[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.

[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.

[Carriage of A Allele of Polymorphic Marker G(-238)A of TNF Gene Is Associated With Unfavorable Prognosis in Patients With Chronic Systolic Heart Failure].

AIM: to elucidate association between polymorphic markers of interleukin-6 (Il-6) and tumor necrosis factor (TNF) genes and unfavorable outcomes in patients with chronic heart failure (CHF). MATERIAL AND METHODS: We determined levels of TNF and Il-6 and genotypes of polymorphic markers G(-238)A of TNF gene (rs361525) and G(--174)C of IL-6 gene (rs1800795) in 151 patients (mean age 64.5 years) hospitalized because of decompensation of systolic CHF (left ventricular ejection fraction ≤ 40%) after stabilization of their state. Unfavorable outcomes were registered during follow-up for 2 years. RESULTS: Mean levels of NT-proBNP, Il-6, and TNF were 2481.1 ± 199.86 fmol/ml, 21.8 7.46 rg/ml, and 10.07 ± 0.65 rg/ml, respectively. 138 (94.4%), 13 (8.6%) and 0 patients were carriers of genotypes GG, AG, and AA of polymorphic marker G(-238)A of TNF gene, respectively; 54 (35.8%), 69 (45.7%), and 28 (18.5%) patients carried genotypes GG, GC, and CC of polymorphic marker G(-174)C gene IL-6, respectively. There was no association between Il-6, TNF levels and carriage of either of genotypes as well as unfavorable clinical course of CHF. Mean survival time before repetitive episode of CHF decompensation (including lethal one) was significantly shorter among carriers of A allele compared with carriers of G allele of polymorphic marker G(-238)A of TNF gene (243 ± 97.7 and 947 ± 78 days, respectively, p = 0.018). Mean time before all cause death was also shorter in carriers of A compared with carriers of G allele (289 ± 122.9 and 1039 ± 73.3 days, respectively, p = 0.03). The studied polymorphism of IL-6 gene had no prognostic value. CONCLUSION: We obtained data on association between carriage of A allele of polymorphic marker G(-238)A of TNF gene and unfavorable prognosis in patients with CHF and inpraired left ventricular systolic function.

[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, II, 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.

[Carriage of A Allele of Polymorphic Marker G(-238)A of TNF-alfa Gene Is Associated With Unfavorable Prognosis in Patients With Chronic Systolic Heart Failure].

AIM: to elucidate association between polymorphic markers of interleukin- 6 (Il-6) and tumor necrosis factor (TNF) genes and unfavorable outcomes in patients with chronic heart failure (CHF). MATERIAL AND METHODS: We determined levels of TNF and Il-6 and genotypes of polymorphic markers G(-238)A of TNF gene (rs361525) and G(-174)C of IL-6 gene (rs1800795) in 151 patients (mean age 64.5 years) hospitalized because of decompensation of systolic CHF (left ventricular ejection fraction less or equal 40%) after stabilization of their state. Unfavorable outcomes were registered during follow-up for 2 years. RESULTS: Mean levels of NT-proBNP, Il-6, and TNF were 2481.1+/-199.86 fmol/ml, 21.8+/-7.46 rg/ml, and 10.07+/-0.65 rg/ml, respectively. 138 (94.4%), 13 (8.6%) and 0 patients were carriers of genotypes GG, AG, and AA of polymorphic marker G(-238)A of TNF gene, respectively; 54 (35.8%), 69 (45.7%), and 28 (18.5%) patients carried genotypes GG, GC, and of polymorphic marker G(-174)C gene IL-6, respectively. There was no association between Il-6, TNF levels and carriage of either of genotypes as well as unfavorable clinical course of CHF. Mean survival time before repetitive episode of CHF decompensation (including lethal one) was significantly shorter among carriers of A allele compared with carriers of G allele of polymorphic marker G(-238)A of TNF gene (243+/-97.7 and 947+/-78 days, respectively, =0.018). Mean time before all cause death was also shorter in carriers of A compared with carriers of G allele (289+/-122.9 and 1039+/-73.3 days, respectively, p=0.03). The studied polymorphism of IL-6 gene had no prognostic value. CONCLUSION: We obtained data on association between carriage of A allele of polymorphic marker G(-238)A of TNF gene and unfavorable prognosis in patients with CHF and inpraired left ventricular systolic function.

