ВЛИЯНИЕ ПОЧЕЧНОЙ ДИСФУНКЦИИ НА РАННИЕ И ОТДАЛЕННЫЕ РЕЗУЛЬТАТЫ КОРОНАРНОГО ШУНТИРОВАНИЯ

The study is aimed at the comparative assessment of the incidence of adverse cardiovascular events in the inhospital and long-term period in patients with initial renal dysfunction (RD) and without it after coronary artery bypass grafting (CABG).Material and methods: 720 patients with clinical manifestations of coronary atherosclerosis, operated on between 2011 and 2012, were included in the study. All patients underwent preoperative measurement of serum creatinine levels, the estimation of glomerular filtration rate (GFR) using the MDRD formula, and the risk scoring using the additive EuroSCORE model.Results: The cut-off value for GFR was set at 60 mL / min / 1.73 m2 in this study, suggesting significant impact on the patients’ outcomes after CABG. There were differences in the preoperative clinical status among the patients with and without RD. Patients with decreased GFR were more likely to have chronic kidney disease, lower extremity arterial disease, extracranial arterial disease, compared to patients with normal GFR. Patients with RD reported higher rates of adverse cardiovascular and renal complications in the in-hospital period. Patients with decreased GFR < 60 mL / min / 1,73m2 were more likely to have recurrent angina and progression of chronic heart failure one year after CABG. The assessment of the impact of renal dysfunction, defined by the levels of GFR, on the development of adverse outcome reported that patients with RD in the moderate risk group were more likely to have combined adverse outcome, compared to patients without RD one year after CABG. Conclusion: The presence of renal dysfunction has an adverse impact on the in-hospital outcome after CABG. Renal dysfunction had no predictive value on long-term outcome, but it increased the incidence of higher angina class and chronic heart failure.Целью настоящего исследования явилась сравнительная оценка частоты развития неблагоприятных сердечно-сосудистых событий у пациентов, подвергшихся коронарному шунтированию (КШ) в госпитальном и отдаленном периоде с наличием исходной почечной дисфункции (ПД) и без таковой.Материал и методы: в исследование включено 720 пациентов, прооперированных в 2011-2012 гг. по поводу клинически манифестирующего коронарного атеросклероза. Всем пациентам перед проведением КШ определяли концентрацию креатинина в сыворотке крови и рассчитывали скорость клубочковой фильтрации (СКФ) по формуле MDRD, а также определяли балл по аддитивной шкале риска EuroSCORE.Результаты: в проведенном исследовании в качестве порогового значения СКФ выбран уровень 60 мл/мин/1,73 м2, который продемонстрировал значимое влияние на ближайшие исходы у больных, подвергшихся КШ. Выявлены различия в дооперационном клиническом статусе пациентов с наличием и отсутствием ПД. Пациенты со сниженной СКФ чаще имели хроническое заболевание почек в анамнезе, значимое поражение артерий нижних конечностей и экстракраниальных артерий по сравнению с пациентами с нормальной СКФ. В госпитальном периоде выявлено, что среди пациентов с ПД чаще развиваются неблагоприятные сердечно-сосудистые и почечные осложнения. Через год после КШ у пациентов со сниженной СКФ менее 60 мл/мин/1,73м2 чаще возобновляются приступы стенокардии и прогрессирование хронической сердечной недостаточности. При оценке вклада почечной дисфункции, определяемой по уровню СКФ, в развитие неблагоприятного исхода установлено, что только в группе пациентов среднего риска комбинированный неблагоприятный исход развивается чаще среди пациентов ПД по сравнению с пациентами без ПД через 1 год после КШ.Заключение: наличие почечной дисфункции оказывает неблагоприятное влияние на госпитальный исход КШ. В отношении развития отдаленного исхода наличие почечной дисфункции не обладает прогностической ценностью, однако повышает частоту развития стенокардии высокого ФК и хронической сердечной недостаточности

THE ROLE OF MULTIFOCAL ATHEROSCLEROSIS IN DEVELOPMENT OF UNFAVORABLE CARDIOVASCULAR OUTCOMES IN PATIENTS AFTER CORONARY BYPASS GRAFTING

