Aim. To evaluate the influence of genetic markers of inflammation and fibrosis on survival rate of patients with non operated aortic stenosis (AS). The search for novel prognostically adverse factors in calcinated AS patients with none surgical treatment remains actual.Material and methods. During 2,1±0,11 years, 191 patient has been followed up (28,6% males, 78,0±0,60 y. o.) with a “natural course” of AS (aortic valve area ≤2,0 cm2). All fatal outcomes (FO) were collected. Then the clinical, biochemical and echocardiographic parameters were compared, genotypes frequencies and alleles of mononucleotide polymorphisms (MNP) G(-238)A and G(-308)A gene TNF, С(-592)A gene IL-10, Arg25Pro gene TGFβ1 in groups with FO and with none. Life duration towards FO was evaluated.Results. Fatal outcomes were registered in 71 (37,2%) of patients. Death causes were: myocardial infarction in 5, stroke in 8, sudden death in 10, chronic heart failure (CHF) in 29, thromboembolism in 5, non-cardiac cause in 14. Independent factors associated with FO were: presence of CHF III-IV FC NYHA, creatinine level, aortic valve area, myocardial mass index of the left ventricle and carriage of allele Pro MNP Arg25Pro gene TGFβ1 (р<0,05). Associations of MNP G(-238)A and G(-308)A gene TNF, as MNP С(-592)A gene IL-10 with FO were not found. Mean life duration before death in Pro MNP Arg25Pro gene TGFβ1 carriers was 468,6±99,62 days versus 617,6±77,19 days in non-carriers (р<0,05).Conclusion. The carriage of allele Pro MNP Arg25Pro gene TGFβ1 can be regarded as one more predictor of fatal outcome in patients with non-operated AS. It is clear that LV myocardial fibrosis, developing in AS patients, might be a factor significantly influencing prognosis.

Identification of risk factors associated with presence of atrial fibrillation (AF) in patients with aortic valve stenosis (AS) remains to be unraveled.The aim of the study was to investigate relationship between profibrotic biomarkers and presence of AF in AS patientsMethods. 191 patients (29,8% male, 77,7±0,59 years) with AS (defined as aortic valve area (AVA) ≤ 2,0 sm2) were enrolled in the study. Clinical, echocardiographic and biochemical variables, including serum TGFβ1 and osteopontin levels were compared between 2 groups of patients: with and without AF. Results. 83(36,5%) of AS patients had AF. In logistic regression models independent associations between AVA index (p=0,040), left atrial volume (p=0,021), OPN (р=0,009) and presence of AF were found. Patients with serum OPN level > 10,05 ng/ml had twice more higher AF incidence comparedto patients with serum OPN level ≤ 10,05 ng/ml (53,8% and 29,2%, respectively, p=0,020).Conclusion. Serum OPN level was independently associated with presence of AF in AS patients, thus we speculate on it’s predominant profibrotic role in the left atrium.

AIM:To study relationships of serum levels of vascular endothelium growth factor with left ventricular (LV) myocardial hypertrophy (H) and signs of heart failure (HF) in patients with arterial hypertension (AH).METHODS:We examined 47 patients with AH and by echo established thickening ( more or equal 16 mm) of LV wall and 47 patients with AH and normal (<12 mm) thickness of LV wall from control group selected according to "head-to-head" principle by age and sex. Serum VEGF-A165 level was measured by sandwich solid-phase immunoenzyme assay.RESULTS:VEGF-A165 level was significantly lower in the group of patients with LVH compared with control group (273.3+/-41.75 vs. 426.6+/-50.00 pg/ml, =0.016). VEGF-A165 level in patients with LVH and NYHA class III HF (140.4+/-51.49 pg/ml) was highly significantly different (p <0.001) from that in in patients without LVH.CONCLUSION:Presence of LVH and HF in patients with AH was associated with lower levels of VEGF-A165 in peripheral blood.

