[Risk of Stroke After Exacerbation of Ischemic Heart Disease: Data of 3­Years Follow-up].

PURPOSE: to analyze possible associations of clinical and genetic factors with development of ischemic stroke after exacerbation of ischemic heart disease (IHD). MATERIALS AND METHODS: The Russian multicenter study aimed at assessment of risk of unfavorable outcomes after exacerbation of IHD "Exacerbation of IHD: logical probabilistic ways to course prognostication for optimization of treatment" (meaning of Cyrillic acronym - oracle) was conducted in 16 centers of 7 cities in Russia. We included into the study 1 208 patients with unstable angina and ST-elevation or non-ST-elevation myocardial infarction (MI). Data on outcomes were known for 1 193 patients, 15 patients were lost for follow-up. RESULTS: Mean duration of follow-up was 644±14.45 (4-1 995) days. Shortest, longest, and mean time before development of stroke was 22, 1433 and 389±56.6 days after inclusion. Patients with strokes were older, more often had history of IHD prior to index hospitalization, arterial blood pressure level compatible with stage 3 arterial hypertension, less often were smokers, and more often had MI recurrences or repetitive episodes of severe ischemia during the index hospitalization. Patients also more often had documented atrial fibrillation during hospitalization, and lower level of glomerular filtration rate. Of studied genetic markers carriage of A allele of polymorphic marker G (-1082) A of interleukin-10 gene was significantly associated with risk of stroke development. Using linear regression analysis, we constructed a model of estimation of the stroke development risk. Comparison of diagnostic value of different scales for stroke risk assessment showed that area under the curve was 0.656, 0.686, and 0.756 for the GRACE, CHA2DS2­VASc, and ORACLE scores, respectively.

[Genetic Features of Factors of Inflammation and Fibrosis Possible Common Pathway of Formation of Predisposition to Atrial Fibrillation and Chronic Obstructive Pulmonary Disease].

Atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD) have common pathogenetic mechanisms. It is obvious that hereditary predisposition also increases risk of both diseases. In this context consideration of genetic risk factors will enable in perspective distinguishing a group at highest risk among patients with COPD and become a basis for elaboration of novel approaches to treatment.

[Biomarkers in Heart Failure: Apelin Level Is Not Associated With Presence and Severity of the Disease].

We tested possibility of the use of apelin-12 as a biomarker of chronic heart failure (CHF). The study comprised 108 patients with I-IV functional class CHF of various etiology (ischemic heart disease, dilation cardiomyopathy) and 40 healthy volunteers. Blood samples were taken at hospital admission before prescription of pharmacological therapy. In all patients we carried out echocardiography with calculation of end-diastolic and end-systolic volumes (EDV, ESV) and ejection fraction (EF). Blood plasma apelin-12 concentration was compared with CHF market NT-proBNP. Mean apelin-12 concentrations were 0.86 ± 0.22 hg/ml in healthy volunteers and 0.8±0.35, 0.81 ± 0.29, 0.68 ± 0.38, 0.82 ± 0.35 hg/ml in patients with CHF classes I, III, III, IV, respectively. There was no significant differences between appelin-12 concentrations in various classes of CHF. No correlations were found between apelin-12 and EF, EDV, ESV, sex, age, smoking, body mass index, and NT-proBNP level. Concentration of NT pro-BNP level correlated with CHF severity. Thus apelin-12 did not show itself as reliable biomarker of CHF.

[Laboratory monitoring of the efficacy and safety of anticoagulants].

Currently, the pharmaceutical market there are a large number of anticoagulants, each of which has a number of features. An important factor influencing the choice of drug, is whether or not the methodology of fixing its efficacy and safety. The aim of this review is to describe current approaches to the control of the efficacy and safety of anticoagulants.

[Degenerative aortic stenosis: prediction of poor prognosis by 2D left ventricular longitudinal strain in non-operated patients].

