Severity Of Coronary Atherosclerosis Research Articles

Predictive value of the neutrophil percentage-to-albumin ratio for coronary atherosclerosis severity in patients with CKD

BackgroundThe neutrophil percentage-to-albumin ratio (NPAR), which is defined as the percentage of neutrophils divided by the concentration of albumin, is a cost-effective and readily available biomarker of inflammation. This study aimed to evaluate the association between the NPAR and the severity of coronary atherosclerosis in patients with chronic kidney disease (CKD).MethodsA total of 280 CKD patients who underwent coronary angiography were retrospectively enrolled in this study. The severity of coronary atherosclerosis was evaluated using the Gensini score (GS). Patients were divided into low-, medium- and high-NPAR groups according to the tertiles of the NPAR values. Logistic regression analysis was conducted to analyze the relationship between the NPAR and the GS. The cutoff points for the sensitivity and specificity of the NPAR in predicting the GS were estimated via receiver operating characteristic (ROC) analysis.ResultsThere was a higher prevalence of coronary artery disease (CAD) among CKD patients with higher NPARs (P =0.041). More patients in the high-NPAR group had complex CAD (triple-vessel disease and/or left main coronary artery stenosis) and chronic total occlusion lesions, and more of these patients required revascularization therapy (P<0.05). Multivariate logistic regression analysis revealed a significant positive correlation between the NPAR and the severity of coronary stenosis (adjusted OR 2.68, 95% CI 1.25-5.76, p=0.012), particularly among female and older (age ≥65) patients. The ROC analysis indicated that the optimal cutoff value for the NPAR in predicting severe coronary artery stenosis (GS>60) in CKD patients was 1.91 (sensitivity 0.495, specificity 0.749), with an area under the curve (AUC) of 0.650 (95% CI 0.581-0.719, P<0.001). A subgroup analysis according to sex revealed that the NPAR exhibited stronger predictive value in female patients (AUC 0.730, 95% CI 0.643-0.817) than in male patients (AUC 0.565, 95% CI 0.460-0.670) (P<0.001), and the optimal cutoff value for the NPAR in female patients was 1.80 (sensitivity 0.667, specificity 0.705).ConclusionsOur study demonstrated that the NPAR is independently associated with the severity of coronary atherosclerosis in CKD patients, especially in female and elderly patients (≥65 years old). Moreover, the NPAR can effectively predict the severity of coronary atherosclerosis, exhibiting greater predictive value in females than in males.

A Noninvasive Arterial Stiffness Index to Estimate the Severity of Coronary Atherosclerosis in Patients Undergoing Coronary Angiography

The early diagnosis and appropriate treatment of subclinical atherosclerosis before the onset of life-threatening cardiovascular (CV) diseases are major unmet medical needs in current clinical practice. Noninvasive arterial stiffness indices, the arterial velocity–pulse index (AVI) and the arterial pressure–volume index (API) have been associated with CV risks, conventional arterial stiffness indices, and the severity of coronary atherosclerosis. However, few studies have examined the relationship between these indices and the occurrence of CV events. We measured the AVI and API in 113 consecutive patients admitted to Yokohama City University Hospital for cardiac catheterization between June 2015 and March 2016. Patients were followed until September 2022, and the occurrence of CV events was assessed. The mean age was 71.2 ± 10.7 years, and 83 patients (73.5%) were male. In total, 80 patients (70.8%) had hypertension, 87 (77.0%) had dyslipidemia, and 91 (80.5%) had a history of ischemic heart disease (IHD). The mean follow-up duration was 1752 ± 819 days. Patients who received elective percutaneous coronary intervention (PCI) based on the results of coronary angiography (CAG) at the time of enrollment had significantly higher API than those who did not (38.5 ± 12.6, n = 17 vs. 31.3 ± 7.4, n = 96, p = 0.001). The API was independently associated with the risk of elective PCI in multiple logistic regression analysis. In conclusion, the API could be a useful indicator for estimating the need for coronary interventional treatment in patients with a high CV risk.

No causal association between the volume of strenuous exercise and coronary atherosclerosis: a two-sample Mendelian randomization study.

Several observational studies have shown that high-volume and high-intensity exercise training increases the prevalence and severity of coronary atherosclerosis, but the causal effect still remains uncertain. This study aims to explore the causal relationship between the volume of strenuous exercise (SE) and coronary atherosclerosis (CA) using the Mendelian randomization (MR) method. The exposure factors were two basic parameters of the volume of strenuous exercise (duration and frequency of strenuous exercise), the outcome factor was coronary atherosclerosis, and the relevant genetic loci were extracted from the summary data of the genome-wide association study (GWAS) as the instrumental variables, and MR analyses were performed using the inverse variance weighting (IVW) method, the weighted median method, and the MR-egger method. Sensitivity analyses were performed using heterogeneity analysis, pleiotropy analysis, and the "leave-one-out" method. The original results were tested using other coronary atherosclerosis data sets. IVW results showed no causal association between duration of strenuous exercise (DOSE) [OR = 0.9937, 95% CI (0.9847, 1.0028), P = 0.1757] and frequency of strenuous exercise (FOSE) in the last 4 weeks [OR = 0.9930, 95% CI (0.9808, 1.0054), P = 0.2660] and coronary atherosclerosis. All of the above results were validated with other coronary atherosclerosis data sets. The present study supports that the causal association of duration and frequency of SE with CA was not found, and provides valuable insights into the choice of scientific and correct volume of SE to cardiac rehabilitation (CR).

