Atherosclerotic Plaques In Carotid Arteries Research Articles

Development of a Collagen Fibre Remodelling Rupture Risk Metric for Potentially Vulnerable Carotid Artery Atherosclerotic Plaques.

Atherosclerotic plaque rupture in carotid arteries can lead to stroke which is one of the leading causes of death or disability worldwide. The accumulation of atherosclerotic plaque in an artery changes the mechanical properties of the vessel. Whilst healthy arteries can continuously adapt to mechanical loads by remodelling their internal structure, particularly the load-bearing collagen fibres, diseased vessels may have limited remodelling capabilities. In this study, a local stress modulated remodelling algorithm is proposed to explore the mechanical response of arterial tissue to the remodelling of collagen fibres. This stress driven remodelling algorithm is used to predict the optimum distribution of fibres in healthy and diseased human carotid bifurcations obtained using Magnetic Resonance Imaging (MRI). In the models, healthy geometries were segmented into two layers: media and adventitia and diseased into four components: adventitia, media, plaque atheroma and lipid pool (when present in the MRI images). A novel meshing technique for hexahedral meshing of these geometries is also demonstrated. Using the remodelling algorithm, the optimum fibre patterns in various patient specific plaques are identified and the role that deviations from these fibre configurations in plaque vulnerability is shown. This study provides critical insights into the collagen fibre patterns required in carotid artery and plaque tissue to maintain plaque stability.

Gender and cardiovascular risk in rotational shift workers in the Arctic

Objective. To study gender differences in potential risk factors (RF) for cardiovascular diseases in rotational shift workers in the Arctic.Design and methods.Out of 213 examined patients, 183 individuals were enrolled in groups within 6 days of September 2019, in the polar settlement of Yamburg (68 N), on the basis of Health Service LLC “Gazprom Dobycha Yamburg” medical unit. They were comparable by age: 99 were males (M) aged 48 years (41,5; 58,5) and 81 were females (F) aged 49 years (43,6; 58,1) (p = 0,441); by number of years of rotational shift work: 16,5 (9,0; 26,4) years in M and 16,3 (8,5; 26,9) years in F (p = 0,635); by number of individuals with hypertension: 49,5% were M, 43,9% were F (p = 0,344) and normotensive individuals (p = 0,544). Office blood pressure was 149,4 (119,1; 180,2) mmHg in M group, 149,6 (128,5; 178,5) mmHg in F group (p = 0,250). All patients underwent ultrasound examination of carotid arteries (CA) for the detection of atherosclerotic plaque (ASP), and assessment of local stiffness parameters of CA and femoral arteries (FA); cardio-ankle vascular index, and pulse wave velocity. In addition, ambulatory blood pressure monitoring, echocardiography with calculation of HFpEF probability using H2FPEF score (Heavy; Hypertensive; Atrial Fibrillation; Pulmonary Hypertension; Elder; Filling Pressure); blood tests (lipid spectrum, levels of high-sensitivity C-reactive protein (hs-CRP), homocysteine, C-peptide, insulin, brain natriuretic propeptide (NT-pro-BNP)) were performed. The following RF were assessed: smoking, physical activity, and perceived stress level.Results. Overweight (p = 0,039), smoking (p = 0,014) were more common in M than in F. Low self-esteem level of psychosocial stress was more frequently registered in F: 93% vs 54 % (p < 0,0001), while mean level was more often found in M: 46% vs 7 % (p < 0,0001). In M group, there was a significant increase in homocysteine (p < 0,001), which was associated with higher stiffness index β in CA (p = 0,004) and FA (p = 0,004), Peterson’s elastic modulus Ep CA (p = 0,009), higher detection rate of ASP in CA (p = 0,021). F group showed significant increase in hs-CRP (p = 0,03), and NT-pro-BNP, (p < 0,001). Odds ratio of gender-related indicators showed association of male sex with arterial stiffness, formation of ASP in CA, while female sex was associated with markers of systemic inflammation and neurohumoral activation. There were no significant differences between M and F regarding HFpEF probability, assessed by H2FPEF score (p = 0,303).Conclusions. Our data will allow for identifying the most significant factors with high gender-specific cardiovascular risk in rotating shift-workers in the Arctic which can play role in cardiovascular prevention and early diagnosis with the focus on economic efficiency.