Background: The number of disorders caused by atherosclerosis of various arterial tree is constantly increasing worldwide. Multifocal atherosclerosis (MFA) remains to be an important problem limiting effectiveness of coronary bypass grafting.Aim: To compare one-year rates of unfavorable cardiovascular events in patients, who underwent coronary bypass grafting, depending on the degree of non-coronary stenoses (stenoses of extracranial arteries and lower limb arteries).Materials and methods: Two hundred and thirty two patients, that underwent coronary bypass graft surgery in 2006 due to clinical manifest coronary atherosclerosis, were included into the study. Oneyear outcome (10–12 months) was assessed with the following endpoints: coronary and non-coronary death, myocardial infarction, stroke, angina pectoris and severe chronic heart failure (III–IV functional classes). One-year combined outcome after coronary bypass grafting was considered unfavorable if these events were registered.Results: After initial assessment, patients were divided into 2 groups depending on the degree of coronary atherosclerosis; thereafter, each group was subdivided into subgroups depending on presence or absence of MFA. Compared to patients without MFA, those with hemodynamically significant stenosis (≥ 50%) of non-coronary arteries had higher rates of unfavorable one-year outcomes (р = 0.001). They had higher rates of stroke (20% (5) and 5.8% (12) of patients, respectively, р = 0.03) and of recurrent angina (р = 0.001). Patients with hemodynamically non-significant stenoses (≥ 30%) also had significantly higher rates of unfavorable events, compared to patients without stenoses: myocardial infarction, in 12 (11%) and 3 (2%), respectively (p = 0.006), stroke, in 14 (13%) and 3 (2%) (p = 0.001). Eighty four (79%) patients with MFA had clinical manifestations of angina pectoris, whereas among those without MFA, only 23 (18%) of patients (p = 0.0001). Severe chronic heart failure was significantly more frequent in the MFA group, than in patients with isolated coronary atherosclerosis (38 (36%) and 21 (17%) patients, respectively, p = 0.002). In the MFA group, 10 (9%) patients died, while in the group without MFA there was one death (0.8%) (p = 0.003).Conclusion: Taking into account non-coronary stenoses of ≥ 30%, compared to only hemodynamically significant stenoses of ≥ 50%, produces more significant differences in clinical and historical characteristics of patients

N-TERMINAL BRAIN NATRIURETIC PROPEPTIDE AS A MARKER OF MULTIFOCAL ATHEROSCLEROSIS IN PATIENTS WITH ST SEGMENT ELEVATION MYOCARDIAL INFARCTION

Aim. To investigate the association between serum levels of N‑terminal brain natriuretic propeptide(Nt-proBNP)andtheseverityofcoronaryandnon-coronaryatherosclerosisin patients with myocardial infarction and ST segment elevation (STEMI). Material and methods. The study included 186 STEMI patients. All participants underwent coronary angiography and angioplasty with infarct-related artery stenting, as well as the screening assessment of non-coronary atherosclerosis of brachiocephalic arteries and large lower extremity arteries. The measurement of Nt-proBNP levels was performed 10–14 days after the STEMI onset. Results. Nt-proBNP levels were not associated with the severity of coronary atherosclerosis. However, patients with more advanced non-coronary atherosclerosis and a higher number of affected non-coronary vessels demonstrated elevated Nt-proBNP concentrations. After adjustment for age, severity of heart failure and myocardial dysfunction, Nt-proBNP were still associated with atherosclerosis multifocality. Conclusion. In STEMI patients, Nt-proBNP concentrations were associated with severity and multifocality of non-coronary atherosclerosis. This could be used in clinical practice for predicting the risk of repeat atherosclerotic cardiovascular events

CLINICAL AND PREDICTIVE VALUE OF SERUM INTERLEUKINE-18 IN ST ELEVATION MYOCARDIAL INFARCTION

Aim. To assess clinical and predictive value of serum IL-18 in ST elevation myocardial infarction.Material and methods. Totally, 132 patients included, hospitalized to Kemerovo cardiovascular dispensary due to STEMI with <24 hours pain onset. Assessment of IL-18 concentration (pg/ml) was done on 12th day of care.Results. Mean concentration of IL-18 in all patients was 244,02 (172,13-315,91) pg/ml, that was 3,5 times higher than reference range. Correlation analysis showed relation of IL-18 levels with total cholesterol, with low density lipoproteides, left ventricle ejection fraction, glomerular filtration rate (GFR) by CKD-EPI: r=0,18 (р=0,040), r=0,24 (р=0,008), r=-0,19 (р=0,029), r=-0,18 (р=0,039), resp. Median concentration of IL-18 in multifocal atherosclerosis (MFA) patients was 214,75 (129,20-362,35) pg/ml vs. 140,40 (97,80-292,80) pg/ml in non-MFA patients (р=0,010). In those patients without any significant progression of BCA lesion, baseline concentration of IL-18 was 271,0 (128,3-358,4) mg/ml, but in patients with the increase of stenosis grade more than 30% and/or appearance of novel plaques the level of IL-18 was 119,35 (94,61-188,95) pg/ml.Conclusion. In prediction of early (in-hospital) and long-term (3-year) stages of myocardial infarction there was no any clinical and predictive value of IL-18. Concentration of serum IL-18 did not relate to kidney diseases in STEMI patients, but correlates negatively with GFR defined by CKD-EPI. There was significant role of IL-18 in forming of multifocal atherosclerosis. High concentrations of IL-18 at 12th day of hospitalization were related to the increase of total cholesterol and LDL, and with the decrease of contractility of the left ventricle myocardium. In STEMI with MFA there is increase of IL-18 1,5 times. At the same time significant progression of atherosclerotic lesion during one year was found in patients with lower baseline IL-18 level, which requires further studies of the IL-18 role in atherogenesi

