Atherosclerosis Of Peripheral Arteries Research Articles

Lipoprotein(a), atherosclerosis and cardiovascular risk

At the end of the 20th century, the contribution of hyperlipoproteinemia (a) to early development and severity of coronary, cerebral and peripheral artery atherosclerosis was established, and its association with the development of aortic valve stenosis was shown. The results of epidemiological studies allow us to consider lipoprotein(a) (Lp(a)) as a new target for the diagnosis, prevention and pharmacotherapy of atherosclerotic cardiovascular diseases. The atherogenicity of Lp(a) is 6 times higher than that of low-density lipoproteins and can be the cause of early and rapid progression of atherosclerosis. The 2022 European Atherosclerosis Society statement stated that the threshold value of Lp(a) for "excluding" the risk of atherosclerotic cardiovascular diseases is less than 30 mg/dL. The range of Lp(a) values between 30 mg/dL and 50 mg/dL creates the so-called "grey zone" when the possible risks associated with Lp(a) and other cardiovascular risk factors should be considered. At Lp(a) values >180 mg/dL, the risk of cardiovascular diseases is equivalent to the risk of patients with heterozygous familial hypercholesterolemia. This review will discuss the genetic and pathophysiological properties of Lp(a), and the epidemiological data demonstrating its effect on cardiovascular morbidity. Extracorporeal methods for removing excess Lp(a) from blood serum are currently the only proven option to correct this dyslipidemia. Cascade plasmafiltration helps reduce LDLcholesterol and Lp(a) levels by more than 60%, as well as to decrease the level of oxidized phospholipids in plasma. It should be noted that according to 2023 domestic recommendations, the criteria for extracorporeal treatment are Lp(a) >50.0 mg/dl. The review provides recommendations for screening and treatment of patients with elevated Lp(a) levels, as well as a range of pharmacotherapeutic drugs being developed to reduce its level in the blood.

Peripheral arterial atherosclerosis and heart failure: state of the art review

Heart failure is considered as a terminal stage of the cardiovascular continuum, beginning with exposure to risk factors followed by the development of asymptomatic cardiovascular damage, progressing to clinically manifest disease. Conventional risk factors such as arterial hypertension, dyslipidemia, obesity, and diabetes mellitus, on the one hand, directly cause structural and functional changes in the heart, and on the other hand, contribute to the development and progression of atherosclerosis. Despite the fact that the multifocal nature of atherosclerosis is well known, research data on the role of peripheral arterial atherosclerosis in the development of heart failure are extremely limited. The study of potential relationships between atherosclerosis of peripheral arteries and heart failure is relevant in all sex and age groups of patients.

Associations Between Flavonoid Intake and Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis.

Flavonoids may play a role in mitigating atherosclerotic cardiovascular diseases, with evidence suggesting effects may differ between vascular beds. Studies examining associations with subclinical markers of atherosclerosis between subpopulations with different underlying risks of atherosclerosis are lacking. Among 5599 participants from the MESA (Multi-Ethnic Study of Atherosclerosis), associations between dietary flavonoid intakes (estimated from a food frequency questionnaire) and subclinical measures of atherosclerosis (ankle-brachial index, carotid plaques and intima-media thickness, and coronary artery calcification) were examined using repeated measures models. Exposures and outcomes were measured at exam 1 (2000-2002) and exam 5 (2010-2011). Stratified analyses and interaction terms were used to explore effect modification by time, sex, race/ethnicity, and smoking status. In the analytic population, at baseline, ≈46% were men with a median age of 62 (interquartile range, 53-70) years and total flavonoid intakes of 182 (interquartile range, 98-308) mg/d. After multivariable adjustments, participants with the highest (quartile 4) versus lowest (quartile 1) total flavonoid intakes had 26% lower odds of having an ankle-brachial index <1 (odds ratio, 0.74 [95% CI, 0.60-0.92]) and 18% lower odds of having a carotid plaque (odds ratio, 0.82 [95% CI, 0.69-0.99]), averaged over exams 1 and 5. Moderate (quartile 3) to high (quartile 4) intakes of flavonols, flavanol monomers, and anthocyanins were associated with 19% to 34% lower odds of having an ankle-brachial index <1 and 18% to 20% lower odds of having carotid plaque. Participants with the highest intakes of anthocyanins (quartile 4) at baseline had a marginally slower rate of carotid plaque progression than those with moderate intakes (quartiles 2 and 3). There were no significant associations with intima-media thickness or coronary artery calcification. Observed associations did not differ by sex, race/ethnicity, or smoking status. In this multi-ethnic population, higher dietary flavonoid intakes were associated with lower odds of peripheral and carotid artery atherosclerosis. Increasing intakes of healthy, flavonoid-rich foods may protect against atherosclerosis in the peripheral and carotid arteries.

