Carotid Artery Atherosclerosis Research Articles

Plaque Composition as a Predictor of Plaque Ulceration in Carotid Artery Atherosclerosis: The Plaque At RISK Study.

Plaque ulceration is a marker of previous plaque rupture. We studied the association between atherosclerotic plaque composition at baseline and plaque ulceration at baseline and follow-up. We included symptomatic patients with a carotid stenosis of <70% who underwent MDCTA and MR imaging at baseline (n = 180). MDCTA was repeated at 2 years (n = 73). We assessed the presence of ulceration using MDCTA. Baseline MR imaging was used to assess the vessel wall volume and the presence and volume of plaque components (intraplaque hemorrhage, lipid-rich necrotic core, and calcifications) and the fibrous cap status. Associations at baseline were evaluated with binary logistic regression and reported with an OR and its 95% CI. Simple statistical testing was performed in the follow-up analysis. At baseline, the prevalence of plaque ulceration was 27% (49/180). Increased wall volume (OR = 12.1; 95% CI, 3.5-42.0), higher relative lipid-rich necrotic core (OR = 1.7; 95% CI, 1.3-2.2), higher relative intraplaque hemorrhage volume (OR = 1.7; 95% CI, 1.3-2.2), and a thin-or-ruptured fibrous cap (OR = 3.4; 95% CI, 1.7-6.7) were associated with the presence of ulcerations at baseline. In 8% (6/73) of the patients, a new ulcer developed. Plaques with a new ulceration at follow-up had at baseline a larger wall volume (1.04 cm3 [IQR, 0.97-1.16 cm3] versus 0.86 cm3 [IQR, 0.73-1.00 cm3]; P = .029), a larger relative lipid-rich necrotic core volume (23% [IQR, 13-31%] versus 2% [IQR, 0-14%]; P = .002), and a larger relative intraplaque hemorrhage volume (14% [IQR, 8-24%] versus 0% [IQR, 0-5%]; P < .001). Large atherosclerotic plaques and plaques with intraplaque hemorrhage and lipid-rich necrotic cores were associated with plaque ulcerations at baseline and follow-up.

Deoxyribonucleic acid methylation in the enhancer region of the CDKN2A/2B and CDKN2B-AS1 genes in blood vessels and cells in patients with carotid atherosclerosis

Aim. Comparative analysis of the deoxyribonucleic acid (DNA) methylation level in the enhancer region of the CDKN2A/2B and CDKN2B-AS1 genes (9p21.3 locus) in vessels with/without atherosclerotic lesions, as well as in leukocytes of patients with clinically relevant carotid artery (CA) atherosclerosis and healthy individuals.Material and methods. The group of patients with clinically relevant atherosclerosis included 22 individuals with severe stenosis (&gt;80%) of CA. Samples of atherosclerotic plaques, presenting CA regions, and great saphenous veins, as well as peripheral blood samples (leukocytes) were obtained from patients. The control group consisted of 14 individuals with the mild CA stenosis (£24%) and without hemodynamically relevant changes; peripheral blood samples were obtained from each of them. DNA methylation level was assessed by targeted bisulfite sequencing of amplicons.Results. The tissue-specific methylation of 31 CpG-site in the CDKN2A/2B and CDKN2B-AS1 gene enhancer was established: the vascular tissues significantly differed from the peripheral blood leukocytes. At the same time, there was an increase in the methylation level of both certain CpG sites and whole analyzed CA region affected by atherosclerosis (48,6 [34,8; 62,0]%), compared with intact vessels, both arteries (25,2 [23,1; 41,60]%, p=0,0001) and veins (35,0 [31,6; 40,0]%, p=0,0039). Patients had lower methylation levels in all CpG sites in blood leukocytes compared to blood vessel samples (8,7 [6,1; 9,7]%; p&lt;0,05). At the same time, the level of DNA methylation in the blood leukocytes of atherosclerotic patients does not differ from that in healthy individuals (9,3 [8,3; 13,6]%; p&gt;0,8).Conclusion. In the present study, the relationship between an increase in the DNA methylation in the enhancer of the CDKN2A/2B and CDKN2B-AS1 genes in CA and their atherosclerotic lesions was revealed, as well as the tissue-specific DNA methylation between vessels and peripheral blood leukocytes.

