Atherosclerosis remains a leading cause of cardiovascular morbidity and mortality worldwide, traditionally linked to elevated cholesterol levels, particularly low-density lipoprotein cholesterol (LDL-C). However, despite aggressive lipid-lowering strategies, residual cardiovascular risk persists, underscoring the need to explore additional contributing factors. This review examines emerging risk factors beyond cholesterol, including chronic inflammation, gut microbiota composition, oxidative stress, and environmental exposures. Inflammation plays a pivotal role in atherogenesis, with markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) serving as indicators of disease activity. The gut microbiome, particularly metabolites like trimethylamine N-oxide (TMAO), has been implicated in vascular inflammation and plaque development, while beneficial short-chain fatty acids (SCFAs) demonstrate protective effects. Oxidative stress further exacerbates endothelial dysfunction and plaque instability, driven by reactive oxygen species (ROS) and lipid peroxidation. Additionally, environmental factors, including air pollution, heavy metal exposure, endocrine disruptors, and chronic psychological stress, have emerged as significant contributors to cardiovascular disease. Understanding these novel risk factors offers a broader perspective on atherosclerosis pathogenesis and provides new avenues for targeted prevention and therapeutic interventions.

Introduction: Coagulation parameters are important determinants for COVID-19 infection. We conducted meta-analysis to assess the association between early hemostatic parameters and infection severity.Methods: Electronic search was made for papers that addressed clinical characteristics of COVID-19 patients and disease severity. Results were filtered using exclusion and inclusion criteria and then pooled into a meta-analysis to estimate the standardized mean difference (SMD) with 95% confidence interval (CI) for D-dimers, fibrinogen, prothrombin time, platelet count (PLT), activated partial thromboplastin time. To explore the heterogeneity and robustness of our fundings, sensitivity and subgroup analyses were conducted. Publication bias was assessed with contour-enhanced funnel plots and Egger's test by linear regression. Coagulation parameters data from retrospective cohort study of 451 patients with COVID-19 at National Research Center for Cardiac Surgery were included in meta-analysis of published studies.Results: Overall, 41 original studies (17,601 patients) on SARS-CoV-2 were included. For the two groups of patients, stratified by severity, we identified that D-dimers, fibrinogen, activated partial thromboplastin time, and prothrombin time were significantly higher in the severe group [SMD 0.6985 with 95%CI (0.5155; 0.8815); SMD 0.661 with 95%CI (0.3387; 0.9833); SMD 0.2683 with 95%CI (0.1357; 0.4009); SMD 0.284 with 95%CI (0.1472; 0.4208)]. In contrast, PLT was significantly lower in patients with more severe cases of COVID-19 [SMD −0.1684 with 95%CI (−0.2826; −0.0542)]. Neither the analysis by the leave-one-out method nor the influence diagnostic have identified studies that solely cause significant change in the effect size estimates. Subgroup analysis showed no significant difference between articles originated from different countries but revealed that severity assessment criteria might have influence over estimated effect sizes for platelets and D-dimers. Contour-enhanced funnel plots and the Egger's test for D-dimers and fibrinogen revealed significant asymmetry that might be a sign of publication bias.Conclusions: The hemostatic laboratory parameters, with exception of platelets, are significantly elevated in patients with severe COVID-19. The two variables with strongest association to disease severity were D-dimers and fibrinogen levels. Future research should aim outside conventional coagulation tests and include analysis of clotting formation and platelet/platelet progenitors characteristics.

The aims of this study were to analyze cytokine profiles in patients with COVID-19, gain insights into the immune response during acute infection, identify cytokines associated with disease severity and post-COVID complications, and explore potential biomarkers for prognosis and therapeutic targets. Using a multiplex analysis, we studied the cytokine pattern in 294 acute COVID-19 and post-COVID patients with varying severities of infection. Our findings revealed that disease severity was associated with elevated levels of IL-15, IL-8, and fractalkine. Severe/extremely severe forms in comparison with mild/moderate disease were associated with MCP-1, IFNa2, IL-7, IL-15, EGF, IP-10, IL-8, Eotaxin, FGF-2, GROa, sCD40L, and IL-10. The key cytokines of post-COVID are FGF-2, VEGF-A, EGF, IL-12(p70), IL-13, and IL-6. By the sixth month after recovering from a coronavirus infection, regardless of disease severity, some patients may develop complications such as arterial hypertension, type 2 diabetes mellitus, glucose intolerance, thyrotoxicosis, atherosclerosis, and rapid progression of previously diagnosed conditions. Each complication is characterized by distinct cytokine profiles. Importantly, these complications can also be predicted during the acute phase of the coronavirus infection. Understanding cytokine patterns can aid in predicting disease progression, identifying high-risk patients, and developing targeted interventions to improve the outcomes of COVID-19.

