Background: Apolipoprotein B (ApoB), a key component of atherogenic lipoproteins, has been increasingly implicated in cardiometabolic disorders beyond dyslipidemia. However, its role in glycemic dysregulation remains unclear. This study aimed to investigate the association between ApoB levels and glycemic parameters, including fasting glucose, insulin resistance, and glycated hemoglobin (HbA1c), in individuals without diagnosed diabetes. Methods: This study was conducted at the National Research Cardiac Surgery Center (Kazakhstan) over the period between 2023 and 2024 as a cross-sectional analysis. Adults aged ≥ 20 years without diagnosed diabetes and with complete data on their ApoB and glycemic markers were included. Associations between ApoB and fasting plasma glucose (FPG), HbA1c, and HOMA-IR were assessed using multivariable linear and logistic regression models adjusted for demographic, lifestyle, and metabolic covariates. Results: Higher ApoB levels were significantly associated with increased fasting glucose (β = 2.07 mg/dL per 1-SD increase in ApoB, p < 0.001), higher HbA1c (β = 0.06%, p < 0.001), and elevated HOMA-IR (β = 0.54, p < 0.001). Participants in the highest ApoB quartile had 53% higher odds of prediabetes (adjusted OR = 1.53; 95% CI: 1.22–1.91; p < 0.001) compared to the lowest quartile. These associations remained significant after adjusting for BMI, lipid levels, and other confounders. Conclusions: Elevated ApoB is independently associated with adverse glycemic profiles in nondiabetic individuals, suggesting its potential role in early glucose metabolism disturbances.

Background: Long COVID-19 symptoms appeared in many COVID-19 survivors. However, the prevalence and symptoms associated with long COVID and its comorbidities have not been established. Methods: Between May and September 2020, we included 312 patients with post-COVID-19 from 21 primary care centers if they had any persistent symptoms for at least three months from the first onset of the disease. On the 6 months follow up, their lung function was assessed by CT and spirometry, whereas cardiac function was assessed by electrocardiogram (ECG), Holter ECG, Echocardiography, and 24-hour blood pressure monitoring. A six-minute test (6MWT) was conducted on 308 participants during the follow-up visit. All participants were given a questionnaire with items on demographic information, current complaints, comorbidities, and medications, and Chalder Fatigue Scale (CFS) questionnaire. Statistical analysis was done using R vs. 4.1.2. Two-group comparison of continuous variables was performed using a T-test for normally distributed data, and the Mann-Whitney Wilcoxon test, ANOVA, and Kruskal-Wallis tests were applied for multiple comparisons following with Tukey and Dunn tests as post-hoc methods. Hochberg p-value adjustment was used to reduce the false discovery rate during multiple comparisons. Categorical variables were analyzed with Fisher’s Exact test. Results: Of 312 persons investigated, there was no significant gender difference between post-COVID-19 clinical manifestations except for memory dysfunction and anxiety, more prevalent among female participants. Chalder Fatigue Score ≥4 was predominant in female participants (243, 78%). 39 (12.5%) participants reported having type 2 diabetes mellitus, and 158 (50.64%) had hypertension. Among the tested parameters, those positively correlated with comorbid conditions include age, BMI, D-dimers, NT-proBNP, C-reactive protein, neutrophils, fasting glucose, and HbA1c; hypertension also shows three associations that were not found in patients when examining the role of diabetes: increased hemoglobin, fibrinogen, and ferritin. 24-hour blood pressure monitoring revealed significantly higher systolic and diastolic blood pressure, left ventricular hypertrophy, and elevated NT-proBNP in participants with hypertension and subjects with type 2 diabetes. Left ventricular diastolic dysfunction is more frequently present in patients with hypertension. Chest CT was conducted on 227 (72.8%) participants 5.8±0.9 months after the onset of COVID-19. The most common registered CT abnormality was chronic bronchitis (198, 87.2%), followed by fibrotic changes in (83, 36.6%) and mediastinal lymphadenopathy (23, 10.1%). Immunological test results showed that SARS-CoV19 IgG antibodies were present in 241 subjects (77.2%), and SARS-CoV19 IgM antibodies were present in 9 subjects (2.88%). Conclusions: Our study provides valuable clues for long-term post-sequelae in a cohort of the Long COVID-19 subjects. We demonstrated a strong association of signs of cardiac dysfunction, lung fibrotic changes, increased hemoglobin, fibrinogen, and ferritin with hypertension but not with other comorbidities. Our results are of importance for understanding the Long Covid-19 syndrome.