Lipitension – myth or reality? Opinion of a practicing cardiologist (letter to the editor)

The article (letter to the editor) presents current data on the prevalence of arterial hypertension and dyslipidemia according to domestic and foreign epidemiological studies. It is advisable for a clinical practitioner to consider these two leading cardiovascular pathologies (they are also the most common risk factors for the development and progression of atherosclerosis) together for further active correction with drug and non-drug methods of treatment. According to the studies presented in the article, the association of high blood pressure with the risk of myocardial infarction, stroke, heart failure, sudden cardiac death, atherosclerosis of peripheral arteries, chronic kidney disease, regardless of the age of patients with hypertension, is shown. There is no doubt about the positive effect of long-term maintenance of target blood pressure values in patients with an established diagnosis of arterial hypertension in relation to the prevention of cardiovascular complications.At the same time, up to 40 % of patients with arterial hypertension are characterized by the presence of one or another type of dyslipidemia. The opinion was expressed about the legality of using the term "lipitension" in connection with the convenience of designating these two pathologies in the form of a single pro-atherogenic comorbidity. The article presents the opinion of a practicing cardiologist, which is the advisability of distinguishing the term "lipitension" (as a pathological-nosological combination (comorbidity) of two leading risk factors in the population of developed countries – arterial hypertension and dyslipidemia. Understanding the commonality of two key factors limiting the prognosis of patients with cardiovascular diseases allows the practitioner to more confidently, with pathogenetic justification, apply the polytablet strategy (containing lipid-lowering and antihypertensive components), which allows not only to achieve more effective control of blood pressure and lipid profile indicators, but also to improve the prognosis and quality of life of patients in the framework of primary and secondary prevention.

Interactions of the Osteokines, Glucose/Insulin System and Vascular Risk Networks in Patients With Newly Diagnosed Type 2 Diabetes (VNDS 15).

Bone as an endocrine organ regulates metabolic processes independently of mineral metabolism through the production/release of proteins collectively named 'osteokines'. Relevant connections were reported between the insulin/glucose system, calcification of the atherosclerotic plaque, and several osteokines. We aimed to test the hypothesis that the osteokine network could be involved in beta-cell function, insulin sensitivity, and vascular damage in a cohort of people with newly diagnosed type 2 diabetes (T2D). In 794 drug-naive, GADA-negative, newly-diagnosed T2D patients (mean±SD age: 59±9.8years; BMI: 29.3±5.3kg/m2; HbA1c: 6.6±1.3%) we assessed: plasma concentration of osteocalcin (OCN), osteopontin (OPN),RANKL, and its putative decoy receptor osteoprotegerin (OPG); insulin sensitivity (SI) by hyperinsulinemic euglycemic clamp; beta cell function (BCF), estimated by OGTT minimal modelling and expressed as derivative (DC) and proportional (PC) control. Echo-doppler of carotid and lower limb arteries were also performed in 708 and 701 subjects, respectively. OCN, RANKL and OPG were significantly associated with PC (p<0.02); OCN was positively related to DC (p=0.018). OPG was associated with lower IS (p<0.001). Finally, the higher RANKL levels, the greater was the severity of atherosclerosis in common carotid artery (p<0.001). Increased OPG and OPN concentrations were related to subclinical atherosclerosis in peripheral arteries of lower limbs (p=0.023 and p=0.047, respectively). These data suggest that, in patients with newly diagnosed T2D, the osteokine network crosstalks with the glucose/insulin system and may play a role in modulating the atherosclerotic process.

Frailty and risk of systemic atherosclerosis: A bidirectional Mendelian randomization study.

