Carotid Artery Plaque Formation Research Articles

The value of Lp(a) and TG/HDLC in peripheral blood to assess the stability of carotid plaque in patients with ischemic stroke.

The objective of this study was to investigate the relationship between lipoprotein (a) (Lp(a)), triglyceride/high-density lipoprotein cholesterol (TG/HDL-C), and the stability of carotid atherosclerotic plaque in patients with acute ischemic stroke. A total of 142 patients with acute ischemic stroke were selected and divided into group A (59 cases of stable plaque formation) and group B (83 cases of unstable plaque formation) according to the characteristics of carotid artery plaque formation detected by carotid color Doppler ultrasound. The serum Lp(a), lipid metabolism indexes, peripheral blood routine indexes, and related serum inflammatory factors indexes were compared between the two groups. Receiver operating characteristic curve and multivariate logistic regression model were used to analyze the relationship between each index and the formation of carotid unstable plaque. There were no significant differences in serum total cholesterol (TC), HDL-C, and low-density lipoprotein cholesterol (LDL-C) between groups A and B (p > .05). The values of Lp(a), TG, and TG/HDL-C in group B were higher than those in group A, and the differences were statistically significant (p < .05). There were no significant differences in serum TC, HDL-C, and LDL-C between groups A and B (p > .05). The values of Lp(a), TG, and TG/HDL-C in group B were higher than those in group A, and the differences were statistically significant (p < .05). The values of HBA1C, Lp-PLA2, CRP, CysC, Hcy, TNF-α, neutrophils, and NLR in group B were higher than those in group A, and the differences were statistically significant (p < .05). There was no significant difference in FPG, systolic blood pressure, diastolic blood pressure, Hb, white blood cells, platelets, and lymphocytes between groups A and B (p > .05). The results of logistic regression model showed that the increase of Lp(a), TG/HDL-C, HBA1C, Lp-PLA2, CRP, CysC, Hcy, and NLR could increase the risk of carotid artery unstable plaque in patients with ischemic stroke (p < .05). Lp(a) and TG/HDL-C have certain value in evaluating the stability of carotid atherosclerotic plaque in patients with acute ischemic stroke, and the increased levels of LP (a) and TG/HDL-C will significantly increase the risk of carotid unstable plaque in patients.

Factors Affecting Carotid Artery Stenosis in the Elderly Living at High Altitudes.

Factors affecting carotid artery stenosis have been generally investigated. However, considering the protective effect of altitude, studies on elderly individuals at high altitudes are few. Our aim is to investigate the systematic adaptive changes caused by high-altitude exposure through the causes of carotid artery stenosis. Carotid Doppler ultrasound was performed on 250 patients over the age of 50 years. The patients' age, gender, height, weight, smoking history, place of residence, and presence of comorbidities were questioned. Those with diabetes, hypertension, hyperlipidemia, and coronary disease were excluded from the study. Those who did not reside at high altitudes were excluded from the study. One hundred and thirty-five patients were included in the study. Carotid artery Doppler findings and biochemical parameters were recorded. Factors affecting stenosis in the carotid arteries were compared. In our study, the factors affecting carotid stenosis were determined to be age, gender, presence of plaque, plaque type, and mean carotid intima-media thickness (CIMT). The mean CIMT of the patients was calculated as 0.71±0.14 mm. The mean CIMT measurement level was significantly higher in patients with plaque in the carotid artery (p<0.05). According to receiver operating characteristic curves, CIMT values higher than 0.72 mm increase plaque and stenosis formation in the common carotid artery (CCA) and internal carotid artery (ICA) in elderly people living at high altitudes (p<0.05, area under the curve [AUC]: 0.71-0.83). The most important factors affecting carotid stenosis in individuals living at high altitudes are age, gender, CIMT, plaque, and plaque type. When soft plaques were detected, the risk of stenosis was found to be higher than in calcific plaques. Additionally, the number of factors affecting stenosis was greater on the left (ICA). This suggests that the left carotid system is more vulnerable. It can be said that in elderly individuals living at high altitudes, a CIMT higher than 0.72 mm is a cutoff value in the presence of plaque and stenosis in the carotid arteries.

Meta-analysis of risk factors for carotid plaque formation in type 2 diabetes mellitus