Single-Cell Gene-Regulatory Networks of Advanced Symptomatic Atherosclerosis.

While our understanding of the single-cell gene expression patterns underlying the transformation of vascular cell types during the progression of atherosclerosis is rapidly improving, the clinical and pathophysiological relevance of these changes remains poorly understood. Single-cell RNA sequencing data generated with SmartSeq2 (≈8000 genes/cell) in nearly 19 000 single cells isolated during atherosclerosis progression in Ldlr-/-Apob100/100 mice with human-like plasma lipoproteins and from humans with asymptomatic and symptomatic carotid plaques was clustered into multiple subtypes. For clinical and pathophysiological context, the advanced-stage and symptomatic subtype clusters were integrated with 135 tissue-specific (atherosclerotic aortic wall, mammary artery, liver, skeletal muscle, and visceral and subcutaneous, fat) gene-regulatory networks (GRNs) inferred from 600 coronary artery disease patients in the STARNET (Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task) study. Advanced stages of atherosclerosis progression and symptomatic carotid plaques were largely characterized by 3 smooth muscle cells (SMCs), and 3 macrophage subtype clusters with extracellular matrix organization/osteogenic (SMC), and M1-type proinflammatory/Trem2-high lipid-associated (macrophage) phenotypes. Integrative analysis of these 6 clusters with STARNET revealed significant enrichments of 3 arterial wall GRNs: GRN33 (macrophage), GRN39 (SMC), and GRN122 (macrophage) with major contributions to coronary artery disease heritability and strong associations with clinical scores of coronary atherosclerosis severity (SYNTAX/Duke scores). The presence and pathophysiological relevance of GRN39 were verified in 5 independent RNAseq data sets obtained from the human coronary and aortic artery, and primary SMCs and by targeting its top-key drivers, FRZB and ALCAM, in cultured human vascular SMCs. By identifying and integrating the most gene-rich single-cell subclusters of atherosclerosis to date with a coronary artery disease framework of GRNs, GRN39 was identified and independently validated as being critical for the transformation of contractile SMCs into an osteogenic phenotype promoting advanced-stage, symptomatic atherosclerosis.

The relationship between the systemic immune inflammatory index and computerized tomography guided coronary lesion severity in diabetic patients.

The incidence of cardiovascular events is high in diabetic patients. In diabetic patients, the levels of inflammatory parameters in the circulation are increased, which is associated with poor outcome. In this study, we investigated the relationship between the systemic immune inflammatory index (SII), which is a sensitive indicator of the inflammatory response, and the severity of coronary atherosclerosis in diabetic patients. Diabetic patients who underwent coronary computed tomography for chest pain were included in the study. The patients were divided into two groups according to their median systemic immune inflammatory index values, and the predictors of SII elevation were investigated. A total 210 patients were included in the study. The mean age of the patients was 52.6 ± 9.3 and 44.3% were male. In univariate analysis, HDL, triglyceride, lesion severity, and CAR were associated with high SII. In the regression analysis, lesion severity and lower HDL levels were determined as predictor of high SII. Inflammation plays an important role in the development of coronary atherosclerosis. Diabetic patients with elevated SII levels may require further investigation for significant atherosclerosis.

The Impact of Periodontal Inflammation on the Severity of Coronary Atherosclerosis.

Introduction Through plausible biological mechanisms, periodontitis causes systemic inflammatory burden and response, thus resulting in damage far beyond the oral cavity. Studies have demonstrated periodontitis to be a significant risk factor for coronary heart disease (CHD) and stroke. The larger the quantum of periodontal inflamed tissue, the greater the chances of periodontitis eliciting bacteremiaand systemic inflammatory responses. Studies have reported that periodontitis and other common oral infections play an important role in the development of atherosclerosis. Therefore, the quantity of inflamed periodontal tissue assumes significance in determining the severity of atherosclerosis. Hence, this study investigates the impact of periodontal inflamed surface area (PISA) on the severity of coronary atherosclerosis. Materials and methods In this cross-sectional study, a total of 160 patients who presented at the department of periodontics of The British University in Egypt (BUE) from 1 January 2023 to 30 September 2023 were enrolled. Patients were only enrolled if they had undergone coronary angiography within the last six months, were less than 60 years of age, shared their previous medical history and coronary angiographic report, and gave informed written consent. Data on classic coronary risk factors and periodontal inflammatory status and angiographic findings were recorded and subjected to appropriate statistical analysis. Results The results revealed that the periodontal inflamed surface area (p = 0.002) apart from age (p < 0.047) and low-density lipoprotein cholesterol(LDL-C) (p < 0.001) is a significant independent predictor of the severity of coronary atherosclerosis. Conclusions The periodontal inflamed surface area is an independent predictor of the severity of coronary atherosclerosis.