Numerous observational studies have reported an association between frailty and atherosclerosis. However, the causal relationship between frailty and the occurrence of atherosclerosis in different anatomical sites remains unclear. we conducted a bidirectional Mendelian randomization (MR) study to evaluate the causal relationship between the frailty index (FI), and both systemic atherosclerosis and lipids. We obtained summary statistics from large-scale genome-wide association studies (GWAS) of various phenotypes, including frailty (n = 175,226), coronary atherosclerosis (n = 56,685), cerebral atherosclerosis (n = 150,765), peripheral arterial disease (PAD) (n = 361,194), atherosclerosis at other sites (n = 17,832), LDL-C (n = 201,678), HDL-C (n = 77,409), and triglycerides (n = 78,700). The primary MR analysis employed the inverse variance weighted (IVW) method. Furthermore, to assess reverse causality, we employed inverse MR and multivariate MR analysis. Genetically predicted FI showed positive associations with the risk of coronary atherosclerosis (OR = 1.47, 95% CI 1.12-1.93) and cerebral atherosclerosis (OR = 1.99, 95% CI 1.05-3.78), with no significant association (p >0.05) applied to peripheral arterial disease and atherosclerosis at other sites. Genetically predicted FI was positively associated with the risk of triglycerides (OR = 1.31, 95% CI 1.08-1.59), negatively associated with the risk of LDL-C (OR = 0.87, 95% CI 0.78-0.97), and showed no significant association with the risk of HDL-C (p >0.05). Furthermore, both reverse MR and multivariate MR analyses demonstrated a correlation between systemic atherosclerosis, lipids, and increased FI. Our study elucidated that genetically predicted FI is associated with the risk of coronary atherosclerosis and cerebral atherosclerosis by the MR analysis method, and they have a bidirectional causal relationship. Moreover, genetically predicted FI was causally associated with triglyceride and LDL-C levels. Further understanding of this association is crucial for optimizing medical practice and care models specifically tailored to frail populations.

Correlation and risk factors of peripheral and cervicocephalic arterial atherosclerosis in patients with ischemic cerebrovascular disease

Patients with ischemic cerebrovascular disease (ICVD) frequently develop concomitant peripheral artery disease (PAD) or renal artery stenosis (RAS), and multiterritorial atherosclerotic patients usually have a worse prognosis. We aimed to evaluate the status of peripheral atherosclerosis (AS) and cervicocephalic AS (CAS) in ICVD patients with AS, their correlation, and related risk factors contributing to coexisting cervicocephalic-peripheral AS (CPAS). Based on the severity and extent of AS evaluated by computed tomography angiography and ultrasound, the degree of AS was triple categorized to assess the correlation between CAS and PAD/RAS. CAS and PAD/RAS were defined as the most severe stenosis being ≥ 50% luminal diameter in cervicocephalic or lower limb arteries, and a peak systolic velocity at the turbulent site being ≥ 180 cm/s in the renal artery. Among 403 patients with symptom onset within 30 days, CAS, PAD, and RAS occurrence rates were 68.7%, 25.3%, and 9.9%, respectively. PAD was independently associated with the degree of extracranial and intracranial CAS (p = 0.042, OR = 1.428, 95% CI 1.014–2.012; p = 0.002, OR = 1.680, 95% CI 1.206–2.339), while RAS was independently associated with the degree of extracranial CAS (p = 0.001, OR = 2.880, 95% CI 1.556–5.329). Independent CPAS risk factors included an ischemic stroke history (p = 0.033), increased age (p < 0.01), as well as elevated fibrinogen (p = 0.021) and D-dimer levels (p = 0.019). In conclusion, the occurrence rates of RAS and PAD in ICVD patients with AS is relatively high, and with the severity of RAS or PAD increase, the severity of CAS also increase. Strengthening the evaluation of peripheral AS and controlling elevated fibrinogen might be crucial for preventing and delaying the progression of multiterritorial AS in ICVD patients with AS, thereby improving risk stratification and promoting more effective prevention and treatment strategies.