This prospective study evaluates the impact of radiofrequency ablation (RFA) on cardiorespiratory indicators in patients with long-standing persistent atrial fibrillation admitted to the Heart Center UMC between January 2022 and April 2024 in Astana, Kazakhstan. The study aims to assess the functional cardiac benefits of RFA. Out of 717 registered atrial fibrillation patients, 104 were examined before and 3 months after ablation, focusing on cardiorespiratory parameters. A before-and-after analysis using linear mixed models was applied to evaluate changes in cardiorespiratory parameters post-RFA. Significant improvements were noted across various measures. VO₂ max increased from 11.5 ± 4.4 mL/kg/min to 18.0 ± 4.5 mL/kg/min (p < 0.001). Oxygen uptake improved from 7.2 ± 2.6 mL/beat to 11.0 ± 3.4 mL/beat (p < 0.001). The 6-min walking test distance rose from 306 ± 82 m to 400 ± 48 m (p < 0.001). METs increased from 4.4 ± 1.6 to 8.0 ± 1.3 (p < 0.001). Heart rate at peak exercise decreased from 175.5 ± 18.6 to 147.2 ± 12.3 beats per minute (p < 0.001). NT-proBNP levels decreased from 1357 ± 1182 to 415 ± 339 pg/mL (p < 0.001). Patients with persistent atrial fibrillation undergoing RFA showed functional improvements in CPET indicators such as VO₂ max, METs, O₂ pulse, heart rate, and the 6-min walking test. Improvements were also seen in Nt-proBNP analysis. These results emphasize the need for longitudinal follow-up to optimize outcomes and minimize medical risks.

Nowadays, direct oral anticoagulants (DOACs) are the first-line anticoagulant strategy in patients with non-valvular atrial fibrillation (NVAF). We aimed to identify the influence of polymorphisms of the genes encoding P-glycoprotein (ABCB1) and carboxylesterase 1 (CES1) on the variability of plasma concentrations of DOACs in Kazakhstani patients with NVAF. We analyzed polymorphisms rs4148738, rs1045642, rs2032582 and rs1128503 in ABCB1 and rs8192935, rs2244613 and rs71647871 CES1 genes and measured the plasma concentrations of dabigatran/apixaban and biochemical parameters in 150 Kazakhstani NVAF patients. Polymorphism rs8192935 in the CES1 gene (p = 0.04), BMI (p = 0.01) and APTT level (p = 0.01) were statistically significant independent factors of trough plasma concentration of dabigatran. In contrast, polymorphisms rs4148738, rs1045642, rs2032582 and rs1128503 in ABCB1 and rs8192935, rs2244613 and rs71647871 CES1 genes did not show significant influence on plasma concentrations of dabigatran/apixaban drugs (p > 0.05). Patients with GG genotype (138.8 ± 100.1 ng/mL) had higher peak plasma concentration of dabigatran than with AA genotype (100.9 ± 59.6 ng/mL) and AG genotype (98.7 ± 72.3 ng/mL) (Kruskal–Wallis test, p = 0.25). Thus, CES1 rs8192935 is significantly associated with plasma concentrations of dabigatran in Kazakhstani NVAF patients (p < 0.05). The level of the plasma concentration shows that biotransformation of the dabigatran processed faster in individual carriers of GG genotype rs8192935 in the CES1 gene than with AA genotype.

Background: During the acute phase of COVID-19, a number of immunological abnormalities have been reported, but few studies longitudinally analyzed the specific subsets of peripheral blood lymphocytes. Methods: In this observational, prospective, and longitudinal study, adult patients developing acute pneumonia during the COVID-19 pandemic have been followed up for 12 months. Peripheral blood lymphocyte subsets were assessed (with a specific focus on the memory markers) at 6 time points after the disease onset until 12 months. Results: A total of 76 patients with acute pneumonia (characterized by a prevalently interstitial pattern of lung inflammation) at the hospital admission (who completed the 12-month follow-up period) were recruited in this study. They were divided into two groups, namely positive (n = 31) and negative (n = 45) patients for the SARS-CoV-2 PCR test. In the acute phase, the general lymphocyte immunophenotyping profile was comparable for most parameters between these groups, except for B cells. When B and T cells were analyzed according to the expression of memory markers, a significant decrease in naïve CD8⁺ T cells was observed in the SARS-CoV-2-positive pneumonia group during the acute phase. Notably, this aspect was maintained during the follow-up period for at least 9 months. Conclusions: COVID-19 pneumonia seems to be associated with a lower number of naïve CD8⁺ T cells compared to pneumonia patients negative for this virus. This alteration can persist in the convalescent phase.