Longitudinal effects of smoking cessation on carotid artery atherosclerosis in contemporary smokers: The Wisconsin Smokers Health Study

Background and aimsWe quantified the effects of smoking and smoking cessation on carotid artery atherosclerosis and wall thickness in two unique cohorts of smokers making a quit attempt. MethodsOur primary analysis included 726 smokers making a quit attempt in a randomized clinical trial with long-term follow-up. Our secondary analysis included 889 smokers making a quit attempt in a subsequent trial. Participants underwent carotid artery ultrasonography at baseline and up to 3 subsequent visits. Primary outcomes were changes in carotid plaque score and intima media-thickness (IMT). We calculated a smoking burden score (SBS) that reflected the number of visits in which participants reported smoking after the quit attempt. Multivariable regression examined relations between SBS and carotid artery outcomes with adjustments for cardiovascular disease risk factors. ResultsIn the primary analysis, participants were mean (standard deviation) 46.1 (10.3) years old (57.9% female) and smoked 21.1 (8.9) cigarettes per day (CPD). After a median of 7 years, lower SBS predicted less increase in carotid plaque score (Chi-squared = 13.0, p = 0.012). SBS independently predicted change in carotid plaque score (p = 0.007; SBS 0 vs 4) as did baseline CPD (p = 0.024) and age (p<0.0001). SBS did not affect carotid IMT change. In the secondary analysis, increasing SBS was associated with increased likelihood of new plaques over 3 years among participants that smoked ≥15 CPD, (Chi-squared = 6.51, p = 0.011). ConclusionsSmoking cessation is associated with less progression of carotid plaque, but not IMT. Salutary associations of smoking cessation with carotid plaque progression are related to degree of abstinence.

Outcomes and Associated Factors of Discrepant Coronary and Carotid Atherosclerosis.

Some patients exhibit discrepancies in carotid and coronary artery atherosclerosis. This study aimed to define the characteristics and prognosis of these discrepant patients and determine the best strategy to detect pan-vascular atherosclerosis. A database of 5,022 consecutively registered patients who underwent both coronary angiography and carotid ultrasonography, along with clinical and blood laboratory tests, echocardiography, and pulse wave velocity (PWV), was analyzed. The development of cerebro-cardiovascular (CV) events during the follow-up period was also evaluated. A significant proportion of patients (n = 1,741, 35%) presented with a discrepancy between carotid artery plaque and coronary artery disease (CAD). In patients without carotid plaque, male sex (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.20-2.41; P = 0.003), older age (OR, 1.03; 95% CI, 1.01-1.04; P = 0.002), smoking history (OR, 1.58; 95% CI, 1.13-2.20; P = 0.008), lower high-density lipoprotein (HDL) -cholesterol level (OR, 0.97; 95% CI, 0.96-0.98; P < 0.001), and lower common carotid artery end-diastolic velocity (CCA-EDV) (OR, 0.97; 95% CI, 0.95-0.99; P = 0.005) were independently related to the presence of CAD. In patients without CAD, increased PWV was independently related to the presence of carotid plaque. In survival analysis, patients with isolated CAD had a higher probability of composite CV events; those with isolated carotid plaque had a higher probability of heart failure (HF) and mortality than their counterpart groups (P < 0.05). Even in patients without carotid artery plaque, careful coronary evaluation is needed in older or male patients with smoking history, lower HDL-cholesterol level, or lower CCA-EDV. Carotid plaque may be a potential risk factor for HF.

Vascular events from carotid artery atherosclerosis after radiation therapy for laryngeal and hypopharyngeal cancer: the incidence and risk factors.

ABSTRACTIn this retrospective cohort study, we evaluated the incidence of vascular events from carotid artery atherosclerosis after radiotherapy indication for laryngeal and hypopharyngeal cancer. From January 2007 to December 2016, we investigated 111 laryngeal/hypopharyngeal cancer patients who underwent curative radiotherapy and were followed up for ≥1 year (median follow-up duration, 60 months). We evaluated the incidence of vascular events from carotid artery atherosclerosis, defined as a transient ischemic attack or an atherothrombotic cerebral infarction, or from undergoing treatment such as carotid artery stenting for carotid artery stenosis. The median radiation dose was 66 Gy (range, 60–74); 48 patients (43.2%) received concurrent chemotherapy. The 5-year overall survival was 86.2%. Six patients required treatment for carotid artery disease. Carotid stenting was performed in three patients with carotid artery stenosis; three patients developed atherosclerotic cerebral infarction and received medical treatment, with a median of 51.7 months (range, 0.3–78.3) after radiotherapy initiation. The vascular event occurrence rate was 5.4% within 5 years and 10.7% within 8 years. In the univariate analysis, dyslipidemia, diabetes mellitus, and carotid calcification were significant factors for event occurrence. Because three out of six cases occurred out of the irradiated field, no carotid artery or carotid bulb dosimetric parameters showed significant correlation. As laryngeal/hypopharyngeal cancer patients, particularly with complications including dyslipidemia and diabetes mellitus, are at a high risk of carotid artery stenosis after radiotherapy, long-term carotid artery evaluation is necessary. Early intervention by stroke specialists can reduce the risk of fatal cerebral infarction.