Для изучения вклада мерцательной аритмии (МА) при остром коронарном синдроме (ОКС) в долгосрочный про- гноз после стабилизации состояния обследовали 453 больных, проходивших лечение в стационарах Москвы с декабря 2004 г. по июнь 2007 г. Учитывали развитие в течение периода наблюдения любого из следующих событий: фатальный и нефатальный инфаркт миокарда (ИМ), нестабильная стенокардия, фатальный и нефатальный инсульт, смерть от дру- гих причин. Синусовый ритм зарегистрирован при поступлении и сохранялся в течение первых 10 дней у 419 (92,5%) больных, постоянная или персистирующая МА имела место на момент развития ОКС — у 16 (3,5%). У 18 (4,0%) боль- ных был зарегистрирован пароксизм МА. Средняя продолжительность жизни до конечной точки у больных с синусовым ритмом составила 876,5 (±23,25) дня, у больных с постоянной или персистирующей формой МА — 817,3 (±123,30) дня, у больных с пароксизмом МА, развившимся в первые 10 дней ОКС — 549,9 (±113,81) дня (р=0,007). Относи- тельный риск наступления любой конечной точки у больного, перенесшего пароксизм МА, по сравнению с таковым у больного с синусовым ритмом составил 1,897 при 95% доверительном интервале (ДИ) от 1,214 до 2,963 (р=0,005). При многофакторном анализе независимыми предикторами неблагоприятного исхода (наступление фатального и не- фатального ИМ, фатального и нефатального инсульта, НС и смерти от других причин) после ОКС оказались только ИМ в анамнезе (OR=1,969, 95% CI 1,227–3,160, р=0,005), пароксизм МА, развившийся в 10 дней ОКС (OR=1,897, 95% CI 1,214–2,963, р=0,005) и потребность в применении тиазидных диуретиков в период госпитализации (OR=1,936, 95% CI 1,153–3,249, р=0,012). Было выявлено, что при наличии 1 фактора риска развития неблагоприятного клинического события по сравнению с их отсутствием риск составил 2,582 (95% CI 1,629–4,091, р<0,001), при наличии 2 факторов – 2,037 (95% CI 1,567–2,648, р<0,001). Таким образом, пароксизм МА, выявленный в течение первых 10 дней от раз- вития ОКС, ассоциируется с большей вероятностью развития неблагоприятных событий в течение ближайших 1—2 лет. Ключевые слова: острый коронарный синдром, мерцательная аритмия, прогноз. 453 patients who were admitted in Moscow hospitals from December 2004 till June 2007 were examined so as to study the importance of ciliary arrhythmia (CA) at acute coronary syndrome (ACS) for long-term prognosis after patients’ stabilization. The following events which occurred during the follow-up period were taken into consideration: fatal and non-fatal myocardial infarction (MI), non-stable angina pectoris, fatal and non-fatal stroke, death due to other causes. 419 (92,5%) patients had sinus rhythm on admission and during the first 10 days; 16 (3,5%) patients had stable or persisting CA at ACS onset. 18 (4.0%) patients had CA paroxysm. Average survival period till the final point in patients with sinus rhythm was 876.5 (±23.25) days; in patients with stable or persisting CA – 817.3 (±123.30) days; in patients with MA paroxysm which occurred during the first 10 ACS days it was 549.9 (±113.81) days (р=0.007). A relative risk of approaching any final point in patients who had CA paroxysm comparing to patients with sinus rhythm was 1.897 at 95% confidence interval (CI) from 1.214 till 2.963 (р=0,005). While making a multifactor analysis it has been found out that independent predictors of unfavorable outcome (fatal or nonfatal MI, fatal or non-fatal stroke, non-stable angina pectoris and death due to other causes) after ACS were MI in anamnesis (OR=1.969; 95% CI 1.227–3.160; р=0.005), CA paroxysm which occurred during the first 10 ACS days (OR=1.897; 95% CI 1.214–2.963; р=0.005) and the amount of tiazide diuretics prescribed in the hospital (OR=1.936; 95% CI 1.153–3.249; р=0.012). It has been found out that if even one risk factor of unfavorable clinical event is present, the risk is 2.582 (95% CI 1.629–4.091; р<0.001) comparing to the absence of any risk factor; if two risk factors are present – the risk was 2.037 (95% CI 1.567–2.648; р<0.001). Thus, CA paroxysm revealed during the first 10 ACS days is associated with higher risk of developing unfavorable events for the nearest 1–2 years. Key word: acute coronary syndrome, ciliary arrhythmia, prognosis.

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.

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".

We investigated the association of polymorphisms of genes FGB G(-455)A and PROCC(-1654)T 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 1.14 +/- +/- 0.33 years (the maximum term 3.2 years). The group studied do not differ significantly with respect to the distributions of G(-455)A alleles and genotypes. However in case of gene PROC C(-1654)T polymorphism we determined that patients with CAD diagnose and Talleles of PROC gene had unfavorable outcome more often than patients with homozygous C alleles. Survival time from end point from carrier phenotype TT and CTis 2.19 +/- 0.18 r. years against 2.46 +/- 0.16 from carrier phenotype CCgene PROC. The obtained data allows to assume the important role of the genes which are responsible for functioning of system of a hemostasis, in the accelerated formation of failures at the patients who had a coronary syndrome.