РЕГУЛЯЦИЯ СИСТЕМНОГО ВОСПАЛИТЕЛЬНОГО ОТВЕТА У ПАЦИЕНТОВ С МУЛЬТИФОКАЛЬНЫМ АТЕРОСКЛЕРОЗОМ

Introduction. Data on the role of inflammation in the progression and manifestation of multifocal atherosclerosis (MFA) are contradictory. The systemic process of multiple lesions of different vascular beds in patients with an established diagnosis of coronary heart disease (CHD) is due to several parallel pathological mechanisms. In general, in the pathogenesis of both coronary atherosclerosis and atherosclerosis of peripheral arteries, one of the factors is the variability of immune response genes and cytokines, regulators of the inflammatory response. The aim of this work was to determine the role of variability in the genes of cytokines and innate immune response receptors in the structure of mechanisms associated with the development of MFA in patients with coronary artery atherosclerosis. Materials and methods. 260 patients with CAD (mean age 58 years) were examined. Of all those included in the study, at the time of the survey, MFA was found in 180 people (69.23%), while the incidence of MFA in men and women is comparable (70.33 vs. 64.71%, respectively). There is also no significant difference in the incidence of MFA in the two age groups (up to 60 years, 45% have lesions of two or more vascular beds, and in people older than 60 years, MFA was found in 55% of cases). All patients were informed about the course of the study and voluntarily signed an informed consent. Blood was collected from the cubital vein into Vacutainer tubes with K3EDTA. DNA isolation was carried out using the phenol-chloroform extraction method. Genotyping of 47 polymorphic sites with a single nucleotide change (SNV) of 19 genes proven to be associated with the regulation of the systemic inflammatory response (cytokines, innate immunity receptors) was performed in a 96-well format using TaqMan technology (LifeTechnologies, USA) and real-time result detection with using the ViiATM 7 RealTime PCR System (LifeTechnologies, USA) for polymerase chain reaction in accordance with the instructions. Associations were analyzed using Snpstats (https://www.snpstats.net/start.htm). Odds ratio (OR) and 95% CI for OR were calculated for risk assessment. Results. One association has been established that demonstrates a negative impact and increases the risk of developing MFA in young and middle age. Carriage of the G rs11685424 IL1RL1 allele increases the risks of earlier development of peripheral arterial lesions by 2 times (OR 2.11 (95% CI 1.09-4.06), p = 0.024) according to the recessive inheritance model. At the same time, variability in three sites (rs1974675; rs6758936; rs3755276) of the IL18 receptor gene (IL18R1) reduces the risk of MFA detection by three times (p=0.12; p=0.034: p=0.026, respectively) and this pattern is also observed in patients older age group. In the carriers of the A/A rs1974675, T/T rs3755276 and A/A rs6758936 genotypes in persons over 60 years of age, MFA was diagnosed less frequently (p=0.024; p=0.037; p=0.011, respectively). Conclusion. It has been shown that in patients with significant coronary atherosclerosis, the progression of peripheral vascular atherosclerosis is more associated with the variability of the genes responsible for the regulation of the systemic inflammatory response, rather than genes and their variants that determine the severity and strength of the immune response.

Skin autofluorescence as an indicator of advanced glycation end-product accumulation in the prognosis of age-related cardiovascular disease: literature review

Advanced glycation end products (AGEs) are represented by heterogeneous molecular structures and their accumulation in organs and tissues reflects the intensity of oxidative stress and glycemia. As a physiological process, aging is associated with AGE accumulation and changing the morphology and functions of the vascular wall. Accelerated AGE accumulation initiates inflammation, contributing to the development of cardiovascular diseases, such as arterial hypertension, coronary heart diseases, and atherosclerosis of peripheral arteries; conditions associated with high cardiovascular risks such as prediabetes, diabetes mellitus type 2, and chronic kidney diseases are also characterized by the accelerated AGEs accumulation. The ability of AGEs to fluorescence underlies noninvasively in blood serum, tissues, and skin using a well-proven technique of autofluorescence, which is little known to domestic specialists. This review presents the possibilities of autofluorescence to reflect arterial wall remodeling, which includes stiffness, vascular endothelial function, atherosclerotic plaque formation, and instability, using modern materials. The review emphasizes the evidence base regarding the ability of this method to predict mortality and cardiovascular events in a large population from low to high risk.

Ultrasound Score of Liver Steatosis Severity in the Diagnosis of Peripheral Arterial Atherosclerosis in Patients with Nonalcoholic Fatty Liver Disease

Ultrasound Score of Liver Steatosis Severity in the Diagnosis of Peripheral Arterial Atherosclerosis in Patients with Nonalcoholic Fatty Liver Disease

Apolipoprotein A-IV of diabetic-foot patients upregulates tumor necrosis factor α expression in microfluidic arterial models.