Plaque erosion is associated with less systemic atherosclerosis than other plaque types of acute coronary syndrome

Abstract Background Previous studies have demonstrated that plaque erosion is associated with less atheromatous plaque at both culprit and non-culprit lesion than other plaque types of acute coronary syndrome (ACS). However, the status of systemic atherosclerosis in patients with plaque erosion remains to be elucidated. Purpose To clarify if plaque erosion is associated with less systemic atherosclerosis than other plaque types of ACS. Methods A total of 239 consecutive patients with ACS who underwent optical coherence tomography (OCT) imaging of the culprit lesion were enrolled. Patients were classified into either plaque erosion (PE, n=45) or non-plaque erosion (non-PE, n=194) including plaque rupture and calcified nodule based on OCT findings of the culprit lesions. The status of systemic atherosclerosis was assessed by the findings of carotid echography, the severity of aortic arch calcification (AAC; grade 0–3) on chest X-ray, brachial-ankle pulse wave velocity (baPWV) and ankle-brachial pressure index (ABPI). Results The maximum intima media thickness (IMT) was significantly thinner in the PE group than in the non-PE group (1.9±0.8 vs. 2.3±0.9 mm, p=0.023) (Panel A). The prevalence of heterogeneous plaque and calcified plaque was significantly lower in the PE group than in the non-PE group (25.0 vs. 50.4%, p=0.010, 18.8 vs. 38.5%, p=0.037, respectively). The prevalence of AAC grade was significantly different between the two groups with a tendency toward lower AAC grade in the PE group than the non-PE group (Panel B). The mean baPWV (1588.1±420.6 vs. 1686.5±363.5 cm/sec, p=0.186) and ABPI (1.1±0.1 vs. 1.1±0.1, p=0.270) was comparable between the two groups. Conclusion Plaque erosion was associated with less atherosclerosis in carotid artery and aortic arch than non-plaque erosion. These findings may help further clarify the distinct pathophysiology of plaque erosion. Funding Acknowledgement Type of funding source: None

Sex-dependent association between day-by-day morning blood pressure variability and common carotid artery intima-media thickness: the J-HOP study

Abstract Background Day-by-day home systolic blood pressure variability (BPV) was shown to be associated with increased common carotid artery (CCA) intima-media thickness (IMT) in the hypertensives. Recently, 24 hour ambulatory BPV was revealed to serve as an indicator of higher CCA-IMT only in males. However, there have been no studies that reported the sex-dependent relationship between day-by-day BPV and CCA-IMT. Purpose We assessed the hypothesis that day-by-day BPV was associated with higher CCA-IMT in the Japanese males at high-risk of cardiovascular disease. Methods Among 4310 patients with one or more cardiovascular risks recruited for the Japan Morning Surge-Home Blood Pressure Study, carotid ultrasound in CCA was performed in the 1365 patients (mean age 65.6 years old, male 52%). The home blood pressure (BP) readings during mean 11.2 days were used to calculate home mean levels and variability in morning systolic BP (SBP). Day-by-day BPV was measured as standard deviation [SD] and delta (maximum-minimum) in SBP. Results Average mean CCA-IMT of left and right side was 1.046±0.4mm. Mean (r=0.118, p&amp;lt;0.0001), SD (r=0.120, p&amp;lt;0.0001) and delta (r=0.149, p&amp;lt;0.0001) in morning SBP were significantly correlated with CCA-IMT. In the multiple regression analysis adjustment for confounders including age, gender, body mass index, total cholesterol, high density lipoprotein and mean morning SBP, SD (B: 0.008, 95% CI: 0.001–0.015, p&amp;lt;0.05) or delta (B: 0.004, 95% CI: 0.002–0.006, p&amp;lt;0.001) in morning SBP each had a significant association with CCA-IMT. According to the gender, SD (p&amp;lt;0.01) or delta (p&amp;lt;0.01) in morning SBP each was significantly associated with CCA-IMT only in the male group while neither SD (p=0.4) nor delta (p=0.4) in morning SBP was associated with CCA-IMT in the female group. Conclusions In addition to the conventional risk factors, day-by-day morning SBP variability was a significant indicator of increased CCA-IMT in the high-risk Japanese population. The significant relationship between day-by-day morning SBP variability and CCA-IMT was observed only in the males. Gender specific impact of day-by-day morning home systolic BPV on carotid artery atherosclerosis should be taken into account in the high-risk elderly at cardiovascular disease. Funding Acknowledgement Type of funding source: None