Определены частоты неблагоприятных исходов в группе пациентов, перенесших острый коронарный синдром, в зависимости от генотипов полиморфных маркеров G(–174)C гена IL6 и G(–1082)A гена IL10. Исследовали 1145 больных, госпитализированных в кардиологические стационары Москвы, Санкт-Петербурга, Казани, Челябинска, Перми, Ставрополя и Ростова-на-Дону в связи с обострением ИБС. Средний срок наблюдения – 9.10 ± 5.03 мес. (максимальный срок 18 мес.). Анализ выживаемости больных, перенесших острый коронарный синдром и являющихся носителями аллеля A, показал, что в случае маркера G(–1082)A гена IL10 чаще наблюдается неблагоприятный исход – по сравнению с носителями генотипа GG. Время дожития до конечной точки у носителей генотипов GA и AA составило 11.68 ± 0.67 мес. против 12.69 ± 0.65 мес. у носителей генотипа GG гена IL10 ( 2 = 4.13, р = 0.042). В случае маркера G(–174)C гена IL6 анализ выживаемости показал, что значимой ассоциации с риском развития неблагоприятного исхода нет. Однако при одновременном рассмотрении полиморфных маркеров обоих генов обнаружено, что в случае больных, перенесших острый коронарный синдром и являющихся носителями генотипа GG гена IL6 и генотипов GA и AA гена IL10, чаще наблюдался неблагоприятный исход (время дожития 11.01 ± 1.24 мес.) – по сравнению с носителями генотипов CC и CG гена IL6 и генотипа GG гена IL10 (время дожития 13.28 ± 0.83 мес., 2 = 10.23, р = 0.017). Эти данные позволяют предположить, что гены IL6 и IL10, продукты которых контролируют воспалительные процессы, играют важную роль, увеличивая вероятность неблагоприятных исходов у больных, перенесших острый коронарный синдром.

Association between the rates of poor outcomes in the patient cohort with acute coronary syndrome and polymorphisms G(−174)C in the IL6 gene and G(−1082)A in the IL10 gene were determined. In total, 1145 patients hospitalized for coronary artery disease to cardiological hospitals of Moscow, St. Petersburg, Kazan, Chelyabinsk, Perm, Stavropol, and Rostov-on-Don were examined. The mean observation period was 9.10 ± 5.03 months (maximal, 18 months). Analysis of the survival of the patients with acute coronary syndrome that carried allele A has demonstrated that the presence of IL10 gene polymorphism G(−1082)A is associated with more frequent poor outcomes as compared with GG genotype. The survival time to endpoint for the carriers of GA and AA genotypes was 11.68 ± 0.67 months versus 12.69 ± 0.65 months for the carriers of GG genotype in IL10 gene (χ2 = 4.13, p = 0.042). As for the IL6 gene polymorphism G(−174)C, survival rate analysis did not detect any significant association with the risk for poor outcome. However, joint analysis of these polymorphisms in both genes has demonstrated that characteristic of the patients with acute coronary syndrome that carry GG genotype of IL6 gene and GA and AA genotypes of IL10 is a higher rate of poor outcomes (time to endpoint, 11.01 ± 1.24 months) as compared with the carriers of IL6 gene CC and CG genotypes and IL10 gene GG genotype (time to endpoint, 13.28 ± 0.83 months (ξ2 = 10.23, p = 0.017). These data suggest that the genes IL6 and IL10, whose products are involved in the control of inflammatory response, play an important role by increasing the probability of poor outcomes in the patients with acute coronary syndrome.

Associations of polymorphisms of genes FGB G(−455)A and PROC C(−1654)T with the frequency of poor outcomes in patients with the history of acute coronary syndrome (ACS) were studied in the Russian population. A total of 1145 patients admitted to cardiological hospitals of Moscow, St. Petersburg, Kazan, Chelyabinsk, Perm, Stavropol, and Rostov-on-Don with ischemic heart disease exacerbation were examined. The mean follow-up time was 1.14 ± 0.33 years, and the maximum follow-up time was 3.2 years. The risk of poor outcome did not depend on the carriership of genotypes of the polymorphic G(−455)A marker in the FGB gene. However, the PROC C(−1654)T polymorphism patients with ACS history and allele T of the PROC gene had a poor outcome more often than patients homozygous for allele C . The survival time to the endpoint for carriers of the TT and CT genotypes of the PROC gene was 2.19 ± 0.18 years vs. 2.46 ± 0.16 years for carriers of the CC genotype. On the base of these results it is suggested that hemostasis-related genes play an important role in early failures in patients with ACS history.

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.