Diabetic peripheral arterial atherosclerosis is one of the important characteristics of diabetic foot syndrome. Apolipoprotein (Apo A-IV) participates in various physiological processes, and animal studies have shown that it has roles of anti-atherosclerosis, prevention of platelet aggregation and thrombosis. Apo A-IV glycosylation is closely related to the occurrence and development of diabetic peripheral atherosclerosis. This study aimed to explore the mechanism of diabetic peripheral arterial lesions caused by glycosylated Apo A-IV. Type 2 diabetes mellitus (T2DM) and T2DM with diabetic foot patients (T2DM-F; n = 45, 30) were enrolled in this study, and individuals without diabetes (n = 35) served as normal controls (NC). In T2DM group, serum Apo A-IV content was higher than those in NC and T2DM-F group, as carboxymethyl lysine (CML) glycosylation of Apo A-IV in mixed serum from T2DM-F group was identified to be more significant than those in two other groups. Within a microfluidic arterial chip model, Apo A-IV from T2DM and T2DM-F group significantly increased transcription and protein levels of tumor necrosis factor alpha (TNF-α) in chip arteries, and CML expression was observed in T2DM-F group, which were associated with increased nuclear receptor subfamily 4 group A member 3 (NR4A3) expression. Recombinant human Apo A-IV could reverse the stimulating effect of serum Apo A-IV from T2DM-F group on TNF-α expression, and NR4A3 blocking peptide downregulated TNF-α expression by inhibiting NR4A3 expression. In the chip arteries, Apo A-IV from T2DM and T2DM-F increased TNF-α expression and turn them into a pre-atherosclerotic state, which might be one of the important mechanisms of glycosylated Apo A-IV to induce diabetic peripheral arterial lesions and eventually lead to diabetic foot.

The Association Between Metabolic Dysfunction-Associated Fatty Liver Disease and Peripheral Arterial Disease in the Chinese Population.

Emerging evidence suggested that metabolic dysfunction-associated fatty liver disease (MAFLD) was significantly associated with atherosclerotic diseases. Atherosclerosis in the peripheral arteries is the most common cause of peripheral arterial disease (PAD), which has not been substantially controlled in the past. We aimed to investigate the association between MAFLD and PAD in the Chinese population. This observational study covered 102,115 participants who underwent health checkups with detailed examinations for PAD and MAFLD. PAD was measured by ankle-brachial index, and MAFLD was diagnosed by abdominal ultrasound. The generalized linear mixed models and random-effects Cox proportional hazards models were used to analyze the relationship between MAFLD and PAD. The baseline characteristics showed that patients with MAFLD had higher prevalence of PAD compared with those without MAFLD (2.7% vs 2.2%). Compared to non-MAFLD, the individuals with MAFLD were associated with a higher risk of the presence of PAD (adjusted odds ratio: 1.30, 95% confidence interval (CI): 1.19-1.42, P < 0.001). In the prospective cohort study, 6833 participants underwent a follow-up of 2.76 (standard deviation: 1.36) years, and MAFLD at baseline was a higher risk of associated with incident PAD (adjusted hazards ratio: 1.67, 95% CI: 1.17-2.38, P = 0.005). Moreover, with the accumulation of metabolic abnormalities, the risk of the PAD was increased in the individuals with MAFLD. Furthermore, MAFLD attributed risk of PAD was more evident in participants without metabolic comorbidities. MAFLD was associated with a significantly higher risk for the prevalence and incidence of PAD in the Chinese population. The finding suggested that individuals with MAFLD are not only have a higher risk of coronary heart diseases but also have an increased risk of atherosclerosis in peripheral arteries.

TP53-mediated clonal hematopoiesis confers increased risk for incident atherosclerotic disease.

Somatic mutations in blood indicative of clonal hematopoiesis of indeterminate potential (CHIP) are associated with an increased risk of hematologic malignancy, coronary artery disease, and all-cause mortality. Here we analyze the relation between CHIP status and incident peripheral artery disease (PAD) and atherosclerosis, using whole-exome sequencing and clinical data from the UK Biobank and Mass General Brigham Biobank. CHIP associated with incident PAD and atherosclerotic disease across multiple beds, with increased risk among individuals with CHIP driven by mutation in DNA Damage Repair (DDR) genes such as TP53 and PPM1D. To model the effects of DDR-induced CHIP on atherosclerosis, we used a competitive bone marrow transplantation strategy, and generated atherosclerosis-prone Ldlr-/- chimeric mice carrying 20% p53-deficient hematopoietic cells. The chimeric mice were analyzed 13-weeks post-grafting and showed increased aortic plaque size and accumulation of macrophages within the plaque, driven by increased proliferation of p53-deficient plaque macrophages. In summary, our findings highlight the role of CHIP as a broad driver of atherosclerosis across the entire arterial system beyond the coronary arteries, and provide genetic and experimental support for a direct causal contribution of TP53-mutant CHIP to atherosclerosis.