Insights from microRNAs into the pathophysiology of coronary and multiterritorial atherosclerosis

Abstract Introduction The mechanisms underlying the different phenotypic presentations of atherosclerosis are still poorly understood. MicroRNAs regulate genetic expression at the post-transcriptional level and each has specific biological functions. MicroRNAs could therefore be useful for understanding the epigenetic drivers for development of isolated coronary atherosclerosis and more extensive disease (coronary and extra-coronary). We evaluated if the expression profile of circulating microRNAs was associated with coronary and multiterritorial atherosclerosis. Methods We prospectively recruited three groups of age- and sex-matched participants, with: 1) no coronary atherosclerosis (calcium score=0, no soft plaques in coronary angioCT scan), neither carotid or inferior limbs atherosclerosis (controls); 2) isolated obstructive coronary artery disease (CAD) (≥50% for the left main, ≥70% for other epicardial vessels) (isolated CAD group); 3) obstructive disease of the coronary, inferior limbs and carotid arterial beds (multi-territorial disease group). Obstructive atherosclerosis of carotid and inferior limbs arteries (≥50% stenosis by Doppler or angioCT imaging) was assessed in all participants. Acute atherosclerotic events or coronary revascularization within 12 months, heart failure, infections, malignancy and severe renal dysfunction were exclusion criteria. Six microRNAs with diverse mechanisms of action were selected (mir-21, miR-27b, miR-29a, miR-126, miR-146, miR-218) and measurements of their circulating levels were performed in a blinded fashion, using RT-PCR SYBR Green. Results Twenty four patients were included, including 8 patients in each group. Mean age was 61±9 years, and 83% were male. In patients with atherosclerosis, classical cardiovascular risk factors were globally more prevalent. The expression of miR-146 and miR-218, both of which regulate endothelial function, was significantly decreased in the isolated CAD group compared to controls (Figure; data are expressed as median [IQR]). There was a further decrease in the expression of both microRNAs in patients with multiterritorial atherosclerosis compared to patients with isolated CAD. The expression of other microRNAs did not differ. Smoking was associated with the presence of isolated CAD and multiterritorial atherosclerosis (14% vs 30% vs 56% of smokers across groups, p=0.002), and with a decreased expression of miR-218 (1.6 [0.02–83] fold vs 0.1 [0.001–0.7] fold, p=0.023). Conclusions The expression of the endothelial regulators miR-146 and miR-218 was decreased in patients with isolated CAD compared to controls, and even more hampered in patients with multiterritorial atherosclerosis. Higher degrees of endothelial dysfunction may therefore contribute to a more diffuse atherosclerotic presentation through miR-146 and miR-218. Atherogenesis related to smoking may be partially mediated by miR-218. Funding Acknowledgement Type of funding source: None

Quercetin modulates AMPK/SIRT1/NF-κB signaling to inhibit inflammatory/oxidative stress responses in diabetic high fat diet-induced atherosclerosis in the rat carotid artery.

Inflammation and oxidative stress serve interrelated roles in the development of atherosclerosis and other vascular diseases. Quercetin has been previously reported to exhibit numerous beneficial properties towards several metabolic conditions and cardiovascular disease. The present study aimed to evaluate the effects of quercetin on the 5'adenosine monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/NF-κB signaling pathway and inflammatory/oxidative stress response in diabetic-induced atherosclerosis in the carotid artery of rats. Male Wistar rats were used to create a diabetes-induced atherosclerosis model by the administration of high fat diet (HFD) with streptozotocin, which lasted for 8 weeks. Control and diabetic rats received quercetin (30 mg/kg/day; orally) for the last 2 weeks of the diabetic period. Plasma lipid profile and vascular levels of oxidative stress markers, inflammatory cytokines, NF-κB signaling proteins and SIRT1 expression were evaluated using ELISA and western blotting. Quercetin treatment in HFD diabetic rats was reported to improve the lipid profile and reduce the number of atherosclerotic lesions, atherogenic index and malondialdehyde levels, whilst increasing the activity of enzymatic antioxidants in the carotid artery. Additionally, the inflammatory response was suppressed by quercetin administration, as indicated by the reduced NF-κB and IL-1β levels, and increased IL-10 levels. Furthermore, SIRT1 expression was revealed to be significantly increased in response to quercetin treatment compared with non-treated HFD rats. However, these effects of quercetin were abolished or reversed by the administration of compound-C (0.2 mg/kg), a specific AMPK blocker, in HFD rats. Therefore, quercetin may have promising potential in ameliorating atherosclerotic pathophysiology in the rat carotid artery by inhibiting oxidative stress and inflammatory responses mechanistically by modulating the AMPK/SIRT1/NF-κB signaling pathway.

