Monomeric form of C-reactive protein in the assessment of the residual inflammatory cardiovascular risk in patients with subclinical carotid atherosclerosis.

Aim      To study the relationship between monomeric C-reactive protein (mCRP) and the progression of asymptomatic carotid atherosclerosis in patients with a moderate risk for cardiovascular diseases (CVD) as assessed with the SCORE model.Material and methods  The study included 80 men and women aged 53.1±5.8 years assigned to the category of a moderate risk for CVDs by the SCORE model with a low-density lipoprotein cholesterol (LDL-C) level of 2.7-4.8 mmol/l and asymptomatic, hemodynamically insignificant (<50% luminal narrowing) carotid atherosclerosis according to ultrasonic data. All patients were prescribed atorvastatin to achieve a LDL-C level <2.6 mmol/l. After 7 years of follow-up, ultrasonic examination of carotid arteries was performed, and concentrations of high-sensitivity C-reactive protein (hsCRP) and mCRP were measured.Results A concentration of LDL-C <2.6 mmol/l was achieved in all patients. The progression of atherosclerosis as determined by an increased number of atherosclerotic plaques (ASPs), was observed in 45 (56 %) patients. At 7 months of follow-up, concentrations of cCRP were higher in the group of patients with progressive carotid atherosclerosis, while the levels of hsCRP did not differ between the groups. Increased mCRP concentrations were associated with changes in variables of the "atherosclerotic load", including the number of ASPs, total ASP height, and the intima-media thickness (IMT). In patients with a median mCRP concentration of 5.2 [3.3; 7.1] µg/l and more, the increases in mean ACP number and total ASP height were considerably higher than in patients with mCRP concentrations lower than the median (3.9 and 2.7 times, respectively), whereas the odds ratio for the progression of asymptomatic carotid atherosclerosis was 5.5 (95 % confidence interval, CI: 2.1-14.6; p=0.001). ROC analysis showed that the concentration of hsCRP had no predictive value for prognosis of asymptomatic carotid atherosclerosis (p=0.16), while the area under the ROC curve (AUC) for mCRP was 0.75±0.056 (95 % CI: 0.64-0.86; p=0.001).Conclusion      According to the results of 7-year follow-up, the plasma concentration of mCRP was significantly higher in patients with an increased number of ASPs than in patients without this increase. An increased level of mCRP may indicate a higher inflammatory risk of CVD.

Factors of Progression and Occurrence of Atherosclerosis in Rheumatoid Arthritis.

Aim      To determine in a prospective study factors of progressive atherosclerotic lesion of blood vessels in patients with rheumatoid arthritis (RA).Material and methods  This prospective study included 124 patients with RA and suspected ischemic heart disease (IHD) and 30 patients with IHD (comparison group) aged 58 [52; 63] years. On enrollment to the study and at 3 years of follow-up, all patients underwent clinical and instrumental examination according to European and Russian guidelines for diagnosis and treatment of stable IHD (2013), including coronography as indicated. For all RA patients of the comparison group, risk factors (RF) were evaluated, including arterial hypertension, smoking, excessive body weight, family history of cardiovascular diseases (CVD), diabetes mellitus, and dyslipidemia. The following laboratory data were evaluated: blood count; biochemistry, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), rheumatoid factor (RhF), cyclic citrullinated peptide antibodies, and high-sensitivity C-reactive protein (hsCRP). Proinflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF- α), were measured in RA patients once, at 3 years of follow-up.Results Incidence of FRs for CVD was similar in RA patients and in the comparison group. Median RA duration before inclusion into the study was 11 years, and median DAS28 index score was 3.8. Incidence of dyslipidemia due to increased TC, LDL-C, and HDL-C was higher for RA patients at baseline. The LDL-C goal (<1.8 mmol/l) was achieved only in 3 (10 %) patients of the comparison group and 10 (8 %) RA patients. RA patients had higher levels of the inflammation indexes, hsCRP (0.75 mg/dl vs. 0.16 mg/dl; p<0.05) and erythrocyte sedimentation rate (ESR) (15 mm/h vs. 11.5 mm/h; p<0.05). In the RA group at baseline, atherosclerotic plaques with carotid artery (CTA) stenosis of 20% or more were found in 94 (77 %) patients; in 3 of them, CA stenosis was >50%. Patients with RA frequently had unchanged or slightly changed coronary arteries (CA) (47% of patients), and less frequently they had hemodynamically significant multi-arterial coronary atherosclerotic lesions (7 % vs. 57 % of patients in comparison group). At 37.5 months, 21 (23 %) of 94 RA patients had progressive atherosclerosis in CA and/or CTA; 12 (13 %) RA patients had only progressive CA atherosclerosis; 7 (8 %) had only progressive CTA atherosclerosis; and 2 (2 %) had simultaneous progression of CA and CTA atherosclerosis. Two groups of RA patients were formed, with the progression of atherosclerosis (n=21) and without the progression of atherosclerosis (n=69). RFs for the development/progression of atherosclerosis in RA patients included smoking, family history of CVD, and duration of the disease. Levels of lipids did not differ. Levels of proinflammatory cytokines (IL-1ß, IL-6, TNF-α) were higher in RA patients with progressive atherosclerosis. No effects of the anti-rheumatic therapy on the progression of atherosclerosis were observed.Conclusion      Progression of atherosclerosis in RA remains in disease with low and moderate activity during the anti-rheumatic and hypolipidemic treatment. The development of atherosclerosis in RA is determined by lipid, inflammatory, and immune disorders.

