospective 12-year observation. Material and methods. Totally, 41 patient included, with MVA (40 females/1 male), mean age at the moment of inclusion 43±4,1 y.o., 15% smokers). Endotheliumdependent vasodilation (EDV) of coronary arteries was assessed via intracoronary acetylcholine load, EDV of brachial artery — via high-resolution ultrasound in active hyperemia test. Results . It was found that in brachial EDV <4,7% group the risk of cardiovascular complications (p<0,05) is higher for 9-18 years of observation. Baseline EDV of coronary arteries in the study did not influence survival rate in MVA patients. Conclusion. Significant influence on cardiovascular events occurring in long-term follow-up of MVA patients, had the risk factors as smoking and brachial artery endothelial dysfunction.

Endothelial dysfunction is associated with major adverse cardiovascular events in peritoneal dialysis patients.

Endothelial dysfunction is implicated in increased cardiovascular risk in nondialyzed population. However, the prognostic impact of endothelial dysfunction on cardiovascular outcome has not been investigated in peritoneal dialysis (PD) patients.We prospectively determined endothelial function by brachial artery endothelium-dependent vasodilation (flow-mediated dilation [FMD]) in 143 nondiabetic PD patients and 32 controls. Primary outcome was a major adverse cardiac and cerebrovascular event (MACCE).Brachial FMD was significantly lower in PD patients than in controls (2.9% [1.3–4.7] vs 6.2% [5.4–8.3], P < 0.001). During a mean follow-up of 42 months, primary outcome was observed in 25 patients (17.5%). When patients were dichotomized by the median value of FMD (2.9%), incidence rates of MACCEs were significantly higher in the group with lower FMD compared with higher FMD (7.2 vs 3.0/100 person-years, P = 0.03). In multivariate Cox analysis, low FMD (≤2.9%) was a significant independent predictor of MACCEs (hazard ratio = 2.73, 95% confidence interval = 1.03–7.22, P = 0.04). Furthermore, multivariate fractional polynomial analysis showed that the risk of MACCE decreased steadily with higher FMD values.Impaired brachial FMD was a significant independent predictor of MACCEs in PD patients. Estimating endothelial dysfunction by brachial FMD could be useful for stratifying cardiovascular risk in these patients.

CLINICAL IMPORTANCE OF ENDOTHELIAL DYSFUNCTION AND INSULIN RESISTANCE SYNDROME IN PATIENTS WITH GOUT ASSOCIATED WITH ARTERIAL HYPERTENSION

Aim. To study the endothelium status and determine the correlation between endothelial dysfunction and glucose metabolism in men with gout associated with arterial hypertension (HT). Material and methods. Patients (n=175, all are males) with gout were enrolled into the study. Ambulatory blood pressure monitoring (ABPM) was performed in all patients. Endothelial function was studied in tests with reactive hyperemia (endothelium-dependent reaction) and nitroglycerin (endothelium independent reaction) in brachial artery by ultrasonic Doppler examination. The level of nitrite-nitrate and endothelin-1 in blood serum was determined by ELISA technique. Fasting blood glucose and oral glucose tolerance tests were performed as well as fasting insulin blood level was determined by immunoenzyme method. Insulin-resistance index (HOMA-IR) was calculated. Patients with HOMA- IR>2.77 were considered as insulin-resistant. Results. Patients with gout demonstrated endothelial deterioration associated with activation of nitroxid producing function, elevation in endothelin-1 serum level (1.36 fmol/ml [0.91; 2.32 fmol/ml] vs 0.19 fmol/ml [0.16; 0.27 fmol/ml] in controls, p<0.05) and impairments of endothelium-dependent vasodilation (6.4% [3.3; 7.3%] vs 17.8% [12.7; 23.9%] in controls, p<0.05). The revealed changes were the most marked in patients with gout associated with HT. The correlation between some endothelial dysfunction in- dices and glucose metabolism was observed. Conclusion. ABPM, brachial artery endothelium-dependent vasodilation and glucose metabolism status should be studied in patients with gout. Complex treatment of cardiovascular diseases in patients with gout should include ω-3 polyunsaturated fatty acids, angiotensin receptor antagonists should be used for antihypertensive therapy.