Introduction. Established in 2021, the Lipid Clinic Network of Kazakhstan is dedicated to creating a global framework for consistent standards in diagnosing, managing, and treating lipid disorders, guided by the European Society of Cardiology and European Atherosclerosis Society (further - ESC/EAS) Guidelines on dyslipidaemia management. The aim is to evaluate pillars for LCN in Kazakhstan and assess the feasibility of dyslipidemia clinics and implementation atherosclerosis project in Kazakhstan. Materials and methods. This is a cross-sectional survey with 8 questions to explore the organization of a lipid clinic network in Kazakhstan. 28 clinics took part and respondents were anonymous. The questionnaire was based on EAS LCN evaluation. Results. 54 % of dyslipidemia clinics are located in outpatient department and 11% of clinics are located as a sub-department within a cardiology department or similar in the hospital. 71% of clinics (20) show connections to hospital departments including diabetes, endocrinology and rare disease units. The staff composition of LCN Kazakhstan is: physicians - 26, nurses - 20, geneticist expert in dyslipidemias’ - 1, dietitian – 4, nutritionist - 0. A majority of clinics (53.60%) are situated in outpatient departments, highlighting a prevalent reliance on outpatient care for lipid-related services. The physician and nurse staffing levels align with LCN-EAS standards, the lack of nutritionists, geneticists, and dietitians represents a significant gap in the multidisciplinary care model advocated by the EAS. Capacity to provide therapeutic education on lifestyle changes, cardiovascular disease (CVD) prevention, and adherence to treatment is present in 16 clinics. Conclusion. Some criteria of LCN Kazakhstan are aligned with EAS LCN requirements in terms of data management, location, facility and the, management of the interaction with the patients. However, composition of staff, clinical trial management and connection within the health service infrastructure and patient referral need to be enhanced. Введение: Липидная Клиническая Сеть (далее – ЛКС) Казахстана, созданная в 2021 году, посвящена созданию глобальной структуры для стандартизированного подхода к диагностике, управлению и лечению липидных нарушений, руководствуясь рекомендациями Европейского общества кардиологии и Европейского общества атеросклероза (далее – ЕОК/ЕОА) по управлению дислипидемией. Цель. Оценка основных направлений Липидной клинической сети Казахстана и оценка осуществимости работы клиник по лечению дислипидемий и реализации проекта по атеросклерозу в Казахстане. Материалы и методы: Исследование было выполнено методом поперечного опроса, состоящего из 8 вопросов, направленных на изучение организации сети липидных клиник в Казахстане. В исследовании приняли участие 28 клиник, респонденты опроса были анонимными. Анкета была разработана на основе оценки ЛКС Европейского общества атеросклероза. Результаты: 54% клиник дислипидемии расположены в амбулаторных отделениях, и 11% клиник функционируют в качестве подотделов в кардиологических отделениях или аналогичных подразделениях больниц. 71% клиник (20) демонстрируют связь с больничными отделениями, такими как диабетология, эндокринология и отделения редких заболеваний. Согласно результатам опроса, персонал ЛКС Казахстана распределен следующим образом: врачи – 26, медсестры – 20, специалист по генетике дислипидемий – 1, диетолог – 4, нутриционистов нет. Значительное большинство клиник (53,60%) расположено в амбулаторных отделениях, что подчеркивает зависимость от амбулаторной помощи в предоставлении липидных услуг. Количество врачей и медсестер соответствует стандартам ЛКС-ЕОА, однако нехватка нутриционистов, генетиков и диетологов представляет значительный пробел в многопрофильной модели ухода, рекомендованной ЕОА. Возможность предоставить терапевтическое обучение по изменению образа жизни, профилактике сердечно-сосудистых заболеваний (ССЗ) и соблюдению режима лечения присутствует в 57% клиник. Заключение: Некоторые критерии ЛКС Казахстана соответствуют требованиям ЕОА в части управления данными, местоположения, инфраструктуры и взаимодействия с пациентами. Однако...

