Institute of Clinical Cardiology

Moscow, Russia

Institute of Clinical Cardiology

Moscow, Russia

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Buryachkovskaya L.,Institute of Experimental Cardiology | Sumarokov A.,Institute of Clinical Cardiology
Inflammation Research | Year: 2013

Introduction Historical overview of development investigations on inflammation in Russia up to date is presented. Material and methods Analysis of modern Russian language literature (1950-2010) on history of medicine and researchers' activity on inflammation, as well as Russian language content of internet on this theme, was made. Many names of Russian researchers are still little known to the English-speaking Western readers. Results Starting in the eighteenth century, the mystery of the inner workings of the inflammation process attracted the interest of physicians and biologists of the Russian Empire. Accumulated knowledge focused mainly on the etiological factors of inflammation. In the nineteenth century, scientific schools emerged for studying inflammation and established close contacts with leading scientists in other countries. At this time, Ilya Mechnikov formulated his famous biological theory of inflammation, according to which inflammation is a protective adaptation response to an injury. He also developed his teaching on phagocytosis and was awarded the Nobel Prize. In the twentieth century, Russian scientists participated in the discovery of viruses and new bacterial pathogens, and in the investigation of the mechanics of the genesis and development of inflammatory processes. Conclusion Today interest in studies of inflammation in Russia is on the increase; scientists united by the Russian Inflammation Society continue their quest to investigate inflammatory mediators, and study molecular and cellular mechanisms and approaches in the treatment of complications associated with inflammation. © Springer Basel 2013.


Lonn E.M.,Hamilton Health Sciences | Lonn E.M.,McMaster University | Bosch J.,Hamilton Health Sciences | Bosch J.,McMaster University | And 38 more authors.
New England Journal of Medicine | Year: 2016

BACKGROUND Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear. METHODS In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years. RESULTS The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P = 0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P = 0.02 and P = 0.009, respectively, for trend in the two outcomes). CONCLUSIONS Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. Copyright © 2016 Massachusetts Medical Society. All rights reserved.


Yusuf S.,Hamilton Health Sciences | Yusuf S.,McMaster University | Lonn E.,Hamilton Health Sciences | Lonn E.,McMaster University | And 36 more authors.
New England Journal of Medicine | Year: 2016

BACKGROUND Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially. METHODS In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years. RESULTS The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P = 0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P = 0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups. CONCLUSIONS The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. Copyright © 2016 Massachusetts Medical Society. All rights reserved.


Yusuf S.,Hamilton Health Sciences | Yusuf S.,McMaster University | Bosch J.,Hamilton Health Sciences | Bosch J.,McMaster University | And 35 more authors.
New England Journal of Medicine | Year: 2016

BACKGROUND Previous trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease. Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons. It is unclear whether the benefits of statins can be extended to an intermediate-risk, ethnically diverse population without cardiovascular disease. METHODS In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included revascularization, heart failure, and resuscitated cardiac arrest. The median follow-up was 5.6 years. RESULTS The overall mean low-density lipoprotein cholesterol level was 26.5% lower in the rosuvastatin group than in the placebo group. The first coprimary outcome occurred in 235 participants (3.7%) in the rosuvastatin group and in 304 participants (4.8%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.64 to 0.91; P = 0.002). The results for the second coprimary outcome were consistent with the results for the first (occurring in 277 participants [4.4%] in the rosuvastatin group and in 363 participants [5.7%] in the placebo group; hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P<0.001). The results were also consistent in subgroups defined according to cardiovascular risk at baseline, lipid level, C-reactive protein level, blood pressure, and race or ethnic group. In the rosuvastatin group, there was no excess of diabetes or cancers, but there was an excess of cataract surgery (in 3.8% of the participants, vs. 3.1% in the placebo group; P = 0.02) and muscle symptoms (in 5.8% of the participants, vs. 4.7% in the placebo group; P = 0.005). CONCLUSIONS Treatment with rosuvastatin at a dose of 10 mg per day resulted in a significantly lower risk of cardiovascular events than placebo in an intermediate-risk, ethnically diverse population without cardiovascular disease. Copyright © 2016 Massachusetts Medical Society. All rights reserved.