AIM: To investigate relationship between global longitudinal peak strain (GLPS) of the left ventricle (LV) and clinical routine echocardiographic (ECHO) and electrocardiographic (ECG) parameters in patients with non-operated aortic stenosis (AS) of all degrees. Also we evaluated the prognostic value of GLPS in patients with AS. METHODS: Patients with AS (n = 80) and control patients (n = 49) matched by age, sex and main cardio-vascular diseases were examined. Examination included medical history, serum cholesterol and creatinine, ECG, routine ECHO, tissue Doppler imaging (TDI), and GLPS in apical views. Correlation analysis and unifactorial regression analysis for assessment of one year prognosis were performed in AS group. RESULTS: Average GLPS (GLPS_Avg) for whole LV was significant lower in AS group than in control group (-17.4 +/- 3.85 vs -19.3 +/- 3.99, p < 0.05). In AS group GLPS_Avg correlated with aortic valve area (r = 0.318, p = 0.004), LV ejection fraction (r = 0,305, p = 0,006), thickness of interventricular wall (r = -0.246, p = 0.028), QRS duration (r = -0.225, p = 0.045), and Cornell (r = -0.338, p = 0.003) and Gubner (r = -0.281, p = 0.013) ECG hypertrophy indexes. The GLPS_Avg below -13% was associated with risk of unfavorable one-year outcome in patients with AS. CONCLUSION: . GLPS for the whole LV correlated with early ECG and ECHO parameters of LV hypertrophy. GLPS has prognostic value for one-year outcomes in patients with degenerative non-operated AS.

[Mechanisms of development of thromboembolic complications in patients with atrial fibrillation].

Thomboembolism is the most threatening complication in patients with atrial fibrillation. Main source of embolism is the left atrial thrombosis. Mechanisms of development of thromboembolic complications in patients with arrhythmias are far from being deciphered. In this review we discuss possible mechanisms of formation of intracardiac thrombus - abnormalities of functioning of the hemostasis system, endothelial dysfunction, inflammatory reactions, fibrosis of the left atrial wall, genetic traits.

[Features of the use of rosuvastatin in clinical practice].

This review is devoted to new data on the effects of rosuvastatin in patients with high risk for cardiovascular complications. There were analyzed new data on complications of statin therapy, and information on the effects of the drug in patients with diabetes, pneumonia and kidney failure.

[The role of direct-acting P2Y12 inhibitors in acute coronary syndrome].

P2Y12 receptor inhibitors are recommended for treatment of patients with acute coronary syndrome and/or percutaneous coronary intervention as a part of dual antiplatelet therapy. While thienopyridine group of P2Y12 inhibitors remains to be widely used treatment for patients with ACS, there are still complications for its application. Emerging antiplatelet treatments expand therapy strategies for management of ACS. The purpose of this article is to define the developing role of novel non-thienopyridine reversible P2Y12 inhibitor ticagrelor to present its pharmacokinetic, pharmacodynamic, and pharmacogenetic characteristics, based on current evidence.

[Biomarkers of inflammation in patients with chronic heart failure and implanted devices for cardiac resynchronization therapy].

The aim of the study was to assess the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and inflammatory markers in patients with congestive heart failure (CHF) treated with cardiac resynchronization therapy (CRT). 97 patients (age 54.9+/-9.9 years; 87% men) with implanted CRT devices (median period after implantation 19.9+/-19.3 months) were enrolled. According to NT-proBNP level patients were divided into tertiles: first (n=36) - less than 848 pg/ml, second (n=29) - from 848 to 2936 pg/ml, and third (n=32) - more than 2936 pg/ml. We didnt find a relationship between inflammatory mediators, NT-probNP level and time after implantation. In the total group NT-proBNP significantly correlated with structural and functional parameters of the heart. In the first group in comparison with the third group levels of IL-6 were lower (pI-III=0.019) and levels of IL-l - higher (pI-III=0.006). IL-10, CRP, TNF- did not differ between groups. In the first group IL-l straightly correlated with IL-6, TNF- , IL-10 and left ventricular ejection fraction (LVEF), in the third group IL-6 straightly correlated with CRP, while correlation of IL-l with LVEF became negative. We suppose that in patients with mild HF IL-l can play an adaptive role. High levels of IL-6, CRP probably can be used as markers of CHF progression in patients treated with CRT.

[Association of parameters of heart rate variability with severity of bronchial obstruction and presence of pulmonary hypertension in patients with chronic obstructive pulmonary disease].