Objective: To investigate the risk factors of carotid artery plaque formation in type 2 diabetes mellitus in China through meta-analysis. Methods: The literature on the risk factors of carotid plaque formation in type 2 diabetes mellitus in China was retrieved from China Journal Full-text Database (CNKI), Wanfang Digital Journal Full-text Database (Wanfang), VIP journal Resource integration Service platform (VIP) and PubMed database. Newcastle-Ottawa Scale(NOS) used the most comprehensive case-control trial data collection to evaluate the quality of the literature excerpts combined with inclusion and exclusion criteria.Literatures with scores ≥7 were included in the study, and finally meta-analysis was conducted by RevMan5.4. Results: 32 literatures met the inclusion criteria, and the cumulative number of cases and controls were 5710 and 5405, respectively. The results of meta-analysis showed that the risk factors of carotid plaque formation in type 2 diabetes mellitus in China were as follows: Triglyceride (TG) (OR= 2.74, 95%CI: 2.25-3.33), total cholesterol (TC) (OR=2.50, 95%CI: 2.22-2.83), glycosylated hemoglobin (HbA1c) (OR=1.41, 95%CI:1.33 ~ 1.50), history of hypertension (OR=2.03, 95%CI:1.69 ~ 2.44), low density lipoprotein (LDL-C) (OR=1.64, 95%CI:1.31 ~ 2.06), age (OR=1.12, 95%CI:1.09 ~ 1.14), diabetes duration (OR=1.04, 95%CI:1.03 ~ 1.06), smoking (OR=1.30, 95%CI:1.18 ~ 1.44), systolic blood pressure (SBP) (OR=1.04, 95%CI:1.02 ~ 1.05). Conclusion: TG, TC, HbA1c, hypertension history, LDL-C, age, diabetes course, smoking and SBP are independent risk factors for carotid plaque formation in type 2 diabetes mellitus. Smoking cessation, balanced diet, prevention and active treatment of hypertension have great significance for the formation of carotid plaque in type 2 diabetes mellitus.

Analysis of Risk Factors for Vulnerable Plaque Formation and Pathogenic in Carotid Artery.

The formation of vulnerable carotid artery plaque may be closely related to a single factor or caused by multiple factors. This paper discusses the pathogenic risk factors for vulnerable plaque in patients with severe internal carotid artery (ICA) stenosis who received endarterectomy through regression analysis. A total of 98 patients with a complete clinical and laboratory assessment underwent carotid endarterectomy. Metabolic syndrome (MetS) and MetS components, ICA plaque thickness and ICA peak systolic velocity, previous ischemic stroke or transient ischemic attack (TIA), and other risk factors were included in the pathogenic risk factor for vulnerable plaque. Univariate logistic regression analysis was used to determine vulnerable carotid plaque risk factors. If P <0.2, it was considered potential confounders. Binary logistic regression model was controlled for potential confounders. Among the 98 patients, stable carotid plaques 38 (39%) and unstable carotid plaques 60 (61%), male 76 (77.6%) and female 22 (22.4%), and Han Chinese 68 (68.4%) and Mongols 30 (30.6%). Univariate logistic regression to P <0.2 has 6 risk factors, which are previous ischemic stroke or TIA, ICA peak systolic velocity, ICA plaque thickness, body mass index, total cholesterol, and alcohol consumption. The significant result of the binary logistic regression analysis was the previous ischemic stroke or TIA (OR=4.52; 95% CI, 1.67-12.09), P =0.003 and ICA peak systolic velocity (OR=1.01; 95% CI, 1.00-1.02), P =0.014. The patients with previous ischemic stroke or TIA and higher ICA peak systolic velocity are associated with vulnerable plaque pathogenic features. There is no obligatory association between MetS and formation of carotid plaque vulnerability.

Gut-flora metabolites is not associated with synchronous carotid artery plaque and non-alcoholic fatty liver disease in asymptomatic adults: A STROBE-compliant article.

Synchronous non-alcoholic fatty liver disease (NAFLD) and carotid artery plaque formation increase the risk of mortality in patients with cardiovascular disease (CVD). Metabolic status and host gut flora are associated with NAFLD and CVD, but the risk factors require further evaluation.To evaluate the risk factors associated with NAFLD and CVD, including gut-flora-related examinations.This cross-sectional study included 235 subjects aged over 40 years who underwent abdominal ultrasound examination and carotid artery ultrasound examination on the same day or within 12 months of abdominal ultrasound between January 2018 and December 2019. All subjects underwent blood tests, including endotoxin and trimethylamine-N-oxide.The synchronous NAFLD and carotid artery plaque subjects had a higher proportion of men and increased age compared with those without NAFLD and no carotid artery plaque. The synchronous NAFLD and carotid artery plaque group had increased body mass index (BMI), blood pressure, hemoglobin A1C (5.71% vs 5.42%), triglyceride (TG) (164.61 mg/dL vs 102.61 mg/dL), and low-density lipoprotein (135.27 mg/dL vs 121.42 mg/dL). In multiple logistic regression analysis, increased BMI, mean systolic blood pressure, and TG > 110 mg/dL were independent risk factors for synchronous NAFLD and carotid artery plaque formation. Endotoxin and trimethylamine-N-oxide levels were not significantly different between the 2 groups.Host metabolic status, such as elevated BMI, TG, and systolic blood pressure, are associated with synchronous NAFLD and carotid artery plaque in asymptomatic adults. Aggressive TG control, blood pressure control, and weight reduction are indicated in patients with NAFLD.

Possible Gender Difference in the Association Between Abdominal Obesity, Chronic Inflammation, and Preclinical Atherosclerosis in the General Population.

