[Influence of intensive hypolipidemic therapy on blood concentration of lipoprotein-associated phospholipase A2 in patients with ischemic heart disease].

AIM: To assess the impact of combined treatment with simvastatin and ezetimibe or treatment with simvastatin only on lipoprotein-associated phospholipase A2 in patients with ischemic heart disease. METHODS: One hundred patients with angiographically documented coronary atherosclerosis took part in the investigation. Lp-PLA2 mass and cholesterol fractions were determined at baseline and after 6 months of treatment. Lp-PLA2 mass was determined by enzyme immunoassay method, using two highly specific monoclonal antibodies. RESULTS: Combined treatment with ezetimibe and simvastatin led to significantly greater declines in Lp-PLA2 and cholesterol fractions compared with treatment only with simvastatin: Lp-PLA2 decreased by 46 vs 38%, total cholesterol by 35 vs 28%, LDL cholesterol by 50 vs 40%, respectively (p<0.05). Combination therapy with ezetimibe and simvastatin 20 and 40mg/day proved to be as effective as monotherapy with simvastatin 80 mg/day on the effect on Lp-PLA2 mass and cholesterol fractions (p<0.05). Lp-PLA2 correlated positively with total cholesterol (r=0.28) and LDL-C (r=0.33). CONCLUSIONS: Combined treatment led to greater reduction of total cholesterol and LDL-C, as well as significantly reduced level of Lp-PLA2 mass. The latter can be considered as target for suppression of inflammation and achievement of stabilization of atherosclerotic plaque.

[Myocardial infarction secondary to blunt chest trauma in a man of 25 years].

This paper describes the clinical case - anterior myocardial infarction after blunt chest trauma in a 25-year-old man.

[Clinical role of lipoprotein-associated phospholipase A2].

Inflammation plays an important role in origin and progression of atheromatous plaque. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered a biomarker of inflammation and a predictor of vascular events. Lp-PLA2 is an enzyme secreted by leukocytes and associated with circulating lipoproteins and macrophages in atherosclerotic plaques. Lp-PLA2 hydrolizes phospholipids of oxidized low density lipoproteins and generates two proinflammatory mediators, lysophosphatidylcholine and oxidized nonesterified fatty acids, which play a major role in the development of atherosclerotic lesions, myocardial infarction and ischemic stroke. Recently the first publications appeared about selective inhibitor of phospholipase A2 - darapladib as a novel therapeutic approach for the treatment of patients with coronary artery disease. However, first results need to be confirmed by ongoing large long-term randomized clinical trials.

[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.

[High level of lipoprotein (a) as a predictor of poor long-term prognosis after coronary artery bypass surgery].

Study aim was to investigate the association of lipoprotein (a) [Lp(a)] level with the development of cardiovascular complications in long-term follow-up period after coronary artery bypass grafting (CABG). Patients with chronic ischemic heart disease (IHD) (n = 361, 88% men, mean age 55 +/- 9 years) who had had CABG were included in the study. Before surgery we assessed presence of classical risk factors, left ventricular ejection fraction, concentrations of lipids and Lp(a) in blood serum. During follow-up (from 1 to 140, mean 66 +/- 34 months) we registered cardiac deaths, nonfatal myocardial infarctions (MI), strokes, repeat procedures of revascularization, and hospitalizations due to relapse or progression of angina pectoris. Information on prognosis was obtained from 263 patients. In 109 of them we registered 142 serious events including cardiac death n = 20 (14%), nonfatal MI n = 14 (10%), myocardial revascularization (n = 35), 29 (20%) with stenting), repeat CABG n = 6 (4%), hospitalization due to angina pectoris n = 53 (37%), stroke n = 4 (3%), noncardiac outcome n = 16 (10%). In subjects with hyperlipidemia (a) [HLp(a) - Lp(a) > 30 mg/l] survival after CABG was lower (log rank p < 0.001): 11 of 93 (11.3%) and 9 of 170 (5.2%) patients died among those with Lp(a) > 30 and < 30 mg/I, respectively. Relative risk (RR) of any cardiovascular complication was 3.24 (95% confidence interval [CI] 2.18 to 4.83, p < 0.001), of death - 2.89 (95% CI 1.31 to 6.35, p < 0.01), and of MI A 1.01 (95% CI 1.00 to 1.02; p = 0.02). RR of development of MI and cardiac death in patients with HLp(a) in 5 years was 2.61 (95% CI 1.11 to 5.74; p = 0.02), in 10 years - 2.95 (95% CI 1.50 to 5.79; p < 0.001). In patients with chronic IHD high level of Lp(a) can serve as independent predictor of unfavorable events including death and nonfatal MI during 10 years after CABG.