With the aim of assessing parameters of heart rate variability (HRV) and heart rhythm turbulence (HRT) in patients with chronic obstructive pulmonary disease (COPD) in dependence on severity of the course of this disease and presence of pulmonary hypertension (PH) we examined 73 patients (28 with COPD and 45 healthy subjects). Invasive measurement of central hemodynamics was conducted. Compared with the control group in patients with COPD we revealed lowering of temporal as well as frequency HRV parameters. No significant changes of HRV parameters depended on severity of COPD course. However a tendency to maximal lowering of HRV parameters was noted in the group of patients with COPD with first sec forced expiratory volume <50%. Comparison of patients with and without PH with controls revealed tendency to maximal lowering of HRV parameters in the PH group. Thus measurement of HRV can be used for supplementary assessment of severity of the disease and detection of PH.

[The pulse wave velocity and fatal events rate in hypertensive patients have gone through acute coronary syndrome].

There are several stratification scales of major cardiovascular events rate for patients have gone through acute coronary syndrome (ACS). None of them is perfect one. Arterial hypertension is included into some scales for post ACS patients but the features of it and its impact on coronary artery disease after ACS have never studied before. We studied the reasonability of Pulse Wave Velocity (PWV) measurement for fatal events rate in hypertensive patients have gone through ACS. 326 patients were examined. They were enrolled into the study in stable condition on 10th day after ACS has occurred. As a result of two years observation the increase PWV on carotid-femoral segment associated with the most negative (fatal) events in hypertensive patients have gone through ACS.

[Polymorphic markers Ala455Val of the THBD gene and Arg353Gln of the F7 gene and association with unfavorable outcomes of coronary atherosclerosis in patients with a history of acute ischemic heart disease].

The polymorphic markers Ala455Val of the THBD gene and Arg353Gln of the F7 gene were tested for association with the frequency of unfavorable outcomes in patients with a history of acute ischemic heart disease. The study involved 1145 patients hospitalized in cardiology clinics of Moscow, St. Petersburg, Kazan, Chelyabinsk, Perm, Stavropol, and Rostov-on-Don because of acute ischemic heart disease. The patients were followed up for up to 62.5 months. None of the markers displayed a significant association with the time to an endpoint. The patients were then grouped by sex. In females, the frequency of unfavorable outcomes (fatal or nonfatal myocardial infarction and fatal or nonfatal stroke) was higher in carriers of allele Val of the Ala344Val polymorphic marker of the THBD gene and carriers of genotype Arg/Arg of the Arg353Gln polymorphic marker of the F7 gene, but the difference was not statistically significant. Such an increase in frequency was not observed in males. To study the combined effect of the polymorphic markers of the THBD and F7 genes, the course of ischemic heart disease was compared for two female subgroups. One included carriers of allele Val of the Ala344Val polymorphic marker of the THBD gene and genotype Arg/Arg of the Arg353Gln polymorphic marker of the F7 gene; the other subgroup included carriers ofgenotype Ala/Ala of the Ala455Val polymorphic marker of the THBD gene and allele Gln of the Arg353Gln polymorphic marker of the F7 gene. The frequency of unfavorable outcomes in the first subgroup was higher than in the second one. The time to an endpoin was 40.5 months (95% confidence interval (CI) 33.5-47.6) in the first subgroup and 51.6 months (95% CI 45.0-58.1) in the second subgroup (chi2 = 4.15, P = 0.042). The results made it possible to assume that the F7 and THBD genes play an important role in genetic predisposition to unfavorable outcomes in patients with a history of acute ischemic heart disease.

[Risk and benefit of oral anticoagulants in atrial fibrillation].

Thromboembolism is the main cause of death and disability of patients with atrial fibrillation. Indirect anticoagulants are effective means of primary and secondary prevention of thromboembolic complications. However in a number of patients risk associated with therapy with indirect anticoagulants might exceed potential benefit. The principle problem requiring solution in a patient with atrial fibrillation is individual comparative assessment of risk of development of thromboembolic and hemorrhagic complications. Modern stratification scales which allow solving this problem are considered in this review.

[Anatomical, functional, and genetic peculiarities of myocardial hypertrophy in athletes].

