Carotid Atherosclerosis Group Research Articles

Correlation between novel inflammatory markers and carotid atherosclerosis: A retrospective case-control study.

Carotid atherosclerosis is a chronic inflammatory disease, which is a major cause of ischemic stroke. The purpose of this study was to analyze the relationship between carotid atherosclerosis and novel inflammatory markers, including platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to neutrophil ratio (PNR), neutrophil to lymphocyte platelet ratio (NLPR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), in order to find the best inflammatory predictor of carotid atherosclerosis. We included 10015 patients who underwent routine physical examinations at the physical examination center of our hospital from January 2016 to December 2019, among whom 1910 were diagnosed with carotid atherosclerosis. The relationship between novel inflammatory markers and carotid atherosclerosis was analyzed by logistic regression, and the effectiveness of each factor in predicting carotid atherosclerosis was evaluated by receiver operating characteristic (ROC) curve and area under the curve (AUC). The level of PLR, LMR and PNR in the carotid atherosclerosis group were lower than those in the non-carotid atherosclerosis group, while NLR, NLPR, SII, SIRI and AISI in the carotid atherosclerosis group were significantly higher than those in the non-carotid atherosclerosis group. Logistic regression analysis showed that PLR, NLR, LMR, PNR, NLPR, SII, SIRI, AISI were all correlated with carotid atherosclerosis. The AUC value of NLPR was the highest, which was 0.67, the cut-off value was 0.78, the sensitivity was 65.8%, and the specificity was 57.3%. The prevalence rate of carotid atherosclerosis was 12.4% below the cut-off, 26.6% higher than the cut-off, and the prevalence rate increased by 114.5%. New inflammatory markers were significantly correlated with carotid atherosclerosis, among which NLPR was the optimum inflammatory marker to predict the risk of carotid atherosclerosis.

The predictive value of plasma uridine for type 2 diabetes and its atherosclerotic complications.

Uridine might be a common link between pathological pathways in diabetes and cardiovascular diseases. This study aimed to investigate the predictive value of plasma uridine for type 2 diabetes and type 2 diabetes with atherosclerosis. Individuals with type 2 diabetes (T2D) and healthy controls (n=218) were randomly enrolled in a cross-sectional study. Patients with T2D were divided into two groups based on carotid ultrasound: patients with carotid atherosclerosis (CA) (group DCA), and patients without CA (group D). Plasma uridine was determined using high-performance liquid chromatography-tandem mass spectrometry. Correlation and logistic regression analyses were used to analyze the results. Fasting and postprandial uridine were significantly increased in patients with T2D compared with healthy individuals. Logistic regression suggested that fasting and postprandial uridine were independent risk factors for T2D. The receiver operating characteristic (ROC) curve showed that fasting uridine had a predictive value on T2D (95% CI,0.686-0.863, sensitivity 74.3%, specificity 71.8%). Fasting uridine was positively correlated with LDL-c, FBG, and PBG, and negatively correlated with CP-0h and HOMA-IS. The change in postprandial uridine from fasting baseline (Δ uridine) was smaller in T2D patients with CA compared with those without (0.80(0.04-2.46) vs. 2.01(0.49-3.15), P=0.010). Δuridine was also associated with T2D with CA and negatively correlated with BMI, CP-0h, and HOMA-IR. Fasting uridine has potential as a predictor of diabetes. Δuridine is closely associated with carotid atherosclerosis in patients with T2D.

Transcriptomics Analysis Revealed Key Genes Associated with Macrophage Autophagolysosome in Male ApoE-/- Mice Aortic Atherosclerosis.

Atherosclerosis (AS) is the most common cause of cardiovascular and cerebrovascular diseases. However, the mechanisms underlying atherosclerotic plaque progression remain unclear. This study aimed to investigate the genes associated with the development of atherosclerosis in the aorta of ApoE-/- male mice, which could serve as novel biomarkers and therapeutic targets in interventions to halt plaque progression. Eight-week-old ApoE-/- mice were fed a normal purified laboratory diet or a Western Diet (WD) for 6 or 22 weeks. High-throughput sequencing technology was used to analyze the transcriptomes of the aortas of four groups of mice that were exposed to different dietary conditions. We retrieved and downloaded the human Arteriosclerosis Disease Chip dataset GSE100927 from the Gene Expression Omnibus (GEO) database and selected 29 cases of carotid atherosclerotic lesions and 12 cases of normal carotid tissues as the experimental and control groups, respectively, to further verify our dataset. In addition, we used quantitative reverse transcription polymerase chain reaction (QT-PCR) to verify the expression levels of the core genes in an atherosclerosis mouse model. There were 265 differentially expressed genes (DEGs) between the ApoE-/- Male mice AS22W group and Sham22W group. In addition to the well-known activation of inflammation and immune response, t the autophagy-lysosome system is also an important factor that affects the development of atherosclerosis. We identified five core genes (Atp6ap2, Atp6v0b, Atp6v0d2, Atp6v1a, and Atp6v1d) in the protein-protein interaction (PPI) network that were closely related to autophagosomes. Hub genes were highly expressed in the carotid atherosclerosis group in the GSE100927 dataset (P < 0.001). QT-PCR showed that the RNA level of Atp6v0d2 increased significantly during the development of atherosclerotic plaque in ApoE-/- male mice. Five core genes which affect the development of aortic atherosclerosis through the autophagy-lysosome system, especially Atp6v0d2, were screened and identified using bioinformatic techniques.