Chronic inflammation due to abdominal obesity plays a major role in the development of cardiovascular disease (CVD). Gender differences are well characterized in the development of CVD; however, in the association among abdominal obesity, chronic inflammation, and preclinical atherosclerosis, gender differences in the general population remain to be clarified. We retrospectively analyzed 1,163 subjects who underwent voluntary health checkups at our institute. We defined carotid artery plaque formation as carotid intima-media thickness ≥ 1.1 mm. Multiple regression analysis showed that waist circumference was a major independent predictor of increase in serum C-reactive protein (CRP) level in both men and women. Serum CRP level was significantly increased in men with carotid artery plaque formation, but not in women. Multivariable logistic regression analysis demonstrated that serum CRP level, as well as age and hypertension, was independently associated with carotid artery plaque formation only in men. This result may suggest a potential of gender-specific difference in the association between serum CRP level and the prevalence of carotid artery plaque formation. Further investigations are required to confirm our results and to clarify the underlying mechanism.

Study on the effect of antibiotics application in perioperative period on carotid artery and serum interleukin-6 in periodontitis rats with hyperlipidemia or diabetes

Objective: To investigate the effect of antibiotics application in perioperative period on carotid artery and serum interluekin-6 (IL-6) in chronic periodontitis (CP) rats with hyperlipidemia (HL) or diabetes mellitus (DM). Methods: The models of CP rats with HL or DM were established in different batches. The rats were divided into groups as follows: A and A' were normal control groups, n=7 in each group; B(HL) and B'(DM) were groups of HL and DM, n=7 in each; C(HL+CP) and C'(DM+CP) were groups of CP with HL and CP with DM, n=21 in each. After the establishment of the models, groups C and C' were divided into C1 and C1' non-intervention group, C2 and C2' simple tooth extraction group and C3 and C3' antibiotic-assisted tooth extraction, with 7 rats in each of the groups. Two time interventions were performed to extract experimental teeth (bilateral maxillary first and second molars) in groups C2, C2', C3 and C3'. Serum samples were collected at 5 time points before and after tooth extraction (T1: before the first tooth extraction; T2: one week after the first tooth extraction; T3, T4, T5: the first, third and fifth week after the second tooth extraction), respectively. The absolute content of IL-6 in serum was detected by enzyme-linked immunosorbent assay (ELISA). Ratio of the absolute content in the experimental groups and control groups were calculated as the relative content of IL-6. At the end of the experiments, all rats were euthanasia and the bifurcation vascular tissues of carotid artery were collected for the observation of the carotid artery pathology and plaque formation and the measurement of the thickness of carotid intimal-medial layer (IMT). Results: Carotid artery pathology observation showed the IMT in group C was significantly thickened and the group C2 was the most thickened one (compared with group A, P＜0.01). Elastic fibers in groups C1 and C2 were disordered or even broken and disappeared, presenting typical atherosclerotic plaques, which were diffuse calcium salt deposits in the intimal-medial layers and protrude into the lumen. Elastic fibers in group C3 were ranged in ordered relatively without obvious fracture and the number of plaques was significantly reduced. The vascular walls in rats of groups B' and C' were incomplete, the IMTs had no obvious changes, elastic fibers were ranged disorderly and broken and the smooth muscle cells had vacuolar changes. In group C2', the vascular wall was significantly thinned and calcified plaques appeared in the artery, which showed multiple calcification lesions penetrating through the intimal-medial layer or even the whole layer. The vascular wall of group C3' was integrity and the elastic fibers arranged relatively clutter-free, the number of plaques was reduced. Results of detections of IL-6 showed the relative contents of IL-6 in groups B, B', C1, and C1' increased with time. At T3 time point, the relative contents of IL-6 in groups C2 and C3 reached the peak, C2 was 10.4 times of group A and C3 was 9.5 times of group A, and then decreased to different low levels. At T5 point, comparisons of the relative contents of IL-6 showed C3 < C2 < C1 (3.2 times, 5.4 times, 9.6 times of group A, respectively). The relative contents of IL-6 in groups C2' and C3' reached the peak at T2 point (4.9 times and 4.5 times of group A, respectively), and then decline with time. At T5 point, comparisons of the relative contents of IL-6 showed C3'< C2'< C1' (1.2 times, 1.4 times and 3.1 times of group A, respectively). Conclusions: Blood vessels were observed more obvious thickened in the tooth extraction without antibiotic of HL+CP rats with calcifications increase. Blood vessels of DM+CP rats became thin and fragile and even the integrity was damaged. Perioperative use of antibiotics might reduce the carotid artery lesions and decrease serum levels of inflammatory cytokines.

Neopterin derivatives - a novel therapeutic target rather than biomarker for atherosclerosis and related diseases.

