[Platelet adhesion mediated by von Willebrand factor in patients with premature coronary artery disease].

Aim    To study platelet adhesion mediated by von Willebrand factor (VWF) in patients with premature ischemic heart disease (IHD).Material and methods    This study enrolled 58 patients with stable IHD, including 45 men younger than 55 years with the first manifestation of IHD at the age of <50 years and 13 women younger than 65 years with the first manifestation of IHD at the age of <60 years. The control group consisted of 33 patients, 13 men younger than 55 years and 20 women younger than 65 years without IHD. Platelet adhesion to the collagen surface at the shear rate of 1300 s-1 was studied by evaluating the intensity of scattered laser light from the collagen-coated optical substrate in a flow chamber of a microfluidic device after 15-min circulation of whole blood in the chamber. Decreases in platelet adhesion after addition to the blood of monoclonal antibodies (mAb) to platelet receptors glycoproteins Ib (GPIb) to inhibit the receptor interaction with VWF were compared for patients of both groups. Results    In patients with premature IHD, the decrease in platelet adhesion following the platelet GPIb receptor inhibition was significantly less than in patients of the control group (74.8 % (55.6; 82.7) vs. 28.9 % (-9.8; 50,5), p <0.001). For the entire sample, the median decrease in platelet adhesion following the GPIb receptor inhibition was 62.8 % (52.2; 71.2). With an adjustment for traditional risk factors of IHD, a decrease in platelet adhesion of >62.8% after blocking GPIb receptors increased the likelihood of premature IHD (OR=9.84, 95 % CI: 2.80-34.59; p <0.001).Conclusion    Blocking the interaction of GPIb receptors with VWF in patients with premature IHD and increased shear rate induced a greater decrease in platelet adhesion than in patients without this disease. This suggested that an excessive interaction of VWF with platelets might contribute to the pathogenesis of premature IHD.

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.

[The Diagnostic Accuracy of Сoronary Сomputed Tomography Angiography in the Diagnosis of Stable Coronary Artery Disease in Patients Aged 70 Years and Older].

AIM: The purpose of this study was to evaluate the diagnostic accuracy of сoronary сomputed tomography angiography (CCTA) in the diagnosis of stable coronary artery disease (CAD) in patients aged ≥70 years. MATERIALS AND METHODS: The study included 390 patients aged ≥70 years with symptoms suggested stable CAD which underwent elective coronary artery angiography (CAG). Initially the prevalence of angiographically significant CAD was estimated according to the gender and chest pain character, and identifications of patients in whom CCTA was appropriate. After that diagnostic accuracy and сost-efficiency of CCTA in the diagnosis of stable CAD in 82 patients with atypical angina and non-anginal chest pain were evaluated. RESULTS: The prevalence of obstructive CAD in patients with typical angina was very high and they were excluded from the final analysis. Among 82 patients with atypical angina and non-anginal pain which underwent CCTA 48 (59%) patients had obstructive CAD. CСTA data matched with results of CAG in all cases. Among 34 patients that had non-obstructive CAD the results of CCTA and CAG matched in 88% cases. CCTA has sensitivity, specificity, positive predictive value, negative predictive value of 100%, 88%, 92% and 100% respectively. The likelihood ratio for positive result was 8.3, likelihood ratio for negative result was 0.3. Positive result increased post-test probability of obstructive CAD from 42% to 86%, negative result reduced post-test probability of obstructive CAD to 0%. CONCLUSION: negative CCTA result in patients aged 70 years and older with atypical angina and non-anginal pain allows to exclude the presence of obstructive CAD.  The likelihood ratio for positive result indicates a moderately difference between the pre-test and post-test probability of the presence of obstructive CAD. In patients aged ≥70 years with atypical angina or non-anginal chest pain which have inconclusive results of functional testing or unable undergo functional testing CCTA allows to increase diagnostic yield of CAG and reduce the frequency of minor complications and diagnostic evaluation costs.

[The Diagnostic Accuracy of Exercise Treadmill Testing and Stress Echocardiography for the Detection of Obstructive Coronary Artery Disease in Patients Aged ≥ 70 Years].

