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Safarova M.S.,Russian Cardiology Scientific and Production Center | Trukhacheva E.P.,Russian Cardiology Scientific and Production Center | Ezhov M.V.,Russian Cardiology Scientific and Production Center | Afanasieva O.I.,Russian Cardiology Scientific and Production Center | And 4 more authors.
Kardiologiya | Year: 2011

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 (HDLAC), Lp(a), lipoprotein Aassociated phospholipase A2 (Lp-PL-2), high-sensitivity C-reactive protein (hsCRP), complex of tissuetype 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.

Dergilev K.V.,Russian Cardiology Scientific and Production Center | Rubina K.A.,Russian Cardiology Scientific and Production Center | Parfenova E.V.,Russian Cardiology Scientific and Production Center
Kardiologiya | Year: 2011

The search for sources of stem/progenitor cells the use of which has a potential to affect course of ischemic heart disease and chronic heart failure is conducted nowadays in many countries. Resident cardiac stem cells (CSC) were revealed during recent years on the basis of expression of c-kit, sca-1, MDR1, and islet-1 markers. In vitro experiments demonstrated possibility of their differentiation into cardiomyocytes, smooth muscle cell and endothelial cells. Introduction of CSC in injured myocardium in animals facilitated its partial repair and short term improvement of cardiac function. This holds promise for the use of these cells in the future. In the review we have attempted to summarize literature data on resident CSC and their application for the treatment of heart diseases. Key words: cardiac stem cells; c-kit cells; sca-1 cells; side population cells; islet-1 cells; cardiospheres.

Khayutini V.M.,Russian Cardiology Scientific and Production Center | Lukoshkova E.V.,Russian Cardiology Scientific and Production Center | Ermishkin V.V.,Russian Cardiology Scientific and Production Center | Sonina R.S.,Russian Cardiology Scientific and Production Center
Kardiologiya | Year: 2010

History of development of the method of measurement of duration of the preelection (DPE) period - characteristic of left ventricular (LV) contractility is presented. On the basis of physiological prerequisites a novel computerized method of DPE measurement in each consecutive cardiocycle has been created. Distinct features of this method are: 1) principle of measurement - tetrapolar impedancemetry, with signal electrodes located along projection of the ascending aorta, one in the center of presternum, second - 5 cm caudally; 2) starting point for DPE counting - the point on ascending portion of R-wave of electrocardiogram at which the first derivative of ECG signal reaches maximum, stopping point - the point of maximum of the second derivative of the primary impedance signal on the ascending front of its pulse wave. The method has been tested on healthy people for 10 functional tests. The results are presented characterizing dynamic peculiarities of changes of LV contractility during veloergometer exercise test with staderly increasing work load and reflecting development of positive inotropic action of sympathetic nervous system. Special characteristics of this action: small concealed period, preservation of achieved elevated level during lowering of work load (before its switching off) and subsequent slow (compared with chronotropic effect) diminution, as well as turning on at low loads.

Ezhov M.V.,Russian Cardiology Scientific and Production Center | Safarova M.S.,Russian Cardiology Scientific and Production Center | Afanasieva O.I.,Russian Cardiology Scientific and Production Center | Il'ina L.N.,Russian Cardiology Scientific and Production Center | And 2 more authors.
Kardiologiya | Year: 2011

Study aim was to investigate the association of lipoprotein (a) [Lp(a)] level with the development of cardiovascular complications in longterm 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 (Ml), 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 Ml 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/l, 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 Ml A 1,01 (95% CI 1.00 to 1.02; p=0.02). RR of development of Ml 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 Ml during 10 years after CABG.