Noninvasive prediction of carotid artery atherosclerosis by multiple abdominal fat indices measured via ultrasonography.

PurposeThe purpose of this study was to evaluate the efficiency of multiple abdominal fat indices as measured via ultrasonography for predicting the presence and severity of carotid artery atherosclerosis and to compare the predictive capacity of ultrasonographic measurements to that of anthropometric measurements.MethodsA total of 92 patients were included in this study. All participants underwent clinical and laboratory assessments, and anthropometric measurements were obtained. Ultrasound examinations were performed to measure the values of all abdominal fat indices and the intima-media thickness, as well as to detect the presence of atherosclerotic plaques. Univariate and multivariate logistic regression analyses were performed.ResultsIn the multivariate analysis, significant associations were detected between carotid artery atherosclerosis and posterior right perinephric fat thickness (PRPFT) (hazard ratio [HR], 15.23; P<0.001), preperitoneal fat thickness (PPFT) (HR, 4.31; P=0.003), visceral adipose tissue volume (VAT) (HR, 7.61; P<0.001), visceral fat thickness (VFT) (HR, 8.84; P<0.001), the ratio of VFT to subcutaneous fat thickness (VFT/SCFT) (HR, 9.39; P<0.001), and waist-to-height ratio (WHtR) (HR, 2.65; P=0.046). In the multivariate analysis, significant associations were also detected between carotid artery plaque and PRPFT (HR, 7.09; P<0.001), the abdominal wall fat index (AFI) (HR, 3.58; P=0.010), and VFT/SCFT (HR, 4.17; P=0.006).ConclusionMany abdominal fat indices as measured by ultrasound were found to be strong predictors of carotid artery atherosclerosis, including PRPFT, VFT/SCFT, VFT, VAT, PPFT, and WHtR. Moreover, PRPFT, VFT/SCFT, and AFI were identified as strong predictors of the presence of carotid artery plaque.

Association of menopause with risk of carotid artery atherosclerosis

ObjectivesObservational studies suggest that the risk of cardiovascular disease increases during menopause; however, the menopause-related risk of subclinical atherosclerosis is unclear. The aim of the current study is to evaluate menopause and the risk of subclinical carotid atherosclerosis through a retrospective analysis of data from a population-based prospective cohort study. Study designThe study sample comprised 879 women in the Beijing community enrolled in the Chinese Multi-provincial Cohort Study at baseline study in 1992 and followed up to at least one carotid ultrasound examination at three on-site follow-up surveys. Age at menopause was categorized as <40 years (premature menopause), 40-44 years (early menopause), 45-49 years (relatively early menopause), 50-51 years (reference), and >51 years (relatively late menopause). Menopause staging at baseline was categorized as: reproductive, menopausal transition/perimenopause, early postmenopause, and late postmenopause. Menopause as a time-varying covariate was calculated using waiting time to menopause and menopause status at the last follow-up (2012). Main outcome measuresThe main outcome measures included carotid plaque and intima-media thickening. Gray's test was performed to assess the equality of cumulative incidence functions between age groups at menopause and between menopause stages. Multivariate Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) associated with menopause. ResultsOf the 879 women included (mean [SD] age at baseline, 48.6 [8.1] years), 573 (65.2%) developed carotid plaques and 430 (48.9%) developed intima-media thickening during follow-up. Menopause was significantly associated with risk of developing carotid plaques (HR 1.93, 95% CI 1.05-3.54; P = 0.03) after adjustment for age at baseline, age at menopause, use of oral estrogen due to menopause, and traditional cardiovascular risk factors at baseline. No significant association was found between age at menopause and risk of carotid atherosclerosis. ConclusionMenopausal women, irrespective of age at menopause, had an increased risk of carotid plaque.

Bilaterally Asymmetric Associations Between Extracranial Carotid Artery Atherosclerosis and Ipsilateral Middle Cerebral Artery Stenosis in Symptomatic Patients: A CARE-II Study.

