Treatment of acute pulmonary embolism after catheter-directed thrombolysis with dabigatran vs warfarin: results of a multicenter randomized RE-SPIRE trial.

BACKGROUND: Thrombolytic therapy is effective method in the high-risk acute pulmonary embolism (PE) treatment. Reduced-dose thrombolysis (RDT) plus oral anticoagulation therapy is effective and safe method in the moderate and severe PE treatment. It is leading to good early and intermediate-term outcomes. In the RE-COVER and RE-COVER II studies, dabigatran showed similar effectiveness as warfarin in the treatment of acute PE. Dabigatran leads to fewer hemorrhagic complications and is not inferior in efficacy to warfarin in the prevention of PE after mechanical fragmentation and RDT (catheter-directed treatment [CDT]+RDT) in patients with high and intermediate to high PE risk. We sought to evaluate the efficacy and safety (incidence of clinically significant recurrence of venous thromboembolic complications and deaths) during a 6-month course of treatment with dabigatran or warfarin in patients with high and intermediate to high acute PE risk after endovascular mechanical thrombus fragmentation procedure with RDT (CDT+RDT). METHODS: The RE-SPIRE is a prospective, multicenter randomized double-arm study. Over a 5-year period, 66 consecutive patients with symptomatic high and intermediate to high PE risk after endovascular mechanical thrombus fragmentation procedure with RDT (CDT+RDT) were randomized into two groups within the next 48 hours. The first group continued treatment with dabigatran 150 mg twice a day for 6 months; the second group continued treatment with warfarin under the control of international normalized ratio (2.0-3.0) for 6 months. Both groups received low molecular weight heparins for 2 days after surgery. Then, group 1 continued to receive low molecular-weight-heparin for 5 to 7 days, followed by a switch to dabigatran at a dosage of 150 mg two times a day. Group 2 received both low-molecular-weight heparin and warfarin up to an international normalized ratio of >2.0, followed by heparin withdrawal. The follow-up period was 6 months. RESULTS: There were 63 patients who completed the study (32 in the dabigatran group and 31 in the warfarin group). In both groups, there was a statistically significant decrease in the mean pulmonary artery pressure. The mean pulmonary artery pressure at the 6-month follow-up after surgery was 24 mm Hg (interquartile range, 20.3-29.25 mm Hg) in the dabigatran group and 23 mm Hg (interquartile range, 20.0-26.3 mm Hg) in the warfarin group. The groups did not differ statistically in the deep vein thrombosis dynamics. Partial recanalization occurred in 52.0% vs 73.1% in the dabigatran and warfarin groups, respectively (P = .15). Complete recanalization occurred in 28.0% vs 19.2% in the dabigatran and warfarin groups, respectively (P = .56). The groups did not differ in the frequency of major bleeding events according to the International Society for Thrombosis and Hemostasis (0% vs 3.2% in the dabigatran and warfarin groups, respectively; P = 1.00). However, there were more nonmajor bleeding events in the warfarin group than in the dabigatran group (16.1% vs 0%, respectively; P = .02). CONCLUSIONS: The results of the study show that dabigatran is comparable in effectiveness to warfarin. Dabigatran has greater safety in comparison with warfarin in the occurrence of all cases of bleeding in the postoperative and long-term periods. Thus, dabigatran may be recommended for the treatment and prevention of PE after CDT with RDT in patients with high and intermediate to high PE risk.

The Role of Insulin Resistance in the Development of Complications after Coronary Artery Bypass Grafting in Patients with Coronary Artery Disease.