Improvement of quality of life indicators in patients with metabolic syndrome after correction of hemodynamically significant coronary stenoses and dyslipidemia

It is known that metabolic syndrome is currently the leading cause of the development of cardiovascular pathology, which occupies a leading position in the structure of mortality not only in the Russian population, but also in the world. The prevalence of MS is growing, which is associated with stressful professions, eating disorders. The presence of MS is associated with arterial hypertension and atherosclerosis of the arteries of any localization. In this regard, the purpose of our study was to study the quality of life in patients with MS, depending on the severity of coronary atherosclerosis. Materials and methods: The study included 239 patients (142 men, 97 women) with MS with atherosclerosis of the coronary and carotid arteries. The number of subjects in group 1 (n=141), of which 101 were men and 40 were women. The second group consisted of 84 male and 14 female patients (n=98). The control group consisted of 70 people (27 men, 43 women) with grade 1-3 hypertension. The age of the subjects was 31-56 years. All patients underwent: collection of complaints and anamnesis, assessment of body mass index (BMI); determination of the lipid spectrum, blood glucose, glycated hemoglobin. Microalbuminuria and glomerular filtration rate were determined. Instrumental studies were carried out: ultrasound examination of brachiocephalic vessels with determination of the thickness of the intima-media complex and the percentage of carotid artery stenosis; coronary angiography on the General Electric Innova 3100 angiographic complex. Based on the results of coronary angiography, the patients were divided into two subgroups: group 1 - with coronary artery stenosis of less than 50% (n=141), group 2 - with stenosis of 50% or more (n=98), group 3 (control) without stenotic lesions of the coronary arteries. A non-specific questionnaire “SF-36 Health Status Survey” was used to assess the quality of life. Results: assessing physical functioning and mental health, there was a significant decrease in these indicators in patients of group 2, in whom, according to coronary angiography, hemodynamically significant coronary artery stenoses were diagnosed, a strong correlation (r=0.730; p=0.005) was revealed between deterioration in quality of life and hemodynamically significant stenosis of the carotid and coronary arteries. Restriction of physical activity and reduction of daily activities were more significant in group 2 compared to groups 1 and 3. The feeling of uncertainty with restless expectation and fears, as well as a feeling of depression prevailed in men. However, patients after percutaneous coronary intervention, as well as with lipidogram correction, assessed the quality of life with some restriction of physical activity, but with significant social functioning. Conclusions: hemodynamically significant atherosclerosis of the carotid and coronary arteries is a predictor of deterioration in the quality of life, especially in men. The use of the international questionnaire “SF-36 Health Status Survey” is appropriate for assessing the health and vital activity in patients with MS and hypertension, with signs of atherosclerosis. The interaction of a cardiologist, an endocrinologist and a psychotherapist are justified for the most optimal management of patients with comorbid pathology.

Association of FoxP3&lt;sup&gt;+&lt;/sup&gt; T regulatory lymphocytes with epicardial adipose tissue thickness in patients with coronary heart disease

Background. Increase ofthe epicardial adipose tissue (EAT) thickness isassociated with development of inflammation and cardiovascular complications, however, there is no data on the relationship between EAT thickening and the number of immunosuppressive regulatory T lymphocytes.The aim. To study the number of circulating T regulatory lymphocytes and nuclear translocation ofthe FoxP3 transcription factor in patients with stable coronary heart disease (CHD) depending on the epicardial adipose tissue thickness.Materials and methods. We examined 30 patients with chronic stable CHD. The EAT thickness was measured by echocardiography. Patients were divided into groups depending on the presence and absence of EAT thickening above 5 mm (groups 1 and 2, respectively). Imaging flow cytometry was used to determine the number of T regulatory lymphocytes and the level of FoxP3 nuclear translocation. The concentration of cytokines and high sensitivity C-reactive protein (hsCRP) was determined using enzyme-linked immunosorbent assay in blood serum.Results. Anthropometric indicators of obesity and the severity of atherosclerosis were comparable between groups. In group 2, there was an increase in low-density lipoprotein cholesterol concentration (p = 0.043), ratio of low-density lipoprotein cholesterol tohigh-density lipoprotein cholesterol (p = 0.017) and the concentration ofhsCRP (p = 0.044) andIL-1β (p = 0.005), adecrease in the number and relative count of Tregulatory lymphocytes (p = 0.020 andp = 0.026, respectively), aswellas thenumber of cells withFoxP3 nuclear translocation (p = 0.018) compared togroup1. According tomultiple logistic regression, the concentration ofhsCRP, IL-1β and T regulatory lymphocytes relative count in total were the predictors of EAT thickening (accuracy 80 %; sensitivity 75 %; specificity 84,6 %; AUC = 0.89).Conclusions. Thickening of epicardial adipose tissue inpatients withcoronary heart disease is associated with a decrease in the number of T regulatory lymphocytes andFoxP3 nuclear translocation inthem in presence of comparable anthropometric parameters of obesity and the severity of coronary atherosclerosis.