Kuzmin V.S.,Russian Cardiology Scientific and Production Center | Rosenshtraukh L.V.,Russian Cardiology Scientific and Production Center
Kardiologiya | Year: 2010

In this review we discuss mechanisms of antiarrhythmic and adverse proarrhythmic action of class III drugs. Special attention is given to ionic currents and channels which determine specific features of their effects (1 Kr' 1Ka' 1Kur). We consider general patterns of changes of bioelectrical activity in atria and ventricles leading to development of arrhythmias or stabilization of rhythm. We also discuss value of QT-interval as predictor of torsade de pointes. Perspectives and limitations of development of novel class III antiarrhythmic drugs are discussed as well. We present consideration of efficacy and mechanisms of action of such compounds as dronedarone and vernacalant suggested for termination of atrial fibrillation and maintenance of sinus rhythm. Special attention is given to RG-2 - a novel compound with class III activity.

Shakhmatova O.O.,Russian Cardiology Scientific and Production Center | Komarov A.L.,Russian Cardiology Scientific and Production Center | Panchenko E.P.,Russian Cardiology Scientific and Production Center
Kardiologiya | Year: 2010

Classical risk factors of development of cardiovascular diseases does not allow to detect all persons needing active prevention. Because of this reason great attention is given to novel biomarkers one of which is homocysteine. Most widely-spread causes of elevation of homocysteine level are such factors as deficit of folic acid and B6 and B12 vitamins, as well as genetic peculiarities. Main damaging effect of homocysteine is activation of atherothrombosis. Therapy with folic acid causes significant lowering of homocysteine level. Effect of therapy with vitamins on the risk of development of cardiovascular diseases has been assessed both in observational epidemiological studies and large prospective randomized trials. Their results are controversial. The present review is devoted to the analysis of these trials.

Gabbasov Z.A.,Russian Cardiology Scientific and Production Center | Kozlov S.G.,Russian Cardiology Scientific and Production Center | Saburova O.S.,Russian Cardiology Scientific and Production Center | Titov V.N.,Russian Cardiology Scientific and Production Center | Lyakishev A.A.,Russian Cardiology Scientific and Production Center
Kardiologiya | Year: 2010

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/pL, 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/uL, respectively p<0.001). Moreover in patients with level of eosinophils exceeding 170 cells/pL rate of development of restenosis was 74% against 5% in patients with number of eosinophils less than 170 cells/pL (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 diveloped 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.

Ageev F.T.,Russian Cardiology Scientific and Production Center | Makarova G.V.,Russian Cardiology Scientific and Production Center | Patrusheva I.F.,Russian Cardiology Scientific and Production Center | Orlova Ya.A.,Russian Cardiology Scientific and Production Center
Kardiologiya | Year: 2010

The study was aimed to assess the efficacy and safety of treating coronary heart disease (CHD) patients complicated with COPD using the combination of tolerable doses of β-blocker bisoprolol and inhibitor If-channel ivabradine, compared with bisoprolol alone. A total of SO patients were included (88% men, mean age 62.8±7.2 years) with stable angina and clinical signs of bronchoobstruction (84% with COPD and 16% with bronchial asthma in remission phase). At the study start, all patients received bisoprolol, the dose of which was titrated until the clinical signs of intolerance (most common - bronchoobstruction) appeared or worsened. Average dose of bisoprolol at the time of forced titration stop was 6.3±2.2 mg/day, mean heart rate (HR) decreased from 82.1±8.4 to 72.2±8.5 bpm. Then, the patients were randomized into two groups: patients of the first group (n=25) continued to take bisoprolol in tolerable dose, and patients of the second group were added ivabradine (5-15 mg, mean dose 10.7± 3.1 mg/day). In contrast to the bisoprolol alone, combination therapy resulted in further decrease of HR to an average of 62.6±4.1 bpm over 6 month of follow-up. This was associated with additional decrease of the number of angina attacks (by 4.68±4.40 per week vs. 2.48±4.70, p<0.05), nitrates consumption (by 206.0±153.6 mg/week vs. 95.6±134.2 mg/week, p<0.01) and score of negative components of quality of life (by 5.16±3.3 vs. 2.24±4.5, p<0.05), compared with the first group, respectively. In combination therapy group there was also the decrease of the inhaled broncholytics consumption (from 2.88±3.23 to 1.88±2.65 per week, p<0.05), that was not evident in the first group. Average number of hospitalizations per 1 patient decreased over 6 months of follow-up, compared to the same period before the trial, in both groups, but more prominently in the combination therapy group (-0.31±0.55 vs. -0.56±0.76, accordingly, p<0.1). Therefore, in the treatment of patients with CHD, stable angina and concomitant bronchoobsrtuctive manifestations, if not possible to administer β-blockers in the adequate HRAreducing dose, the addition of ivabradine to the treatment could be the treatment of choice. The combination of tolerable doses of bisoprolol and ivabradine is safe and allows to achieve adequate HR decrease. This is associated with maximal antianginal effect, decrease in the need for broncholytic therapy, improvement of the quality of life and decrease of the number of hospitalizations, compared with - the treatment with bisoprolol alone.