PS-P05-7: WEIGHT OF EVIDENCE OF LONG-TERM EFFECTS OF HEAVY METALS ON THE CARDIOVASCULAR SYSTEM AT A POPULATION LEVEL

Background/Objectives: Heavy metals chronic exposure is a major contributor to cardiovascular diseases (CVD) at the population level, and regions with high levels of heavy metals contamination showed increased rate of mortality rate from cardiovascular diseases. Among different heavy metals; Arsenic, Lead, Mercury, and Cadmium are the most toxic to human health. The purpose of the study was to weigh the amount of evidence presented in the literature for an association between each heavy metal and five cardio-vascular diseases: coronary heart disease, cerebrovascular disease, peripheral arterial disease, hypertension, and atherosclerosis. Methods: Literature review was done. PubMed, google scholar, and science direct were searched using keywords cardiovascular diseases and 4 heavy metals, separate and all together. Irrelevant articles were excluded, and only relevant epidemiological articles were included. Bradford Hill criteria of causality was used to assess the association of each of the heavy metals with the five CVD. Results: The results of recent studies showed that the correlation between the four heavy metals and CVD are inconsistent with those of earlier studies and the general picture of the correlation between exposure to heavy metals and CVD presented by these studies is either inconsistent or not conclusive. Conclusion: Among the nine-criterion mentioned by Sir Bradford Hill, this study was only compatible with two out of nine criterions mentioned. The first criterion is the strength of the association, and the second criterion is the consistency of the association. Other criterions are not compatible with this study. Although this study tried to examine the effect of 4 heavy metals on CVD, most studies linked only 1 heavy metal to 1 or 2 CVD, due to the interactive effects of heavy metals, and the absence of clear understanding to the mode of action. Nonetheless, there is a great need to do further research and explore more about the effect of these 4 metals on CVD.

Aromatic Amino Acids: Phenylalanine and Tyrosine in Patients with Hypertension and Coronary Artery Disease

Aim. To evaluate changes in the profile of aromatic amino acids (AAA) in patients with cardiovascular diseases (CVD): hypertension and coronary artery disease (CАD) in comparison with healthy study participants.Material and methods. One hundred and thirty-one participants were included in the study: 58 participants were included in the hypertension group, 46 in the CАD group, and 27 participants without signs of CVD in the control group. We used ultrahigh-performance liquid chromatography in combination with a triple quadrupole analyzer to measure plasma AAA: phenylalanine and tyrosine (Phe, Tyr) in all study participants. The association of AAA with biochemical blood test parameters, echocardiography (EchoCG) parameters, blood pressure level and clinical characteristics was analyzed.Results. A statistically significant difference in the level of concentration of Phe and Tyr was revealed (p=0,002 and p=0,024, respectively), comparing the three groups. Post-hoc analysis showed differences in the circulating level of both amino acids in patients with CAD vs the control group (Phe p=0,008 and Tyr p=0,020). Also a statistically significant difference in the level of Phe of the hypertension and CАD groups (p=0,017) was found. A negative correlation of low-density lipoproteins (LDL) with the level of Phe (r=-0,685, p&lt;0,05) and Tyr (r=-0,583, p&lt;0,05), as well as the level of Phe with total cholesterol (r=-0,461, p&lt;0,05) was found in the group without CVD. In the hypertension group, only a weak positive correlation was found between very low-density lipoproteins and AAA levels (Phe r=0,326 and Tyr r=0,365, p&lt;0,05), while in patients with CAD, the level of Phe and Tyr was negative correlated with high-density lipoprotein (r=-0,378 and r=-0,543, respectively, p&lt;0,05), and the level of Tyr with LDL (r=0,349, p&lt;0,05). When isolating the group with proven atherosclerosis of peripheral and/or coronary arteries, a statistically significant difference was revealed between the group of patients with CVD and clinical and instrumental signs of atherosclerosis and the group of patients with CVD without proven atherosclerosis in Phe level (p=0,019).Conclusion. Concentrations of AAA were higher in patients with CVD, comparing with the control group. At the same time, an increase of the Phe level was associated with the presence of peripheral or coronary atherosclerosis. The revealed correlations of AAA with EchoCG parameters and lipid spectrum parameters require further study to understand the involvement of AAA in pathogenesis of CVD and its potential role as treatment target.