The severity of internal carotid artery stenosis is associated with the circulating Th17 level.

AIM: Immune and inflammatory reactions contribute to the progression of atherosclerosis. The walls of the different arteries and segments of the arteries have heterogeneous haemodynamic and histological features. We aimed to explore the relationship between the circulating T-cell subsets and the abundance of carotid atherosclerosis in different segments of carotid arteries. METHODS: 70 patients underwent ultrasound duplex scanning to determine the degree of stenosis of the common carotid artery (CCA), the CCA bifurcation or the internal carotid artery (ICA). The blood frequencies of T-, B-, NK-cells, regulatory T cells (Treg), activated T-helpers (Th), IL10-producing Th, Th1 and Th17, as well as blood levels of hsCRP, sCD25, IL10 and IL17a were assessed. RESULTS: The frequencies of Th17 were increased in patients with ICA stenosis >35% and >50% vs. patients with ICA stenosis <35%. Th17 blood level ≥0.55 % of lymphocytes was associated with more severe stenosis of ICA (OR 4.3 (1.0-17.6), p < 0.05 for ICA stenosis of 35-50% and 6.8 (1.3-35.0), p < 0.05 for ICA stenosis >50%). BMI positively correlated with the CCA bifurcation stenosis degree (r = 0.33, p < 0.05). CONCLUSION: The severity of ICA stenosis can be associated with the circulating Th17 level.

Rate of Complications at Early Removal of Compression Bandage After Transradial Coronary Angiography.

PURPOSE: to compare rates of access site complications at early (after 4 hours) and traditional (after 24 hours) removal of a compression bandage after diagnostic transradial (TR) coronary angiography (CA) in patients not receiving anticoagulants. MATERIALS AND METHODS: We included into this study 392 patients (mean age 63±8.7 years, 62.8% men) who underwent transradial coronary angiography. Patients were divided into 2 groups. In group 1 patients (n=221) compression bandage was removed from puncture site in 4 hours after procedure with subsequent control of radial artery patency using presence of pulse metric curve during ulnar artery compression (the reverse Barbeau test with pulse oximeter). In patients of group 2 (n=171) compression band was removed after 24 hours. In both groups control of radial artery patency was carried out after 24 hours using the reverse Barbeau test. Upon detection of radial artery occlusion (RAO) ultrasound imaging of the forearm arteries was performed. RESULTS: No RAO was detected in group 1 while in group 2 number of detected RAO was 15 (8.8%) (р<0.05). Rates of hematomas at puncture site were not significantly different. Puncture site bleeding after band removal requiring repeated banding occurred in 1 patient of group one (0.6%); no such cases were registered in group 2 (p>0.05). CONCLUSION: Compared with traditional method early removal of compression bandage after TR CA was associated with lower rate of RAO.