Reduced Residual Renal Function is Associated with Endothelial Dysfunction in Patients Receiving Peritoneal Dialysis

Endothelial dysfunction, which contributes to atherosclerosis and arteriosclerosis, commonly accompanies end-stage renal disease (ESRD). However, little is known about the role of residual renal function (RRF) in endothelial protection in ESRD patients. This study aimed to investigate the relationship between endothelial function and RRF in patients undergoing peritoneal dialysis (PD). This was a cross-sectional study involving 72 prevalent PD patients. Demographic and clinical data were recorded and residual glomerular filtration rate (GFR), Kt/V urea, and serum concentrations of inflammatory markers were measured. Endothelial function was assessed by brachial artery endothelium-dependent vasodilation [flow-mediated dilation (FMD)] to reactive hyperemia following 5 minutes of forearm ischemia. In patients with FMD% above the median value (FMD > 2.41%), residual GFR was significantly higher compared to that in patients with FMD% below the median [1.50 (0 - 9.64) vs 0.48 (0 - 3.89) mL/min/1.73 m(2), P = 0.026]. Correlation analyses revealed that residual GFR (ρ = 0.381, P = 0.001) and total Kt/V urea (γ = 0.408, P < 0.001) were positively correlated with FMD%, whereas PD duration (γ = -0.351, P = 0.003), high-sensitivity C-reactive protein (ρ = -0.345, P = 0.003), pulse pressure (γ = -0.341, P = 0.003), and age (γ = -0.403, P < 0.001) were inversely correlated with FMD%. In contrast, there was no correlation between peritoneal Kt/V urea and FMD%. In multivariate linear regression analysis adjusted for these factors, residual GFR was found to be an independent determinant of FMD% (β = 0.317, P = 0.017). This study shows that RRF is independently associated with endothelial dysfunction in ESRD patients on PD, suggesting that RRF may contribute to endothelial protection in these patients.

Long-term successful weight loss improves vascular endothelial function in severely obese individuals.

Obesity is associated with increased cardiovascular risk. Although short-term weight loss improves vascular endothelial function, longer term outcomes have not been widely investigated. We examined brachial artery endothelium-dependent vasodilation and metabolic parameters in 29 severely obese subjects who lost > or =10% body weight (age 45 +/- 13 years; BMI 48 +/- 9 kg/m(2)) at baseline and after 12 months of dietary and/or surgical intervention. We compared these parameters to 14 obese individuals (age 49 +/- 11 years; BMI 39 +/- 7 kg/m(2)) who failed to lose weight. For the entire group, mean brachial artery flow-mediated dilation (FMD) was impaired at 6.7 +/- 4.1%. Following sustained weight loss, FMD increased significantly from 6.8 +/- 4.2 to 10.0 +/- 4.7%, but remained blunted in patients without weight decline from 6.5 +/- 4.0 to 5.7 +/- 4.1%, P = 0.013 by ANOVA. Endothelium-independent, nitroglycerin-mediated dilation (NMD) was unaltered. BMI fell by 13 +/- 7 kg/m(2) following successful weight intervention and was associated with reduced total and low-density lipoprotein cholesterol, glucose, hemoglobin A(1c), and high-sensitivity C-reactive protein (CRP). Vascular improvement correlated most strongly with glucose levels (r = -0.51, P = 0.002) and was independent of weight change. In this cohort of severely obese subjects, sustained weight loss at 1 year improved vascular function and metabolic parameters. The findings suggest that reversal of endothelial dysfunction and restoration of arterial homeostasis could potentially reduce cardiovascular risk. The results also demonstrate that metabolic changes in association with weight loss are stronger determinants of vascular phenotype than degree of weight reduction.

Alcohol Acutely Increases Vascular Reactivity together with Insulin Sensitivity in Type 2 Diabetic Men

Moderate alcohol consumption is associated with increased insulin sensitivity and reduced cardiovascular risk. We hypothesized that this relates to a direct effect of alcohol and therefore investigated whether acute alcohol intake altered insulin sensitivity or endothelial function in patients with type 2 diabetes. In an open-label two period design, the effect of a single oral dose of 40 g of alcohol (168 ml 40% vodka) on an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT) and on endothelium-dependent (flow mediated, FMD) or endothelium-independent (glyceroltrinitrate (GTN)-induced) vasodilation of the brachial artery measured by ultrasound was studied. Experiments were carried out in twelve male patients with type 2 diabetes mellitus (64+/-6 years, body mass index 28.4+/-5.7 kg/m (2)). Baseline insulin sensitivity index (S (I)) was 1.10+/-0.34 min (-1).microU (-1).ml, baseline FMD was +4.1+/-3.0%, and GTN-induced vasodilation +7.4+/-2.3% from resting brachial artery diameter. Acute alcohol intake increased alcohol plasma levels to 0.33+/-0.04 per thousand, S (I) to 1.86+/-0.45 min (-1).microU (-1).ml (p<0.05), and FMD to +8.2+/-2.8% (p<0.05), while GTN-induced dilation remained unchanged. No relationship was detectable between the observed changes. We conclude that alcohol intake acutely increases endothelium-dependent brachial artery vasodilation in patients with type 2 diabetes together with insulin sensitivity. This acute effect might explain some beneficial effects of low alcohol consumption in epidemiological observations.