RELATIONSHIP OF MULTIFOCAL ATHEROSCLEROSIS AND RENAL DYSFUNCTION WITH IN-HOSPITAL COMPLICATIONS AFTER CORONARY BYPASS OPERATION IN ISCHEMIC HEART DISEASE

Aim. To assess the occurence of hemodynamically non-significant multifocal atherosclerosis (from 30% and more), renal dysfunction and their influence on the outcomes of in-hospital period of patients underwent coronary bypass surgery (CABG).Material and methods. The perioperational period of 720 patients analyzed, who were operated in 2011-2012 y. Before CABG all patients were assessed by colored duplex scanning of extracranial arteries and arteries of lower extremities to reveal the signs of multifocal atherosclerosis (MFA), also the creatinine concentration was measured in 1 day before and 7 days after CABG, and GFR was calculated by MDRD equation. The prevalence of worse outcomes was assessed after the operation (myocardial infarction, stroke, acute renal failure, remediastinotomy, death) during in-hospital period.Results. The prevalence of hemodynamically non-significant MFA (30% and more) in patients with CHD after CABG was 48%. Renal dysfunction (RD), by a decrease of GFR <60 ml/min/1,73 m2, developed in 16% of patients underwent CABG. Concomitance of MFA and RD was 21,3%. It was found that in a quarter of patients after CABG there was an adverse outcome that was more prevalent among only those with RD: in 37,9% vs. 22,3% (p=0,03). There were no significant differents found by the prevalence of an adverse outcome in patients only with MFA. Concomitance of MFA and RD was associated with higher chance of adverse outcome in CABG with CHD: in 39,7% cases vs. 23,8% (p=0,006).Conclusion. The high prevalence of MFA and RD (21,3%) was reveled in CHD patients, underwent CABG. Concomitance of MFA and RD is associated with the development of adverse outcome in CABG. It is stated that this exact group of patients is characterized by the highest amount of earlier CABG complications. The main influence on this is of RD, however it is not possible to definitely distinguish the grade of prognostic value of MFA and RD due to common pathophysiological factors of the development of both and quite complicated mechanisms of their influence and worsening

Application of biological markers of kidney injury for prognosis of long-term adverse outcomes in patients with ST-segment elevation myocardial infarction

Objective: To study the prognostic significance of serum NGAL (sNGAL) and cystatin C in the acute phase of ST-segment elevation myocardial infarction (STEMI) in the late disease period. Material and Methods: 357 patients with STEMI, admitted to hospital within 24 h of symptom onset, were included in the study. Serum creatinine levels with the calculation of glomerular filtration rate (GFR) using the MDRD as well as levels of sNGAL and cystatin C were measured on day 1 and 12–14. Results: All patients were divided into 2 groups according to their estimated GFR: with and without renal dysfunction (RD), defined as a decrease of GFR < 60 ml/min/1.73 m2. Within 3 years of follow-up, the composite endpoint (CEP) were assessed (CEP – death + non-fatal cardiovascular events). The ROC curve analysis was used to determine the thresholds for every biomarker, involved in the CEP development: NGAL (≥ 1.25 ng / ml) and cystatin C (≥ 1.9 mg / l). On day 12–14 of hospitalization elevated NGAL ≥ 1.25 ng / mL was associated with a 3-fold increased risk for adverse cardio vascular events in a 3-year follow up after STEMI; whereas, elevated cystatin C ≥ 1.9 mg/l – with a 2-fold increased risk for the CEP, and signs of RD, found in patients before the discharge from the hospital, – with a 1.5-fold increased cardiovascular risk. The model considering an increase of NGAL over 1.25 ng / l has the highest prognostic value, while the models based on the levels of cystatin C and GFR are of equal prognostic value. Conclusion: The most promising issue in the prognosis of long-term adverse outcomes in patients with STEMI may be considered the assessment of RD using new biomarkers such as sNGAL