AIM: to compare diagnostic accuracy of exercise treadmill testing and stress echocardiography in the diagnosis of stable coronary artery disease (CAD) in patients aged >70 years. MATERIALS AND METHODS: The study included 390 patients aged >70 years with suspected stable ischemic heart disease, who underwent elective coronary artery angiography (CAG). Exercise treadmill testing (ETT) according to the modified Bruce protocol was carried out in 189 patients (48 %), bicycle stress echocardiography - in 179 patients (46 %). Initially we determined the prevalence of angiographically significant CAD according to the gender and chest pain character, and identified persons in whom stress testing was appropriate. After that diagnostic accuracy of both tests was evaluated in patients with atypical angina and non-anginal chest pain. RESULTS: Among 72 patients with atypical angina and non-anginal pain who underwent ETT and had unequivocal results, 38 (53 %) had obstructive CAD. ETT for detection of obstructive CAD had sensitivity 79 %, specificity 82 %, positive likelihood ratio (LR+) 4.4, and negative likelihood ratio (LR-) 0.3. Positive result increased probability of obstructive CAD from 53 % to 83 %, negative result reduced probability of obstructive CAD to 25 %. Among 111 patients with atypical angina and non-anginal pain who underwent stress echocardiography and had unequivocal results, 69 (62 %) had obstructive CAD. Sensitivity, specificity, LR+, and LR- of stress echocardiography were equal to 89 %, 95 %, 17.8, and 0.1, respectively. Positive result increased probability of obstructive CAD from 62 % to 95 %, negative result reduced probability of obstructive CAD to 16 %. CONCLUSION: bicycle stress echocardiography was found to be more accurate than ETT to rule in or rule out obstructive CAD in patients aged ≥ 70 years with atypical angina and non-anginal pain.

[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.

[The CD45-positive thrombocytes and neutrophils/lymphocytes level ratio in evaluation of risk of development of re-stenosis шт patients with chronic ischemic heart disease and diabetes mellitus type II.]

The purpose of study is to investigate significance of detection of number of CD45-positive thrombocytes and ratio neutrophils/lymphocytes in evaluation of risk of development of re-stenosis after implantation of drug-eluting stents in patients with chronic ischemic heart disease and diabetes mellitus type II. The examination was applied to 126 patients with chronic forms of ischemic heart disease who passed through repeat coronary angiography during first year after implantation of drug-eluting stents. The patients were separated on two groups depending on availability of diabetes mellitus type II. In both groups, the patients passed through comparing of angiography and clinical characteristics. Also, a logistic model was developed prognosticating development of re-stenosis. The re-stenosis developed more often in patients with diabetes mellitus type II (54.5%) than in patients without diabetes mellitus type II (32.4%; p=0.01). The comparative analysis of more than 35 characteristics permitted to establish risk factors of development of re-stenosis with the highest prognosticating capacity among patients with diabetes mellitus type II. These risk factors were CD45-positive thrombocytes and ratio neutrophils/lymphocytes. To prognosticate development of re-stenosis a logistic regression model was developed comprising number of circulating CD45-positive thrombocytes, ratio neutrophils/lymphocytes and availability of diabetes mellitus type II. The model demonstrated high prognosticating value as regards development of re-stenosis: OR = 15.1 (95% CI 4.81-31, p < 0.001). The square under ROC-curve: AUC = 0.83 (95% CI 0,72-0,92; р < 0,001). The increasing of number of circulating CD45-positive thrombocytes and ratio neutrophils/lymphocytes can be considered as a valuable risk factors of development of re-stenosis in case of diabetes mellitus type II.

Relationship between the Level of Circulating CD45+ Platelets and Development of Restenosis after Implantation of Drug-Eluting Stents to Patients with Coronary Heart Disease.

The study was carried out in 126 patients with stable angina pectoris, who underwent elective coronary artery stenting with drug-eluting stents and follow-up angiography within 6-12 months thereafter. Five significant risk factors of restenosis were identified by binary comparisons of different variables. The logistic regression equation that included the level of CD45-positive platelets, diabetes, small vessel stenting, number of simultaneously implanted stents in one patient, and lesion length demonstrates the highest level of prediction of in-stent restenosis (OR=22.8; p<0.001). ROC-analysis demonstrated high prognostic value of the logit model (area under ROC curve 0.87, p<0.001). The data suggest that a close relationship exists between the development of restenosis and the level of circulating CD45+ platelets.