Significance of heterogenity in endothel-dependent vasodilatation occurrence in healthy individuals with or without coronary risk factors

Brachial artery flow-mediated dilation (FMD) is extensively used for non-invasive assessment of endothelial function. Traditionally, FMD is calculated as a percent change of arterial diameter from the baseline value at an arbitrary time point after cuff deflation (usually 60 seconds). Considerable individual differences in brachial artery temporal response to hyperemic stimulus have been observed, potentially influenced by the presence of atherosclerotic risk factors (RF). The importance of such differences for the evaluation of endothelial function has not been well established. The aim of the study was to determine the time course of maximal brachial artery endothelium-dependent dilation in healthy adults with and without RF, to explore the correlation of RF with brachial artery temporal response and to evaluate the importance of individual differences in temporal response for the assessment of endothelial function. A total of 115 healthy volunteers were included in the study. Out of them, 58 had no RF (26 men, mean age 44 +/-14 years) and 57 had at least one RF (29 men, mean age 45 +/-14 years). High-resolution color Doppler vascular ultrasound was used for brachial artery imaging. To determine maximal arterial diameter after cuff deflation and the time-point of maximal vasodilation off-line sequential measurements were performed every 10 seconds from 0 to 240 seconds after cuff release. True maximal FMD value was calculated as a percent change of the true maximal diameter from the baseline, and compared with FMD value calculated assuming that every participant reached maximal dilation at 60 seconds post cuff deflation (FMD60). Correlation of different RF with brachial artery temporal response was assessed. A maximal brachial artery endothelium-dependent vasodilation occurred from 30-120 seconds after cuff release, and the mean time of endothelium-dependent dilation was 68 +/-20 seconds. Individuals without RF had faster endothelium-dependent dilation (mean time 62 +/-17 seconds), and a shorter time-span (30 to 100 seconds), than participants with RF (mean time 75 +/-21 seconds, time-span 40 to 120 seconds) (p < 0.001). Time when the maximal endothelium-dependent dilation occurred was independently associated with age, serum lipid fractions (total cholesterol, LDL and HDL cholesterol), smoking, physical activity and C-reactive protein. True maximal FMD value in the whole group (6.7 +/-3.0%) was significantly higher (p < 0.001) than FMD60 (5.2 +/-3.5%). The same results were demonstrated for individuals with RF (4.9 +/- 1.7% vs 3.1 +/- 2.3%, p < 0.001) and without RF (8.4 +/- 2.9% vs 7.2 +/- 3.2%, p < 0.05). The temporal response of endothelium-dependent dilation is influenced by the presence of coronary FR and individually heterogeneous. When calculated according to the commonly used approach, i.e. 60 seconds after cuff deflation, FMD is significantly lower than the true maximal FMD. The routinely used measurement time-points for FMD assessment may not be adequate for the detection of true peak vasodilation in individual persons. More precise evaluation of endothelial function can be achieved with sequential measurement of arterial diameter after hyperemic stimulus.

Implications and Treatment of Acute Hyperglycemia in the Setting of Acute Myocardial Infarction

A 52-year-old obese male without a prior history of diabetes mellitus (DM) presented with angina and an anterior ST-segment–elevation myocardial infarction (STEMI). Physical examination and chest x-ray were consistent with congestive heart failure. Admission glucose was 230 mg/dL. Coronary angiography revealed an occluded left anterior descending coronary artery, and stenting reestablished TIMI grade 2 flow in that artery within 90 minutes of symptom onset. Left ventricular ejection fraction was 35% with severe anterior hypokinesis. Peak creatine kinase was 600 IU. The next day, fasting glucose was 180 mg/dL. An echocardiogram performed 6 weeks after discharge revealed an ejection fraction of 35% without change in the anterior wall motion. Fasting glucose as an outpatient was 156 mg/dL. The scenario described above is commonly encountered and illustrates how hyperglycemia can affect the outcome of patients with STEMI. Hyperglycemia could have affected the following features of this case: (1) Congestive heart failure was present despite only modest myocardial injury by creatine kinase level; (2) despite successful percutaneous coronary intervention, subnormal coronary perfusion was observed; and (3) left ventricular recovery after STEMI did not occur. Cardiologists need to be cognizant of the hazards associated with hyperglycemia in this setting because these patients will be encountered more frequently as a result of the increasing prevalence of insulin resistance syndromes. Acute hyperglycemia is common in patients with STEMI even in the absence of a history of type 2 DM. Hyperglycemia is encountered in up to 50% of all STEMI patients, whereas previously diagnosed DM is present in only 20% to 25% of STEMI patients.1 The prevalence of type 2 DM or impaired glucose tolerance may be as high as 65% in MI patients without prior DM when oral glucose tolerance testing is performed.2 Elevated …