[Atrial myocarditis in a patient with Takayasu arteritis].

Takayasu arteritis belongs to the group of systemic vasculitis with a predominant lesion of large - caliber vessels and the development of stenosis of their lumen. In world practice, to establish the diagnosis of arteritis Takayasu apply the criteria proposed by the American College of rheumatologists. Currently, there are no randomized clinical trials related to the disease, and the diagnosis and treatment of patients are based on a number of small studies, a series of clinical cases and expert opinion. The described clinical observation of a patient with Takayasu arteritis is of interest in connection with the detected atrial myocarditis during MRI diagnosis of the heart with contrast, which allows us to discuss the feasibility of this imaging technique in complex and doubtful cases.

[Dynamics of asymptomatic atherosclerosis of carotid arteries depending on the achieved level of cholesterol in moderate-risk patients]. / Dinamika bessimptomnogo ateroskleroza sonnykh arterii v zavisimosti ot dostignutogo urovnia kholesterina u patsientov s umerennym riskom.

The study was aimed at assessing the dynamics of asymptomatic atherosclerosis of carotid arteries (CA) depending upon the achieved level of low-density lipoprotein cholesterol (LDLC) in patients with moderate total risk by the SCORE scale. We followed up a total of eighty-two 40-to-65-year-old patients with the LDLC level above 2.6 mmol/l, being at moderate total risk by the SCORE scale and having symptom-free atherosclerosis of the extracranial portion of brachiocephalic arteries (up to 50% narrowing of their lumen) as diagnosed by duplex scanning. The patients were randomly divided into two groups. Group One patients (n=41) received therapy with atorvastatin in order to achieve the LDLC level less than 1.8 mmol/l. Group Two patients (n=41) were treated in order to achieve the LDLC level below 2.6 mmol/l. At 12 months of follow up we compared the dynamics of carotid atherosclerosis (change in the number, total height, structure, echogenicity, as well as the state of the surface of atherosclerotic plaques, alteration of the thickness of the CA intima-media complex). Group Two patients were found to have an increase in the number and average sum of the heights of atherosclerotic plaques. An increase of the maximum thickness of the intima-media complex of the wall of the right and left CA was more pronounced as compared with that in Group One patients. Aggressive hypolipidemic therapy aimed at achieving the LDLC level below 1.8 mmol/l turned out to be more effective in slowing down the progression of asymptomatic carotid atherosclerosis in patients with moderate cardiovascular risk than therapy targeted at achieving the LDLC level below 2.6 mmol/l.

[Subpopulation Composition of CD4+ T-lymphocytes as Factor Contributing to the Progression of Atherosclerosis of Carotid Arteries].

AIM: to assess prognostic significance of blood content of regulatory and effector T-lymphocytes for progression of atherosclerosis (AS) of carotid arteries. MATERIAL AND METHODS: We enrolled in this study 33 men with various severity of carotid AS. Carotid artery duplex scan was done at admission and in 1 year after enrollment. AS progression was defined as appearance of novel stenosis in common or internal carotid artery or more or equal 5% increase of preexisting stenosis. Peripheral blood lymphocyte phenotyping was performed by direct immunofluorescence and flow cytometry at the enrollment. T-helpers (Th) 1 were identified as CD4+IFNgamma+ cells, Th2 - CD4+IL4+, activated T-cells (T-act) - D4+CD25lowCD127high, regulatory T-cells (T-reg) - D4+CD25highCD127 low and CD4+FoxP3+, Th17 - CD4+IL17a+ cells. RESULTS: Progression of carotid AS was observed in 18 patients. Basal values of Th17 were higher while ratio T-reg/Th17 was lower in patients with compared with those without AS progression. ROC-analysis showed high sensitivity and specificity of blood levels of Th17, T-act and T-reg/Th17 ratio for carotid AS progression during one year in patients with low density lipoprotein cholesterol (LDLCH) level below 3.5 mmol/l. CONCLUSION: The imbalance between circulating levels of regulatory T-cells and T-helpers 17 with the prevalence of proinflammatory T-helpers 17 may reflect a predisposition for carotid AS progression, what also refers to patients with relatively low LDLCH.