[Vasorenal Hypertension and Primarily Contracted Kidney in a Man Aged 44 years: Is Invasive Intervention Needed?]

Presentation of a clinical case of vasorenal hypertension in a patient with chronic renal artery occlusion and primarily contracted kidney is accompanied by discussion of current recommendations concerning indications to invasive intervention in patients with vasorenal arterial hypertension.

[Level of Soluble Receptor for Glycation End-Products in Patients With Restenosis After Coronary Artery Stenting].

The purpose of research - the study of the level of soluble receptor for advanced glycation end products (CNG) in patients with coronary heart disease (CHD) with angina pectoris who have emerged restenosis after implantation of drug-eluting stents.

[Role of eosinophil granulocytes in the occurrence of restenosis in patients after coronary stenting with drug-eluting stents].

AIM: To study the role of eosinophil granulocytes in the development of restenosis after drug-eluting stent (DES) implantation. MATERIALS AND METHODS: The blood levels of eosinophils, eosinophil cationic protein (ECP), immunoglobulin E (IgE), and C-reactive protein (CRP) were compared in 170 patients with coronary heart disease (CHD) and stable angina who had undergone recoronarography within the first year after endovascular myocardial revascularization using DES. The blood level of eosinophils was determined by the results obtained employing the FACS Calibur flow cytofluorometer (Becton Dickinson, USA). That of ECP, IgE, and CRP was estimated by enzyme immunoassay by means of an Immulite-100 analyzer (Siemens, Germany). The data were presented as median (25th percentile and 75th percentile). RESULTS: The blood eosinophil level was 272 (234; 292) cells/µl in patients with restenosis while that was 134 (85; 156) cells/µl in those without restenosis (p = 0.002). The plasma ECP level proved to be greater in the patients who had developed restenosis after DES implantation than in those who had not [17.7 (11.2; 24) and 9 (6.4; 12.9) ng/ml, respectively (p = 0.017). At 6 months after DES implantation, the level of ECP was significantly higher (8.6 (7.3; 9.7) ng/ml) than the baseline level (p = 0.04). Later on, there was an even greater increase in ECP levels. No significant changes were noted in blood ECP levels after bare stent implantation. CONCLUSION: The findings suggest that there is a relationship between the occurrence of restenosis and the enhanced activity of eosinophil granulocytes in CHD patents after DES implantation.

[Structural and functional status of arteries in young and middle-aged men with ischemic heart disease].

Aim of the study was to determine whether structural and functional status of arteries differ between young and middle-aged men with ischemic heart disease (IHD). A total of 78 men aged 28 to 50 years were recruited in this study: 49 with angiographically proven obstructive atherosclerosis of coronary arteries, 29 without clinical manifestations of IHD (control group). Those with arterial hypertension, diabetes mellitus or marked hypercholesterolemia (LDL cholesterol more or equal 4.5 mmol/l) were excluded from the study. All patients underwent carotid ultrasound, endothelial function, and arterial stiffness measurements. Patients with IHD more often had multiple carotid plaques (86.7% vs 13.7%, p<0.001), and increased aortic pulse wave velocity (PWV) assessed by ultrasound duplex scanning (53.1% vs. 24.1%, p=0.02). Aortic PWV was related to the severity of coronary atherosclerosis. Presence of a carotid intima-media thickness more or equal 0.9 mm and abnormal flow-mediated dilatation (FMD) of the brachial artery was not significantly different between the groups.

[Eosinophilic cation protein and development of restenosis of drug covered stents].