[Pleiotropic effects of nicotinic acid therapy in men with coronary heart disease and elevated lipoprotein(a) levels].

PURPOSE: To assess effects of niacin on risk factors of atherosclerosis in men with coronary heart disease (CHD) and high lipoprotein(a) [Lp(a)] levels. MATERIAL AND METHODS: Sixty men (mean age 54+/-6 years) with angiographic evidence of CHD were randomized into two groups. Active group (n=30) received extended release nicotinic acid 1500 mg, control group consisted of remaining 30 patients. All patients received basic therapy with atorvastatin 10-40 mg qd. Blood samples were collected for total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), Lp(a), lipoprotein-associated phospholipase A2 (Lp-PL-2), high-sensitivity C-reactive protein (hsCRP), complex of tissue-type plasminogen activator with plasminogen activator inhibitor type 1 (tPA/PAI-1). Carotid intima media thickness (CIMT) was measured at baseline and after 6-months therapy. RESULTS: There was no statistically significant difference between the groups in the clinical and biochemical characteristics. During the study lipid profile data were within the target levels. In the active group median percent decrease of Lp(a) level was 23% (from 84+/-40 to 67+/-25 mg/dl after 6 weeks and up to 65+/-37 mg/dl after 6 months of treatment, p<0.01); LDL-C, TG, tPA/PAI-1, and Lp-PL-2 mass levels decreased by 25, 20, 25, and 32%, respectively; HDL-C increased by 16% (p<0.05 vs baseline, respectively). Nicotinic acid treatment produced statistically significant reduction nicotinic acid of the mean CIMT (right: 0.83+/-0.16 vs 0.77+/-0.17 mm, p<0.05; left: 0.88+/-0.21 vs 0.82+/-0.17, p<0.05). In control group no changes of CIMT or blood tests were observed. CONCLUSION: In men with CHD and Lp(a) excess of addition to atorvastatin results in regression of CIMT on an average of 0.06 mm in 6 months. Such rapid and significant effect on the arterial wall structure can be attributed to the complex influence of nicotinic acid on Lp(a), lipids, Lp-PL-2 and thrombogenic factors. This is the first study providing the evidence of using Lp(a) as one of therapeutic targets in patients with high Lp(a) levels for achieving beneficial effect on a surrogate marker of atherosclerosis.

[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.

[Immediate results of endovascular treatment of coronary arteries in patients with ischemic heart disease].

AIM: To assess immediate results of percutaneous coronary interventions (PCI) and finding the predictors of the successful outcomes in various subgroups of patients with coronary artery disease (CAD). MATERIAL: Patients (n=1066, (average age 55.7+/-9.2 years, women 12%) treated with coronary artery stenting between 1999 and 2004. According to coronary angiography, 383 (36%) patients had 1-vessel, 502 (47%) - 2-vessel, and 181 (17%) - 3-vessel CAD. The endovascular treatment was made on 1694 coronary stenoses (in average 1.6 stenosis/patient), 356 stenoses (21%) was defined as type A, 745 (44%) - type capital B, and 593 (35%) - type C. PCI was performed with use of inhibitors of glycoprotein receptors IIb/IIIa in 107 (18%) patients. RESULTS: The complete or partial immediate procedural success of PCI (elimination of at least one coronary stenosis) was achieved in 1002 (94%) patients. The immediate success was achieved in 1575 stenoses (93%). Total rate of major adverse cardiac events (MACE) was 1.3%. There were no deaths, 11 patients (1%) had acute myocardial infarctions, 3 (0.28%) patients had an emergent coronary artery bypass grafting. The immediate procedural success was significantly lower in patients with chronic coronary occlusions (76%) than in patients without coronary occlusions (97%, p<0.0001), as well in patients with stenoses type C as compared with stenoses type A, and B (success rate 77%, 98% and 100%, accordingly, p<0.0001). CONCLUSION: By multifactorial analysis, independent predictors of procedural failure were stenosis type C (small p<0.0001) and chronic occlusion of coronary artery (p=0,03).