Background. Bilirubin is a byproduct of the breakdown of erythrocytes. Bilirubin levels can potentially serve as a biomarker for cardiovascular risk assessment. In this study, we would be investigating most recent manuscripts, published in the last 5 years, that studied association of serum bilirubin level to atherosclerosis progression to elicit how strongly low level of total bilirubin can prognose the disease progression. Methods. Using Pubmed search engine, all articles that included keywords “bilirubin” and “atherosclerosis” were retrieved. In total 67 search results emerged for the 2019-2023 timeline, the last 5 years.6 population-based studies that studied association between total bilirubin concentration and atherosclerosis development were used for the meta-analysis. Results. Increasing blood total bilirubin level seems to decrease the odds of developing atherosclerosis, meaning that there is an inverse correlation between total bilirubin level and arterial plaque formation or stenosis. Pooled odds ratio was found to be 0.86 (95% CI 0.83-0.9), suggesting that there is 14% decreased chance of developing atherosclerosis for each mmol/L increase in bilirubin levels. Overall, higher total serum bilirubin levels were associated with a significantly decreased risk of progression to atherosclerosis. Conclusion. The meta-analysis indicates a significant inverse association between low total bilirubin levels and the risk of developing atherosclerosis, suggesting that higher bilirubin levels may be protective against the progression of this disease.

Introduction. Cardiovascular diseases, including atherosclerosis (AS), are the leading cause of morbidity and mortality worldwide, including in Kazakhstan. Lipid metabolism disorders, in particular, hypertriglyceridemia, which is recognized as an independent risk factor, play an important role in the development of AS. Genetic features associated with genes regulating lipid and carbohydrate metabolism (GCKR, SLC22A5, LPL, FLCN, LDLR, APOE) have a significant impact on the formation of dyslipidemia and determine individual metabolic characteristics. Studying the prevalence and effects of these genetic variants in the Kazakh population is particularly important, given its underrepresentation in global genetic research. Aim. The objective of this study was to study the frequency of genetic polymorphisms in genes involved in the regulation of lipid metabolism (GCKR, SLC22A5, LPL, FLCN, LDLR, APOE) in a group of Kazakhstani patients with hypertriglyceridemia and atherosclerosis. Additionally, we analyzed the relationship of the identified genetic variants with the biochemical parameters of the lipid profile. Materials and methods. The study analyzed data from 402 patients with cardiovascular diseases, 144 of whom had hypertriglyceridemia. To identify the genetic determinants of lipid metabolism disorders, full-exome sequencing was performed with a focus analysis of the GCKR, SLC22A5, LPL, and FLCN genes. The identified genetic variants were annotated and classified according to the recommendations of ACMG/AMP. The association of genetic polymorphisms with lipid profile parameters in patients with AS was studied. Results. Sequencing of the entire exome of patients with varying degrees of cardiovascular risk revealed genetic variations affecting triglyceride metabolism. Elevated triglyceride levels were reported in patients of all risk categories, with the highest frequency in very high-risk individuals (82 patients). Analysis of the lipid profile showed that total cholesterol was significantly higher in the high-risk group compared with the low-risk group (228.8±35.2 versus 207.8±30.3 mg/dl; p=0.0467). The level of HDL-C showed an inverse relationship with the level of risk, being the lowest in the very high-risk group (44.6±10.5 versus 50.1±9.9 mg/dl; p=0.0411). Although LDL and non-lipoprotein cholesterol did not show statistically significant differences, there was a tendency to increase them. Triglycerides also tended to increase, but without achieving statistical significance (p>0.05). There was a significant decrease in apolipoprotein A at high risk (p0.05). Conclusions. The study did not reveal a statistically significant association between APOE (p.T388C) and GCKR genotypes with cardiovascular risk. Larger-scale studies are required, taking into account additional factors and an increased sample size. Введение. Сердечно-сосудистые