This review provides an updated overview of the emerging roles of neopterin derivatives in atherosclerosis. Neopterin, a metabolite of guanosine triphosphate, is produced by interferon-γ-activated macrophages and is expressed at high levels in atheromatous plaques within the human carotid and coronary arteries as well as in the aorta. Plasma concentrations of neopterin are higher in patients with carotid, cerebral, and coronary artery diseases as well as aortic aneurysm. The concentration of neopterin is positively correlated with the severity of coronary artery disease. However, a prospective cohort study showed that neopterin contributes to protection against plaque formation in carotid arteries in patients with atherosclerosis. Moreover, using both in vitro and in vivo experiments, a recent study has shown the atheroprotective effects of neopterin. Neopterin suppresses the expression of monocyte chemotactic protein-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in endothelial cells, and thereby suppresses the adhesion of monocytes to endothelial cells. It also suppresses the inflammatory phenotype of monocyte-derived macrophages. In addition, neopterin suppresses oxidized low-density lipoprotein-induced foam cell formation in macrophages and the migration and proliferation of vascular smooth muscle cells. Neopterin injection into apolipoprotein E-deficient (Apoe-/-) mice suppresses the development of atherosclerotic lesions. A neopterin derivative tetrahydroneopterin (BH4), also known as a cofactor for nitric oxide (NO) synthases, suppresses atherosclerosis and vascular injury-induced neointimal hyperplasia in Apoe-/- mice. BH4 administration improves endothelial dysfunction in patients with coronary artery disease. These findings suggest that neopterin production may increase to counteract the progression of atherosclerosis, as neopterin contributes to atheroprotection. Otherwise, the increased neopterin levels in atherosclerosis may reflect a compensatory mechanism associated with inducible NO synthase upregulation in macrophages to supply BH4 for high output NO production caused by decreased endothelial NO synthase in atherosclerosis. Therefore, neopterin derivatives are a novel therapeutic target for atherosclerosis and related diseases.

Comparison of the Diagnostic Performances of Ultrasound, High-Resolution Magnetic Resonance Imaging, and Positron Emission Tomography/Computed Tomography in a Rabbit Carotid Vulnerable Plaque Atherosclerosis Model.

Our study aimed to evaluate the diagnostic performances of 3 routine examination methods for cerebrovascular disease in a rabbit carotid artery atherosclerosis model. A total of 12 New Zealand rabbits were included: 4 in a control group and 8 in an experimental group. A clinically relevant atherosclerosis rabbit model was induced by left common carotid artery ligation and a 12-week high-fat diet. Atherosclerosis was further confirmed by a histopathologic analysis. Then carotid ultrasound (US) imaging, high-resolution magnetic resonance imaging (HRMRI), and positron emission tomography (PET)/computed tomography (CT) were performed on this model to evaluate the diagnostic performances. Carotid US showed plaque formation in the left common carotid artery and little plaque in the right common carotid artery in the experimental group. In addition, HRMRI showed stenosis formation in the left common carotid artery in the experimental group. At the horizontal level, plaques were found in the left common carotid artery, and no plaques were found in the right common carotid artery in the experimental group. Also, PET/CT showed local hypermetabolism and vulnerable plaques in the left common carotid artery of the experimental group, whereas no hypermetabolism was found in the right common carotid artery of the experimental group. Moreover, the soft plaques detected by carotid US were different from the vulnerable plaques detected by PET/CT. The unstable plaques on HRMRI were the same as the hypermetabolic vulnerable plaques on PET/CT. High-resolution MRI is recommended for the evaluation of neck and intracranial vascular stenosis and plaque properties in patients with stroke.

Honokiol inhibits carotid artery atherosclerotic plaque formation by suppressing inflammation and oxidative stress.

Honokiol is a natural active compound extracted from Chinese herbal medicine, Magnolia officinalis. In this study, the role of honokiol in the development of carotid artery atherosclerotic lesions was evaluated in an ApoE-/- mouse model fed with a normal diet (ND) or a Western-type diet (WD) for ten weeks. After first two weeks, a perivascular collar was surgically placed on the right common carotid arteries of the mice. Then, WD-fed mice were intraperitoneally injected with honokiol (10 or 20 mg/kg) or administrated with 10 mg/kg atorvastatin calcium by gavage once a day for eight weeks. After that, the right common carotid arteries were excised for further experiments. The result showed that honokiol substantially inhibited the development of atherosclerotic lesions. Furthermore, honokiol downregulated the expression of pro-inflammatory markers, like tumor necrosis factor-α, interleukin (IL)-6, and IL-1β. Additionally, honokiol treatment decreased reactive oxygen species level and enhanced superoxide dismutase activity. Nitric oxide level, inducible nitric oxide synthase (iNOS) expression, and aberrant activation of nuclear factor-κB pathway were also significantly inhibited by honokiol treatment. Together, these findings suggest that honokiol protects against atherosclerotic plaque formation in carotid artery, and may be an effective drug candidate for the treatment of carotid artery atherosclerotic stenosis.

Carotid Atherosclerosis in Patients with Atrial Fibrillation.