[An experience of the use of stents with drug coating in patients with long and diffuse coronary artery lesions].

Treatment of long and diffuse lesions of coronary arteries remains one of most complicated sections of endovascular treatment. From 2003 to 2005 treatment with the use of stents with drug coating was conducted in 198 patients with long and diffuse coronary artery lesions. This made up 26% of total number of patients subjected to percutaneous coronary intervention during this time. Mean age of patients was 58 +/- 11 years, 164 (83%) of them were men, 37 (19%) had chronic occlusions of coronary arteries, in 91 (46%) side branches went out from the damaged segment. Patients were divided in two groups: 1st (n=136) comprised patients with lesion length from 22 to 33 mm, 2nd consisted of patients in whom lesion length exceeded 33 mm. Control group comprised 54 patients with lesion length less than 23 mm subjected to endovascular treatment with the use of stents with drug coating during same period of time. Average length of stented segment was 27.3 +/- 3.6 mm in the first group, 44.5 +/- 9.8 mm in the second group and 14 +/- 3.6 in the control group. Immediate success of the procedure was somewhat lower in group II compared with group I (87 and 91%, respectively). Hemopericardium and cardiac tamponade requiring urgent surgery developed in 2 group II patients (3.2%) during first 2 hours after attempt of recanalization of long chronic occlusions of the anterior descending artery. One patient (1.6%) had small-focal myocardial infarction after procedure, in another patient (1.6%) subacute occlusion developed after stenting of venous graft to the right coronary artery which we failed to eliminate. In the first group in 2 patients (1.4%) small-focal myocardial infarction developed. There were no complications in the control group. In 8 months after procedure angiographic restenosis developed in 6 patients (5%) in the 1st group, in 4 (8%) in the second and in 1 (2%) in the control group, however differences were not significant. Rates of repeat revascularizations of the target stenosis were 3, 5 and 0%, respectively. Of 10 cases of restenosis in patients with long stenoses in 5 cases restenosis was located inside stent and was focal (length less than 10 mm), in 3 cases it was located proximal or distal to stent, and in 2 patients manifested as complete occlusion of the stented segment. Treatment of long and diffuse lesions with the use of stents with drug coating appears safe and effective. Overall rate of development of perioperative complications is higher in treatment of stenoses longer than 33 mm compared with stenoses with length 23-33 cm (6.4 vs. 1.4%). Probability of restenosis and repeat revascularization of target stenosis after 8 months is not high.

[Coronary calcium and statins therapy].

AIM: Assessment of the dynamics of coronary calcium score (CCS) evaluated with electron-beam tomography (EBT) under the influence of statin therapy in patients with coronary heart disease (CHD) and hyperlipidemia. MATERIAL AND METHODS: A total of 119 hyperlipidemic CHD patients (mean age 62.1 +/- 9.3 years, 75% males) were included in the study. 69 patients were treated with statins (the study group), 50 patients rejected statins (the control group). CCS was calculated according to Agatson. Initial study parameters in the groups were similar. Mean follow-up was 25.3 +/- 10.6 months. RESULTS: A mean increase of CCS in the study group was 62 +/- 84 units (27.1%) and 122 +/- 180 units (65.2%) in the control group (p = 0.044). Total plasma cholesterol (TC) in the study group decreased by 25.1% from 6.99 +/- 0.92 to 5.24 +/- 0.54 mmol/l), in the control group--by 0.5% (from 6.67 +/- 1.01 to 6.63 +/- 1.0 mmol/l). A weak but significant negative correlation was found between a fall in total cholesterol and CCS increment (r = -0.243, p = 0.008). CONCLUSION: Calcium scoring with EBT or multispiral computed tomography can be used both for pre-clinical diagnosis of coronary atherosclerosis and for monitoring of coronary atherosclerosis progression under influence of hyperlipidemic therapy.

[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.