The role of soluble leptin receptor in the pathogenesis of coronary heart disease

Introduction. The participation of soluble leptin receptor (SLR) in the formation of hyperleptinemia and leptin resistance in patients with coronary artery disease (CAD) in combination with obesity is discussed. Aim. Study of the role of SLR in the pathogenesis of ischemic heart disease. Materials and methods. A cohort study of 744 patients was performed: 465 patients with CAD (56 years old, Q1=44; Q3=62), 270 patients without CAD (52 years old, Q1=44; Q3=56). Methods: EchoCG, heart computed tomography, coronary angiography. In the blood serum, the lipids, glucose, creatinine, uric acid, and c-reactive protein were assessed using a highly sensitive method (HF-CRP). Concentrations of SLR, leptin (LN), adiponectin (total and high molecular weight), fatty acid binding protein-4 (FABP-4) tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), serum insulin were determined by enzyme immunoassay. Results. The level of SLR in blood serum in men and women with CAD is lower than in men without CAD (p <0.001). In CAD patients, obesity was associated with a low SLR level in the blood serum and a high free LN index. At a serum SLR concentration of <7.5ng/ml in men with CAD, the incidence of obesity was higher simultaneously with signs of visceral obesity of the heart, the presence of atherosclerotic plaques in the common carotid arteries, high glycaemic levels, insulin, IL-6, and LN in serum, serum LN/adiponectin ratio and a high HOMA-IR index. Diabetes mellitus, visceral obesity, high levels of hs-CRP, TNF-α, FABP-4, serum insulin, and HOMA-IR index were more often detected in women with coronary artery disease with SLR <10.2 ng/ml. In men and women with CAD, there were no differences in SLR concentration depending on the extent of coronary atherosclerosis. Conclusion. An increase in the free LN index indicates the disruption of connections in the leptin-receptor system and reflects the mechanisms of compensation for overcoming the resistance of peripheral tissues to leptin, which is confirmed by a noticeable negative relationship between the levels of SLR and leptin in the serum of men with coronary artery disease. A low concentration of SLR in patients with CAD is associated with obesity, pro-atherogenic and pro-inflammatory markers of cardiovascular diseases.

Cardiovascular risk factors and cervical carotid plaque features on CT angiography.

Little is known about the impact that cardiovascular (CV) risk factors have on the formation of various carotid atherosclerotic plaque features. This study set out to assess the association between CV risk factors and plaque characteristics on computed tomography (CT) angiography (CTA). A retrospective review was completed of consecutive patients that underwent a carotid endarterectomy and had CTA imaging of the head and neck vasculature. Atherosclerotic plaques of both carotid arteries were evaluated for calcification(s), low-density plaque (LDP) components, ulceration(s), and degree of stenosis. Various clinical CV risk factors were assessed using medical records. Last recorded laboratory levels were dichotomized into categories: total cholesterol <200 or ≥200 mg/dL, low-density lipoprotein (LDL) <130 or ≥130 mg/dL, high-density lipoprotein <35 or ≥35 mg/dL, and triglyceride <200 or ≥200 mg/dL. Of 97 included patients, 62 were male (63.9%); the average age was 72.7 (standard deviation = 9.5). Calcifications were in 95/97 (97.9%) of patients (one or both carotid plaques); LDP components were in 73/97 (75.3%), and ulcerations were in 21/97 (21.6%). Elevated total cholesterol and elevated LDL levels were both associated with a higher likelihood of LDP components (p = 0.004 and p = 0.02, respectively). There were no other statistically significant associations between individual plaque features or severity of arterial stenosis and CV risk factors. In carotid atherosclerotic plaques, LDP components are more frequently present in one or both carotid arteries in patients with elevated total cholesterol and/or LDL levels. Such findings raise the possibility that cholesterol levels may be directly related to the formation of specific high-risk plaque features.

Endothelial function and structural markers of atherosclerosis: relationship in old and senile age

Endothelial dysfunction (ED), intima-media thickness (IMT), and atherosclerotic plaques (ASPs) of the carotid arteries (CAs) are considered mutually associated markers of subclinical and clinical atherosclerosis. How true this statement is for older age groups remains unclear.Aim. To study the relationship of flow-dependent vasodilation (FDV) with CA IMT and ASPs in a population sample over 58 years old.Material and methods. The study was carried out in a population sample of men and women aged 58-82 years (Novosibirsk, HAPIEE project, n=788, 424 women). CA ultrasound was performed to assess IMT and ASPs. Endothelial function was assessed by postocclusive hyperemia ultrasound test; an increase in brachial artery initial diameter (FDV%) &lt;10% was regarded as ED.Results. The average IMT in men was 0,95 mm (SD 0,18) and was significantly higher than in women: 0,88 mm (SD 0,17), p&lt;0,001. The average FDV% values in men were 2,7% (SD 7,32), while in women — 3,2% (SD 7,19) and did not differ significantly by sex. The incidence of ED was 88,2% in men and 85,8% in women. There was no a significant linear relationship between FDV and IMT neither in men (β=-1,76, SD 2,25, p=0,436), nor in women (β=-2,19, SD 2,15, p=0,309). Also, there were no differences in average IMT and ASP frequency in the groups with and without ED among men and women. When divided into age groups, ED was associated with an increase in IMT only in women aged &lt;78 versus women without ED (p=0,047).Conclusion. In the population sample of 58-82 years old, mutual associations of subclinical markers of atherosclerosis (ED, IMT, ASP of CAs) have not been confirmed. Only in women aged &lt;78 years, ED was associated with an increase in IMT. The results obtained indicate that the treatment approaches proposed for young and middle-aged people may be less effective in old and senile age.

