Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

Changes in the structural and functional characteristics of the epicardial adipose tissue (EAT) are recognized as one of the factors in the development of cardiometabolic diseases. However, the generally accepted quantitative assessment of the accumulation of EAT does not reflect the size of adipocyte and presence of adipocyte hypertrophy in this fat depot. Overall contribution of adipocyte hypertrophy to the development and progression of coronary atherosclerosis remains unexplored. Objective: To compare the morphological characteristics of EAT adipocyte and its sensitivity to insulin with the CAD severity, as well as to identify potential factors involved in the realization of this relationship. The present study involved 24 patients (m/f 16/8) aged 53–72 years with stable CAD, who underwent coronary artery bypass graft surgery. Adipocytes were isolated enzymatically from EAT explants obtained during the operation. The severity of CAD was assessed by calculating the Gensini score according to selective coronary angiography. Insulin resistance of EAT adipocytes was evaluated by reactivity to insulin. In patients with an average size of EAT adipocytes equal to or exceeding the median (87 μm) the percentage of hypertrophic adipocytes was twice as high as in patients in whom the average size of adipocytes was less than 87 μm. This group of patients was also characterized by the higher rate of the Gensini score, lower adiponectin levels, and more severe violation of carbohydrate metabolism. We have revealed direct nonparametric correlation between the size of EAT adipocytes and the Gensini score (rs = 0.56, p = 0.00047). The number of hypertrophic EAT adipocytes showed a direct nonparametric correlation with the Gensini score (rs = 0.6, p = 0.002). Inverse nonparametric correlations were found between the serum adiponectin level and size (rs = −0.60, p = 0.001), hypertrophy of adipocytes (rs = −0.67, p = 0.00), and Gensini score (rs = −0.81, p = 0.00007). An inverse nonparametric correlation was found between the Gensini score and sensitivity of EAT adipocytes to insulin, estimated by the intracellular redox response (rs = −0.90, p = 0.037) and decrease in lipolysis rate upon insulin addition (rs = −0.40, p = 0.05). The intracellular redox response of adipocytes to insulin was directly correlated with fasting insulin and inversely with postprandial insulin. Our data indicate that the size and degree of hypertrophy of the epicardial adipocytes are related to the CAD severity. According to our results, insulin resistance of adipocytes may be considered as one of the factors mediating this relationship.

Background: Monocytes are recognized as central cells in the progression of atherosclerosis, and are subcategorized into classical (CD14++CD16 lo), intermediate (CD14++CD16 hi) and non-classical (CD14+CD16 hi) subsets. Purpose: The present study aimed to assess the relationships between different subsets of monocytes, metabolic and inflammatory factors in patients with stable coronary heart disease. Methods: A total of 26 patients (both men and women) with stable ischemic heart disease (IHD) were recruited. Among all the recruited patients, 17 patients had significant coronary artery disease defined as diameter stenosis more than 70%. Severity of CHD was assessed by the Gensini score (GS). Counts of CD14++CD16 lo , CD14++CD16 hi , and CD14+CD16 hi monocytes were evaluated by flow cytometry. Gating was verified and expression of CD163 was determined by imaging flow cytometry. Key cardiac markers, cytokines, and chemokines were detected in serum and in 24-hour-culture medium for peripheral blood mononuclear cells (PBMC) by multiplex analysis. The Mann-Whitney U-test and Spearman's rank correlation coefficient (r) were used for statistical analysis. Results: Patients with stenosis <70% tended to have higher frequency of CD14+CD16 hi monocytes compared to patients with coronary artery stenosis >70%. The frequencies of CD163+CD14++CD16 hi and CD163+CD14+CD16 hi monocytes were elevated in patients with stenosis >70%. In patients with stenosis <70%, the frequency of classical monocytes positively correlated and the frequency of non-classical monocytes negatively correlated with the value of GS (R ¼ 0.757; p ¼ 0.018 and R ¼-0.757; p ¼ 0.018, respectively). Conclusions: In patients with ischemic heart disease, the frequency of classical monocytes was directly correlated with the severity of atherosclerosis, while the frequency of non-classical monocytes was correlated inversely. The effects of these monocyte subsets in the development of myocardial ischemia still need to be elucidated.