[Carotid Plaque Instability in Patients With Acute Coronary Syndrome as Assessed by Ultrasound Duplex Scanning].

AIM: to study carotid plaques structure in patients with acute coronary syndrome by ultrasound duplex scanning. MATERIALS AND METHODS: We included in this study143 patients with acute coronary syndrome (ACS) aged 32-83 years and 28 patients with documented coronary heart disease (CHD) aged 46-83 years. Duplex scanning of carotid arteries was carried out with Philips iU22 ultrasound system and L9-3 linear array transducer. Atherosclerotic plaques in CCA, CCA bifurcation, and ICA from right and left side were investigated. Off-line analysis of B-mode images and plaque gray scale median (GSM) was performed with computer semiautomated workstation MultiVox. RESULTS: 378 plaques of ACS and 59 plaques of CHD patients were studied. We assessed traditional (heterogenous structure, hypoechogenic component, irregular plaque surface) as well as additional (positive remodeling, "layered" structure of plaque, local calcification) criteria of plaque instability. In ACS compared with CHD group there were more plaques with hypoechogenic component (43.4 and 28.8%, p=0.0459), heterogenous structure (77.8 and 64.4%, p=0.0327), irregular surface including irregularities more than 2.0 mm (22.5 and 6.8%, p=0.0048, respectively). There was significant difference in "layered" structure (55.7 and 35.8%, p=0.0011) and insignificant difference in positive remodeling (16.3 and 7.5%, p=0.06, respectively). There were no differences of GSM value (53.1 and 57.2, p=0.24) and local calcification (23.2 and 24.5%, p=0.23, respectively). CONCLUSION: In our study ultrasound duplex scanning revealed that signs of plaque instability in carotid arteries in patients with ACS were more frequent than in patients with stable CHD. The newly introduced parameter "layered" structure of atherosclerotic plaque was found to be most significant.

Specific Lipoprotein(a) apheresis attenuates progression of carotid intima-media thickness in coronary heart disease patients with high lipoprotein(a) levels.

BACKGROUND: To date, there have been no studies evaluating the effect of isolated lipoprotein(a) (Lp(a)) lowering therapy on carotid atherosclerosis progression. METHODS: We enrolled 30 patients who had coronary heart disease (CHD) verified by angiography, Lp(a) level ≥50 mg/dL, and low density lipoprotein cholesterol (LDL-C) level ≤2.6 mmol/L (100 mg/dL) on chronic statin therapy. Subjects were allocated in a 1:1 ratio to receive apheresis treatment on a weekly basis with immunoadsorption columns ("Lp(a) Lipopak"(®), POCARD Ltd., Russia) added to atorvastatin, or atorvastatin monotherapy. The primary efficacy end-point was the change from baseline in the mean intima-media thickness (IMT) of the common carotid arteries. RESULTS: After one month run-in period with stable atorvastatin dose, LDL-C level was 2.3 ± 0.3 mmol/L and Lp(a) - 105 ± 37 mg/dL. As a result of acute effect of specific Lp(a) apheresis procedures, Lp(a) level decreased by an average of 73 ± 12% to a mean of 29 ± 16 mg/dL, and mean LDL-C decreased by 17 ± 3% to a mean of 1.8 ± 0.2 mmol/L. In the apheresis group, changes in carotid IMT at 9 and 18 months from baseline were -0.03 ± 0.09 mm (p = 0.05) and -0.07 ± 0.15 mm (p = 0.01), respectively. In the atorvastatin group no significant changes in lipid and lipoprotein parameters as well as in carotid IMT were received over 18-month period. Two years after study termination carotid IMT increased by an average of 0.02 ± 0.08 mm in apheresis group and by 0.06 ± 0.10 mm in the control group (p = 0.033). CONCLUSION: Isolated extracorporeal Lp(a) elimination over an 18 months period produced regression of carotid intima-media thickness in stable CHD patients with high Lp(a) levels. This effect was maintained for two years after the end of study. TRIAL REGISTRATION: Clinicaltrials.gov (NCT02133807).