Detection of heteroplasmic mitochondrial genome mutations by NGS method in patients with atherosclerotic plaques in carotid arteries

Background and Aims: The aim of the study was to identify heteroplasmic mutations mtDNA associated with atherosclerotic plaques in carotid arteries (AP CA) by the NGS (next-generation sequencing) method.

Shear wave elastography as a method of evaluation the stability of atherosclerotic plaque of carotid arteries - comparison with cotrast enhanced ultrasonography

Background and Aims: The aim of the study was to evaluate the usefulness of elastography in the diagnosis of atherosclerotic plaque stability.

Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease

Long non-coding RNAs (lncRNAs) have emerged as critical regulators in human disease including atherosclerosis. However, the mechanisms involved in the post-transcriptional regulation of the expression of disease-associated lncRNAs are not fully understood. Gene expression studies revealed that Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) lncRNA expression was increased by >2-fold in peripheral blood mononuclear cells (PBMCs) derived from patients with coronary artery disease (CAD) or in carotid artery atherosclerotic plaques. We observed a linear association between NEAT1 lncRNA expression and prevalence of CAD which was independent of age, sex, cardiovascular traditional risk factors and renal function. NEAT1 expression was induced by TNF-α, while silencing of NEAT1 profoundly attenuated the TNF-α-induced vascular endothelial cell pro-inflammatory response as defined by the expression of CXCL8, CCL2, VCAM1 and ICAM1. Overexpression of the RNA editing enzyme adenosine deaminase acting on RNA-1 (ADAR1), but not of its editing-deficient mutant, upregulated NEAT1 levels. Conversely, silencing of ADAR1 suppressed the basal levels and the TNF-α-induced increase of NEAT1. NEAT1 lncRNA expression was strongly associated with ADAR1 in CAD and peripheral arterial vascular disease. RNA editing mapping studies revealed the presence of several inosines in close proximity to AU-rich elements within the AluSx3+/AluJo‐ double-stranded RNA complex. Silencing of the stabilizing RNA-binding protein AUF1 reduced NEAT1 levels while silencing of ADAR1 profoundly affected the binding capacity of AUF1 to NEAT1. Together, our findings propose a mechanism by which ADAR1-catalyzed A-to-I RNA editing controls NEAT1 lncRNA stability in ASCVD.

Identification of Periopathogens in Atheromatous Plaques Obtained from Carotid and Coronary Arteries.

Increasing attention has been paid to the possible link between periodontal disease and atherosclerosis over the past decade. The aim of this study is to investigate the presence of five periopathogens: Porphyromonas gingivalis (P.g.), Aggregatibacter actinomycetemcomitans (A.a.), Tannerella forsythia (T.f.), Treponema denticola (T.d.), and Prevotella intermedia (P.i.) in atheromatous plaques obtained from the carotid and coronary arteries in patients who underwent coronary artery bypass graft surgery and carotid endarterectomy. Group I (carotid arteries) consisted of 30 patients (mean age: 54.5 ± 14.8), and group II (coronary arteries) consisted of 28 patients (mean age: 63 ± 12.1). Clinical periodontal examinations consisted of plaque index, gingival index, sulcus bleeding index, and periodontal probing depth and were performed on the day of vascular surgery. The presence of periopathogens in periodontal pockets and atherosclerotic vessels was detected using polymerase chain reaction. In both subgingival plaque and atherosclerotic plaque of carotid arteries, P.g., A.a., T.f., T.d., and P.i. were detected in 26.7%, 6.7%, 66.7%, 10.0%, and 20.0%, respectively, while for coronary arteries, P.g. was detected in 39.3%, A.a. in 25%, T.f. in 46.4%, T.d. in 7.1%, and P.i. in 35.7%. The presence of five periopathogens in carotid and coronary atherosclerotic vessels showed correlation in regard to the degree of periodontal inflammation. The present study suggests the relationship between periodontal pathogenic bacteria and atherogenesis. Further studies are necessary in relation to the prevention or treatment of periodontal disease that would result in reduced mortality and morbidity associated with atherosclerosis.