Cystatine C role in predicting the in-hospital adverse outcomes of coronary artery bypass graft surgery

Aim. To assess the clinical value of cystatin C for the prediction of the in-hospital complication risk among patients with coronary heart disease (CHD) who underwent coronary artery bypass graft surgery (CABG). Material and methods. The perioperative period data were analysed for 583 patients who underwent CABG in March-November 2011. Before the surgery, all patients underwent colour duplex ultrasound of peripheral arteries. One day before CABG and at Day 7 after the surgery, serum levels of creatinine and glomerular filtration rate (GFR; MDRD formula) were assessed. In 150 participants, cystatin C concentration was measured one day before the surgery and at Day 7 after CABG. The incidence of in-hospital adverse outcomes of CABG, such as myocardial infarction, stroke, acute renal failure, and repeat mediastinotomy, was evaluated. In all participants, the risk levels by the EuroSCORE scale were measured. Results. Pre- and post-surgery levels of serum creatinine and GFR did not differ significantly between the low, intermediate, and high EuroSCORE risk groups. Moreover, pre- and post-CABG levels of serum creatinine and GFR were similar in patients with favourable and adverse outcomes. However, the concentration of cystatin C, both before and after CABG, was significantly higher in patients with adverse outcomes, compared to participants with favourable outcomes. Conclusion. These findings suggest that cystatin C could be used as a universal prognostic marker of cardiovascular complications and renal dysfunction in post-CABG patients

ROLE OF THE SERUM NGAL FOR ASSESSMENT OF HOSPITAL PROGNOSIS IN MEN WITH ST ELEVATION MYOCARDIAL INFARCTION

Aim. To evaluate clinical significance of serum NGAL in ST elevation myocardial infarction (STEMI) patients in relation with the occurrence of in-hospital period complications.Material and methods. Totally 260 men included with STEMI, hospitalized in 24 hours after the onset of clinical symptoms of the disease. The measurement of serum NGAL concentration (ng/ml, sNGAL) at 1st and 2nd day of hospitalization was done with the hard-phase immune-enzyme analysis by Hycult® biotech assay (USA), registration was done on the plain reader “UNIPLAN” (SPF “PIKON”, Russia). At the stage of in-hospital treatment we registrated endpoints — signs of coronary failure (early post infarction angina, recurrent MI), grade of acute coronary failure (Killip I-IV class), grade of chronic heart failure (by NYHA), hospital mortality.Results. Patients were selected into 2 groups depending on the endpoints occurrence at hospital stage. Adverse hospital outcome (at least one endpoint) was found in 83 (32%) patients. The level of renal damage sNGAL, measured on the 1st day did not reveal any difference between groups with adverse or benign course of MI in hospital, and on 12th day the sNGAL concentration was significantly higher in group with adverse course — 2,1 ng/ml (1,44; 2,8) vs 1,55 ng/ml (1,11; 2,3), p=0,033. Monofactor analysis showed significance for adverse outcome, the factors as 2nd type diabetes, age &gt;60 y., the fact of glomerular filtration rate decline during hospitalization, increase of sNGAL by 12th day. By the result of multifactor analysis — increase of the age by 1 year increases the chance of adverse outcome by 14%, increase of sNGAL by 12th day of MI increases adverse outcome chance by 3,2 times. the level of sNGAL ≥1,046 ng/ml associated with complicated course of in-hospital MI period.Conclusion. The level of sNGAL, measured on 1st day of MI did not have prognostic value for the inhospital complications, however concentration of sNGAL on 12th day was associated with already occured adverse outcomes, being a marker of MI severity

Modulation of Notch Signaling at Early Stages of Differentiation of Human Induced Pluripotent Stem Cells to Dopaminergic Neurons

Elaboration of protocols for differentiation of human pluripotent stem cells to dopamine neurons is an important issue for development of cell replacement therapy for Parkinson’s disease. A number of protocols have been already developed; however, their efficiency and specificity still can be improved. Investigating the role of signaling cascades, important for neurogenesis, can help to solve this problem and to provide a deeper understanding of their role in neuronal development. Notch signaling plays an essential role in development and maintenance of the central nervous system after birth. In our study, we analyzed the effect of Notch activation and inhibition at the early stages of differentiation of human induced pluripotent stem cells to dopaminergic neurons. We found that, during the first seven days of differentiation, the cells were not sensitive to the Notch inhibition. On the contrary, activation of Notch signaling during the same time period led to significant changes and was associated with an increase in expression of genes, specific for caudal parts of the brain, a decrease of expression of genes, specific for forebrain, as well as a decrease of expression of genes, important for the formation of axons and dendrites and microtubule stabilizing proteins