The aim of the study was to investigate the effect of carbohydrate metabolism disorders and insulin resistance indices on the immediate results of coronary artery bypass grafting (CABG). METHOD: Patients with coronary artery disease who underwent CABG (n = 383) were examined to determine glycemic status, free fatty acid and fasting insulin levels, and insulin resistance indices (Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), McAuley index, Quantitative Insulin Sensitivity Check Index (QUICKI), Revised-QUICKI). Patients were assessed for the development of perioperative complications and their length of stay in the hospital. Two groups were formed: group 1, patients with a combined endpoint (CEP, any complication and/or duration of hospital stay >10 days), n = 291; and group 2 (n = 92) without a CEP. Perioperative characteristics were analyzed, and predictors of hospital complications and prolonged hospital stay were evaluated. RESULTS: Patients in the CEP group were older, and there were more women among them (p = 0.003). Additionally, in this group, there were more patients with diabetes mellitus (37.5% vs 17.4%, p < 0.001), obesity (p < 0.001), and a higher percentage of combined operations (p = 0.007). In the group with a CEP, the levels of glucose (p = 0.031), glycated hemoglobin (p = 0.009), and free fatty acids (p = 0.007) and the Revised-QUICKI (p = 0.020) were higher than in the group without complications. In a regression analysis, the independent predictors of complications were combined operations (p = 0.016) and the predictors of a long hospital stay (>14 days) were female gender, the left atrium size, and diabetes mellitus (p < 0.001). The predictors of a composite endpoint included female gender, age, the left atrium size, and free fatty acid levels (p < 0.001). CONCLUSIONS: In the group with in-hospital complications after CABG, not only was the presence of diabetes mellitus more often detected, but there were also higher levels of free fatty acids and a higher Revised-QUICKI. Therefore, additional assessments of insulin resistance and free fatty acid levels are advisable in patients before CABG.

Association of Alternative Markers of Carbohydrate Metabolism (Fructosamine and 1,5-Anhydroglucitol) with Perioperative Characteristics and In-Hospital Complications of Coronary Artery Bypass Grafting in Patients with Type 2 Diabetes Mellitus, Prediabetes, and Normoglycemia.

Patients with type 2 diabetes make up 25 to 40% of those referred for coronary bypass surgery, and the impact of diabetes on the results of the operation is studied in various aspects. To assess the state of carbohydrate metabolism before any surgical interventions, including CABG, daily glycemic control, and the determination of glycated hemoglobin (HbA1c) is recommended. Glycated hemoglobin reflects the glucose concentration for the 3 months prior to the measurement, but alternative markers that reflect glycemic fluctuations over a shorter period of time may be useful in preoperative preparation. The aim of this study was to study the relationship between the concentration of alternative markers of carbohydrate metabolism (fructosamine and 1,5-anhydroglucitol) with patients' clinical characteristics and the rate of hospital complications after coronary artery bypass grafting (CABG). METHOD: In the cohort of 383 patients, besides the routine examination, additional markers of carbohydrate metabolism were determined before and on days 7-8 after CABG: glycated hemoglobin (HbA1c), fructosamine, and 1,5-anhydroglucitol. We evaluated the dynamics of these parameters in groups of patients with diabetes mellitus, prediabetes, and normoglycemia, as well as the association of these parameters with clinical parameters. Additionally, we assessed the incidence of postoperative complications and factors associated with their development. RESULTS: In all groups of patients (diabetes mellitus, prediabetes, normoglycemia), there was a significant decrease in the level of fructosamine on the 7th day after CABG compared with baseline (p1st-2nd point 0.030, 0.001, and 0.038 in groups 1, 2, and 3, respectively), whereas the level of 1,5-anhydroglucitol did not change significantly. The preoperative level of fructosamine was associated with the risk of surgery according to the EuroSCORE II scale (p = 0.002), as were the number of bypasses (p = 0.012), body mass index and overweightness (p < 0.001 in both cases), triglyceride (p < 0.001) and fibrinogen levels (p = 0.002), preoperative and postoperative glucose and HbA1c levels (p < 0.001 in all cases), left atrium size (p = 0.028), multiplicity of cardioplegia, cardiopulmonary bypass duration and aortic clamp time (p < 0.001 in all cases). The preoperative level of 1,5-anhydroglucitol showed an inverse correlation with fasting glucose and fructosamine levels before surgery (p < 0.001 in all cases), intima media thickness (p = 0.016), and a direct correlation with LV end-diastolic volume (p = 0.020). The combined endpoint (presence of significant perioperative complications + extended hospital stay after surgery >10 days) was identified in 291 patients. In binary logistic regression analysis patient age (p = 0.005) and fructosamine level (p = 0.022) were independently associated with the development of this composite endpoint (presence of significant perioperative complications + extended hospital stay after surgery >10 days). CONCLUSIONS: This study demonstrated that in patients after CABG there was the significant decrease in the level of fructosamine compared with baseline, whereas the level of 1,5-anhydroglucitol did not change. Preoperative fructosamine levels were one of the independent predictors of the combined endpoint. The prognostic value of preoperative assessment of alternative markers of carbohydrate metabolism in cardiac surgery deserves further study.