заболевания, в том числе атеросклероз (АС), являются основной причиной заболеваемости и смертности во всем мире, включая Казахстан. Важную роль в развитии АС играют нарушения липидного обмена, в частности, гипертриглицеридемия, которая признана самостоятельным фактором риска. Генетические особенности, связанные с генами, регулирующими метаболизм липидов и углеводов (GCKR, SLC22A5, LPL, FLCN, LDLR, APOE), оказывают значительное влияние на формирование дислипидемий и определяют индивидуальные метаболические характеристики. Изучение распространенности и влияния этих генетических вариантов в казахстанской популяции особенно важно, учитывая ее ограниченное представительство в глобальных генетических исследованиях. Целью данного исследования было изучить частоты встречаемости генетических полиморфизмов в генах, участвующих в регуляции липидного обмена (GCKR, SLC22A5, LPL, FLCN, LDLR, APOE), в группе казахстанских пациентов с гипертриглицеридемией и атеросклерозом. Дополнительно мы анализировали взаимосвязь выявленных генетических вариантов с биохимическими параметрами липидного профиля. Материал и методы. В рамках исследования были проанализированы данные 402 пациентов с сердечно-сосудистыми заболеваниями, из которых 144 имели гипертриглицеридемию. Для выявления генетических детерминант нарушений липидного обмена было выполнено полноэкзомное секвенирование с анализом генов GCKR, SLC22A5, LPL и FLCN. Выявленные генетические варианты были аннотированы и классифицированы в соответствии с рекомендациями ACMG/AMP. Проведена оценка ассоциации генетических полиморфизмов с нарушениями липидного профиля в казахстанской популяции пациентов с сердечно-сосудистыми заболеваниями....

Background: Evidence describing the longitudinal effectiveness and tolerability of tirzepatide in adults with obesity and heart failure with preserved ejection fraction (HFpEF) remains limited, particularly from prospective cohorts with repeated cardiometabolic assessments. This study evaluated longitudinal changes in weight, metabolic health, and treatment-emergent symptoms during tirzepatide therapy in a Kazakhstan cohort with obesity and HFpEF. Methods: We conducted a preliminary analysis of the tirzepatide-treated cohort enrolled at one center within a broader prospective interventional study. The present analysis included adults with obesity and HFpEF who received once-weekly tirzepatide according to a prospectively defined treatment protocol. Participants underwent scheduled assessments from baseline through Week 41. Longitudinal changes in anthropometric, metabolic, inflammatory, renal, and body composition outcomes were analyzed using linear mixed-effects models. Individual treatment-emergent symptoms were summarized descriptively, while longitudinal regression models were used for aggregated adverse-event outcomes and symptom burden. Complete-case and exploratory predictor analyses were performed as sensitivity analyses. Results: Twenty-four participants with obesity and HFpEF contributed longitudinal observations, including 16 with mature Week-41 follow-up. Tirzepatide treatment was associated with significant reductions in body weight, BMI, waist circumference, fasting glucose, triglycerides, and selected inflammatory markers over time. Mean percentage weight loss at Week 41 was 17.2±8.1%, corresponding to 18.7±7.0 kg. Among the 16 participants with paired baseline and Week-41 measurements, all achieved ≥5% weight loss, while 87.5%, 50.0%, and 25.0% achieved ≥10%, ≥15%, and ≥20% weight loss, respectively. Gastrointestinal symptoms were reported in 25.0% of participants, with nausea (20.8%) and vomiting (12.5%) being the most frequently recorded. No serious adverse events were observed during the study period. No statistically significant association was detected between gastrointestinal symptom occurrence or burden and longitudinal weight loss; however, these analyses were exploratory given the small number of gastrointestinal events. Conclusions: In this preliminary analysis of a prospective tirzepatide-treated cohort of adults with obesity and HFpEF from Kazakhstan, tirzepatide was associated with substantial and sustained weight loss accompanied by favorable cardiometabolic changes. Gastrointestinal symptoms were reported in a minority of participants, although their severity was not formally graded. These findings should be interpreted within the specific clinical context of obesity with concomitant HFpEF.