Metabolomics to identify fingerprints of carotid atherosclerosis in nonobese metabolic dysfunction-associated fatty liver disease

Background/aimsNonobese metabolic dysfunction-associated fatty liver disease (MAFLD) is paradoxically associated with improved metabolic and pathological features at diagnosis but similar cardiovascular diseases (CVD) prognosis to obese MAFLD. We aimed to utilize the metabolomics to identify the potential metabolite profiles accounting for this phenomenon.MethodsThis prospective multicenter cross-sectional study was conducted in China enrolling derivation and validation cohorts. Liquid chromatography coupled with mass spectrometry and gas chromatography-mass spectrometry were applied to perform a metabolomics measurement.ResultsThe study involved 120 MAFLD patients and 60 non-MAFLD controls in the derivation cohort. Controls were divided into two groups according to the presence of carotid atherosclerosis (CAS). The MAFLD group was further divided into nonobese MAFLD with/without CAS groups and obese MAFLD with/without CAS groups. Fifty-six metabolites were statistically significant for discriminating the six groups. Among the top 10 metabolites related to CAS in nonobese MAFLD, only phosphatidylethanolamine (PE 20:2/16:0), phosphatidylglycerol (PG 18:0/20:4) and de novo lipogenesis (16:0/18:2n-6) achieved significant areas under the ROC curve (AUCs, 0.67, p = 0.03; 0.79, p = 0.02; 0.63, p = 0.03, respectively). The combination of these three metabolites and liver stiffness achieved a significantly higher AUC (0.92, p < 0.01). In obese MAFLD patients, cystine was found to be significant with an AUC of 0.69 (p = 0.015), followed by sphingomyelin (SM 16:1/18:1) (0.71, p = 0.004) and de novo lipogenesis (16:0/18:2n-6) (0.73, p = 0.004). The combination of these three metabolites, liver fat content and age attained a significantly higher AUC of 0.91 (p < 0.001). The AUCs of these metabolites remained highly significant in the independent validation cohorts involving 200 MAFLD patients and 90 controls.ConclusionsDiagnostic models combining different metabolites according to BMI categories could raise the accuracy of identifying subclinical CAS.Trial registration The study protocol was approved by the local ethics committee and all the participants have provided written informed consent (Approval number: [2014] No. 112, registered at the Chinese Clinical Trial Registry, ChiCTR-ChiCTR2000034197)Graphical

Correlation Study of Serum Dickkopf 4 Level with Metabolic Syndrome and Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus

To investigate the characteristics of Dickkopf 4 changes in patients with type 2 diabetes mellitus and its correlation with carotid atherosclerosis, is the objective of the study. A cross-sectional survey was performed and eligible patients with type 2 diabetes mellitus were taken as the subjects. Lifestyle, physical measurements, blood biochemical parameters and relevant imaging examinations were collected from all participating subjects. 237 type 2 diabetes mellitus patients were included in present study and divided into four groups according to the quartiles of serum Dickkopf 4. The incidence of body mass index, fasting plasma glucose, fasting C-peptide, glycated haemoglobin, insulin resistance index, total cholesterol, triglycerides, low-density lipoprotein, C-reactive protein, high-density lipoprotein, and non-alcoholic fatty liver disease, carotid atherosclerosis were compared between groups, p<0.05. Dickkopf 4 was positively correlated with body mass index, C-reactive protein, fasting plasma glucose, fasting C-peptide, glycated haemoglobin, total cholesterol, triglycerides, low-density lipoprotein, insulin resistance index and creatinine, and negatively correlated with high-density lipoprotein and estimated glomerular filtration rate, p<0.05. Non-metabolic syndrome group and metabolic syndrome group were compared and non-carotid atherosclerosis group and carotid atherosclerosis group were compared for all the parameters (p<0.05). High Dickkopf 4 was an independent risk factor for metabolic syndrome (odds ratio=2.023, 95 % confidence interval: 1.042-3.926, p=0.037). Binary logistic regression analysis, high Dickkopf 4 was an independent risk factor for carotid atherosclerosis (odds ratio=2.513, 95 % confidence interval: 1.379-2.513, p=0.003). High Dickkopf 4 is a risk factor for hypertension and non-alcoholic fatty liver disease in type 2 diabetic patients and an independent risk factor for metabolic syndrome and carotid atherosclerosis in type 2 diabetic mellitus patients.