[Randomized FARVATER study. Part 2. Effect of atorvastatin on endothelial function, distensibility and stiffness of vascular wall].

AIM: To elucidate effect of two doses of atorvastatin (10 and 20 mg/day) on endothelial function, distensibility and stiffness of vascular wall. MATERIAL AND METHODS: Patients (n=50) with documented ischemic heart disease and hyperlipidemia were randomized to 10 or 20 mg/day of atorvastatin (Atoris, KRKA). Endothelial function and common carotid artery wall distensibility and stiffness were assessed at baseline and after 12 and 24 weeks of treatment. RESULTS: Administration of both 10 and 20 mg/day doses of atorvastatin for 6 weeks was associated with significant lowering of total cholesterol (CH), triglycerides (TG) and low density lipoprotein (LDL) CH (24.5, 18.4, 34.9% and 29.1, 28.2, 40.9%, respectively). After 24 weeks LDL CH lowering from baseline reached 34.9 and 43.9% (p<0.001) and that of TG - 22 and 15%, in 10 and 20 mg/day groups, respectively. There were no significant differences between 10 and 20 mg/day groups in baseline values of endothelium dependent vasodilation (EDV), carotid artery distensibility and stiffness (7.28 and 6.64%, 21.60 and 20.15, 8.04 and 9.19 U, in 10 and 20 mg/day groups, respectively). After 3 months of treatment there occurred significant 38.4% (10 mg/day) and 45.4% (20 mg/day) increases of EDV. Significant 27.6% (10 mg/day) and 28.8% (20 mg/day) enhancement of vascular distensibility was noted after 24 weeks. Vascular wall stiffness decreased 33.4% (p=0.008) and 31.3% (p=0.002) in 10 and 20 mg/day groups, respectively.

[Influence of valsartan, fluvastatin extended release and their combination on arterial pressure, parameters of lipid metabolism, and endothelial function in patients with hypertensive disease].

BACKGROUND: Search of new optimal treatment strategies, allowing to decrease the risk of atherosclerosis development and cardiovascular events is determined by high prevalence of hyperlipidemia in hypertensive patients. AIM: To study the vasoprotective effects and security of Valsartan (V) or Fluvastatin extended release (XL) (F) and their combination in stage 1 and 2 essential hypertension (EH) with moderate hyperlipidemia. METHODS: 32 patients with EH after 14 days of wash-out period were randomized to receive either V (160 mg o.d.) or F (80 mg o.d.). After 8 weeks of monotherapy combination of V+F was administered to each patient for the next 8 weeks. At baseline, after 8 weeks of monotherapy, and at the end of the study sitting BP, lipids, NOs level and endothelial function were assessed. Endothelial function was measured as flow-mediated vasodilation (FMD) by high resolution ultrasound. Valsartan (Diovan) and Fluvastatin (Lescol XL) were provided by Novartis Pharma AG (Basel, Switzerland). RESULTS: Combination of F (80 mg o.d) with initial therapy by V (160 mg o.d.) led to more significant decrement of BP and significant improvement of FMD.

[Randomized FARVATER Study. Part 1. Effect of 10 and 20 mg/day atorvastatin on levels of lipids, C-reactive protein, and fibrinogen in patients with ischemic heart disease and hyperlipidemia].

Main aim of the clinical study FARVATER was comparison of effects of 10 and 20 mg/day of atorvastatin on levels of lipids, high-sensitivity C-reactive protein (CRP), fibrinogen (F), and structural-functional state of vascular wall in patients with documented and primary hyperlipidemia (HLP). Fifty patients (mean age 60.8 years) with documented ischemic heart disease and HLP were randomized to continuous administration of 10 and 20 mg/day atorvastatin for 24 weeks. Initial levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDLCH), high density lipoprotein cholesterol (HDL CH), CRP and F were 6.22, 1.86, 4.15, 1.24 mmol/l, 1.46 and 2.93 g/l, respectively. After 6 weeks lowering of TCH, TG and LDLCH was significant both in 10 (24.5, 18.4, and 34.9%, respectively) and 20 mg (29.1, 28.2, and 40.9%, respectively) groups. After 24 weeks TG levels decreased by 22 and 15% in 10 and 20 mg subgroups, respectively. Changes of HDLCH (+11 and +12% in patients treated with 10 and 20 mg, respectively) were not significant. There were no significant changes of CRP and F levels. Seven side effects (4%) were registered during 24 weeks; 2 were related to study drug (allergy and symptomless elevation of creatine kinase).