Aim of the study was to assess activation of eosinophils as well as allergic and inflammatory reactions of the body in development of restenosis after implantation of stents with drug covering. We included into the study 32 patients with ischemic heart disease (IHD) and stable angina subjected to repeat coronary angiography during first year after endovascular myocardial revascularization with the help of stents with drug covering, and 11 healthy persons. Levels of eosinophilic cation protein (ECP), immunoglobulin E (IgE), and C-reactive protein (CRP) in blood plasma of patients and healthy persons was determined by immunoenzyme assay. According to results of angiographic study patients were divided into 2 groups: the first comprised 19 patients in whom no instent restenosis was found, the second comprised 13 patients in whom formation of restenosis at least in one stent was noted. Patients in these groups did not differ by age, sex, smokers and nonsmokers ratio, presence of hyperlipidemia, and angiographical characteristics of involved arteries. In patients with restenosis of stents blood plasma ECP level was 17.7 (11.2-24.0) g/ml and significantly higher than in patients without restenosis [9.0 (6.4-12.9) g/ml; p=0.017]. Blood level of IgE in these groups of patients did not differ [58.8 (42.1-164.0) and 52.9 (12.8-76.1) mg/ml, respectively; p=0.40] and did not differ from IgE level in blood of healthy volunteers [32.0 (21.2-80.8) mg/ml; p=0.91]. CRP level in patients with IHD was higher than in healthy volunteers [0.36 (0.1-0.75) mg/ml; p=0.0008)], but did not differ significantly in groups of patients with and without restenosis [2.38 (0.30-4.08) and 1.63 (0.61-2.47) mg/ml, respectively; p=0.52]. It was found that in the group of patients with low blood level of ECP (<11 g/ml) restenoses were revealed in 19% while in the group with higher blood level of ECP (>11 g/ml) - in 62% of cases (p=0,019). In patients subjected to coronary stenting with higher level of ECP in blood we noted more frequent development of restenoses than in patients with low level of this protein. The data obtained allow to suggest presence of relationship between development of restenosis and elevated activity of eosinophilic granulocytes in patients with IHD after revascularization.

[Stromal progenitor cells and blood leukocytes after implantation of drug-eluting stents].

Aim of the study was to assess participation in development of restenosis of circulating in blood progenitor cells of stromal line of differentiation and polymorphonuclear granulocytes. We compared levels of osteonectin positive progenitor cells, neutrophils, eosinophils, and basophils in blood of patients with ischemic heart disease (IHD) in whom according to data of angiographic study after endovascular myocardial revascularization with the help of stents with drug coating (Cypher, Cordis Corp, USA) restenosis was detected (n=15), in patients without restenosis (n=23), and in healthy persons (n=17). Levels of stromal progenitor cells and polymorphonuclear granulocytes in blood were measured with the help of methods of flow cytometry. In groups of patients with IHD with and without restenosis number of osteonectin positive cells in blood was higher than in healthy subjects (2.4+/-0.7 and 2.5+/-0.9 vs 1.5+/-0.5 cells/ microL, respectively, p=0.004) without significant differences between groups (p=0.59). These 2 groups of patients did not differ by numbers of leukocytes, neutrophils, and basophils in blood. At the same time we found that in patients with restenosis number of eosinophils in blood was significantly greater than in the group of patients without restenosis (262+/-68 vs 124+/-67 cells/ microL, respectively p<0.001). Moreover in patients with level of eosinophils exceeding 170 cells/ microL rate of development of restenosis was 74% against 5% in patients with number of eosinophils less than 170 cells/ microL (p<0.001). Thus level of stromal progenitor cells in blood of patients with IHD was higher than in healthy persons and remained equally high in groups with and without restenosis. Number of blood eosinophilic leukocytes in patients who had been subjected to coronary stenting in whom later restenosis developed was significantly higher than in patients without restenosis. The data obtained indicate at the presence of link between development of in - stent restenosis and elevated content of eosinophilic granulocytes in blood of patients with IHD.

[Effect of Type 2 Diabetes on Results of Endovascular Treatment of Ischemic Heart Disease With Drug Covered Stents (Results of 1 Year Follow-up).].

Aim of the study was to determine the impact of sirolimus-eluting stents (SES) on clinical outcomes in patients with type 2 diabetes mellitus (DM) undergoing coronary revascularisation. The study enrolled 99 diabetic patients with de novo lesions in native coronary arteries. Medically treated DM was present in 61 patients (62%), 7 (7%) of whom required insulin. 53 patients received 78 SES and 46 patients received 57 bare metal stents. The differences in clinical outcomes between diabetic patients treated with SES and bare metal stents were assessed. Major adverse cardiac events (MACE) defined as death, myocardial infarction (MI), repeat revascularizations, and recurrences of angina were analyzed at 12-month follow-up. In the SES group the rate of recurrence of angina was 17%, the rate of coronary artery bypass surgery was 3,8%, the rate of repeat coronary angioplasty was 5,7%. In the bare metal stent group the rate of recurrence of angina was 37,8%, the rate of coronary artery bypass surgery was 2,2%, the rate of MI was 4,4%, the rate of repeat coronary angioplasty was 22,2%. Implantation of SES in patients with type 2 diabetes mellitus reduces recurrence of angina and major adverse cardiac events during first year after coronary angioplasty.