ВведениеП о данным Всемирной организации здравоохра-нения (ВОЗ), с 1980 г. число лиц во всем мире, страдающих ожирением, более чем удвоилось. В 2014 г. более 1,9 млрд людей в возрасте 18 лет и старше имели избыточный вес, из этого числа свыше 600 млн страдали от ожирения [1]. Эпидемия ожирения стала одной из наиболее важных проблем, лежащих в основе развития сердечно-сосудистых заболеваний (ССЗ) и метаболических нарушений, таких как артериальная гипертензия, инсулинорезистентность, дислипидемия. Данные об ассоциации ожирения с кардиоваскуляр-ными заболеваниями до настоящего времени неодно-значны и противоречивы. Многие популяционные исследования демонстрируют парадоксальные выводы относительно прогностического значения ожирения ФГБНУ «Томский национальный исследовательский медицинский центр Российской академии наук», Томск Кологривова И.В.*, Винницкая И.В., Кошельская О.А., Суслова Т.Е.Вопрос прогностического значения ожирения в развитии сердечно-сосудистых заболеваний до сих пор остается открытым. Различный вклад висцеральной и подкожной жировой ткани в формирование кардиометаболического риска освещен во мно-гих исследовательских работах. Данные ряда эпидемиологических исследований подтверждают связь висцерального ожи-рения с формированием аномального метаболического профиля и повышенным сердечно-сосудистым риском, в то время как подкожной жировой ткани приписывают относительные протективные свойства. Патофизиологические механизмы, опосредующие связь висцерального ожирения с развитием атеросклероза, остаются недостаточно изученными. Установлено, что половые гормоны, эстрогены и андрогены принимают участие в перераспределении жировой ткани, поддержании энер-гетического гомеостаза, оказывают влияние на секрецию адипокинов и иммунорегуляцию жировой ткани. При этом широко представленные в жировой ткани клетки иммунной системы, в том числе и адаптивного иммунитета, вносят вклад в развитие системного воспаления при ожирении и участвуют в атерогенезе. По данным последних исследований, нарушение продукции стероидных гормонов может быть взаимосвязано с развитием локального субклинического воспаления и влиять на характер кардиометаболических эффектов жировой ткани. В обзоре обсуждаются возможные механизмы, за счет которых осущест-вляется данная взаимосвязь и реализуется сердечно-сосудистый риск при ожирении. The issue of the prognostic value of obesity in the development of cardiovascular diseases still remains open. Different input of visceral and subcutaneous adipose tissue in the formation of cardiometabolic risk is highlighted in many research works. A range of epidemiological studies provides data confirming relation of the visceral adiposity with abnormal metabolic profile and increased cardiovascular risk, while subcutaneous adipose tissue is attributed with relative protective properties. Pathophysiological mechanisms mediating interconnection of visceral adiposity with the development of atherosclerosis remain studied incompletely. It was stated that sex hormones, estrogens and androgens, participate in the redi...