[Effect of therapy with rosuvastatin on lipid spectrum, factors of inflammation and endothelial function in patients with ischemic heart disease].

Rosuvastatin (10 mg) was given for 3 months to 30 men (mean age 57+/-9 years) with total cholesterol (CH) above 5.2 mmol/l. Questioning, physical examination, registration of ECG, measurement of levels of total, low density lipoprotein (LDL), high density lipoprotein (HDL) CH, and triglycerides (TG), assessment of endothelium-dependent brachial artery dilation were carried out at baseline and in 3 months. It was noted that 3 months therapy with rosuvastatin exerted positive effect on blood lipid spectrum: lowering of concentration of total CH (-31%, baseline 6.52+/-0.92, after therapy 4.47+/-0.96 mmol/l, p<0.0001), TG (-39%, baseline 2.73+/-1.56, after therapy 1.67+/-0.71 mmol/l, p<0.001), LDLCH (-44%, baseline 4.11+/-0.85, after therapy 2.40+/-0.90 mmol/l, p<0.0001), elevation of HDLCH (+6%, baseline 1.15+/-0.27, after therapy 1.22+/-0.34 mmol/l, p=0.08). Target LDL CH level (<2.6 mmol/l) was achieved in 23 patients (77%). Significant lowering of concentration of C-reactive protein (CRP) (-56%) and interleukin 6 (-25%) was also established. Before beginning of therapy mean flow dependent dilation was 6.1+/-1.64%, after therapy -- 10.4+/-5.0% (p<0.05). Treatment of men with ischemic heart disease with rosuvastatin (10 mg for 3 months) led to achievement of target values of LDLCH in 77% of them, to significant lowering of concentrations of CRP and interleukin 6, and to improvement of endothelial function.

[Effects of isosorbide-5-mononitrate on clinical condition, bicycle ergometry results, endothelium-dependent vasodilation in patients with ischemic heart disease with stable effort angina].

AIM: Assessment of efficacy of treatment of coronary heart disease (CHD) patients suffering from stable effort angina of functional class II-III with the drug isosorbide-5-mononitrate Mono Mac 50 depo (MM 50 D). MATERIAL AND METHODS: Clinical indices, exercise tolerance, endothelial function (the study of brachial artery in reactive hyperemia and sublingual intake of nitroglycerin) were studied in 30 patients with stable angina FC II-III before the treatment, 1 and 3 months after the treatment. RESULTS: MM 50D significantly widens diameter of the brachial artery (by 11.6%), lowers nitroglycerin-dependent vasodilation (from 16% to 10.4% in a month and to 10.2% in 3 months) and blood flow speed in reactive hyperemia. An absolute increment of the brachial artery diameter in reactive hyperemia test remained unchanged. The ratio flow-dependent vasodilation/nitroglycerin-dependent vasodilation increased in the course of therapy from 0.67 to 0.91. The drug produced clinical improvement (anginal attacks rate diminished by 70 and 85%, respectively) and increased exercise tolerance (the threshold performance rose by 28%, total load time--by 30%). CONCLUSION: It is important to use complex assessment of hemodynamic component of endothelial function in the treatment with nitrates.

[Atorvastatin in the treatment of patients with hereditary hypercholesterolemia]. / Atorvastatin pri lechenii bol'nykh s nasledstvennoi giperkholesterinemiei.