This review aims to explore the relationship between AF and carotid atherosclerosis, and the impact on the outcomes of cardiovascular and cerebrovascular events. Also, our aim is to critically review current knowledge and delineate future directions for effective treatment or prevention as well as strategies for improvement of the quality of life and survival. Atrial fibrillation (AF) is the most common arrhythmia, increasing the risk of stroke and cardiovascular morbidity and mortality representing a significant worldwide public health problem. On the other hand, carotid artery atherosclerosis can also significantly increase the risk of stroke, transient ischemic attack (TIA), and death. Firstly, we report epidemiological data on AF patients in different countries and regions having carotid artery abnormalities such as carotid artery plaque formation, atherosclerotic, and even stenosis. Despite geographical variations, these abnormalities were more frequent in AF patients and correlated with the duration of AF and the value of CHA2DS2-VASc score. Moreover, it is evident that AF patients with carotid artery abnormalities have significantly increased risk of adverse outcomes from the heart and brain. According to the CHA(2)DS2 (-VASc) score, AF patients are managed with anticoagulation therapy. Reviewing existing data on the treatment for stroke prevention in patients with AF, carotid artery disease, or both, we found that antiplatelet therapy could be combined with anticoagulant therapy appropriately in certain circumstances. In addition, some emerging technologies, such as the percutaneous permanent carotid filter, may be used safely and effectively to prevent the occurrence of stroke in patients both with AF and carotid artery atherosclerosis.

Association of Lipidomic Profiles With Progression of Carotid Artery Atherosclerosis in HIV Infection

Lipid metabolism disruption and excess risk of cardiovascular disease (CVD) have been observed in HIV-infected individuals, but the associations among HIV infection, plasma lipidome, and CVD risk have not been well understood. To evaluate plasma lipidomic profiles and their associations with carotid artery atherosclerosis in individuals with HIV and individuals without HIV. Prospective analysis in the Women's Interagency HIV Study and Multicenter AIDS Cohort Study during a 7-year follow-up (from 2004-2006 to 2011-2013) at multicenter HIV cohorts in the United States. The study included 737 participants aged 35 to 55 years (520 with HIV and 217 without HIV) without CVD or carotid artery plaque at baseline. Data were analyzed between April 2017 and July 2019. Two hundred eleven plasma lipid species. Poisson regression was used to examine the associations of baseline lipid species with risk of plaque measured by repeated B-mode carotid artery ultrasonography imaging. Of the 737 included participants, 398 (54%) were women, 351 (48%) were African American (non-Hispanic), 156 of 737 (21%) were nonwhite Hispanic, and the mean (SD) age was 45 (6) years. After adjusting for demographic and behavioral factors, we identified 12 lipid species, representing independent signals for 10 lipid classes, associated with risk of plaque. Nine lipid species remained significant after further adjusting for conventional CVD risk factors, although many of them showed moderate to high association with conventional blood lipids (eg, total and low-density lipoprotein cholesterols and triglycerides). Cholesteryl ester (16:1) (risk ratio [RR] per standard deviation, 1.28; 95% CI, 1.08-1.52), ceramide (16:0) (RR, 1.29; 95% CI, 1.02-1.63), lysophosphatidylcholine (20:4) (RR, 1.28; 95% CI, 1.05-1.58), lysophosphatidylethanolamine (16:0) (RR, 1.28; 95% CI, 1.05-1.57), phosphatidylethanolamine (38:6) (RR, 1.33; 95% CI, 1.08-1.64), phosphatidylethanolamine-plasmalogen (36:2) (RR, 1.25; 95% CI, 1.04-1.52), phosphatidylserine-plasmalogen (36:3) (RR, 1.19; 95% CI, 1.00-1.43), and triacylglycerol (54:6) (RR, 1.26; 95% CI, 1.04-1.54) were associated with increased risk of plaque, while phosphatidylcholine (36:4) (RR, 0.65; 95% CI, 0.54-0.77) was associated with decreased risk of plaque. Most of these plaque-increased lipid species showed higher levels in individuals with HIV, particularly among individuals with HIV using antiretroviral therapy compared with individuals without HIV. Network analysis identified 9 lipid modules, and 2 modules composed of triacylglycerols and phosphatidylcholines with long and unsaturated acyl chains, respectively, showed the strongest associations with increased risk of plaque. This study identified multiple plasma lipid species associated with carotid artery atherosclerosis, and alterations in these lipid species might be associated with HIV infection and antiretroviral therapy. Our data suggest unfavorable associations of long-chain and unsaturated triacylglycerols and phosphatidylcholines with carotid artery plaque formation.

Elevated Plasma Ceramides Are Associated With Antiretroviral Therapy Use and Progression of Carotid Artery Atherosclerosis in HIV Infection.