Characteristics of adipocytokine expression by local fat depots of the heart: Relationship with the main risk factors for cardio-vascular diseases.

In our study we investigated the relationships between adipocytokines in adipose tissue (AT) and cardiovascular disease (CVD) risk factors; (2) Methods: fat tissue biopsies were obtained from 134 patients with stable CAD undergoing coronary artery bypass grafting and 120 patients undergoing aortic or mitral valve replacement. Adipocytes were isolated from subcutaneous (SAT), epicardial (EAT), and perivascular AT (PVAT) samples, and cultured for 24 h, after which gene expression of adipocytokines in the culture medium was determined; (3) Results: men showed reduced ADIPOQ expression in EAT and PVAT, LEP expression in PVAT, and LEPR expression in SAT and PVAT compared to women. Men also exhibited higher SAT and lower PVAT IL6 than women. Meanwhile, dyslipidemia associated with decreased ADIPOQ expression in EAT and PVAT, LEPR in EAT, and IL6 in PVAT. Arterial hypertension (AH) associated with low EAT and PVAT ADIPOQ, and high EAT LEP, SAT, as well as PVAT LEPR, and IL6 in SAT and EAT. ADIPOQ expression decreased with increased AH duration over 20 years against an increased LEP background in ATs. Smoking increased ADIPOQ expression in all ATs and increased LEP in SAT and EAT, however, decreased LEPR in PVAT. Patients 51-59 years old exhibited the highest EAT and PVAT LEP, IL-6, and LEPR expression compared to other age groups; (4) Conclusions: decreased EAT ADIPOQ expression against an increased pro-inflammatory IL6 background may increase atherogenesis and contribute to CAD progression in combination with risk factors including male sex, dyslipidemia, and AH.

Long-Term Prognosis after Coronary Artery Bypass Grafting: The Impact of Arterial Stiffness and Multifocal Atherosclerosis.

The aim of the study was to study the effect of arterial stiffness and multifocal atherosclerosis on the 10-year prognosis of patients after coronary artery bypass grafting. Methods. Patients with coronary artery disease (n = 274) who underwent coronary artery bypass grafting (CABG), in whom cardio-ankle vascular index (CAVI) was assessed using the VaSera VS-1000 device and the presence of peripheral atherosclerosis in Doppler ultrasound. Groups were distinguished with normal CAVI (<9.0, n = 163) and pathological CAVI (≥9.0, n = 111). To assess the prognosis, coronary and non-coronary death, myocardial infarction, acute cerebrovascular accident/transient ischemic attack, repeated CABG, percutaneous coronary intervention, carotid endarterectomy, peripheral arterial surgery, pacemaker implantation were analyzed. Results. During the observation period, mortality was 27.7%. A fatal outcome from all causes was in 37 (22.7%) patients in the group with normal CAVI and in 39 (35.14%) in the group with pathological CAVI (p = 0.023). Death from cardiac causes was more common in the group with CAVI ≥ 9.0­in 25 cases (22.52%) than in the group with CAVI < 9.0­in 19 (11.6%, p = 0.016). The combined endpoint in patients with pathological CAVI was detected in 66 (59.46%) cases, with normal CAVI values­in 76 (46.63%) cases (p = 0.03). The presence of diabetes mellitus, multifocal atherosclerosis (p = 0.004), pathological CAVI (p = 0.063), and male gender were independent predictors of death at 10-year follow-up after CABG. The presence of multifocal atherosclerosis and pathological CAVI during the preoperative examination of patients were independent predictors of the combined endpoint development. Findings. Patients with coronary artery disease with pathological CAVI before CABG were more likely to experience adverse events and death in the long-term follow-up than patients with normal CAVI. Further studies are needed to investigate the possibility of correcting pathological CAVI after CABG after secondary prevention and the possible impact of this correction on prognosis.