Single Cell High Dimensional Analysis of Human Peripheral Blood Mononuclear Cells Reveals Unique Intermediate Monocyte Subsets Associated with Sex Differences in Coronary Artery Disease.

Monocytes are associated with human cardiovascular disease progression. Monocytes are segregated into three major subsets: classical (cMo), intermediate (iMo), and nonclassical (nMo). Recent studies have identified heterogeneity within each of these main monocyte classes, yet the extent to which these subsets contribute to heart disease progression is not known. Peripheral blood mononuclear cells (PBMC) were obtained from 61 human subjects within the Coronary Assessment of Virginia (CAVA) Cohort. Coronary atherosclerosis severity was quantified using the Gensini Score (GS). We employed high-dimensional single-cell transcriptome and protein methods to define how human monocytes differ in subjects with low to severe coronary artery disease. We analyzed 487 immune-related genes and 49 surface proteins at the single-cell level using Antibody-Seq (Ab-Seq). We identified six subsets of myeloid cells (cMo, iMo, nMo, plasmacytoid DC, classical DC, and DC3) at the single-cell level based on surface proteins, and we associated these subsets with coronary artery disease (CAD) incidence based on Gensini score (GS) in each subject. Only frequencies of iMo were associated with high CAD (GS > 32), adj.p = 0.024. Spearman correlation analysis with GS from each subject revealed a positive correlation with iMo frequencies (r = 0.314, p = 0.014) and further showed a robust sex-dependent positive correlation in female subjects (r = 0.663, p = 0.004). cMo frequencies did not correlate with CAD severity. Key gene pathways differed in iMo among low and high CAD subjects and between males and females. Further single-cell analysis of iMo revealed three iMo subsets in human PBMC, distinguished by the expression of HLA-DR, CXCR3, and CD206. We found that the frequency of immunoregulatory iMo_HLA-DR+CXCR3+CD206+ was associated with CAD severity (adj.p = 0.006). The immunoregulatory iMo subset positively correlated with GS in both females (r = 0.660, p = 0.004) and males (r = 0.315, p = 0.037). Cell interaction analyses identified strong interactions of iMo with CD4+ effector/memory T cells and Tregs from the same subjects. This study shows the importance of iMo in CAD progression and suggests that iMo may have important functional roles in modulating CAD risk, particularly among females.

Correlation of serum ferredoxin 1 and lipoic acid levels with severity of coronary artery disease

To analyze the correlation of copper death inducer ferredoxin 1 (FDX1) and lipoic acid (LA) with the occurrence and severity of coronary atherosclerosis and explore their roles in coronary heart disease (CHD). We analyzed the data of 226 patients undergoing coronary artery angiography (CAG) in our hospital between October, 2021 and October, 2022, including 47 patients with normal CAG findings (control group) and 179 patients with mild, moderate or severe coronary artery stenosis (CHD group). Serum FDX1 and LA levels were determined with ELISA for all the patients. We also examined pathological changes in the aorta of normal and ApoE-/- mice using HE staining and observed collagen fiber deposition with Sirius red staining. Immunohistochemistry was used to detect the expression and distribution of FDX1 and LA in the aorta, and RT-PCR was performed to detect the expressions of FDX1, LIAS and ACO2 mRNAs in the myocardial tissues. Compared with the control patients, CHD patients had significantly lower serum FDX1 and LA levels, which decreased progressively as coronary artery stenosis worsened (P < 0.01) and as the number of involved coronary artery branches increased (P < 0.05). Serum FDX1 and LA levels were positively correlated (r=0.451, P < 0.01) and they both negatively correlated with the Gensini score (r=-0.241 and -0.273, respectively; P < 0.01). Compared with normal mice, ApoE-/- mice showed significantly increased lipid levels (P < 0.01) and atherosclerosis index, obvious thickening, lipid aggregation, and collagen fiber hyperplasia in the aorta, and significantly reduced expressions of FDX1, LA, LIAS, and ACO2 (P < 0.05). Serum FDX1 and LA levels decrease with worsening of coronary artery lesions, and theirs expressions are correlated with coronary artery lesions induced by hyperlipidemia.

