[Left ventricular global function index as a predictor of adverse cardiovascular events in patients with acute coronary syndrome].

Aim      To evaluate the prognostic significance of the left ventricular global function index (LV GFI) in patients with acute coronary syndrome (ACS) using echocardiography (EchoCG).Material and methods             The LV GFI is an index that integrates LV cavity volumes, stroke volume, and myocardial volume. This study included 2169 patients with ACS (1340 (61.8%) men) aged 64.1±12.6 years from two observational multicenter studies, ORACLE I and ORACLE II. 1800 (83 %) cases were associated with increased concentrations of myocardial injury markers, including 826 (38.1 %) cases of ST segment elevation myocardial infarction (MI). The observation was started on the 10th day of clinical condition stabilization and lasted for one year. EchoCG was performed with evaluation of LV GFI, which was calculated as a ratio of LV stroke volume to LV global volume. The LV global volume was calculated as a sum of mean LV cavity volume (LV end-diastolic volume + LV end-systolic volume / 2) and LV myocardial volume.Results The main outcome of the study was all-cause death (n=193); recurrent coronary complications (n=253) were analyzed separately. The only EchoCG parameter indicating an adverse outcome during the one-year follow-up was a LV GFI decrease to below 22.6 % with a sensitivity of 72 % and a specificity of 60% (area under the curve, AUC=0.63). A LV GFI <22.6 % was an independent predictor of all-cause death (p=0.019) along with age (p=0.0001), history of MI (p=0.034), and presence of heart failure (HF) (p=0.044), diabetes mellitus (p=0.012), and peripheral atherosclerosis (p=0.001). The LV GFI <22.6 %, (p=0.044), heart rate upon discharge from the hospital (p=0.050), history of MI (p=0.006), presence of HF (p=0.014), and peripheral atherosclerosis (p=0.001) were also independent predictors for recurrent coronary complications. Decreased LV GFI was associated with the risk of fatal outcomes independent of the LV ejection fraction at baseline.Conclusion      In patients with ACS, the left ventricular global function index is an independent predictor for all-cause death and recurrent coronary complications and may be used for risk stratification.

[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.

[Family History of Cardiovascular Disease in Patients With Early Development of Acute Coronary Syndrome].

The aim of the study was to analyze clinical features of patients with premature acute coronary syndrome (ACS) in relation to family history of cardiovascular disease (CVD) and familial hypercholesterolemia (FH). MATERIALS AND METHODS: Of 2832 patients included in ORACUL 1 and ORACUL 2 multicenter observational trials 512 pts who developed premature ACS (≤55 years for men, ≤60 years for women) and had known family history and LDL level were selected for this study. Of these patients 297 had positive family history (51 with FH, 246 no FH), 215 had negative family history. RESULTS: Among patients with positive family history there were more women (31 vs 20.9 %), while among patients with negative family history there were more men (79.1 vs 69 %). The fact of regular alcohol consumption was significantly more frequently observed among patients with positive family history but without FH, compared to patients with positive family history with FH (69.6 vs 47.1 %). Women with positive family history smoked more frequently than females with negative family history (51.1 vs 31.1 %). Among patients with negative family history compared with patients with positive family history there were more people who at admission had hyperglycemia exceeding 11.1 mmol / l (10.3 vs 4.4 %). Multiple vessel disease and coronary calcinosis were present in 73.2 and 24.7 %, respectively, of patients with positive family history, and in 56.9 and 9.8 %, respectively, of those with negative family history. Among patients with positive family history multivessel disease was more frequent in the subgroup with FH, while coronary calcinosis was more frequent in the subgroup without FH. CONCLUSION: Thus, premature development of ACS might be associated not only with genetic factors but also with family history ("inheritance") of adverse habits. Herewith coronary calcinosis is more prevalent in patients with FH.

[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.

[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 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.

[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.

[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.

[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.

[Peroxisome proliferator activated nuclear receptors: possible role in the development of atherosclerosis]. / Iadernye retseptory, aktiviruemye peroksisomal'nym proliferatorom: vozmozhnaia rol' v razvitii ateroskleroza.

Peroxisome proliferator activated nuclear receptors (PPAR) belong to steroid receptors and are represented by 3 types: PPAR alpha, PPAR beta, PPAR gamma. PPAR alpha is a key regulator of fatty acid beta-oxidation, participates in development of inflammatory reaction and atherosclerosis formation. Main effects of fibrates are mediated through PPAR alpha activation. PPAR gamma plays important role in lipid metabolism, processes of cell differentiation and growth, participates in glucose utilization and mechanisms of insulin resistance. Specific activators of PPAR gamma are glytazones--a group of antidiabetic drugs. The role of PPAR beta in atherosclerosis formation has not been elucidated yet however results of some studies indicate participation of this receptor in atherosclerosis. Data of studies devoted to the role of PPARs and polymorphic markers of these receptors in the process of atherosclerosis are reviewed.