[Frailty syndrome as an independent predictor of adverse prognosis in patients with chronic heart failure].

This review presents results of clinical studies of senile asthenia ("fragility") syndrome and chronic heart failure (CHF). Recent reports of the "fragility" prevalence in patients with CHF are described. The review presents specific features of pathophysiological pathways underlying the development of both senile asthenia syndrome and CHF; the role of "fragility" in the progression and complications of CHF is addressed. Senile asthenia syndrome associated with CHF is regarded as an independent predictor of unfavorable prognosis and high mortality in this patient category. The authors concluded that methods for "fragility" evaluation in CHF patients followed by risk stratification and selection of individual management tactics should be implemented in clinical practice.

Relationship between Epicardial and Coronary Adipose Tissue and the Expression of Adiponectin, Leptin, and Interleukin 6 in Patients with Coronary Artery Disease.

Adipose tissue (AT) is an endocrine and paracrine organ that synthesizes biologically active adipocytokines, which affect inflammation, fibrosis, and atherogenesis. Epicardial and perivascular fat depots are of great interest to researchers, owing to their potential effects on the myocardium and blood vessels. The aim of the study was to assess the expression and secretion of adipocytokine genes in the AT of patients with coronary artery disease (CAD) and patients with aortic or mitral valve replacement. This study included 84 patients with CAD and 50 patients with aortic or mitral valve replacement. Adipocytes were isolated from subcutaneous, epicardial (EAT), and perivascular AT (PVAT), and were cultured for 24 h. EAT exhibited the lowest level of adiponectin gene expression and secretion, regardless of nosology, and high expression levels of the leptin gene and interleukin-6 (IL-6). However, EAT adipocytes in patients with CAD were characterized by more pronounced changes in comparison with the group with heart defects. High leptin and IL-6 levels resulted in increased pro-inflammatory activity, as observed in both EAT and PVAT adipocytes, especially in individuals with CAD. Therefore, our results revealed the pathogenetic significance of alterations in the adipokine and cytokine status of adipocytes of EAT and PVAT in patients with CAD.

IL18-family Genes Polymorphism Is Associated with the Risk of Myocardial Infarction and IL18 Concentration in Patients with Coronary Artery Disease.

BACKGROUND: Atherogenesis is mainly determined by endothelial dysfunction, lipid metabolism disorders and inflammation. The atherogenesis-related inflammatory process is a complex interaction between serum blood lipoproteins, inflammatory cells, endothelial and smooth muscle cells and extracellular matrix; the role of chronic inflammation in atherogenesis was proposed. MATERIAL AND METHODS: A pathogenetic role of polymorphism in NF-kB pathway genes in coronary artery disease and associated pathological conditions has been suggested in a case-control retrospective study. 260 coronary artery disease patients permanently living in a large industrial region of Russian Federation (Kemerovo region) were recruited in the study. We examined nine single nucleotide polymorphisms in IL18, IL18R1 and IL18RAP genes by polymerize chain reaction; and serum blood level of IL18 by enzyme-linked immunosorbent assay. RESULTS: Polymorphic variants rs13015714 (IL18R1) and rs917997 (IL18RAP) are associated with the risk of myocardial infarction and high serum levels of IL18. Minor alleles of rs13015714 and rs917997 sites are associated with high risk of developing multifocal atherosclerosis and arterial hypertension in patients with stable coronary artery disease after myocardial infarction. CONCLUSIONS: Thus, polymorphism in the genes of IL18 receptor is determine the IL18 contents and important in the development of coronary atherosclerosis, associated pathological conditions and the risk of acute coronary events; prospective monitoring of patients with early clinical signs of adverse events is required to confirm the role of IL18, IL18R1, and IL18RAP genes polymorphism in atherogenesis.