Efficacy and tolerability of atorvastatin (20 mg/day) were assessed in a 3 month study on 19 patients (5 men, 14 women, mean age 52.3 years) with familial hypercholesterolemia. Average baseline levels of total cholesterol (CH) and low density lipoprotein (LDL) CH were 10.7 and 8.6 mmol/l, respectively. By the end of 3 months levels of CH, LDL CH, triglycerides and atherogeneity index decreased by 32, 41, 16 and 45%, respectively. This was accompanied by 21% increase of high density lipoprotein CH level. There were no cases of AST or ALT activity elevation above 3 upper limits of normal values. However 1 patient had asymptomatic elevation of ALT activity up to 53 U/l which did not cause interruption of therapy. Creatine kinase remained normal throughout the study period. Three patients (16%) stopped taking atorvastatin because of side effects. Thus in patients with familial hypercholesterolemia the dose of atorvastatin 20 mg/day was sufficiently well tolerated and provided effective control of lipid levels.

[Determination of nitric oxide in serum and plasma of human blood. Method of high pressure liquid chromatography]. / Opredelenie oksida azota v syvorotke i plazme krovi cheloveka. Metod vysokoéffektivnoi zhidkostnoi khromatografii.

Two methods of measurement of nitrite and nitrate determination in human serum and plasma (a colorimetric method based on Griess reaction and a HPLC method) have been compared HPLC method revealed extremely low level of nitrites blood plasma, which was roughly the same (about 3 microM or less) in healthy donors, patients with diabetes and hypertension. The level of nitrates in the group of healthy donors (29.9 +/- 2.8 microM) is lower than in patients with diabetes (58.6 +/- 6.9 microM), and in patients with hypertension (35.4 +/- 2.5 microM). Comparison of data obtained by colorimetric and HPLC methods revealed close correlation (r = 0.77, p < 0.001). Methodical requirements for preparation of samples of serum and plasma of blood for analysis and correct intepretation of results are discussed in view of biochemical properties of nitric oxide molecule.

[Effect of atorvastatin on endothelial function in patients with familial hypercholesterolemia]. / Vliianie atorvastatina na funktsional'noe sostoianie éndoteliia u bol'nykh s nasledstvennoi giperkholesterinemiei

AIM: To study the influence of treatment with HMG-CoA reductase inhibitor atorvastatin on endothelial function in patients with familial hypercholesterolemia type IIa. MATERIALS AND METHODS: Sixteen patients (5m/11w, 51-/+3 years) with familial hypercholesterolemia were studied before and after 3 months of therapy with atorvastatin 20 mg/day. EDRF release test (D.Celermajer, 1992) was used to assess flow-mediated endothelium-dependent vasodilatation (FMD) of the brachial artery in response to reactive hyperemia. Plasma nitrite/nitrate (NOx) levels were measured as an indirect index of nitric oxide (NO) production in vivo using HPLC. RESULTS: Atorvastatin treatment resulted in a 32% reduction in total serum cholesterol (CH), 41% reduction in low density lipoprotein (LDL) CH, 16% reduction in triglycerides and a 21% increase in high density lipoprotein CH. Flow mediated dilatation (FMD) was impaired at baseline (5.8-/+0.9%) and significantly improved up to 9.5-/+0.9% after 3 month atorvastatin therapy (p<0.002). Change in FMD inversely correlated with baseline FMD (r = -0.58, p<0.05). There was no significant correlation between FMD and neither total serum CH nor LDL CH levels at baseline. During atorvastatin therapy significant reduction of plasma NOx levels occurred from 53.4-/+5.1 mcmol/l at baseline (range 42.6-86.2 mcmol/l) to 35.5-/+5.1 mcmol/l (18.4-46.0 mcmol/l) after treatment (p<0.02, n=7). CONCLUSION: In patients with familial hypercholesterolemia atorvastatin produced beneficial effect on endothelial function (increase in flow-mediated dilatation, decrease in NOx).

[Effect of L-arginine on platelet aggregation, endothelial function adn exercise tolerance in patients with stable angina pectoris]. / Vliianie L-arginina na agregatsiiu trombotsitov, funktsiiu éndoteliia i tolerantnost' k fizicheskoi nagruzke u patsientov so stabil'noi stenokardiei napriazheniia.