"Athletes Heart" (AH) is a complex of structural, electrophysiological, and functional changes - a consequence of physiological adaptation to regular physical exercise. AH is characterized by biventricular hypertrophy of ventricular myocardium at the background of unchanged parameters of systolic and diastolic function and depends on the type of exercise, body dimensions, sex, and genotype. Although degree of hypertrophy in AH in most cases does not exceed generally accepted limits problems of differential diagnostics of AH and other cardiovascular diseases manifesting by myocardial hypertrophy appear to be most actual. Contemporary possibilities of molecular genetic methods for detection of cause of myocardial hypertrophy are described.

[Association of a polymorphic marker Trp719Arg of KIF6 gene with effects of atorvastatin and simvastatin in patients with early ischemic heart disease].

Action of statins is characterized by pronounced variability what is caused by effects of a multitude of factors. Main of these factors appears to be genetic peculiarity of patients. We studied influence of polymorphic marker Trp719Arg of KIF6 gene on lipid and nonlipid effects of atorvastatin and simvastatin. The studied genetic marker is associated with risk of development of ischemic heart disease and myocardial infarction as well as efficacy of therapy with statins according to data of a number of large multicenter studies. We examined 60 men with ischemic heart disease which had manifested in young age when genetic factors were most expressed and had special significance. Efficacy of 40 mg/day simvastatin did not depend on genotypes of polymorphic marker Trp719Arg of KIF6. Therapy with 10 mg/day atorvastatin was more effective in carriers of polymorphic marker Trp719Arg of KIF6 gene by action on dynamics of changes of high sensitivity C-reactive protein and dispersion of high density lipoprotein response. Increase of atorvastatin dose to 80 mg/day abolished influence of genotypes. Thus for the first time we discovered influence of polymorphic marker Trp719Arg of KIF6 gene on individual response to therapy with 10 mg/day of atorvastatin, while and apoA1, structural protein of high density lipoproteins can be considered as a marker of "fast response".

[Cystatin C level is independently related to risk of unfavorable outcome after acute coronary syndrome in individuals with normal or moderately reduced renal function].

We studied relation between cystatin C level and risk of unfavorable outcome (unstable angina, fatal and nonfatal myocardial infarction [MI], fatal and nonfatal stroke, and death) in patients stabilized after exacerbation of ischemic heart disease. Patients (n=272) were included on day 10 after onset of acute coronary syndrome. No relationship between studied outcomes and cystatin was found in a group as a whole. In patients with normal of slightly reduced renal function (glomerular filtration rate more or equal 60 ml/min/1.73 m2) unfavorable outcomes were independently associated with history of myocardial infarction and stroke, elevated levels of brain natriuretic peptide and cystatin. In subjects with moderately or severely reduced renal function elevation of cystatin level lost its significance. Risk of development of unfavorable outcomes among these subjects was independently related to history of MI and GFR <60 ml/min/1.73 m2 (OR 2.130, 95% CI 1.010-4,489; =0,047). Our data confirm possibility of use of cystatin C level measured early after ACS in patients with normal or slightly lowered renal function as a parameter characterizing risk of cardiovascular complications and death.

[Prognostic value of levels of brain natriuretic peptide and genetic factors in patients after acute coronary syndrome].

Prognostication of the course of disease in patients with high risk of unfavorable outcome of ischemic heart disease (IHD) is of great importance for creation of individualized strategy of treatment. We have investigated contribution of levels of brain natriuretic peptide (BNP) and genetic factors in the risk of development of complications of atherosclerosis in patients who have had acute coronary syndrome. We started to follow 324 patients on day 10 of stable state after acute coronary syndrome (55.1% with Q-wave myocardial infarction, 18.5% with non-Q myocardial infarction, 25.5% with unstable angina, men BNP level 624.5+/-32.13 mol/ml [70.3 - 4276.6]). Duration of followup was 2 years. Baseline BNP level in patients with unfavorable outcome during followup (fatal and nonfatal myocardial infarction and stroke) was 872.47+/-91.42 compared with 592.45+/-35.97 mol/ml in patients without unfavorable outcome (p=0,001). Multifactorial Cox analysis showed that carriage of T allele of polymorphic marker (--1654) of protein C gene, elevated BNP level, symptomatic atherosclerosis of peripheral arteries, history of MI, and use of thiazide diuretics were independently associated with unfavorable outcomes (p=0.026, <0.0001, <0.0001, =0.001, =0.024, respectively). Thus genetic factors and study of BNP allow to improve prediction of unfavorable outcome after exacerbation of IHD.