PubMed | Russian National Research Medical University and Russian Cardiology Scientific and Production Center
Type: Journal Article | Journal: Molekuliarnaia biologiia | Year: 2016

Carriage frequencies of alleles and genotypes of polymorphic loci of inflammation genes (49A>G CTLA4, 41G>A and 87C>T PDE4D, -590C>T IL4, -308A>G TNF, 252G>A LTA, 874A>T IFNG, -509>, 869T>C and 915G>C TGFB1) were determined in a sample of 200 patients diagnosed with ischemic stroke and in the control group similar in gender and age (146 individuals), all ethnic Russians. The positive association of the allele PDE4D*87C ( = 0.028) and genotype TGFB1*-509/ ( = 0.02) carriage with ischemic stroke was shown. The association of the disease with the carriage of the allele PDE4D*41 ( = 0.009) in individuals under the age of 60 and with carriage of the allele IFNG*874 ( = 0.02) in individuals older than 60 was observed among the subgroups of patients stratified by age when they suffered the stroke compared to a control group of the same age. In subgroups stratified by gender, carriage of the genotype TGFB1*915G/G ( = 0.0015) was identified as a risk factor in male patients, while no significant differences between female patients and healthy women were observed. Multilocus analysis was undertaken to search for the association of several combinations of studied gene variants with ischemic stroke. The polymorphic locus-174G>C of the IL6 gene, for which an association with the disease was previously demonstrated, was also included in this analysis. The disease-predisposing biallelic combinations include the IL6*-174G, PDE4D*87C, TGFB1*-509 and TGFB1*915G alleles. In the subgroups stratified by gender, the allelic combinations mainly include the similar risk alleles as in the total group, while between the subgroups stratified by age (patients who suffered the first stroke at the age of 18 and no older than 60 years and older than 60 years), greater differences were observed. However, a new risk allele, LTA*252G, was identified in combination with PDE4D*41 in women. These findings demonstrate the important role of inflammation in ischemic stroke. The identified single and combined markers may be used further to determine an individual risk for ischemic stroke.

PubMed | Russian Cardiology Scientific and Production Center
Type: Journal Article | Journal: Acta naturae | Year: 2012

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Proteins of the immune system, as well as proteins that are involved in the infiltration of activated immune cells in the CNS, play an important role in the pathogenesis of MS. We investigated the association and linkage with MS of the following immune-system genes polymorphisms: HLA-DRB1,CTLA4,TGFB1,IL4,CCR5 andRANTES, as well as of the matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1) genes polymorphisms. For this purpose we used the transmission disequilibrium test (TDT). The group investigated was comprised of 100 nuclear families of Russian ethnicity, each consisting of an affected offspring and his nonaffected parents. It was found that HLA-DRB1*15alleleandMMP9*-1562C allele were transmitted from healthy heterozygous parents to affected children more frequently than alternative alleles (p = 0.02 andp = 0.04, respectively). Another family-based method, AFBAC (affected family-based control), showed MS association with HLA-DRB1*15, but not with theMMP9*-1562C allele.

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