AIM: Examination of the action of donor NO (L-arginine) on platelet aggregation, endothelial function and exercise tolerance in patients with stable angina of effort (SAE). MATERIAL AND METHODS: 42 patients with SAE (functional class I-II) and 10 healthy volunteers (control group) were assigned to two groups. 22 patients of group 1 were randomized to cross-over. They received cardiket (60 mg/day for 10 days or cardiket (60 mg/day) in combination with L-arginine (15 g/day for 10 days). 20 SAE patients of group 2 and control group received L-arginine (15 g/day for 10 days). In each group blood lipids were examined, and bicycle exercise test (BET) was performed. In addition, platelet aggregation and endothelial function were studied in group 2 and control group before and after the course of L-arginine. RESULTS: Compared to control group, endothelial function significantly improved in group 2 (from 5.0 +/- 2.9 to 7.8 +/- 4.1% vs 7.1 +/- 1.9 to 6.6 +/- 4.8%) (M +/- SD). BET duration increased in all the patients. After ADP addition in concentrations 1.5, 2.0, and 5.0 micromol/l platelet aggregation declined in 17 patients except 3 in whom the aggregation remained unchanged. CONCLUSION: Positive effect of L-arginine on endothelial function, exercise tolerance and platelet aggregation was observed in patients with stable angina of effort (functional class I-II). Therefore, arginine can be recommended as an adjuvant in the treatment of patients with ischemic heart disease.

[Noninvasive investigation of endothelial function in patients with hypertension and hypercholesterolemia (HCE)]. / Neinvazivnoe opredelenie funktsii éndoteliia u bol'nykh gipertonicheskoi bolezn'iu v sochetanii s giperkholesterinemiei.

AIM: Functional assessment of endothelium by endothelium-dependent and non-endothelium dependent response of the brachial artery (BA) in patients with risk factors for atherosclerosis. MATERIALS AND METHODS: The ACUSON 128 XP/10 unit furnished with linear meter with phase grid (7.0 MHz) was employed in two-direction scanning mode to measure BA diameter at rest, under reactive hyperemia (endothelium-dependent response) and after sublingual intake of 0.01 mg of nitroglycerin (non-endothelium-dependent response) in 12 patients with blood hypertension (group 3), 10 subjects with family hypercholesterolemia (group 2) and 10 healthy subjects (group 1, control). RESULTS: The flow-dependent dilatation remained unchanged in BH patients (9.4%) and lowered in HCE patients (3.0%) compared to controls (9.5%). Nitroglycerin-induced dilatation was not significantly different in patients with family hypercholesterolemia (16.6%), hypertensive subjects (14.5%) and healthy controls (20.5%). CONCLUSION: The ultrasound method of detection of endothelial dysfunction is demonstrated. Endothelial dysfunction in patients with familial hypercholesterolemia may contribute to development of atherosclerosis.

Non-invasive ultrasound detection of endothelial dysfunction.

With high resolution ultrasound we assessed endothelial function in subjects at risk of atherosclerosis. We used ACUSON 128XP/10 system with 7.0 MHz linear array transducer. Three groups of patients (pts) were studied: 12 patients with essential hypertension, ten patients with 2A familial hyperholesterolamia and ten controls without vascular risk factors. We measured the diameter of brachial artery at rest, during reactive hyperaemia (with increased flow causing endothelium-dependent dilation), and after sublingual 0.01 mg nitroglycerin (causing endothelium-independent dilation). Flow-mediated dilation is not impaired in essential hypertension (9. 4%) compared with controls (9.5%) and impaired in patients with familial hyperholesterolaemia (3.0%). NTG-induced dilation is not impaired in familial hyperholesterolaemia (16.6%) and essential hypertension (14.5%) compared with controls (20.5%). The effect of hypolipidaemic influence (probucol and plasmapheresis) was assessed in a separate study. These results demonstrate the capability of ultrasound in detection of endothelial dysfunction, and suggest that endothelial dysfunction in patients with familial hyperholesterolaemia is one of the risk factors for atherosclerosis. The parameters of endothelial function may be used as markers of hypolipidemic influence on patients with hyperholesterolaemia.