Ceramides have been implicated in the pathophysiology of HIV infection and cardiovascular disease. However, no study, to our knowledge, has evaluated circulating ceramide levels in association with subclinical cardiovascular disease risk among HIV-infected individuals. Plasma levels of 4 ceramide species (C16:0, C22:0, C24:0, and C24:1) were measured among 398 women (73% HIV+) and 339 men (68% HIV+) without carotid artery plaques at baseline from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. We examined associations between baseline plasma ceramides and risk of carotid artery plaque formation, assessed by repeated B-mode carotid artery ultrasound imaging over a median 7-year follow-up. Plasma levels of C16:0, C22:0, and C24:1 ceramides were significantly higher in HIV-infected individuals compared with those without HIV infection (all P<0.001), and further analysis indicated that elevated ceramide levels were associated with antiretroviral therapy use, particularly protease inhibitor use, in HIV-infected individuals (all P<0.001). All 4 ceramides were highly correlated with each other ( r=0.70-0.94; all P<0.001) and significantly correlated with total-cholesterol ( r=0.42-0.58; all P<0.001) and low-density lipoprotein cholesterol ( r=0.24-0.42; all P<0.001) levels. Of note, C16:0 and C24:1 ceramides, rather than C22:0 and C24:0 ceramides, were more closely correlated with specific monocyte activation and inflammation markers (eg, r=0.30 between C16:0 ceramide and soluble CD14; P<0.001) and surface markers of CD4+ T-cell activation. A total of 112 participants developed carotid artery plaques over 7 years, and higher levels of C16:0 and C24:1 ceramides were significantly associated with increased risk of carotid artery plaques (relative risk [95% CI]=1.55 [1.29, 1.86] and 1.51 [1.26, 1.82] per standard deviation increment, respectively; both P<0.001), after adjusting for demographic and behavioral factors. After further adjustment for cardiovascular disease risk factors and immune activation markers, these associations were attenuated but remained significant. The results were consistent between men and women and between HIV-infected and HIV-uninfected participants. In 2 HIV cohorts, elevated plasma levels of C16:0 and C24:1 ceramides, correlating with immune activation and inflammation, were associated with antiretroviral therapy use and progression of carotid artery atherosclerosis.

SUN-070 Asymptomatic Patients with Homozygous Familial Hypercholesterolemia: A Challenge

Background: Homozygous familial hypercholesterolemia (HoFH), a very rare autosomal dominant disease, mainly caused by LDL receptor (LDL-R) alterations, with aortic valve compromise reaching nearly 100% and vascular calcifications that can progress independently of marked decrease in total and LDL cholesterol levels. Clinical case: A 21-year-old Hispanic woman diagnosed with HoFH at the age of 6 was referred to our hospital for follow up. Her father had died of acute myocardial infarction at the age of 40. Her mother had an LDLc of 309 mg/dl (8.06 mmol/l) and total cholesterol (TC) 400 mg/dl (10.44 mmol/l) with Achilles tendon xanthomas. She had one elder-brother and sister with elevated levels of TC without xanthomas. She had initially been treated with a statin and ezetimibe at age of 15, but had discontinued these drugs several years ago. Her lipid profile showed TC 700 mg/dl (18.2 mmol/l), triglycerides (Tg) 100 mg/dl (1.31 mmol/l), high density lipoprotein cholesterol (HDL-C) 32 mg/dl (0.83 mmol/l) and LDL-C 546 (14.2 mmol/l). Physical examination showed, xanthomas in Achilles tendons and elbows, and tuberous xanthomas on the knees. She had a systolic ejection murmur, which irradiated to the axillar region. Her EKG was normal. Carotid arterial intima-media thickness (cIMT) revealed non-obstructive plaque formation in both right and left carotid arteries. CT coronary angiography showed severe calcification in the right coronary, left anterior descending arteries, ascending and descending aorta with calcium score of 890 AU. Strain echocardiography showed thickened and flared valves in the aortic, tricuspid and mitral regions. PET/CT with 18F Sodium-Fluoride (18F-NaF) radiotracer showed significant aortic valve uptake with active tissue calcifications. The patient is currently receiving PCSK-9 inhibitor bi-monthly. Conclusion: Despite of the symptoms and cholesterol levels, the clinical course of atherosclerotic manifestations in HoHF individual is highly variable. Premature malignant atherosclerosis leading to aortic valve and root abnormalities is a recognized complication of HoFH and has a strong correlation with age and calcium scores. Greater access to imaging techniques are critical to define the clinical variability of HoFH that have important prognostic and therapeutic implications. Reference: M. Cuchel, E. Bruckert, H.N. Ginsberg, et al., Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society, Eur. Heart J. 35 (32) (2014) 2146e2157 ehu274

Helicobacter pylori infection combined with non-alcoholic fatty liver disease increase the risk of atherosclerosis: Focus in carotid artery plaque.

Atherosclerosis has severe consequences on human health. Carotid artery plaques are a condition typically caused by atherosclerosis. Previous studies showed that nonalcoholic fatty liver disease (NAFLD) and Helicobacter pylori (H pylori) are risks factors for carotid artery plaque formation. We hypothesize that the combination of NAFLD with H pylori infection increases the risk of carotid artery plaque formation.A total of 4669 subjects aged > 40 years who underwent routine health checkups between January 2006 and December 2015 were retrospectively reviewed. A serial examination, including abdominal ultrasound, carotid artery ultrasound and esophago-gastroduodenoscopy (EGD), and biopsy urease testing, was conducted.In total, 2402 subjects were enrolled. There were no differences in H pylori infection status among patients with or without NAFLD. There was a trend of more participants with both NAFLD and H pylori infection (number [N]=583) presenting carotid artery plaque (N = 187,32.08%) than participants without NAFLD and H pylori infection (N = 589) who presented plaque formation (N = 106, 18.00%). Participants who had both H pylori infection and NAFLD had the highest risk of any carotid artery plaque (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.413–2.636) based on a multivariate logistic regression analysis. This analysis also showed that age >60 years, male sex, low-density lipoprotein (LDL) >130 mg/dL, and H pylori infection were independent risk factors for concomitant NAFLD and carotid artery plaque formation.The combination of H pylori infection and NAFLD increases carotid artery plaque formation. H pylori eradication and NAFLD control may be warranted to prevent carotid artery plaque formation.