Mentz R.J.,Duke University | Cotter G.,Momentum Research Inc. | Cleland J.G.F.,University of Hull | Stevens S.R.,Duke Clinical Research Institute | And 15 more authors.
European Journal of Heart Failure | Year: 2014

Aims The implications of geographical variation are unknown following adjustment for hospital length of stay (LOS) in heart failure (HF) trials that included patients whether or not they had systolic dysfunction. We investigated regional differences in an international acute HF trial. Methods and results The PROTECT trial investigated 2033 patients with acute HF and renal dysfunction hospitalized at 173 sites in 17 countries with randomization to rolofylline or placebo. We grouped enrolling countries into six regions. Baseline characteristics, in-hospital management, and outcomes were explored by region. The primary study outcome was 60-day mortality or cardiovascular/renal hospitalization. Secondary outcomes included 180-day mortality. Of 2033 patients, 33% were from Eastern Europe, 19% from Western Europe, 16% from Israel, 15% from North America, 14% from Russia, and 3% from Argentina. Marked differences in baseline characteristics, HF phenotype, in-hospital diuretic and vasodilator strategies, and LOS were observed by region. LOS was shortest in North America and Israel (median 5 days) and longest in Russia (median 15 days). Regional event rates varied significantly. Following multivariable adjustment, region was an independent predictor of the risk of mortality/hospitalization at 60 days, with the lowest risk in Russia (hazard ratio 0.39, 95% confidence interval 0.23-0.64 vs. Western Europe) due to lower rehospitalization; mortality differences were attenuated by 180 days. Conclusions In an international HF trial, there were differences in baseline characteristics, treatments, LOS, and rehospitalization amongst regions, but little difference in longer term mortality. Rehospitalization differences exist independent of LOS. This analysis may help inform future trial design and should be externally validated. © 2014 European Society of Cardiology.


Sobenin I.A.,Russian Academy of Medical Sciences | Zhelankin A.V.,Russian Academy of Medical Sciences | Sinyov V.V.,Institute of Clinical Cardiology | Bobryshev Y.V.,University of New South Wales | And 2 more authors.
Gerontology | Year: 2015

Atherosclerosis is a complex disease which can be described as an excessive fibrofatty, proliferative, inflammatory response to damage to the artery wall involving several cell types such as smooth muscle cells, monocyte-derived macrophages, lymphocytes, dendritic cells and platelets. On the other hand, atherosclerosis is a typical age-related degenerative pathology, which is characterized by signs of cell senescence in the arterial wall including reduced cell proliferation, irreversible growth arrest and apoptosis, increased DNA damage, the presence of epigenetic modifications, shortening of telomere length and mitochondrial dysfunction. The most prominent characteristics of mitochondrial aging are their structural alterations and mitochondrial DNA damage. The mechanisms of mitochondrial genome damage in the development of chronic age-related diseases such as atherosclerosis are not yet well understood. This review focuses on the latest findings from studies of those mutations of the mitochondrial genome which may play an important role in the development of atherosclerosis and which are, at the same time, also markers of mitochondrial aging and cell senescence. © 2014 S. Karger AG, Basel.


Mironov N.Yu.,Institute of Clinical Cardiology | Golitsyn S.P.,Institute of Clinical Cardiology
Kardiologiya | Year: 2013

Potassium channels and currents play essential roles in cardiac repolarization. Potassium channel blockade by class III antiarrhythmic drugs prolongs cardiac repolarization and results in termination and prevention of cardiac arrhythmias. Excessive inhomogeneous repolarization prolongation may lead to electrical instability and proarrhythmia (Torsade de Pointes tachycardia). This review focuses on molecular structure, physiology, pathophysiology and therapeutic potential of potassium channels of cardiac conduction system and myocardium providing information on recent findings in pathogenesis of cardiac arrhythmias, including inherited genetic abnormalities, and future perspectives.