Beneficial Effects of a Short Course of Physical Prehabilitation on Neurophysiological Functioning and Neurovascular Biomarkers in Patients Undergoing Coronary Artery Bypass Grafting.

This study aimed to evaluate the effects of a short course of physical prehabilitation on neurophysiological functioning and markers of the neurovascular unit in patients undergoing coronary artery bypass grafting (CABG). We performed a prospective randomized study involving 97 male CABG patients aged 45-70 years, 47 of whom underwent a 5-7-day preoperative course of aerobic physical training (PhT). Both groups of patients were comparable with respect to baseline clinical and anamnestic characteristics. An extended neuropsychological and electroencephalographic (EEG) study was performed before surgery and at 7-10 days after CABG. Markers of the neurovascular unit [S100ß, neuron-specific enolase (NSE), and brain-derived neurotrophic factor (BDNF)] were examined as metabolic correlations of early postoperative cognitive dysfunction (POCD) at three time points: before surgery, within the first 24 h after surgery, and 7-10 days after CABG. POCD developed in 58% of patients who underwent preoperative PhT, and in 79.5% of patients who did not undergo training, 7-10 days after CABG. Patients without prehabilitation demonstrated a higher percentage of theta1 power increase in the relative change values as compared to the PhT patients (p = 0.015). The short preoperative course of PhT was associated with low plasma S100ß concentration, but high BDNF levels in the postoperative period. Patients who underwent a short preoperative course of PhT had better cognitive and electrical cortical activity indicators. Markers of the neurovascular unit indicated lower perioperative brain injury after CABG in those who underwent training. A short course of PhT before CABG can decrease the brain's susceptibility to ischemia and reduce the severity of cognitive impairments in cardiac surgery patients. Electrical brain activity indicators and neurovascular markers, such as S100ß and BDNF, can be informative for the effectiveness of cardiac rehabilitation programs.

Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation.

An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca2+-binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.

Long-Term Neurophysiological Outcomes in Patients Undergoing Coronary Artery Bypass Grafting

Abstract Introduction: This study aims to evaluate late postoperative neurophysiological outcomes in patients after coronary artery bypass grafting (CABG). Methods: Forty-five male patients with stable coronary artery disease aged 45-69 years underwent extended neuropsychological assessment using the software Status PF and electroencephalographical examination 3-5 days before CABG and 5-7 years after CABG. Postoperative decline in cognitive functions was determined by a 20% decrease in the cognitive indicator compared to that at baseline on 20% of the tests included in the Status PF battery. Statistical analysis was performed using the software STATISTICA 10.0. Multiple regression was used to identify demographic, clinical, and electroencephalographical variables associated with adverse cognitive outcomes. Results: Cognitive decline was observed in 54% of the patients in the long-term postoperative period. Five to seven years after CABG, all patients have shown an increase in the theta rhythm power compared to the preoperative values, which is most pronounced in the frontal and temporal areas of the right hemisphere (P=0.04), along with a decrease in the alpha rhythm in the posterior areas of the cortex (P=0.005). Multiple regression has reported that the main predictors of cognitive impairment are slower mean alpha frequency, decreased theta-2 rhythm with eyes closed in the right temporal area, and increased theta-2 rhythm with eyes open in the left temporal area (F(5.39)=8.81; P<0.00007; adjusted R-squared=0.57). Conclusion: Our findings indicate that 54% of the patients suffer from postoperative cognitive decline associated with increased theta and decreased alpha rhythms 5-7 years after CABG.

Screening for Glucose Metabolism Disorders, Assessment the Disse Insulin Resistance Index and Hospital Prognosis of Coronary Artery Bypass Surgery.