The Role of Shear Stress in Atherosclerotic Plaque Progression, Destabilization and Rupture

The pathophysiology of atherosclerosis is complex and multifactorial, involving systemic risk factors and biomechanical stimuli. Atherosclerotic plaques predominantly form in regions that are exposed to low shear stress of the blood at the vessel wall, whereas regions of moderate and high shear stress are generally protected. For more than 20 years, my research group performs studies to investigate the role of shear stress in atherosclerotic plaque formation and rupture in coronary and carotid arteries of patients and laboratory animals. For that reason, new technology was developed to 3D reconstruct arteries based on fusion of multiple invasive and non-invasive imaging modalities. These 3D reconstructions were used as input for computational fluid mechanics to derive the local shear stress. We noticed that if the lumen was not affected by the disease, because of outward remodeling, plaques were mainly located at low shear stress regions. However, at later stages of the disease if lumen narrowing occurred, the plaque is also exposed to high shear stress. Until now it is not fully clear, what the influence is of high shear stress on these advanced lumen intruding plaques. Evidence is accumulating for a role of high shear stress in changes in plaque composition towards plaque destabilization and eventually plaque rupture. Moreover, not much studies investigated the influence of multidirectional shear stress on plaque progression and destabilization. In this lecture I will present the research that my group performed to investigate the role of (multidirectional) shear stress on plaque progression, destabilization and rupture at different stages of the atherosclerotic disease.

Zhixiong Capsule (ZXC), a traditional Chinese patent medicine, prevents atherosclerotic plaque formation in rabbit carotid artery and the related mechanism investigation based on network pharmacology and biological research

Background and aimsChinese patent medicine Zhixiong Capsule (ZXC) has been used in clinical treatment against blood stasis-induced dizziness and headache for many years in China. Hypothesis/PurposeRecent clinical observations demonstrated a good efficacy of ZXC against atherosclerotic plaque formation in carotid arteries. The aims of this study were to verify the plaque-preventing efficacy of ZXC in animals and to investigate the underlying mechanisms. Study design/MethodsZXC (185 mg/kg and 370 mg/kg) was administrated to rabbits which received collar implantation accompanied with high fat diet administration (12 days). The blood-dissolved components of ZXC were identified by an UPLC-QTOF-MS method. The key components and targets of ZXC were then predicted based on network pharmacology analysis and biological investigations. ResultsCompared with vehicle control group, ZXC administration (185 mg/kg) significantly prevented plaque formation and attenuated intima thickening in the collar-implanted carotid arteries, markedly decreased blood lipid level, and increased plasma IL-4 level in rabbits. A total of 23 blood-dissolved components were identified. Four ingredients (namely, kaempferol, daidzein, puerarin, miltirone) along with leech, and three targets (namely, JUN, FOS and TP53) were recognized to play important roles for ZXC bioactivity. ConclusionIt could be concluded that ZXC could be applied to prevent atherosclerotic plaque formation and intimal thickening in carotid arteries at the current clinical dose.

Rituximab (R)-CHOP Therapy Has Progressed Arteriosclerosis with an Elevation of Von Willebrand Factor (vWF) in Patients with Malignant Lymphoma

Introduction: An increased incidence of arteriosclerosis has been noted in cancer survivors. Until now, only a few reports have been reported on relationship between arteriosclerosis and chemotherapy. As a mechanism for developing arteriosclerosis by chemotherapy, reduction of nitric oxide from endothelial cells has been reported. We have reported a case who was 68-year-old female with follicular lymphoma, clinical stage IVA showing the plaque formation of carotid artery and the elevation of cardio-ankle vascular index (CAVI) after eight courses of R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) without complication of diabetes mellitus and hyperlipidemia (2017, JCMR). In this study, we evaluated the incidence of developing arteriosclerosis with chemotherapy using CAVI as an arterial stiffness parameter, carotid artery ultrasonography and the value of von Willebrand factor (vWF) as an endothelial damage in patients with malignant lymphoma who were treated with R-CHOP therapy.Materials and methods: Between March 2017 and February 2018, thirteen patients with B-cell malignant lymphoma who were treated with R-CHOP chemotherapy were enrolled after obtaining written informed consent. We evaluated the arteriosclerosis with CAVI index, carotid artery ultrasonography and the value of vWF during each chemotherapy. This study was approved by the Ethics Committee of Toho University.Results: Twelve men and one woman were registered (the median age, 73 years old, range, 59 - 82). One patient was treated with 4 courses of R-CHOP followed by irradiation and the remaining 12 patients were treated with 6-8 courses of R-CHOP. All patients achieved complete remission. The mean value of vWF was significantly elevated from 147 ± 40.0 % to 192 ± 39.8 % after one course of R-CHOP (p = 0.001). Then, the value of vWF was elevated significantly at the each time point compared with the pretreatment value (after 3 cycles; 190 ± 53.5, p = 0.0017, 6 cycles; 198 ± 32.5, p = 0.0024) (Figure 1). The value at after the final chemotherapy (175 ± 41.3) decreased significantly comparing the value of final treatment (207 ± 38.9, p = 0.0112). Nine patients showed the progression of arteriosclerosis with new plaque formation or progression of intima-media thickness by carotid artery ultrasonography. Plaque score after completing the therapy was elevated significantly from 6.4 ± 4.33 to 6.8 ± 4.65 (p = 0.0313) as shown in Figure 2. Some patients showed the elevation of CAVI index with the progression of treatment. However, there was no significant elevation of the index during the treatment.Conclusions: We reported that malignant lymphoma patients showed the significant elevation of vWF and new plaque formation in carotid artery during the R-CHOP therapy. vWF elevation might have progressed the arteriosclerosis in the patients with R-CHOP therapy. Further study will be required to clarify the relationship between chemotherapy and arteriosclerosis. DisclosuresNo relevant conflicts of interest to declare.