Histopathological Association of Non-alcoholic Fatty Liver Disease With Coronary Artery Atherosclerosis Grade

Background: The association between the severity of coronary atherosclerosis and histopathologic findings in patients with non-alcoholic fatty liver disease (NAFLD) is not entirely understood. Considering the gold standard method, this study evaluates the histopathologic association between the severity of NAFLD and the grades of coronary atherosclerosis. Methods: In this descriptive-analytical study, data from 205 cadavers who were referred to an Iranian (Tabriz) forensic medicine organization between 2015 and 2017 and underwent simultaneous liver and coronary artery biopsies were examined. Finally, 168 cases were entered based on the inclusion criteria. First, pathological slides of these cadavers were extracted from the forensic medicine archive and re-examined. Then, the selected cases’ blocks were extracted from the tissue block bank, and again, after preparing a new slide, they were stained with trichrome for accurate estimation of liver fibrosis. Results: The assessment of NAFLD histological status in the studied cases revealed that 75.6% of the cases were classified as severity I, 18.4% as severity II, and 6% as severity III. Most cases with coronary atherosclerosis were classified as American Heart Association staging (AHA), type V (19.6%), and normal (19.6%). There was no statistically significant relationship between the severity of simple steatosis, steatohepatitis, and NAFLD, with coronary atherosclerosis. In subjects with higher severity of coronary atherosclerosis, the liver fibrosis rate is also higher, but no statistically significant difference was observed. Conclusion: The present study revealed no significant histopathological association between NAFLD and coronary artery atherosclerosis grade.

Gut microbiome-based noninvasive diagnostic model to predict acute coronary syndromes.

Previous studies have shown that alterations in the gut microbiota are closely associated with Acute Coronary Syndrome (ACS) development. However, the value of gut microbiota for early diagnosis of ACS remains understudied. We recruited 66 volunteers, including 29 patients with a first diagnosis of ACS and 37 healthy volunteers during the same period, collected their fecal samples, and sequenced the V4 region of the 16S rRNA gene. Functional prediction of the microbiota was performed using PICRUSt2. Subsequently, we constructed a nomogram and corresponding webpage based on microbial markers to assist in the diagnosis of ACS. The diagnostic performance and usefulness of the model were analyzed using boostrap internal validation, calibration curves, and decision curve analysis (DCA). Compared to that of healthy controls, the diversity and composition of microbial community of patients with ACS was markedly abnormal. Potentially pathogenic genera such as Streptococcus and Acinetobacter were significantly increased in the ACS group, whereas certain SCFA-producing genera such as Blautia and Agathobacter were depleted. In addition, in the correlation analysis with clinical indicators, the microbiota was observed to be associated with the level of inflammation and severity of coronary atherosclerosis. Finally, a diagnostic model for ACS based on gut microbiota and clinical variables was developed with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.963 (95% CI: 0.925-1) and an AUC value of 0.948 (95% CI: 0.549-0.641) for bootstrap internal validation. The calibration curves of the model show good consistency between the actual and predicted probabilities. The DCA showed that the model had a high net clinical benefit for clinical applications. Our study is the first to characterize the composition and function of the gut microbiota in patients with ACS and healthy populations in Southwest China and demonstrates the potential effect of the microbiota as a non-invasive marker for the early diagnosis of ACS.

A combined analysis of TyG index, SII index, and SIRI index: positive association with CHD risk and coronary atherosclerosis severity in patients with NAFLD.

Insulin resistance(IR) and inflammation have been regarded as common potential mechanisms in coronary heart disease (CHD) and non-alcoholic fatty liver disease (NAFLD). Triglyceride-glucose (TyG) index is a novel biomarker of insulin resistance, System immune-inflammation index(SII) and Systemic inflammation response index(SIRI) are novel biomarkers of inflammation, these biomarkers have not been studied in CHD with NAFLD patients. This study investigated the correlation between the TyG index, SII index, and SIRI index and CHD risk among NAFLD patients. This cross-sectional study included 407 patients with NAFLD in the Department of Cardiology, The Second Hospital of Shanxi Medical University. Of these, 250 patients with CHD were enrolled in the NAFLD+CHD group and 157 patients without CHD were enrolled as NAFLD control. To balance covariates between groups, 144 patients were selected from each group in a 1:1 ratio based on propensity score matching (PSM). Potential influences were screened using Lasso regression analysis. Univariate and multivariate logistic regression analyses and the Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to assess independent risk and protective factors for CHD. Construction of nomogram using independent risk factors screened by machine learning. The receiver operating characteristic(ROC) curve was used to assess the ability of these independent risk factors to predict coronary heart disease. The relationship between the Gensini score and independent risk factors was reflected using the Sankey diagram. The LASSO logistic regression analysis and Logistic regression analyses suggest that TyG index (OR, 2.193; 95% CI, 1.242-3.873; P = 0.007), SII index (OR, 1.002; 95% CI, 1.001-29 1.003; P <0.001), and SIRI index (OR,1.483;95%CI,1.058-2.079,P=0.022) are independent risk factors for CHD. At the same time, Neutrophils, TG, and LDL-C were also found to be independent risk factors in patients, HDL-C was a protective factor for CHD in patients with NAFLD. Further analysis using three machine learning algorithms found these independent risk factors to have good predictive value for disease diagnosis, SII index shows the highest predictive value. ROC curve analysis demonstrated that combining the SII index, SIRI index, and TyG index can improve the diagnostic ability of non-alcoholic liver cirrhosis patients with CHD.ROC curve analysis showed that the combined analysis of these independent risk factors improved the predictive value of CHD(AUC: 0.751; 95% CI: 0.704-0.798; P <0.001). TyG index, SII index, and SIRI index are all independent risk factors for CHD in patients with NAFLD and are strongly associated with prediction and the severity of CHD.