[Combination therapy with fluvastatin and fenofibrate in ischemic heart disease patients with combined hyperlipidemia and type 2 diabetes]. / Kombinirovannaia terapiia fluvastatinom i fenofibratom bol'nykh ishemicheskoi bolezn'iu serdtsa i sakharnym diabetom 2-go tipa so smeshannoi giperlipidemiei.

AIM: To assess efficacy of combination therapy with fluvastatin and fenofibrate in ischemic heart disease (IHD) patients with combined hyperlipidemia and type 2 diabetes. MATERIAL: Patients with IHD and combined hyperlipidemia with (n=56)) or without type 2 diabetes (n=30). METHODS: After 8-week diet period the patients were randomized to 4 weeks monotherapy with either fluvastatin (40 mg/day) or micronized fenofibrate (200 mg/day). In patients whose low-density lipoprotein cholesterol (LDL CH) remained > 2,6 mmol/1 and triglycerides (TG) > 2.3 mmol/1 combination of fluvastatin 40 mg/day and fenofibrate 200 mg/day was used for the next 12 weeks. RESULTS: Target levels of LDL CH and TG were achieved in 75 and 88%, respectively, of diabetics, and in 73 and 88%, respectively, of non-diabetics. CONCLUSION: The use of combination of fluvastatin and fenofibrate was more effective then monotherapy for correction of lipid abnormalities in combined hyperlipidemia both in diabetics and non-diabetics with IHD.

[Effect of hormone replacement therapy on blood serum lipids in postmenopausal women with type 2 diabetes]. / Dinamika pokazatelei lipidnogo obmena pod vliianiem zamestitel'noi gormonal'noi terapii u zhenshchin v postmenopauze s sakharnym diabetom 2-go tipa.

There are limited data concerning influence of hormone replacement therapy (HRT) on lipid profile in women with type 2 diabetes. Aim of the study was to compare changes of blood lipids during HRT in postmenopausal women with and without type 2 diabetes. Seventy seven women included in the study were assigned to 1 of 4 groups, basing on being diabetic or nondiabetic, and further subdivided into users of estrogen alone (ERT), and of estrogen plus progestin (EPRT). Effect of 6-month ERT (oral estradiol valerate 2 mg/day) and EPRT (oral estradiol valerate 2 mg/day sequentially combined with cyproterone acetate 1 mg/day) on total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides and lipoprotein (a) [Lp(a)] was separately assessed. EPRT and ERT caused decrease in LDL-C by 15% and 12%, and increase in HDL-C by 12% and 13%, respectively, in patients with diabetes (p<0.05 in all cases). LDL-C decreased by 11% and 15%, respectively, in women without diabetes (p<0.05 in all cases). Lp(a) was also reduced 25% with EPRT (p<0.01) and ERT (p<0.05). HDL-C increased 10% (p<0.05) with ERT but remained unchanged with EPRT. In conclusion, changes in all lipid parameters except Lp(a) caused by ERT and EPRT were comparable in postmenopausal women with and without type 2 diabetes.

Autoantibodies to gangliosides in sera of atherosclerotic patients.

Using ELISA we studied the levels and clinical correlation of serum antibodies against gangliosides and 5-hydroxytryptamine (5-HT) in patients with atherosclerosis and clinical manifestations of cardiovascular disease. A range of 70-80% of the patients showed higher titers of anti-GM3(L) and anti-5HT as compared to normal serum. The anti-GM3(L) antibodies appeared to be directed mainly against GM3 present in platelets and were much less reactive against GM3 isolated from the aorta. We concluded that the antigens responsible for the elevated anti-GM3(L) and anti 5-HT levels in atherosclerotic sera are released by vessel-wall activated platelets. These results provide further evidence of on-going autoimmune processes in atherosclerosis. The content of total sialic (TS) and lipid-bound sialic acid (LBS) was measured in sera of patients with IHD and of similar numbers of healthy donors. In the patient groups the average TS and LBS concentration was about 25% higher than in the control group. These changes appeared to be associated with higher degrees of protein sialylation and larger amounts of LDL in the patient sera than in those of healthy controls.