Application of cardiovascular risk scales to identify carotid atherosclerosis in patients with rheumatoid arthritis

To evaluate the cardiovascular risk (CVR) and analyze its relationship with detection of early carotid artery atherosclerotic lesion in patients with rheumatoid arthritis (RA). One hundred and nine RA patients aged 45 to 60 without established cardiovascular diseases (CVD) were included in the study. The median age was 52 [48; 54] years, duration of RA was 120 [36; 204] months, DAS28 was 4.7 [3.5; 5.6] points. CVD risk was calculated with mSCORE, Reynolds Risk Score (RRS), ASSIGN, QRISK3, ERS-RA scales and Carotid Artery Doppler Ultrasound Exam was performed for all patients. High risk was found in 5, 5, 14, 6, and 38% of patients according to mSCORE, RRS, ASSIGN, QRISK3, ERS-RA scales, respectively. Atherosclerotic plaques of carotid arteries were found in 30% of patients. It was found that carotid intima-media thickness is correlated to all CVR calculators, age, systolic and diastolic blood pressure, cholesterol, erythrocyte sedimentation rate, interleukin-6 levels. The sensitivity and specificity of the CVR algorithms in prognostication of atherosclerotic carotid artery lesions were 73 and 67% for mSCORE, 64 and 63% for RRS, 64 and 56% for ASSIGN, 73 and 49% for QRISK3, respectively, p0.05 in all cases, 67 and 50% for ERS-RA, p=0.06. RRS, mSCORE, ASSIGN, QRISK3 calculators equally predict atherosclerotic carotid artery damage in RA patients. The optimal ratio of specificity and sensitivity is shown for the mSCORE scale. Stratification of CVR in RA patients should include assessment of the carotid intima-media thickness. To identify CVR in RA patients, the most informative methods are mSCORE calculation and carotid intima-media thickness determination.

Visual Scale as a Non-Invasive Method for Evaluation of Risk and Severity of Coronary Atherosclerosis.

Aim To evaluate quantitative and qualitative characteristics of atherosclerotic plaques (ASP) in carotid arteries (CA) and femoral arteries (FA) and to use these data for developing a visual scale (VS) for noninvasive diagnosis and determination of severity of coronary atherosclerosis.Material and methods This study included 216 patients (115 men and 101 women) aged 24 to 87 years (mean age, 61.5±10.73 years). All patients underwent coronary angiography (CAG) for detecting and determining severity of CA atherosclerosis and duplex scanning (DS) for detecting atherosclerosis of CA and FA.Results Analysis of ultrasound parameters of ASP in CA and FA showed that the maximal ASP height, moderate stenosis and maximal stenosis of the arterial bed had higher predictive values than other ultrasound parameters. These parameters were used for forming diagnostic complexes, on the basis of which two individual VSs for CA and FA were developed. Based on the high prognostic value of both scales, they were combined into one that was named VSCOMB. A ROC analysis determined cut-off points of the VSCOMB for diagnosis of CA atherosclerosis of various severity. VSCOMB scores &gt;4 indicated pronounced CA atherosclerosis with sensitivity of 86.1 % and specificity of 87.5 % whereas VSCOMB scores ≤4 excluded it. Thus, VSCOMB score 0-1 indicated the absence of CA atherosclerosis; score 2-4 indicated the presence of subclinical CA atherosclerosis; and score &gt;4 indicated severe CA atherosclerosis.Conclusion A VSCOMB was developed that includes a set of ultrasound parameters for CA and FA and is useful for noninvasive diagnosis of CA atherosclerosis of various severity. Simple and convenient use of VSCOMB allows it to be used at the screening stage to detect subclinical CA atherosclerosis and to prevent its progression.

Assessment of neovascularization of carotid artery atherosclerotic plaques using superb microvascular imaging: a comparison with contrast-enhanced ultrasound imaging and histology.