Regarding the paradox of increased coronary atherosclerosis among highly trained athletes: Might hepcidin be the culprit?

Recent studies have shown that participants of lifelong high-intensity exercise, such as ultramarathon running, compared to individuals engaging in less intense exercise forms, have exhibited more prevalent and severe coronary atherosclerosis. This is counterintuitive to the purported benefits of exercise and this paradox eludes explanation. Interestingly, prolonged bouts of high-intensity exercise have been shown to increase hepcidin concentrations for several hours after exercise. Hepcidin, a hepatic peptide hormone and a central regulator of iron homeostasis, downregulates the expression of the only cellular iron exporter, ferroportin. As such, we posit that the repeated elevations of hepcidin over time among elite athletes lead to increases in arterial wall macrophage iron content, resulting in a proatherogenic macrophage phenotype and subsequent atherosclerosis. Mechanisms and clinical implications are discussed, and more research is suggested.

BDNF/TrkB signaling in stable coronary artery disease

Aim. To study the serum content of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) in patients with coronary artery disease (CAD) and evaluate the relationship of BDNF/TrkB signaling with the severity of coronary atherosclerosis, systemic inflammation (IL-2, IL-4, IL-6, IL-10, TNF-α) and angiogenesis (VEGF).Material and methods. The study included 99 patients with stable CAD who underwent coronary angiography and 30 healthy volunteers. Coronary atherosclerosis was assessed using the Gensini score (GS). In blood serum, the concentrations of BDNF, TrkB, VEGF, IL-2, IL-4, IL-6, IL-10, TNF-α were determined using the enzyme immunoassay. Cluster, correlation, and regression analyzes were used.Results. In patients with CAD, a wide range of variations in BDNF concentrations was observed. To determine homogeneous groups using the k-means clustering, three clusters with different BDNF/TrkB axis vectors were identified. Patients differed in the severity of coronary atherosclerosis, the manifestation of the inflammatory reaction, and the intensity of angiogenesis. In patients with initial and moderate atherosclerotic changes in the coronary arteries, a normal concentration of BDNF and an increased level of TrkB (22,35/1,18 ng/ml) were noted. In patients with severe coronary atherosclerosis, two different BDNF/TrkB variants have been identified. Decreased BDNF and increased TrkB (6,0/1,52 ng/ml) were associated with low VEGF and increased IL-6. Elevated BDNF and normal TrkB values (26,95/0,96 ng/ml) were characteristic of patients with high VEGF expression, indicating angiogenesis activation and/or vulnerable plaques. A direct relationship between BDNF and VEGF (r=0,536, p&lt;0,001) and an inverse relationship with TrkB (r=-0,301, p=0,019), IL-6 (r=-0,306, p=0,002) was revealed. TrkB levels were correlated with TNF-α (r=0,403, p=0,001). Regression analysis showed that BDNF expression is influenced by TrkB (β=-0,237, p=0,009), VEGF (β=0,490, p&lt;0,001), IL-6 (β=-0,339, p&lt;0,001).Conclusion. In patients with stable CAD, different levels of BDNF/TrkB expression were found, which were associated with coronary atherosclerosis severity. BDNF/TrkB signaling is involved in the regulation of inflammation and angiogenesis in stable CAD.

99mTc-MIBI washout rate as a marker of myocardial mitochondrial dysfunction: A systematic review and meta-analysis

BACKGROUND: This review outlines the features of the pharmacokinetics of the perfusion radiopharmaceutical 99mTc-MIBI, which allows the assessment of myocardial mitochondrial dysfunction, and shows the main clinical applications of the phenomenon of increased 99mTc-MIBI washout rate. AIM: To systematize the data of fundamental (experimental) and clinical studies evaluating and estimating mitochondrial dysfunction according to myocardial perfusion scintigraphy data and perform meta-analysis of clinical studies in this field. MATERIALS AND METHODS: PubMed, Scopus, Google Scholar, and eLibrary databases were searched until mid-2023. The following keywords, their combinations, and Russian-language counterparts were used: mitochondrial dysfunction, 99mTc-MIBI, 99mTc-Tetrofosmin, myocardial perfusion scintigraphy, reverse redistribution, washout, and washout rate. In the meta-analysis, a random-effects model was used to calculate the mean difference estimate. RESULTS: Forty articles were selected for systematic analysis: 13 were experimental, 24 were original clinical papers, 2 were clinical cases, and 1 was a review. Six studies using a case–control design were selected for the meta-analyses. The total number of patients in the systematic review and meta-analysis were 551 and 196, respectively. In the analysis of the literature, the severity of the reverse redistribution phenomenon and 99mTc-MIBI washout rate correlated with mitochondrial and myocardial microstructure, left ventricular contractility and hemodynamics, natriuretic peptide levels, exercise tolerance, coronary atherosclerosis severity, myocardial oxidative metabolism, and risk of cardiovascular events. The meta-analysis showed that the washout rate was statistically significantly accelerated in individuals with cardiac pathologies, relative to controls (mean difference score, 9.5771 [95%]; confidence interval, 6.6001–12.5540; z=6.3053, p 0.0001). CONCLUSION: The assessment of mitochondrial function by 99mTc-MIBI washout evaluation may provide additional insights into the functional status of cardiac muscles.