[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.

[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.

[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.

[Polymorphic markers G(-455)A of gene FGB and C(-1654)T of gene PROC and genetic predisposition to unfavorable outcomes patients undergoing acute coronary syndrome].

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.

[Prognostic value of atrial fibrillation in patients--survivors of acute coronary syndrome].

For the study of contribution of atrial fibrillation (AF) during acute coronary syndrome (ACS) in long-term prognosis after clinical stabilization we examined 453 patients admitted to Moscow hospitals and followed them for 2.07 +/- 0.48 years. The following events were registered: fatal and nonfatal myocardial infarction (MI), unstable angina (UA), fatal and nonfatal stroke, death of other causes. At ACS onset sinus rhythm was noted in 419 (92.5%), permanent or persistent AF-in 16 (3.5%), attack (paroxysm) of AF - in 18 (4.0%) patients. Mean length of life before end point was 884.9 +/- 23.4, 827.3 +/- 123.3 and 514.0 +/- 111.3 days in patients with sinus rhythm, permanent/persistent AF, and attack of AF during first 10 days of ACS, respectively (p<0.001). Compared with patients in sinus rhythm in patients with attack of AF relative risk (RR) of occurrence of any end point was 1.75 (95% confidence interval [CI] 1.284 to 2.873, p< 0.001), of fatal MI - 1.72 (95% CI 1.026 to 2.873, p=0.040), of UA - 2.116 (95% CI 1.249 to 3.585, p=0.005), of stroke - 2.863 (95% CI 1.300 to 6.301, p=0.009). Multifactorial analysis selected history of MI and attack of AF during first 10 days of ACS as independent predictors of unfavorable outcome. Thus paroxysmal form of AF during hospital stay because of ACS is associated with higher probability of development of unfavorable events in the next 1-2 years.

[Polymorphism of genes of factors of hemostasis in patients with early development of ischemic heart disease.].

The review is devoted to analysis of data, related to contribution of genetic peculiarities of the hemostasis system to early development of ischemic heart disease (IHD). Information is presented on polymorphisms of tissue factor, coagulation factors VII, V, prothrombin, thrombomodulin, fibrinogen, thrombin activated fibrinolysis inhibitor, tissue plasminogen activator inhibitor, platelet membrane glycoproteines Ia, Iba, IIIa in patients with early development of IHD. Contradictoriness of existing data on effects of genetic heterogeneity of factors of hemostasis on risk of development of IHD at young age and necessity of further investigations in this area are underlined.

[Associations of hemostasis factors genes with early development of ischemic heart disease and manifestation of myocardial infarction in young age].

AIM: To study polymorphisms of genes of factors of the system of hemostasis in young patients with ischemic heart disease (IHD). MATERIAL: Two groups of patients participated in the study: patients with first manifestation of IHD at the age < or = 50 years (men) or < or = 55 years (women) (n=158), and patients with first IHD manifestation at the age > or = 70 years (n=92). METHODS: We studied polymorphic markers of genes encoding clotting factors V (F5) and VII (F7), subunit IIIa of platelet integrin (ITGB3), beta-chain of fibrinogen (FGB) and tissue plasminogen activator type 1 (PLANH1). RESULTS: After separation of a subgroup of patients with MI without preceding angina we revealed significant differences in distribution of frequencies of genotypes of polymorphic marker C(-426)T of factor V gene: genotype TT was significantly more frequent in young (14.9%) than in old (2%) patients (p=0.008). Multifactorial logistic regression revealed independent association of early IHD with smoking (OR 6.112 [2.567-14.552]; p<0.001) and presence of genotype TT of C(-426)T polymorphic marker of F5 gene (OR=9.410 [1.074-82.459]; p=0.043). CONCLUSION: Thus we obtained data on the presence of independent association between IHD risk and manifestation of MI in young age with genotype TT of polymorphic marker C(-426)T of F5 gene as well as with traditional risk factors of IHD.