OBJECTIVE: To study insulin resistance markers and their relationship with preoperative status and hospital complications of coronary artery bypass grafting (CABG) in patients with type 2 diabetes, prediabetes and normoglycemia. METHODS: We included 383 consecutive patients who underwent CABG. Patients were divided into two groups-with carbohydrate metabolism disorders (CMD, n = 192) and without CMD (n = 191). Free fatty acids and fasting insulin in plasma were determined, and the Disse, QUICKI and revised QUICKI indices were calculated in all patients. Perioperative characteristics and postoperative complications were analyzed in these groups, and their relations with markers of insulin resistance. RESULTS: Screening before CABG increased the number of patients with CMD from 25.3% to 50.1%. Incidence of postoperative stroke (p = 0.044), and hospital stay after CABG > 30 days (p = 0.014) was greater in CMD patients. Logistic regression analysis revealed that an increase in left atrial size, age, aortic clamping time, and decrease in Disse index were independently associated with hospital stay >10 days and/or perioperative complications. CONCLUSIONS: Screening for CMD before CABG increased the patient number with prediabetes and type 2 diabetes. In the CMD group, there were more frequent hospital complications. The Disse index was an independent predictor of long hospital stay and/or poor outcomes.

Long-Term Neurophysiological Outcomes in Patients Undergoing Coronary Artery Bypass Grafting.

INTRODUCTION: This study aims to evaluate late postoperative neurophysiological outcomes in patients after coronary artery bypass grafting (CABG). METHODS: Forty-five male patients with stable coronary artery disease aged 45-69 years underwent extended neuropsychological assessment using the software Status PF and electroencephalographical examination 3-5 days before CABG and 5-7 years after CABG. Postoperative decline in cognitive functions was determined by a 20% decrease in the cognitive indicator compared to that at baseline on 20% of the tests included in the Status PF battery. Statistical analysis was performed using the software STATISTICA 10.0. Multiple regression was used to identify demographic, clinical, and electroencephalographical variables associated with adverse cognitive outcomes. RESULTS: Cognitive decline was observed in 54% of the patients in the long-term postoperative period. Five to seven years after CABG, all patients have shown an increase in the theta rhythm power compared to the preoperative values, which is most pronounced in the frontal and temporal areas of the right hemisphere (P=0.04), along with a decrease in the alpha rhythm in the posterior areas of the cortex (P=0.005). Multiple regression has reported that the main predictors of cognitive impairment are slower mean alpha frequency, decreased theta-2 rhythm with eyes closed in the right temporal area, and increased theta-2 rhythm with eyes open in the left temporal area (F(5.39)=8.81; P<0.00007; adjusted R-squared=0.57). CONCLUSION: Our findings indicate that 54% of the patients suffer from postoperative cognitive decline associated with increased theta and decreased alpha rhythms 5-7 years after CABG.

Expression of adipocytokines in heart fat depots depending on the degree of coronary artery atherosclerosis in patients with coronary artery disease.

In coronary artery disease (CAD) the adipocytokine content in the heart fat depot is altered, but it has not been established whether these changes are associated with the degree of atherosclerotic damage to the coronary artery (CA). Were examined 84 patients with CAD, and according to the degree of atherosclerotic state based on the SYNTAX Score scale, were divided: 39 moderate (≤22 points), 20 severe (23-31 points) and 25 extremely severe (≥32 points). Biopsies of subcutaneous (SAT), epicardial (EAT) and perivascular adipose tissue (PVAT) were obtained during elective coronary artery bypass grafting (CABG). The expression of adipocytokine was determined using real-time PCR. The concentration of the studied adipocytokines in adipocyte culture medium was measured by ELISA. Statistical analysis was performed using logistic regression analysis. In the adipocytes of the cardiac depot of patients with CAD, an increase in the expression and secretion of leptin and IL-6 and a decrease in adiponectin, with a maximum manifestation in severe and extremely severe CA lesions, was observed. EAT adipocytes were characterized by minimal expression of the adiponectin gene maximal gene expression leptin and IL-6 compared to SAT and PVAT adipocytes.