ВЗАИМОСВЯЗЬ УРОВНЯ ПРОВОСПАЛИТЕЛЬНЫХ АДИПОЦИТОКИНОВ И ОБЪЕМНО-ЛИНЕЙНЫХ ПАРАМЕТРОВ ЭКТОПИЧЕСКИХ ЖИРОВОГО ДЕПО У БОЛЬНЫХ С ИШЕМИЧЕСКОЙ БОЛЕЗНЬЮ СЕРДЦА

Abstract. Introduction. Multispiral computed angiography of the coronary arteries is the method of choice for the early noninvasive diagnosis of coronary atherosclerosis and, therefore, coronary heart disease. Quantitative indicators of epicardial fat depot are significantly associated with coronary atherosclerosis and coupled with possible cardiovascular events without reference to traditional risk factors. Aim of this study was to establish the relationship between the proinflammatory adipocytokine levels and the volumetric-linear parameters of paracardial fat depots in patients with coronary atherosclerosis. Materials and Methods. 135 patients (74 men (52%) and 61 women (48%)) with confirmed and suspected coronary heart disease were examined, aged 45 to 80 years. All patients were divided into 2 groups: Study group and comparison group. The study group consisted of 88 patients with coronary atherosclerosis, 56 men (63%) and 32 women (37%). This group included patients with one-, two- and multivessel coronary artery lesions, as well as with hemodynamically insignificant (CAD-RADs≤2) and significant (CAD-RADs≥3) stenosis areas. The comparison group consisted of 47 patients without coronary atherosclerosis. Quantitative indicators of cardiac and abdominal fat depots were calculated for all patients by means of computed tomography. Results and Discussion. The volume of epicardial adipose tissue was significantly higher in individuals with coronary heart disease, as compared to patients in the comparison group. The volume of abdominal adipose tissue was also higher in patients of the main group (p&lt;0.001). The volume of visceral adipose tissue in patients with ischemic heart disease was 1.43 times larger than in the comparison group (p&lt;0.05), the area of epicardial adipose tissue did not statistically differ in the two groups (p˃0.05), and the area of visceral adipose tissue was 1.62 times (p&lt;0.05) larger in patients with ischemic heart disease. Differences in the groups with hemodynamically insignificant and significant coronary artery stenoses were statistically valid (p˂0.05). Conclusions. In patients with coronary artery disease, the degree of increase in epicardial and abdominal fat correlates with the severity of coronary artery atherosclerosis. Laboratory tests of the adipokine-cytokine profiles is an important prognostic factor of coronary atherosclerosis severity.

A rare case of cardiac calcified amorphous tumor in a 34-year-old woman diagnosed at autopsy

Abstract Introduction/Objective Cardiac calcified amorphous tumor (CAT) is an uncommon, non-neoplastic heart lesion with an unknown incidence due to its rarity. Some authors have reported a female predominance of 62.5%. Many cases are associated with end-stage renal disease, diabetes mellitus and coronary artery disease. Dysfunction of calcium- phosphorus metabolism and hypercoagulability are thought to contribute to its pathogenesis. This is the first case reported from our institution. Methods/Case Report We present the case of a 34-year-old woman with a remote history of ulcerative colitis, type 1 diabetes mellitus, hypertension, Hashimoto thyroiditis, cardiomegaly, and end-stage renal disease on continuous hemodialysis. She had multiple hospitalizations for mesenteric ischemia and small bowel resections. She was admitted multiple times in 2021 for complaints of pain in bilateral thighs, shortness of breath, frequent loose stools, and abdominal pain. She was poorly compliant with hemodialysis. A chest x-ray showed severe enlargement of the cardiac silhouette. A CT angiogram of the abdomen and pelvis showed arteriosclerosis of the superior mesenteric, inferior mesenteric and celiac arteries. The patient presented to the hospital in February 2022 with continuous abdominal pain, gluteal pain, and diarrhea. Her creatinine was consistently elevated at 3.52 mg/dL. On the sixth day of admission, she was found unresponsive and was pronounced dead. Autopsy showed cardiomegaly (600 grams) with left ventricular hypertrophy, recent myocardial infarction of the posterolateral left ventricle and moderate to severe coronary artery atherosclerosis. There were lesions composed of calcified amorphous material involving the mitral valve, the endocardium and subendocardial portions of the left and right ventricles, consistent with multifocal cardiac calcified amorphous tumor. The largest lesion measured 4.0 cm. The cause of death was myocardial infarction complicating type 1 diabetes mellitus and end-stage renal disease. Results (if a Case Study enter NA) NA Conclusion CATs are usually asymptomatic but possible symptoms include dyspnea and syncope. As a result, they are often incidental findings. The calcified deposits may embolize, causing pulmonary embolism and cerebral infarction. CAT is most frequently observed in the left heart, especially on the mitral annulus; however, the right side of the heart can also be affected. End-stage renal disease is a predisposing condition, as seen in this patient.