To determine the bilaterally asymmetrical associations between extracranial carotid artery atherosclerosis and ipsilateral middle cerebral artery (MCA) stenosis in symptomatic patients using magnetic resonance vessel wall imaging. Approach and Results: Patients with symptomatic carotid artery atherosclerosis were recruited from the Chinese Atherosclerosis Risk Evaluation, a multicenter study. All subjects underwent intracranial magnetic resonance angiography and extracranial carotid artery magnetic resonance imaging. Severe stenosis (stenosis ≥50%) of MCA, carotid moderate-to-severe stenosis (stenosis ≥50%), plaque compositions, and high-risk plaque on symptomatic side were evaluated in all subjects. Associations between ipsilateral MCA stenosis and extracranial carotid plaque features were evaluated. A total of 363 patients (mean age: 61.2±10.4 years old; 254 males) were included. In the left symptomatic cerebrovascular group (n=186), carotid moderate-to-severe stenosis (odds ratio [OR], 3.00 [95% CI, 1.03-8.79]; P=0.045), intraplaque hemorrhage (OR, 3.68 [95% CI, 1.21-11.19]; P=0.021), fibrous cap rupture (OR, 5.70 [95% CI, 1.60-20.31]; P=0.007), and high-risk plaque (OR, 2.95 [95% CI, 1.19-7.35]; P=0.020) were significantly associated with ipsilateral severe MCA stenosis, after adjusting for confounding factors. In the right symptomatic cerebrovascular group (n=177), severe MCA stenosis was significantly associated with ipsilateral carotid moderate-to-severe stenosis (OR, 3.98 [95% CI, 1.54-10.32]; P=0.004) but not with other extracranial carotid plaque features (all P>0.05), after adjusting for confounding factors. In the symptomatic arteries, vulnerable plaque features are independently associated with ipsilateral severe MCA stenosis on the left side, but this association is not found on the right side, indicating the associations of atherosclerotic disease between intracranial and extracranial carotid arteries are asymmetrical.

Пациент с гомозиготной семейной гиперхолестеринемией: трудное лечение. Клинический случай

Homozygous familial hypercholesterolemia is a severe genetic disorder characterized by extremely high levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C), as well as by rapid atherosclerosis progression in various vascular territories. Objective examination of the affected patients often reveals multiple Achilles tendon xanthomas, xanthomas on the extensor surface of arms, knee joints, etc. The prevalence of such severe inherited hyperlipidemia in many populations is about 1 : 1 000 000, however, the family heterozygous type frequency increase leads to the decrease of this value and to the increase in the affected people number. The paper introduces case report for the patient V.I. aged 16 who was diagnosed with homozygous familial hypercholesterolemia at the age of 12. DNA testing revealed pathogenic mutations in the LDL receptor gene which confirmed the diagnosis. The paper reports the results of the discussed patient treatment using triple-drug combination lipid-lowering therapy with rosuvastatin (40 mg/day), ezetimibe (10 mg/day) and evolocumab (420 mg/day) in the last two years. The total cholesterol level decreased from 20.8 mmol/L (baseline) to 7.3–12.00 mmol/L, and the LDL-C level decreased from 19.9 mmol/L to 4.6–9.9 mmol/L due to therapy, the treatment was well tolerated. During the observation period, a rapid regression of xanthomas on the buttocks, knee and elbow joints, and Achilles tendon was achieved. A series of baseline instrumental tests (2013) revealed severe atherosclerosis of carotid arteries (maximum stenosis up to 50%), and first symptoms of aortic valve stenosis. Another examination in the hospital (2019) revealed slowing the progression of atherosclerosis in the carotid arteries and aorta, however, the arterial hypertension onset required additional prescription of a low dose of enalapril. Exercise testing and Holter ECG monitoring has yet identified no myocardial ischemia. Thus, the timely diagnosis together with long-term triple-drug intensive lipid-lowering therapy make it possible to slow down the atherosclerosis progression in the discussed rare and severe category of patients.

Role of 18F-FDG positron emission tomography in carotid atherosclerotic plaque imaging: A systematic review.