Assessment of Arterial Stiffness by Cardio-Ankle Vascular Index for Prediction of Five-Year Cardiovascular Events After Coronary Artery Bypass Surgery.

The study aim was to investigate the possibility of cardiovascular complications development predicting during a five-year follow-up of patients after coronary artery bypass grafting (CABG) using the cardio-ankle vascular index (CAVI) assessment. Methods: Three hundred and fifty-six patients after elective CABG were enrolled in the study. Prior to surgery, arterial stiffness was assessed in all patients using CAVI. The follow-up was performed five years after the surgery, information was obtained on 238 patients, who were divided into two groups: patients with pathological (≥9.0, n = 88), and normal (<9.0, n = 150) CAVI. Results: Pathological CAVI (≥9.0) was detected in 33% patients before CABG, in stepwise analyses only age and left atrium dimensions statistically significantly predicted CAVI. In patients with pathological CAVI the combined endpoint (major adverse cardiovascular events and hospitalization) and cardiovascular death developed more often in a five-year follow-up after CABG compared with normal CAVI (48.86% versus 34.9%, p = 0.034 and 4.55% versus 0.67%, p = 0.049, respectively). Pathological CAVI (p = 0.021) and the number of coronary bypass grafts (p = 0.023) were independent factors associated with the combined endpoint. Conclusions: Patients with pathological CAVI before CABG surgery are more likely to develop cardiovascular complications and cardiovascular death within a subsequent five-year follow-up. Evaluation of CAVI after CABG in dynamics deserves further study, it is important for monitoring the effects of secondary prevention and the possibility of influencing the prognosis.

EEG and Clinical Factors Associated with Mild Cognitive Impairment in Coronary Artery Disease Patients.

BACKGROUND: Although an impaired cognitive status in patients with coronary artery disease (CAD) is not rare, the neurophysiological and clinical indicators of mild cognitive impairment (MCI) have been insufficiently investigated so far. METHODS: EEG and neuropsychological testing as well as clinical examination were performed on 122 patients with CAD, who were divided into two groups, those with MCI (n = 60; mean age 57.4 ± 5.81 years) and those without MCI (n = 62; mean age 57.0 ± 5.04 years). Binary logistic regression was used to identify the relationship between EEG and clinical variables and the probability of MCI. RESULTS: Higher theta/alpha ratios, theta1 rhythm power with closed eyes in the frontal and occipital areas of the left hemisphere, and alpha2 rhythm power with eyes open in the frontal areas of the right hemisphere were associated with an increased risk for MCI in CAD patients. A low educational level, type 2 diabetes mellitus, and severe coronary lesions according to the SYNTAX Score (≥23 points) increased the risk for MCI as well. CONCLUSIONS: The findings of our study show that a theta activity increase in frontal and occipital sites, as well as high theta/alpha ratios, may be considered as the earliest EEG markers of vascular cognitive disorders.

The prevalence of familial hypercholesterolemia in the West Siberian region of the Russian Federation: A substudy of the ESSE-RF.