Association of lipoprotein(a) with severity of coronary artery atherosclerosis in patients with acute coronary syndromes

Abstract Background Elevated level of lipoprotein (a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease. However, the association of Lp(a) with acute coronary syndromes (ACS) has not been sufficiently studied. Purpose To evaluate the relationship between high serum levels of Lp(a) and (i) factors that play a role in the long-term development of the severity of coronary artery disease (CAD), (ii) extent of CAD amongst patients with ACS. Methods In this study we enrolled 74 consecutive patients hospitalized for ACS in tertiary cardiology center form December 2022 to January 2023. Patients characteristics were compared for patients with Lp(a) &amp;lt;75 nmol/L (53 patients) and ≥75 nmol/L (21 patients). Logistic regression analyses were performed to evaluate the relationship of Lp(a) with severity of CAD. Results In the studied population, the mean age of patients with high Lp(a) levels was 65 years. They were more likely to have arterial hypertension and hypercholesterolemia than those with normal Lp(a) levels (p &amp;lt;0.05). There were no significant differences in distribution of ACS subtype between groups. On univariate analysis, triple vessel CAD [odds ratio (OR) 4.22, 95% confidence interval (CI) 1.34-13.27, p = 0.014), and multivessel CAD (OR 3.05, 95% CI 1.06-8.81, p = 0.040) were significantly associated with abnormal Lp(a) levels. Multivariable determinants of of high Lp(a) levels were also triple vessel CAD (OR 4.19, 95% CI 1.33-13.26, p = 0.013), and multivessel CAD (OR 3.04, 95% CI 1.05-8.80, p = 0.042). Conclusions Lp(a) ≥75 nmol/L was closely associated with the extent and severity of CAD in patients with ACS.

Does the pre-procedural pathophysiological pattern impact post-procedural hemodynamic outcomes and vessel prognosis in multivessel coronary artery disease?

Abstract Aim The pathophysiological pattern of coronary artery disease (CAD) pre-procedure may affect the physiological response to percutaneous coronary intervention (PCI). The aim of this study was to evaluate whether the pathophysiological pattern of CAD, derived from virtual pullbacks of angiography-based fractional flow reserve, impacted the immediate hemodynamic outcome post-PCI. Methods and results Among 503 consecutive patients with chronic coronary syndrome and non-ST elevated acute coronary syndrome treated at least 1 vessel in the Multivessel TALENT trial, 826 quantitative flow ratio (QFR) analysable vessels were enrolled. Pre-procedural pathophysiological patterns in CAD were characterized by the physiological distribution and local severity of coronary atherosclerosis using QFR-derived indexes acquired from pre-PCI angiograms. The physiological distribution of CAD was defined as "predominant diffuse" or "focal" according to a QFR pullback pressure gradient (PPG) index &amp;lt;0.78 and ≥0.78, respectively. Physiological local severity was assessed using QFR gradient per 1 mm (dQFR/ds), with a value ≥ 0.025/mm defining the presence of a "major gradient". The optimal post-PCI QFR value was defined as QFR ≥0.91. Among the 826 vessels, 673 vessels were analysed (excluding vessels which have total occlusions, ostial lesions, and paired QFR not analysable). Mean pre-PCI PPG index was 0.70 with a nadir in the distribution curve. As per the definition, "focal" lesions were 30% of the total analysed vessels and 88% had a "major gradient". The majority of the vessels belong to predominantly diffuse disease with a major gradient (62.7%, Figure 1). Compared to predominantly focal disease with a major gradient, predominantly diffuse disease had a higher risk of a post-PCI QFR &amp;lt;0.91 (OR 1.78, 95%CI 1.23-2.58). The scatterplot between pre-procedural PPGI and post-procedural QFR showed positive correlation (Piason’s R=0.163, p&amp;lt;0.001, Figure 2). The correlation suggested that the vessels with focal lesions more frequently achieved optimal post-PCI QFR values compared to that with diffuse lesions. In multivariable analysis, low QFR PPG index (diffuse disease) was an independent factor for predicting a post-PCI QFR&amp;lt;0.91 (per 0.1 decreases of QFR PPG index, OR:10.3, 95% CI 1.7-63.3, p=0.012). The estimated 2-year VOCE, the powered secondary endpoint of this study, estimated by the post-QFR is 5.9% in treated vessels with predominant diffuse lesion, while 4.9% in that with predominant focal lesion based on the previous substudy of SYNTAX II trial.[1] Conclusions A physiological pattern of diffuse CAD pre-procedure was an independent factor in predicting an unfavourable immediate hemodynamic outcome post-PCI. Pre-procedural PPG index can be the predictor of not only post-PCI physiological value but also vessel base prognosis.pre-PCI pathophysiological patternScatterplot and correlation