Stroke and other thromboembolic events in the brain are often due to carotid artery atherosclerosis, and atherosclerotic plaques with inflammation are considered particularly vulnerable, with an increased risk of becoming symptomatic. Positron emission tomography (PET) with 2-deoxy-2-[Fluorine-18] fluoro-D-glucose (18F-FDG) provides valuable metabolic information regarding arteriosclerotic lesions and may be applied for the detection of vulnerable plaque. At present, however, patients are selected for carotid surgical intervention on the basis of the degree of stenosis alone, and not the vulnerability or inflammation of the lesion. During the past decade, research using PET with the glucose analog tracer 18F-fluor-deoxy-glucose, has been implemented for identifying increased tracer uptake in symptomatic carotid plaques, and tracer uptake has been shown to correlate with plaque inflammation and vulnerability. These findings imply that 18F-FDG PET might hold the promise for a new and better diagnostic test to identify patients eligible for carotid endarterectomy. The rationale for developing diagnostic tests based on molecular imaging with 18F-FDG PET, as well as methods for simple clinical PET approaches, are discussed. This is a systematic review, following Preferred Reporting Items for Systematic Reviews guidelines, which interrogated the PUBMED database from January 2001 to November 2019. The search combined the terms, “atherosclerosis,” “inflammation,” “FDG,” and “plaque imaging.” The search criteria included all types of studies, with a primary outcome of the degree of arterial vascular inflammation determined by 18F-FDG uptake. This review examines the role of 18F-FDG PET imaging in the characterization of atherosclerotic plaques.

The phosphorylation of CHK1 at Ser345 regulates the phenotypic switching of vascular smooth muscle cells both in vitro and in vivo

Background and aimsDNA damage and repair have been shown to be associated with carotid artery restenosis and atherosclerosis. The proliferation and migration of vascular smooth muscle cells (VSMCs) is the main cause of artery stenosis. This study aims to define the relationship between DNA damage and VSMCs proliferation. MethodsA rat carotid artery injury model was established, and human and rat VSMCs cultured in vitro. H2O2 was used to induce DNA damage in vitro. The selected CHK1 inhibitor, LY2603618, was used to inhibit CHK1 phosphorylation both in vivo and in vitro. γH2AX, αSMA and phosphorylated CHK1 were detected both in rat carotid artery and cultured VSMCs from different groups. Hyperplasia ratio of rat carotid artery intimal was measured. ResultsDNA double-strand breaks occur in the rat carotid artery after injury. DNA damage induces CHK1 phosphorylation and down-regulates αSMA expression in VSMCs both in vitro and in vivo. The inhibition of CHK1 phosphorylation rescues αSMA expression in VSMCs both in vitro and in vivo, and rat carotid intimal hyperplasia after injury was suppressed. ConclusionsOur data demonstrated that phosphorylation of CHK1 under DNA damage stress modulates VSMCs phenotypic switching. CHK1 inhibition may be a potential therapeutic strategy for intima hyperplasia treatment.

Assessment of Carotid Artery Distensibility and Elasticity After Laparoscopic Sleeve Gastrectomy: a Prospective Study.

Although it is well known that obesity increases the risk of atherosclerosis in carotid arteries, it is not clear whether this risk changes after obesity surgery. The aim of this study was to investigate whether weight reduction with a laparoscopic sleeve gastrectomy (LSG) has any effect on distensibility and elasticity which show subclinical atherosclerosis in the carotid arteries of obese individuals. This prospective study included 130 patients (body mass index (BMI) 48.21 ± 6.97kg/m2) who underwent LSG. The patients were followed up for 1year. Comparisons were made of the distensibiliy and elasticity values calculated preoperatively and at 1, 3, 6, and 12months, postoperatively. There was a statistically significant increase in distensibility and elasticity values from baseline to 1, 3, 6, and 12months postoperatively (p< 0.001 for both comparisons). The multiple linear regression analysis was used to find the variables affecting both distensibility and elasticity. According to the results, the presence of BMI decreases distensibility percentage change level by 0.38units (β= - 0.38, 95% CI - 0.51;- 0.25, p < 0.001). The presence of fasting plasma glucose decreases elasticity percentage change level by 0.20units. (β= - 0.20, 95% CI - 0.39; - 0.01, p = 0.037). Carotid artery distensibility and elasticity values increase after LSG, and this change could be caused by the change in metabolic parameters and heart geometry. These results may indirectly suggest that subclinical atherosclerosis in carotid arteries has decreased after obesity surgery.

Extracellular Matrix Remodeling Factors as Markers of Carotid Artery Atherosclerosis.