BACKGROUND: The prevalence of familial hypercholesterolemia (FH) in Russia has not previously been evaluated. The aim of our study was to investigate the prevalence of FH in the population of the West Siberian region of Russia, and then estimate the frequency of coronary artery disease (CAD) and treatment with cholesterol-lowering medication in FH patients. METHODS: The sample of our study consisted of participants from the population-based cohort of The Epidemiology of Cardiovascular Risk Factors and Diseases in Regions of the Russian Federation Study (ESSE-RF), conducted in the Tyumen and Kemerovo regions (1,630 and 1,622 people, respectively, aged 25-64). All participants who had LDL-cholesterol higher than 4.9 mmol/l and who had LDL-cholesterol less than or equal to 4.9 mmol/l but had statin therapy were examined and interviewed by experts in FH. RESULTS: The prevalence of patients with definite FH was 0.24% (one in 407) (95% confidence interval [CI]: 0.06%-0.42%), with probable FH was 0.68% (one in 148) (95% CI: 0.38%-0.98%), and with definite or probable FH combined was 0.92% (one in 108) (95% CI: 0.58%-1.26%). 40% (95% CI: 20.8%-59.2%) of patients with definite or probable FH had CAD. However, only 23% (95% CI: 6.3%-39.7%) of patients with definite or probable FH were on statins. The odds ratios for CAD and myocardial infarction (MI), adjusted for age, gender, region, smoking, hypertension, and diabetes mellitus, were 3.71 (95% CI: 1.58-8.72) (p = 0.003) and 4.06 (95% CI: 0.89-18.55) (р = 0.070) respectively for individuals with definite or probable FH relative to those who were unlikely to have FH. CONCLUSIONS: The prevalence of FH in Russia may be significantly higher than previously estimated. There is underdiagnosis and undertreatment of FH in Russia.

CYP2C19 polymorphism frequency in Russian patients in Central Russia and Siberia with acute coronary syndrome.

PURPOSE: The aim of this study is to investigate the frequency of CYP2C19*2, *3 allelic variants, associated with poor response to clopidogrel, and CYP2C19*17, associated with excessive response to clopidogrel, in patients with acute coronary syndrome (ACS) from Siberia and Moscow regions of Russia. PATIENTS AND METHODS: The study included 512 ACS patients who were subsequently treated with coronary arterial stenting. The subjects assigned were from the cities of Central (Novosibirsk, Kemerovo), Eastern (Irkutsk), Northern (Surgut) Siberia regions and from Moscow region. The mean age of patients enrolled was 63.9±10.9 years. Among the assigned subjects, the proportion of men accounted for 80% and women 20%. RESULTS: According to the results obtained in the present study, from 16% up to 27.5% of patients in different regions of Russia have at least one CYP2C19 "poor metabolizer" (PM) allele variant affecting clopidogrel metabolism and, therefore, suppressing its antiplatelet activity. CYP2C19*17 allele variant was identified with the frequency of 15.4% up to 33.3%. The study revealed the presence of statistically significant differences in CYP2C19*3 allele frequency between the Russian ethnic group patients from Eastern and Central Siberia (p=0.001; odds ratio=1.05 [95% confidence interval 1.01-1.09]). CONCLUSION: The study revealed statistically significant differences between the allele frequencies in Eastern and Central Siberia, which can probably be caused by a considerable number of Buryats inhabiting Eastern Siberia.

Serum neutrophil gelatinase-associated lipocalin has an advantage over serum cystatin C and glomerular filtration rate in prediction of adverse cardiovascular outcome in patients with ST-segment elevation myocardial infarction.

BACKGROUND: The aim of this study was to assess significance of serum neutrophil gelatinase-associated lipocalin (sNGAL) and cystatin C (sCC) in prediction of adverse cardiovascular outcome after ST-segment elevation myocardial infarction (STEMI). METHODS: We recruited 357 consecutive patients who were admitted to the hospital within 24 h after onset of STEMI. On the 1st and 12th-14th day after hospital admission, we measured levels of sNGAL and sCC. We also determined presence of renal dysfunction (RD), defined as glomerular filtration rate < 60 mL/min/1.73 m2. After 3 years of follow-up, we performed a logistic regression and assessed the value of RD, sNGAL, and sCC in prediction of combined endpoint, defined as cardiovascular death or any cardiovascular complication. RESULTS: RD, sCC level ≥ 1.9 mg/L, and sNGAL level ≥ 1.25 ng/mL on the 12th-14th day of hospitalization were associated with a 1.6-fold, 1.9-fold, and 2.9-fold higher risk of adverse cardiovascular outcome, respectively. Area under the ROC curve was the highest for the model based on sNGAL level compared to the models based on sCC level or RD presence. CONCLUSIONS: Measurement of sNGAL level in patients with STEMI on the 12th-14th day after hospital admission may improve prediction of adverse cardiovascular outcome.