Differentiating Associations of Glycemic Traits With Atherosclerotic and Thrombotic Outcomes: Mendelian Randomization Investigation.

We conducted a Mendelian randomization analysis to differentiate associations of four glycemic indicators with a broad range of atherosclerotic and thrombotic diseases. Independent genetic variants associated with fasting glucose (FG), 2 h glucose after an oral glucose challenge (2hGlu), fasting insulin (FI), and glycated hemoglobin (HbA1c) at the genome-wide significance threshold were used as instrumental variables. Summary-level data for 12 atherosclerotic and 4 thrombotic outcomes were obtained from large genetic consortia and the FinnGen and UK Biobank studies. Higher levels of genetically predicted glycemic traits were consistently associated with increased risk of coronary atherosclerosis-related diseases and symptoms. Genetically predicted glycemic traits except HbA1c showed positive associations with peripheral artery disease risk. Genetically predicted FI levels were positively associated with risk of ischemic stroke and chronic kidney disease. Genetically predicted FG and 2hGlu were positively associated with risk of large artery stroke. Genetically predicted 2hGlu levels showed positive associations with risk of small vessel stroke. Higher levels of genetically predicted glycemic traits were not associated with increased risk of thrombotic outcomes. Most associations for genetically predicted levels of 2hGlu and FI remained after adjustment for other glycemic traits. Increase in glycemic status appears to increase risks of coronary and peripheral artery atherosclerosis but not thrombosis.

Analysis of differentially expressed genes and signaling pathways involved in atherosclerosis and chronic obstructive pulmonary disease.

Bioinformatics analysis of datasets from Gene Expression Omnibus (GEO) was performed to examine the gene ontology (GO) of common differentially expressed genes (DEGs) in COPD and peripheral arterial atherosclerosis. DEGs were identified using the limma R package with the settings p < 0.05, corrected using the Benjamini & Hochberg algorithm and ǀlog 2FCǀ > 1.0. The GO, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and the protein-protein interaction (PPI) network analysis were performed with the detected DEGs. The biological processes and signaling pathways involving common DEGs from airway epithelial datasets in COPD and tissue in peripheral atherosclerosis were identified. A total of 15 DEGs were identified, comprising 12 upregulated and 3 downregulated DEGs. The GO enrichment analysis demonstrated that the upregulated hub genes were mainly involved in the inflammatory response, reactive oxygen species metabolic process, cell adhesion, lipid metabolic process, regulation of angiogenesis, icosanoid biosynthetic process, and cellular response to a chemical stimulus. The KEGG pathway enrichment analysis demonstrated that the common pathways were Toll-like receptor signaling pathway, NF-kappa B signaling pathway, lipid and atherosclerosis, and cytokine-cytokine receptor interaction. Biological processes and signaling pathways associated with the immune response may link the development and progression of COPD and atherosclerosis.

Management of patients with myocardial infarction and nonobstructive coronary arteries: literature review and own data