This study aimed to investigate the usefulness of superb microvascular imaging (SMI), a novel non-contrast-enhanced ultrasound technique, in characterizing neovessels within carotid atherosclerotic plaques through comparison with contrast-enhanced ultrasound (CEUS) and histology. Patients with carotid plaque were recruited and underwent SMI and CEUS ultrasound imaging of the carotid arteries. The maximum plaque thickness, length, and stenosis of each plaque were measured. Grade of the neovessels was determined by SMI and CEUS, respectively. Grade 0 was defined as no blood flow signal/microbubbles within plaques; grade 1 was defined as moderate blood flow signals/microbubbles confined to the shoulder and/or adventitial side of the plaque; and grade 2 was defined as extensive intraplaque signals/microbubbles. Patients with symptomatic carotid stenosis (stenosis ≥50%) or asymptomatic carotid stenosis (stenosis ≥70%) underwent endarterectomy, and plaque specimens were subjected to immunohistochemical analysis of CD31 expression. The neovessels were quantified by histology. The agreement of SMI with CEUS and histology in characterizing neovessels was analyzed using weighted Kappa statistic and Spearman's correlation analyses. Seventy-eight patients (mean age: 67.3±8.9 years old, 63 males) were recruited. Of these patients, 52 (66.7%) had a unilateral plaque and 26 (33.3%) had bilateral plaques in the carotid arteries. For the 104 carotid plaques detected, the mean plaque thickness and length were 4.3±1.1 and 18.8±6.6 mm, respectively. The prevalence of <50%, 50-69%, and ≥70% stenosis was 43.3%, 24.0%, and 32.7%, respectively. Excellent agreement was found between SMI and CEUS (κ=0.825 at the plaque level; κ=0.820 at the patient level) in evaluating the neovessel grade within the carotid plaques. Of the 25 patients who underwent carotid endarterectomy, a strong correlation (r=0.660, P<0.001) was found between SMI and histology in the evaluation of intraplaque neovessels. SMI had excellent scan-rescan (κ=0.857), intra-reader (κ=0.810), and inter-reader (κ=0.754) agreement in the assessment of intraplaque neovessels. The SMI technique is capable of reliably characterizing neovessels within carotid atherosclerotic plaques and demonstrates good to excellent agreement with histology and CEUS.

Shear-Wave Elastography Enables Identification of Unstable Carotid Plaque

Shear-wave elastography (SWE) is a novel ultrasound technique for quantifying tissue elasticity. The aim of this study was to identify differences in atherosclerotic plaque elasticity measured using SWE among individuals with symptomatic, asymptomatic progressive and asymptomatic stable carotid plaques. Consecutive patients from the Atherosclerotic Plaque Characteristics Associated with a Progression Rate of the Plaque and a Risk of Stroke in Patients with the Carotid Bifurcation Plaque Study were screened for this research. Neurosonography examination of carotid arteries was performed to identify plaque stenosis of ≥50% using B-mode ultrasound and SWE imaging to measure the mean, maximal and minimal elasticity. The set consisted of 97 participants—74 with asymptomatic stable stenosis, 12 with asymptomatic progressive stenosis and 11 with symptomatic stenosis. The mean elasticity in the asymptomatic stable plaque group was significantly higher than in the asymptomatic progressive (52.2 vs. 30.4 kPa; p < 0.001) and symptomatic (52.2 vs. 36.4 kPa; p = 0.033) plaque groups. No significant differences were found between asymptomatic progressive and symptomatic (p > 0.1) plaque groups. Asymptomatic stable, asymptomatic progressive and symptomatic plaques did not differ in echogenicity, calcifications, homogeneity, occurrence of ulcerated surface, or intra-plaque hemorrhage (p > 0.05 in all cases). SWE was a helpful modality for differentiating between stable and unstable atherosclerotic plaques in carotid arteries.

Cardiovascular system status of long-livers in Moscow: the prevalence of cardiovascular diseases and their risk factors

Over the past century, an increase in life expectancy has been observed in Russia and in the world. According to the United Nations, by 2100, the number of centenarians worldwide will reach 25 million. Despite the annual increase in the number of super-centenarians, this age group remains poorly understood.Aim. To estimate the prevalence of cardiovascular diseases (CVD) and the main risk factors among super-centenarians in Moscow.Material and methods. According to the register of long-livers in Moscow, 82 people aged 95 to 105 were included. Participants were examined at home.The history of life and the presence of chronic diseases was collected by participant words. To assess the state of cardiovascular system, an ultrasound of the heart and main arteries was performed.Results. Conventional CVD risk factors were the exception rather than the rule among study participants (smoking — 8 patients (9,8%), alcohol abuse — 4 (4,9%), obesity — 6 (7,3%)). Dyslipidemia was relatively widespread (n=37; 45,1%), however, there were no pronounced abnormalities in the lipid profile: the maximum increase in low-density lipoproteins was 5,6 mmol/L. The most common CVDs among the participants were hypertension (n=64; 78%), coronary artery disease (n=42; 51,2%), and heart failure (n=26; 31,7%); other diseases were much less common. The most common echocardiographic changes were left atrial dilatation (n=38; 74,5%), increased left ventricular mass, thickening of left ventricular posterior wall (n=24; 48%) and interventricular septum (n=51; 100%). Diastolic and systolic heart failure were not widespread among long-livers: 16 (32%) and 2 (3,9%), respectively. Despite a rather large number of atherosclerotic plaques in the common carotid and femoral arteries, the number of hemodynamically significant plaques was low (n=3; 4,6%). An intima-media thickening up to 1,0-1,1 mm was found.Conclusion. Long-livers in Moscow are characterized by a low prevalence of traditional CVD risk factors (with the exception of hypertension) and a fairly high prevalence of atherosclerotic CVDs, which are characterized by a subclinical course.