[Prognostic value of aortic stenosis in patients after acute coronary syndrome].

With the aim to assess prevalence of aortic stenosis (AS) and prognostic value of its detection among survivors of acute coronary syndrome (ACS) we examined 851 patients included into multicenter prospective study of risk factors of serious vascular events and death after acute coronary syndrome. The patients were enrolled into the study in stable condition on 10th day after onset of myocardial infarction (MI) or unstable angina (UA). Examination involved medical history, laboratory tests and echocardiography. Afterwards all cases of death and serious vascular events were registered. Severity of AS was specified by maximal aortic flow rate: 1st degree > 2.5, 2nd degree 3.0-4.0, 3rd degree > 4.0 m/s. AS was detected in 16 patients (1.9%). AS severity was 1st, 2nd and 3rd degree in 9, 4 and 3 patients, respectively. Patients with AS were significantly older (77.4 vs. 61.3 years, p < 0.001), more often had history of chronic heart failure (CHF) (81.3 vs. 53.2%, p = 0.021) and lowered renal function (66.7 vs. 34.0%, p < 0.041). At multifactorial analysis independent prognostic value in relation to development of serious events showed age > 75 years (OR 1,395 [1.023-1.902], p = 0.036), history of CHF (1.319 [1.015-1.713], p = 0.038), history of MI (1.692 [1.320-2.170], p < 0.001), left ventricular diastolic dimention (1.023 [1.005-1.041], p = 0.012), left atrial diameter (1.024 [1.001-1.047], p = 0.037) and presence of AS (3.211 [1.742-.,916], p < 0.001). Prevalence of preexisting AS among patients who have had MI/UA is 1.9% what is similar to data of European Heart Survey ACS-II (1.8%). Presence of AS of any severity in a survivor of ACS worsens prognosis independently of other known risk factors.

[Gene IL6 G(-174)C and gene IL10 G(-1082)A polymorphisms are associated with unfavourable outcomes in patients with acute coronary syndrome].

We investigated the association of gene IL6 G(-174)C polymorphism and gene IL10 G(-1082)A polymorphism with coronary artery disease (CAD) in the Russian population. A total of 1145 patients with CAD diagnose on the basis of clinical studies in cardiological hospitals of Moscow, St -Petersburg, Kazan, Chelyabinsk, Perm, Stavropol and Rostov-on-Don. Supervision term was 9.10 +/- 5.03 months (the maximum term 18 months). In case of gene IL10 G(-1082)A polymorphism we determined that patients with CAD diagnose and A alleles gene IL10 had unfavorable outcome more often than patients with homozygous G alleles. Survival time from end point from carrier genotype GA and AA is 11.68 +/- 0.67 months against 12.69 +/- 0.65 months from carrier phenotype GG gene IL10 (chi2 = 4.13, p = 0.042). The group studied do not differ significantly with respect to the distributions of gene IL6 G(-174)C alleles and genotypes. However in case combined group studies of gene IL10 G(-1082)A polymorphism and IL6 G(-174)C polymorphism we determined that patients with CAD diagnose and carrier genotype GG gene IL6 and genotype GA and AA gene IL10 had unfavorable outcome more often (survival time 11.01 +/- 1.24 months) than patients with genotype CC and CG gene IL6 and genotype GG gene IL10 (survival time 13.28 +/- 0.83 months) chi2 = 10.23, p = 0.017. The obtained data allows assuming the important role of the IL6 and IL10 genes which are responsible for functioning of inflammation system, in the accelerated formation of failures at the patients who had a coronary syndrome.

[Motor protein Kinesin-6 and ischemic heart disease].

The review describes possible role of kinesins in development of coronary heart disease and efficacy of treatment with statins. Fourty five kinesins are represented in human body making up a superfamily of universal and simplest motor proteins which are expressed almost in all tissues. Level of kinesin 6 is 5% higher than expression of other kinesins in some segments of coronary arteries and it is relatively low in organs playing unknown role in susceptibility to atherosclerosis. As a result of several genoms wide association studies the role of polymorphic marker Thr719Arg of kinesin 6 gene in development of ischemic heart disease, myocardial infarction, and in efficacy of therapy with statins was revealed.