B-cell activating factor and related genetic variants in lupus related atherosclerosis

BackgroundSystemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with an increased atherosclerotic risk compared to healthy population, partially explained by traditional cardiovascular (CV) risk factors. Recent data suggest B-cell activating factor (BAFF) as an important contributor in the pathogenesis of both SLE and atherosclerosis. The aim of the current study is to explore whether serum BAFF levels along with variants of the BAFF gene increase lupus related atherosclerotic risk. Patients-Methods250 SLE patients underwent assessment of plaque formation and/or intimal media thickness (IMT) measurements in carotid and femoral arteries by ultrasound. Disease related features and CV traditional risk factors were also assessed. Serum BAFF levels were determined by commercially available ELISA and five single nucleotide polymorphisms (SNPs) of the BAFF gene (rs1224141, rs12583006, rs9514828, rs1041569 and the rs9514827) were evaluated by PCR-based assays in all patients and 200 healthy controls (HC) of similar age and sex distribution. SLE patients were further divided in high and low BAFF groups on the basis of the upper quartile level of the distribution (1358 pg/ml). Genotype and haplotype frequencies in SLE patients and HC were determined by SNPStats and SHEsis software. ResultsHigh-BAFF SLE group displayed increased rates of both plaque formation and arterial wall thickening (defined as IMT>0.90 mm) compared to patients with low BAFF levels (58.1% vs 43.6%, p:0.048 and 38.6% vs 23.2%, p-value: 0.024, respectively). The association remained significant after disease related features were taken into account (ORs [95%CI]: 2.2 [1.0–5.1] and 2.5 [1.1–5.5] for plaque formation and arterial wall thickening, respectively). Moreover, the presence of the AA genotype of the rs12583006 BAFF gene variant increased susceptibility for both lupus and lupus related plaque formation (ORs [95%CI]: 2.8 [1.1–7.1], and 4.4 [1.3–15.4] in the codominant model, respectively). Finally, the haplotype TTTAT was found to be protective for plaque formation among SLE patients (OR 0.3 [0.1–0.9]. No associations between BAFF gene variants with arterial wall thickening were detected. ConclusionsHigh BAFF serum levels in the upper 4th quartile as well as BAFF genetic variants seem to increase susceptibility for both lupus and lupus related subclinical atherosclerosis implying B-cell hyperactivity as a potential contributor in the pronounced lupus related atherosclerotic risk.

Synergistic favorable effect of eicosapentaenoic acid and statin on atherosclerosis

Background and Aims: Combination of Eicosapentaenoic Acid (EPA) and HMG-CoA reductase inhibitor (statin) are known to be an effective therapy for cardiovascular diseases, however, their biological roles in the favorable effect on adverse event have not been studied well. In this study, we aimed to investigate the effect of EPA and statins focusing on plaque formation in a rabbit plaque model. Methods: Rabbit carotid artery was injured with a balloon followed by feeding with a normal diet for 4 w and then with a high-cholesterol diet for 4 w. The rabbits were either received pitavastatin alone, EPA alone, combination (pitavastatin+EPA) or vehicle (control) for 4 w with a high-cholesterol diet. The injured carotid arteries were harvested and analysed morphometrically and immunohistochemically. Results: In control group, smooth muscle cells were located on the luminal side of the plaque and lipidrich macrophages accumulated in the center of the plaque expressing Matrix Metalloproteinase-9 (MMP-9), Tissue Factor (TF), and NF-kB, those are characteristic of unstable plaques. In contrast, EPA reduced the expression of TF and NF-kB and increased the expression of PPAR-α in the plaque. Pitavastatin also reduced the expression of MMP-9, TF, and NF-kB, but not PPAR-α in the plaque. Combination of pitavastatin and EPA significantly reduced the expression of MMP-9, TF, and NF-kB increasing the expression of PPAR-α resulting in the inhibition of intimal hyperplasia and plaque formation in carotid arteries. Conclusions: Pitavastatin and EPA synergistically played a role for inhibitory effect on plaque formation decreasing the expression of inflammation-related molecules and increasing the expression of PPAR-α in injured artery.