Factors associated with the risk subclinical carotid atherosclerosis in rotational shift workers in the Arctic

Objective.To determine the most unfavorable predictors of atherosclerotic plaque (ASP) in carotid arteries (CA) in rotational shift workers in the Arctic using traditional risk factors, clinical and instrumental methods of research.Design and methods. In 2010–2012, we randomly selected 424 males aged 30–59 years from 1708 rotational shift workers at the medical unit of the gas production company “Gazprom dobycha Yamburg” (Yamburg settlement, 68ºN) and performed preventive medical examination. Subjects were divided into 2 groups according to blood pressure (BP) level. Group 1 included 294 patients with hypertension (HTN) of 1 or 2 stages &gt; 140/90 mmHg and group 2 was comprised of 130 people with BP &lt; 140/90 mmHg. The groups did not differ by age, total work experience in the Arctic and rotational shiftwork duration. Ultrasound examination of CA showed presence or absence of ASP and stenosis by NASCET method. In addition, we assessed traditional risk factors and performed 24-hour BP monitoring and blood tests including lipid spectrum, glucose level, creatinine.Results.ASP was found more often in subjects with HTN (group 1) than in people with normal BP in the same age group, 95 % CI 56–60 % vs 95 % CI 14–20 %, (p &lt; 0,0001). The groups did not differ significantly in the nutritional habits (p = 0,067). At the same time, the rate of smoking (p = 0,039), low physical activity (p = 0,007), overweight (p &lt; 0,0001) was significantly higher in group 1 compared to subjects with normal BP. According to multivariate analysis, three variables with the most significant predictors associated with ASP in CA with sensitivity 75,9 % were selected using step-by-step method: diastolic BP 24 (DBP24) (p &lt; 0,0001), glucose (p = 0,017) and total cholesterol (p = 0,044). The linear function was obtained: F = –7,664 + 0,225 × Chol + 0,366 × Glu + 0,057 × DBP24, where the variable “Chol” is the level of total cholesterol in the blood in mmol/l; “Glu” — the level of blood glucose in mmol/l; “DBP24” — average 24-hour diastolic BP. Based on the model, we concluded that DBP24 increment by 1 mmHg increases the risk for developing ASB in CA by 5,9 %, OR = 1,059 (95 % CI: 1,033; 1,087); the increment in glucose and total cholesterol by 1 mmol/l increases the risk by 44,1 % and 25,2 %, respectively: OR = 1,441 (95 % CI: 1,084; 1,966), OR = 1,252 (95 % CI: 1,010; 1,565).Conclusions.Our data enable to determine the most unfavorable predictors of ASP in CA and can potentially serve as a guideline for early diagnosis and medical management to prevent cardiovascular diseases in rotational shift workers in the Arctic.

Colocalization of Erythrocytes and Vascular Calcification in Human Atherosclerosis: A Systematic Histomorphometric Analysis.

Background Intimal calcification typically develops in advanced atherosclerosis, and microcalcification may promote plaque progression and instability. Conversely, intraplaque hemorrhage and erythrocyte extravasation may stimulate osteoblastic differentiation and intralesional calcium phosphate deposition. The presence of erythrocytes and their main cellular components (membranes, hemoglobin, and iron) and colocalization with calcification has never been systematically studied. Methods and Results We examined three types of diseased vascular tissue specimens, namely, degenerative aortic valve stenosis ( n = 46), atherosclerotic carotid artery plaques ( n = 9), and abdominal aortic aneurysms ( n = 14). Biomaterial was obtained from symptomatic patients undergoing elective aortic valve replacement, carotid artery endatherectomy, or aortic aneurysm repair, respectively. Serial sections were stained using Masson–Goldner trichrome, Alizarin red S, and Perl's iron stain to visualize erythrocytes, extracelluar matrix and osteoid, calcium phosphate deposition, or the presence of iron and hemosiderin, respectively. Immunohistochemistry was employed to detect erythrocyte membranes (CD235a), hemoglobin or the hemoglobin scavenger receptor (CD163), endothelial cells (CD31), myofibroblasts (SMA), mesenchymal cells (osteopontin), or osteoblasts (periostin). Our analyses revealed a varying degree of intraplaque hemorrhage and that the majority of extravasated erythrocytes were lysed. Osteoid and calcifications also were frequently present, and erythrocyte membranes were significantly more prevalent in areas with calcification. Areas with extravasated erythrocytes frequently contained CD163-positive cells, although calcification also occurred in areas without CD163 immunosignals. Conclusion Our findings underline the presence of extravasated erythrocytes and their membranes in different types of vascular lesions, and their association with areas of calcification suggests an active role of erythrocytes in vascular disease processes.