Over the past few years, much attention has been paid to the diagnosis and treatment of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA). Its prevalence achieves 5 — 15 %, and impact of risk factors of cardiovascular disease development on the MINOCA onset has some specific features. The following criteria are required to diagnose MINOCA: compliance with the MI criteria, absence of obstructive coronary artery disease (≥ 50 %) and exclusion of an alternative diagnosis. Myocardial ischemia is the underlying cause of cardiomyocyte damage during MINOCA. It can be caused by coronary artery thrombosis due to the rupture of atherosclerotic plaque (type 1 MI), spasm or spontaneous coronary artery dissection (type 2 MI). The aim of our study was to analyse risk factors and the incidence of MINOCA in patients with acute myocardial infarction. A retrospective analysis has been performed on 1358 histories of patients with MI who were hospitalized in Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiac Surgery during the period of 2019 — 2020 years. From them, 60 (4.4 %) patients were selected based on MINOCA diagnostic criteria according to the European Society of Cardiology (2018). The mean age of patients was 58.6 ± 14 years. ST‑segment elevation MI (STEMI) was diagnosed in 87.2 %. Cardiac and non‑cardiac comorbidity has been investigated with the following results: atrial fibrillation (AF) was revealed in 13.3 % of patients, hypertension (AH) — in 85 %, history of coronary heart disease (CHD) — in 31.7 %, recurrent MI — in 11.7 %, chronic heart failure (CHF) — in 75 %, atherosclerosis of peripheral arteries — in 33.3 %, type 2 diabetes mellitus (DM 2) — in 20 %, obesity — in 40.7 %. The proportion of smokers was 43.8 %. According to the results of laboratory studies, dyslipidemia was diagnosed in 44.7 % of patients. According to coronary angiography, 55 % of patients had no coronary artery stenosis, 21.7 % had stenosis of one artery, and stenosis of two or more arteries was defined in 23.3 % of cases. The following distribution by lesions’ types was established: irregularities in the contours of arteries or stenosis up to 30 % in 35 % of cases; stenosis ≥ 30 &lt; 50 % in 18.3 %, and slow evacuation of the contrast agent in 16.7 % of cases. Men prevailed in our research, which is inconsistent with the data of large observational studies, probably due to a small quantity of patients. Hypertension, chronic heart failure, tobacco smoking, obesity and dyslipidemia prevailed among the basic risk factors. Patients with MINOCA require careful evaluation to determine the causative agent and appropriate treatment choices. Conduction of large‑scale studies, in particular, randomized controlled observations, is reasonable and necessary to determine the optimal tactics for management patients with MINOCA.

CD36 expression intensity on different subpopulations of circulating monocytes depending on the extent of subclinical atherosclerosis

It is known that chronic activation of innate immunity and persistent low-intensity inflammation play a crucial role in the initiation and progression of atherosclerosis. It was found that atherogenic lipoproteins can act as inducers of the inflammatory response through ligand-receptor interaction with pattern-recognizing receptors of immunocompetent cells, such as CD36 (SR-B2) and Toll-like receptors. It is suggested that expression of CD36 on circulating monocytes may represent the burden of systemic atherosclerosis and, therefore, act as its diagnostic marker. The aim of the present study was to assess the intensity of CD36 expression on circulating monocytes of different subpopulations in patients without established cardiovascular disease (CVD) depending on the extent of subclinical atherosclerosis of peripheral arteries. One hundred patients without established atherosclerotic CVD, 49 (49.0%) men and 51 (51.0%) women, were included in the study. Monoclonal antibody conjugates were used to phenotype monocyte subpopulations. The expression of CD36 on CD14++CD16- monocytes (classical monocytes), CD14+CD16+ monocytes (intermediate monocytes), CD14+CD16++ monocytes (non-classical monocytes) was determined by the average fluorescence intensity. There was a statistically significant decrease in CD36 expression intensity on classical and non-classical monocytes with increasing number of vascular basins affected by atherosclerosis. A statistically significant decrease in CD36 expression intensity on classical and non-classical monocytes was found in the patients with two vascular beds lesions in comparison with patients with a single vascular bed lesion upon pairwise comparisons.

Essential Fatty Acids as Biomedicines in Cardiac Health.

The destructive impact of cardiovascular diseases on health, including heart failure, peripheral artery disease, atherosclerosis, stroke, and other cardiac pathological conditions, positions these health conditions as leading causes of increased global mortality rates, thereby impacting the human quality of life. The considerable changes in modern lifestyles, including the increase in food intake and the change in eating habits, will unavoidably lead to an unbalanced consumption of essential fatty acids, with a direct effect on cardiovascular health problems. In the last decade, essential fatty acids have become the main focus of scientific research in medical fields aiming to establish their impact for preventing cardiovascular diseases and the associated risk factors. Specifically, polyunsaturated fatty acids (PUFA), such as omega 3 fatty acids, and monounsaturated fatty acids from various sources are mentioned in the literature as having a cardio-protective role, due to various biological mechanisms that are still to be clarified. This review aims to describe the major biological mechanisms of how diets rich in essential fatty acids, or simply essential fatty acid administration, could have anti-inflammatory, vasodilatory, anti-arrhythmic, antithrombotic, antioxidant, and anti-atherogenic effects. This review describes findings originating from clinical studies in which dietary sources of FAs were tested for their role in mitigating the impact of heart disorders in human health.