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Purpose. This work investigates the relations between the production of reactive oxygen species (ROS) by epicardial adipose tissue (EAT) adipocytes and parameters of glucose/insulin metabolism, circulating adipokines levels, and severity of coronary atherosclerosis in patients with coronary artery disease (CAD); establishing significant determinants describing changes in ROS EAT in this category of patients. Material and methods. This study included 19 patients (14 men and 5 women, 53–72 y.o., 6 patients with diabetes mellitus type 2; 5 patients with prediabetes), with CAD, who underwent coronary artery bypass graft surgery. EAT adipocytes were isolated by the enzymatic method from intraoperative explants obtained during coronary artery bypass grafting. The size of EAT adipocytes and ROS level were determined. Results. The production of ROS by EAT adipocytes demonstrated a direct correlation with the level of postprandial glycemia (rs = 0.62, p < 0.05), and an inverse correlation with serum adiponectin (rs = −0.50, p = 0.026), but not with general and abdominal obesity, EAT thickness, and dyslipidemia. Regression analysis demonstrated that the increase in ROS of EAT adipocytes occurs due to the interaction of the following factors: postprandial glycemia (β = 0.95), postprandial insulin (β = 0.24), and reduced serum adiponectin (β = −0.20). EAT adipocytes in patients with diabetes and prediabetes manifested higher ROS production than in patients with normoglycemia. Although there was no correlation between the production of ROS by EAT adipocytes and Gensini score in the total group of patients, higher rates of oxidative stress were observed in EAT adipocytes from patients with a Gensini score greater than median Gensini score values (≥70.55 points, Gr.B), compared to patients with less severe coronary atherosclerosis (<70.55 points, Gr.A). Of note, the frequency of patients with diabetes and prediabetes was higher among the patients with the most severe coronary atherosclerosis (Gr.B) than in the Gr.A. Conclusion. Our data have demonstrated for the first time that systemic impairments of glucose/insulin metabolism and a decrease in serum adiponectin are significant independent determinants of oxidative stress intensity in EAT adipocytes in patients with severe coronary atherosclerosis. The possible input of the interplay between oxidative stress in EAT adipocytes and metabolic disturbances to the severity of coronary atherosclerosis requires further investigation.

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1 Томский национальный исследовательский медицинский центр Российской академии наук, Научно-исследовательский институт кардиологии. Россия, 634012, Томск, ул. Киевская, 111а 2 Национальный исследовательский Томский государственный университет Россия, 634050, Томск, пр. Ленина, 36 Цель. Определить статистически значимые детерминанты наличия анатомического стеноза коронарных артерий (КА)≥70% у пациентов с хронической стабильной ишемической болезнью сердца (ИБС), получающих медикаментозную терапию. Материал и методы. Исследование включало 68 пациентов (возраст 59,6±6,4 лет) со стабильной ИБС, находящихся на терапии, приближающейся к оптимальной. Всем пациентам проводили коронароангиографию. Исследовали основные сывороточные параметры липидного и углеводного обменов, определяли содержание цитокинов, адипокинов и высокочувствительного С-реактивного белка (вчСРБ) методом иммуноферментного анализа. По данным эхокардиографии в В-режиме определяли толщину эпикардиальной жировой ткани (тЭЖТ). Результаты. Построена модель классификации пациентов, позволяющая по показателям каждого пациента определять вероятность P стеноза КА≥70% по формуле , где величина L=0,89-1,09×пол+0,51×ТГ-0,28×ХС-ЛПВП+0,28×вчСРБ (ТГ -триглицериды, ХС-ЛПВПхолестерин липопротеинов высокой плотности). Если расчетная вероятность Р для пациента попадает в интервал (0; 0,228), то его следует отнести в группу риска по стенозу просвета КА≥70%, тогда как при расчетном значении вероятности Р, попадающем в интервал (0,228; 1), пациент должен быть включен в группу со стенозом менее 70%. Хотя в исследованной выборке тЭЖТ не являлась статистически значимой детерминантой стеноза КА≥70%, включение этого показателя в модель в качестве пятой переменной позволило улучшить ее качество: площадь под ROC-кривой для модели без тЭЖТ составила 0,708 (p=0,009), тогда как после включения тЭЖТ площадь под ROC-кривой увеличилась до 0,879 (p=0,011). Заключение. Статистически значимыми детерминантами стеноза КА≥70% являются: мужской пол, содержание в крови ТГ, ХС-ЛПВП и вчСРБ. Наличие в полученной модели уровня ТГ подчеркивает важный вклад данной липидной фракции в модуляцию остаточного кардиоваскулярного риска у пациентов, получающих статины, причем даже в случае ее умеренного возрастания.Ключевые слова: коронарный атеросклероз; триглицериды; фибраты; холестерин липопротеинов высокой плотности; толщина эпикардиальной жировой ткани.