Carotid plaque inflammatory activity assessed by 2-[18F]FDG-PET imaging decrease after a neurological thromboembolic event

BackgroundAtherosclerotic plaque vulnerability is comprised by plaque composition driven by inflammatory activity and these features can be depicted with 3D ultrasound and 2-[18F]FDG-PET, respectively. The study investigated timely changes in carotid artery plaque inflammation and morphology after a thromboembolic event with PET/CT and novel ultrasound volumetric grayscale median (GSM) readings. Patients with a single hemisphere-specific neurological symptom and the presence of an ipsilateral carotid artery atherosclerotic plaque were prospectively included to both 2-[18F]FDG PET/CT and 3D ultrasound scans of the plaque immediately after their event and again three months later. On PET/CT images the maximum standardized uptake value (SUVmax) was measured and the volumetric ultrasound acquisitions were analyzed using a semiautomated software measuring GSM values.ResultsBaseline scans were performed by a mean of 7 days (range 2–14) after the symptom and again after 98 days (range 91–176). For the entire group (n = 14), we found a decrease in average SUVmax from baseline to follow-up of − 0.18 (95% confidence interval: − 0.34 to − 0.02, P = 0.034). GSM did not increase significantly over time (mean change: + 2.21, 95% confidence interval: − 17.02 to 21.44, P = 0.808).ConclusionA decrease in culprit lesion 2-[18F]FDG-uptake 3 months after an event indicates a decrease in inflammatory activity, suggesting that carotid plaque stabilization over time. 3D ultrasound morphological quantitative differences in GSM were not detectable after 3 months.

Association of the increased circulating CD62LloCXCR4hi neutrophil count with carotid atherosclerosis

Introduction. The role of neutrophils in the initiation and progression of atherosclerosis as well as in the development of its complications has received scientific attention only in the recent years. Today, there is growing evidence to support a role of the CXCL12/CXCR4 axis in sustained inflammation during different chronic inflammatory diseases by retaining neutrophils at inflammatory sites.The aim of the study is to assess the diagnostic and prognostic significance of circulating CD62LloCXCR4 hi neutrophils in patients with carotid atherosclerosis.Materials and methods. A total of 75 patients (52% of men and 48% of women) aged 40 to 64 years were examined. None of them were diagnosed with atherosclerotic cardiovascular diseases. All the patients underwent carotid artery duplex scanning. The flow cytometry and CD16, CD11b, CD62L, CD182 (CXCR2) and CD184 (CXCR4) conjugated monoclonal antibodies were used for phenotyping and differentiation of neutrophil subpopulations.Results. Atherosclerotic plaques in carotid arteries were detected in 72% of the patients; most of the patients were diagnosed with stenosis development in more than one of the carotid arteries (CA). The elevated levels of circulating CXCR4h neutrophils were associated with the levels of total cholesterol (r = 0.377; p = 0.001), low-density lipoprotein (LDL) cholesterol (r = 0.293; p = 0.014) and triglycerides (r = 0.388; p = 0.003). The study revealed direct correlation between the circulating CXCR4 hi neutrophil count and the cumulative percentage of CA stenosis (r = 0.300; p = 0.011), including the number of stenosed CA (r = 0.291; p = 0.034). It was also found that CXCR4 hi neutrophil counts demonstrated a statistically significant increase along with the increased number of stenosed CA (p = 0.025). The ROC analysis findings show that the elevated CXCR4 hi neutrophil counts ≥260 cells/μL made it possible to diagnose stenotic lesion of 4 CAs with a sensitivity of 71.4% and specificity reaching 76.6%.Conclusion. In patients with carotid atherosclerosis, the increased count of circulating CD62LloCXCR4 hi neutrophils was associated with the increased number of stenosed CAs, while no significant changes were observed in the other examined subpopulations of neutrophil granulocytes. The increased CD62LloCXCR4 hi neutrophil count made it possible to diagnose stenotic lesion of 4 CAs with a sufficient sensitivity and specificity.