Tsyplenkova V.G.,Institute of Clinical Cardiology
Kardiologiya | Year: 2013

Endomyocardial biopsies performed in patients with various forms of cardiomyopathies (CMP) and chronic myocarditis in the presence of heart failure identified changes indicative of reduction of functioning cardiomyocytes (CMC) at the account of their destruction, dedifferentiation and inefficient hypertroph". Energy apparatus of CMC was represented by large masses of destructed small mitochondria. Myofibrils were driven to periphery of CMC and appeared atrophic. Products of catabolism (lipofuscin, autophagous vacuoles, protein conglomerates) were accumulated in CMC. This led to impairment of CMC main function - to exert contraction. Reduction of number of capillary vessels per unit of myocardial cross-section area was also found. Discussion of problems of morphogenesis of the observed changes and of pathogenetic treatment is presented in the article.


Dmitriev L.F.,Institute of Clinical Cardiology
Klinichescheskaya Laboratornaya Diagnostika | Year: 2015

The control of cellular metabolism is present in many organs and tissues and its loss means development of hypo- and hyperglycemia. The high level of glucose results in glycation of proteins and increase of concentration of ketoaldehyde and methyl glyoxal in cells. The increase of level of this ketoaldehyde and D-lactate in organs and tissues also can be a result of formation of methyl glyoxal in particular enzymatic reactions including decomposition of one of substrates of glycolysis and conversion of aminoacetone catalyzed by semicarbazide-sensitive amine oxydase of endothelium cells. The methyl glyoxal attacks arginine residuals of proteins. This aldehyde is related to interruption in transmission of insulin signal, disorder of pro-antioxidant balance, inhibition of enzymes of glycolysis, etc. The model of cellular metabolism is proposed where methyl glyoxal plays a key role in development of resistance to insulin, hyperglycemia, hypokalemia and hypertension. The modes of increase of consumption of glucose in conditions of low activity of protein tyrosine kinase are considered. The possible involvement of tokopherol (its derivatives) in activation of phosphodiesterase in liver and regulation of carbohydrate metabolism is considered too. The role of tokopherol-carrier proteins and effect of tokopherol on functioning of OI-cells is discussed. It is still unclear if there is a direct relationship between low level of tokopherol-carrier proteins and diabetes or hypertension. However, low level of tokopherol-carrier proteins results in "prolonged oxidative stress".


PubMed | Institute of Clinical Cardiology and Astrazeneca
Type: Journal Article | Journal: Current medical research and opinion | Year: 2016

The OPTIMA II study sought to evaluate rates of major adverse cardiac and cerebrovascular events (MACCEs) during the long-term follow-up of chronic statin users who underwent percutaneous coronary intervention (PCI) with implantation of a drug-eluting stent (DES).OPTIMA II was a non-interventional, observational study conducted at a single center in the Russian Federation. Included patients were aged 18 years with stable angina who had received long-term (1 month) statin therapy prior to elective PCI with DES implantation and who had participated in the original OPTIMA study. Patients received treatment for stable angina after PCI as per routine study site clinical practice. Study data were collected from patient medical records and a routine visit 4 years after PCI.NCT02099565.Rate of MACCEs 4 years after PCI.Overall, 543 patients agreed to participate in the study (90.2% of patients in the original OPTIMA study). The mean ( standard deviation [SD]) duration of follow-up from the date of PCI to data collection was 4.420.58 (range: 0.28-5.56) years. The frequency of MACCEs (including data in patients who died) was 30.8% (95% confidence interval: 27.0-34.7); half of MACCEs occurred in the first year of follow-up. After PCI, the majority of patients had no clinical signs of angina. Overall, 24.3% of patients discontinued statin intake in the 4 years after PCI. Only 7.7% of patients achieved a low-density lipoprotein (LDL) cholesterol goal of <1.8mmol/L. Key limitations of this study related to its observational nature; for example, the sample size was small, the clinical results were derived from outpatients and hospitalized medical records, only one follow-up visit was performed at the end of the study (after 4 years follow-up), only depersonalized medical information was made available for statistical analysis, and adherence to statin treatment was evaluated on the basis of patient questionnaire.Long-term follow-up of patients who underwent PCI with DES implantation demonstrated MACCEs in nearly one-third of patients, which is comparable to data from other studies. PCI was associated with relief from angina or minimal angina frequency, but compliance with statin therapy and the achievement of LDL cholesterol targets 4 years after PCI were suboptimal.

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