Materials and Methods 20 patients undergoing routine carotid endarterectomy and 40 healthy volunteers were enrolled in this study. MMPs activity and OPG and FN concentrations were measured in atherosclerotic plaques and nonchanged contiguous tissue after homogenization as well as in plasma from patients and reference group. The activity of MMPs was evaluated by gelatin zymography, and the concentration of OPG and FN was assessed by ELISA. Results OPG concentration and MMP-9 activity showed differences between plaque and nonchanged tissue; OPG was higher in adjacent tissue (P=0.0009), whereas MMP-9 was higher in plaque (proMMP-9 P=0.0003; MMP-9 P < 0.0001). The OPG plasma concentration and both MMPs plasma activity were higher in patients (OPG P < 0.001; proMMP-2 P=0.0292; and proMMP-9 P=0.0374), while FN plasma concentration was lower in patients than in the reference group (P=0.0004). The ROC curves analysis showed the highest AUC for OPG (0.943) with 85.0% sensitivity and 92.1% specificity. Conclusions The atherosclerotic plaque and the contiguous artery wall are biochemically different. OPG shows the highest potential to be a marker of advanced carotid atherosclerosis.

The coronary artery calcium score is linked to plasma cholesterol synthesis and absorption markers: Brazilian Longitudinal Study of Adult Health.

It is controversial whether atherosclerosis is linked to increased intestinal cholesterol absorption or synthesis in humans. The aim of the present study was to relate atherosclerosis to the measurements of plasma markers of cholesterol synthesis (desmosterol, lathosterol) and absorption (campesterol, sitosterol). In healthy male (n=344), non-obese, non-diabetics, belonging to the city of São Paulo branch of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we measured in plasma these non-cholesterol sterol markers, together with their anthropometric, dietary parameters, traditional atherosclerotic risk factors, and blood chemistry, coronary arterial calcium score (CAC), and ultrasonographically measured common carotid artery intima-media thickness (CCA-IMT). Cases with CAC>zero had the following parameters higher than cases with CAC = zero: age, waist circumference (WC), plasma total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and non-high density lipoprotein-cholesterol (non HDL-C). Plasma desmosterol and campesterol, duly corrected for TC, age, body mass index (BMI), waist circumference (WC), hypertension, smoking, and the homeostasis model assessment-insulin resistance (HOMA-IR) correlated with CAC, but not with CCA-IMT. The latter related to increased age, BMI, waist circumference (WC), and systolic blood pressure (SBP). Plasma HDL-C concentrations did not define CAC or CCA-IMT degrees, although in relation to the lower tertile of HDL-C in plasma the higher tertile of HDL-C had lower HOMA-IR and concentration of a cholesterol synthesis marker (desmosterol). Present work indicated that increased cholesterol synthesis and absorption represent primary causes of CAD, but not of the common carotid artery atherosclerosis.

3-2EXTRACRANIAL ARTERIAL PLAQUE CHARACTERISTICS IN ISCHEMIC STROKE PATIENTS AT DR. M.DJAMIL HOSPITAL 2019

Introduction: Atherosclerosis in carotid arteries cause more than 80% cerebral thromboembolism cases. One of the diagnostic modalities to evaluate the plaque's characteristics is using duplex carotid ultrasonography. In general, the risk of stroke depends on the degree of stenosis, surface, and morphology of formed plaque. Objective: This study aims to determine the characteristics of extracranial arterial plaque in ischemic stroke patients. Method: This study uses a descriptive design. The data was secondary data obtained from the Neurology Department of RSUP Dr. M. Djamil, Padang medical records from January to December 2019. Results: From 140 ischemic stroke patients who underwent duplex carotid ultrasonography, extracranial carotid artery stenosis was found in 30 patients (21%) consist of 17 males (56%). Most patients (80%) are in 45–65 years age group. The mean age is 46 years. Right carotid artery stenosis was found in 18 patients (60%) and left in 12 patients (40%). The degree of stenosis &lt;50% and 50–70% were obtained in 12 patients (40%), respectively, and the degree of stenosis &gt; 70% were obtained in 6 patients (20%). Based on plaque morphology, the soft plaque was found in 18 patients (60%), and a hard plaque was found in 12 patients (40%). Ulcerative plaques were obtained in 17 patients (57%) and non-ulserative in 13 patients (43%). Conclusion: Extracranial artery stenosis is more common in men with 45–65 years of group age. The location of stenosis is more often found in the right carotid artery. The most common degree of stenosis is &lt;70%. Most of the plaque has soft plaque morphology, and the surface has of ulcerated plaque morphology.

Kongcun Town Asymptomatic Intracranial Artery Stenosis study in Shandong, China: cohort profile

PurposeThe population-based Kongcun Town Asymptomatic Intracranial Artery Stenosis (KT-aICAS) study aims to investigate the prevalence of aICAS and major cardiovascular risk factors (CRFs) or biomarkers related to the development and...