The Availability of the α7-Nicotinic Acetylcholine Receptor in Early Identification of Vulnerable Atherosclerotic Plaques: A Study Using a Novel 18F-Label Radioligand PET.

Background: It has been confirmed that the α7-nicotinic acetylcholine receptor (α7nAChR) is an important target for identifying vulnerable atherosclerotic plaques. Previously, we successfully designed and synthesized a series of 18F-labeled PET molecular probes targeting α7nAChR, which are mainly used in the diagnosis of Alzheimer's disease. Based on the characteristics of α7nAChR in blood vessels, we have firstly screened for a suitable novel 18F-labeled PET molecular probe ([18F]YLF-DW), with high selectivity for α7nAChR over α4β2nAChR and a good effect for the imaging of atherosclerotic animal models, to effectively identify vulnerable atherosclerotic plaques at an early stage. Meanwhile, we compared it with the “gold standard” pathological examination of atherosclerosis, to verify the reliability of [18F]YLF-DW in early diagnosis of atherosclerosis.Methods: The vulnerable atherosclerotic plaques model of ApoE-/-mice were successfully established. Then based on the methods of 3D-QSAR and molecular docking, we designed oxazolo[4,5-b] pyridines and fluorenone compounds, which are targeted at α7nAChR. Through further screening, a novel alpha7 nicotinic acetylcholine receptor radioligand ([18F]YLF-DW) was synthesized and automatically 18F-labeled using a Stynthra RNplus module. Subsequently, we employed [18F]YLF-DW for the targeting of α7nAChR in atherosclerotic plaques and control group, using a micro-PET/CT respectively. After imaging, the mice were sacrificed by air embolism and the carotid arteries taken out for making circular sections. The paraffin embedded specimens were sectioned with 5 μm thickness and stained with oil red. After staining, immunohistochemistry experiment was carried out to verify the effect of micro-PET/CT imaging.Results: The micro-PET/CT imaging successfully identified the vulnerable atherosclerotic plaques in the carotid arteries of ApoE-/-mice; whereas, no signal was observed in normal control mice. In addition, compared with the traditional imaging agent [18F]FDG, [18F]YLF-DW had a significant effect on the early plaques imaging of carotid atherosclerosis. The results of oil red staining and immunohistochemistry also showed early formations of carotid plaques in ApoE-/-mice and provided pathological bases for the evaluation of imaging effect.Conclusion: We innovated to apply the novel molecular probe ([18F]YLF-DW) to the identification of vulnerable atherosclerotic plaques in carotid arteries, to detect atherosclerosis early inflammatory response and provide powerful input for the early diagnosis of atherosclerotic lesions, which may play an early warning role in cardiovascular acute events.

Similarities and differences in ultrasound of extracranial brachiocephalic atherosclerotic lesions in patients with ischemic anterior and posterior circulation stroke

Aim. To establish similarities and differences in ultrasound of extracranial brachiocephalic atherosclerotic lesions in patients with ischemic anterior and posterior circulation stroke.Material and methods. The study involved 668 patients (men, 370; women, 298) with carotid territory IS aged 63±11 and 69±9 years, respectively, and 235 patients (men, 129; women, 106) with vertebrobasilar (VB) territory IS aged 59±12 and 63±10 years, respectively, who underwent duplex ultrasound.Results. Atherosclerotic plaques (ASP) in the internal carotid arteries (ICA) were diagnosed significantly more often (p&lt;0,05) (right ICA (ICAr) — 44,0% of cases; left ICA (ICAl) — 48,4%) and the degree of stenosis of ICA mouths was significantly higher (p&lt;0,05) (ICAr —53±23%, ICAl — 54±24%) in carotid territory IS than in VB territory IS (ICAr — 34,0% of cases; average degree of stenosis — 47±18%; ICAl — 33,6%, average degree of stenosis — 46±18%. There were no significant differences in the prevalence of ASP in vertebral arteries and related stenosis in IS in both territories. Also, there were no significant intergroup differences in the prevalence of homogeneous anechoic or hypoechoic and heterogeneous with hypoechoic predominance ASPs in the ICA mouths: in carotid territory IS, such ASPs were detected in each ICA in 33,5% of cases; in VB territory IS, in 29,6% of cases.Conclusion. In patients with carotid and VB territory IS, risky ASPs were recorded with the same frequency, while the overall prevalence of ASPs and the stenosis degree of ICA mouths was significantly higher in carotid IS.