Abstract 588: Attenuation of Flow- and Nitrate-mediated Vasodilation in End-stage Renal Disease by Inflammation, Hyperphosphatemia and Hyperparathyroidism: Correction with Fall in C-reactive Protein by Nocturnal Hemodialysis

Background: Endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation (EIV) are impaired in end-stage renal disease (ESRD), yet improve soon after conversion from conventional (CHD) to nocturnal hemodialysis (NHD). Methods and Results: To test the hypotheses that suppression of inflammation and correction of hyperphosphatemia contribute to such improvement, dialysis dose, blood pressure (BP), brachial artery EDV and EIV, plasma C reactive protein (CRP), phosphate (Pi) and parathyroid hormone (PTH) were determined before, 1 and 2 months after conversion to NHD (n=23; mean age: 43±2 years [mean±SEM]). NHD increased dialysis dose, EDV and EIV (all p&lt;0.05) and lowered simultaneously measured BP, Pi and PTH (all p&lt;0.05) and CRP (from 14.8±3.9 to 6.63±2.1 mg/L after 2 months, p&lt;0.01). Overall, there was a significant inverse relationship between EDV and log 10 CRP (r=−0.35, p=0.008). Pre-specified dichotomization by CHD Pi identified higher BP with Pi &lt;1.8mM (n=10): (147±10/87±7 vs. 131±4/75±2 mmHg, p&lt;0.01), yet after 1 month both groups were normotensive. In those with Pi &lt;1.8mM, 1 month of NHD lowered CRP and increased EDV from −2.4±2.4 to 7.5±1.8% (p&lt;0.05). In contrast, in the high Pi group, NHD lowered Pi (p&lt;0.05) but had no significant effect on CRP, PTH or EDV (−0.8±1.1 vs. −0.6±1.6 %) but after 2 months, Pi and PTH fell and EDV and EIV improved. Conclusions: Correction of uremia and hypertension alone does not improve endothelial and smooth muscle brachial artery dilation in ESRD; contributions of systemic inflammation, altered Pi balance and hyperparathyroidism to impaired EDV and EIV must also be addressed. We provide the first demonstration that NHD reduces CRP.

Effect of Weight Loss on Endothelial Function in Obese Premenopausal Women

Background: Endothelial dysfunction, a pathological feature of obesity, can predict the occurrence of cardiovascular disease. The endothelial function was compared in obese, non-obese, and type 2 diabetic women, and the effect of weight loss on endothelial function in obese premenopausal women was also investigated. Methods: Twenty type 2 diabetes patients, 35 obese and 20 non-obese non-diabetic subjects were recruited. Both the endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation (EIV) were measured. The body composition, serum lipid, serum adiponectin and resistin were also measured. Weight loss in obese women was obtained by 6 months of calorific restriction, aerobic exercise and medication (sibutramine or orlistat). Results: EDV was significantly impaired in the type 2 diabetes and obese groups compared to the control group (6.0 ± 1.3% in diabetes group, 6.7 ± 3.9% in obese group, 12.4 ± 4.1% in control group, P < 0.01, respectively). The mean weight loss after 6 months was 8.5 ± 3.2 kg (P < 0.001) in the obese group. There was a significant increase in EDV after weight loss (from 5.8 ± 3.5% to 12.3 ± 3.9%, P < 0.05). There was no change in EIV after weight loss. In addition, weight loss was associated with significant reductions in the levels of high-sensitivity C-reactive protein (hs-CRP) and serum triglyceride (P < 0.05, respectively). However, there were no significant changes in the serum adiponectin and resistin levels after weight loss. Conclusions: Our data demonstrated that weight loss was associated with improved endothelial function in obese premenopausal women, as assessed by brachial artery EDV and reduced hs-CRP (J Kor Endocrinol Soc 21:506~514, 2006)