Carotid atherosclerosis: An independent risk factor for small fiber nerve dysfunction in patients with type 2 diabetes mellitus.

To explore whether carotid atherosclerosis is an independent risk factor for small fiber nerve dysfunction in type 2 diabetes mellitus patients. A total of 247 type 2 diabetes patients from Nanjing Drum Tower Hospital received carotid ultrasonography and quantitative sensory testing, including cold and warm detection thresholds, and some patients received cold and heat pain detection thresholds, respectively. According to the results of quantitative sensory testing, patients were divided into normal small fiber nerve function (NSF)and small fiber nerve dysfunction (SFD) group. Meanwhile, patients were divided into the non-carotid atherosclerosis group, carotid intimal thickening, unilateral carotid atherosclerosis and bilateral carotid atherosclerosis group. The correlation between carotid ultrasonography with quantitative sensory testing parameters was analyzed by SPSS 26.0. First, the incidence rate of SFD increased significantly in patients with carotid atherosclerosis (72.2%, P < 0.001) especially in bilateral carotid atherosclerosis (81.7%, P < 0.001). Second, compared with the NS group, the carotid intima-media thickness in SFD was thicker (P=0.018) and the size of atherosclerotic plaque was larger (P < 0.001). In addition, the cold detection threshold decreased (P < 0.001), whereas the warm detection threshold (P < 0.001) and heat pain detection threshold (P < 0.001) increased as aggravation of carotid atherosclerosis. In the correlation analysis, the size of atherosclerotic plaque presented a positive correlation with the warm detection threshold (r=0.476, P < 0.001) and heat pain detection threshold (r=0.213, P < 0.001), but presented a negative correlation with the cold detection threshold (r=-0.239, P < 0.01). Furthermore, carotid atherosclerosis (odds ratio 2.326, P=0.017), especially bilateral carotid atherosclerosis (odds ratio 5.042, P=0.001), was an independent risk factor for SFD (P < 0.05). Carotid atherosclerosis was significantly associated with quantitative sensory testing and found to be an independent risk factor for small fiber nerve dysfunction in type 2 diabetes patients.

Circulating microparticles are associated with plaque burden and cause eNOS uncoupling in patients with carotid atherosclerosis.

Aims: The study aimed to evaluate the correlation of different microparticle (MP) phenotypes with plaque burden and their diagnostic value and preliminarily explore the role of MPs in atherosclerosis (AS). Methods: Carotid intima-media thickness (CIMT) and maximal plaque area in 23 patients with carotid atherosclerosis (CAS) and 22 healthy subjects were measured by ultrasound. Transmission electron microscopy, nanoparticle tracking analysis and western blot were used to identify MPs. Flow cytometry assay measured absolute number of MPs, and receiver operating characteristic (ROC) analysis was used to assess the relationship between plaque burden and MPs. To study the preliminary mechanism of MPs in AS, MPs were administered to 32 male Kunming mice, which were randomly divided into control, CAS, healthy, and tetrahydrobiopterin (BH4) groups. Hematoxylin-eosin staining, immunohistochemistry staining, and Western blot were adopted to detect relevant indexes 24h after the injection. Results: The plasma levels of CD45+ leukocyte-derived microparticle (LMP), CD11a+ LMP, CD11a+/CD45+ LMP, and CD31+/CD42b+ platelet-derived microparticle (PMP) in CAS patients were significantly higher than those in healthy subjects, and were positively correlated with the maximal plaque area. Moreover, the levels of CD11a+ LMP, CD11a+/CD45+ LMP were also positively correlated with CIMT. The area under the ROC curve of the four MPs was 0.689, 0.747, 0.741, and 0.701, respectively. Compared with healthy subjects, MPs from CAS patients resulted in a significantly lower expression of endothelial nitric oxide synthase (eNOS) dimer/monomer, and BH4 could improve eNOS uncoupling. Moreover, the level of VCAM-1 in intima in the CAS group was significantly higher than in the other three groups. Conclusion: CD11a+ LMP and CD11a+/CD45+ LMP might be potential biomarkers for CAS prediction. BH4-related eNOS uncoupling occurs in CAS patients, and circulating MPs from them lead to endothelial dysfunction through eNOS uncoupling.

The association of plasma sortilin with essential hypertension and subclinical carotid atherosclerosis: A cross-sectional study.

BackgroundSortilin, a protein that regulates glucose and lipid metabolism, has recently been linked to cardiovascular diseases (CVDs) such as coronary heart disease and carotid artery stenosis. In this study, we measured circulating sortilin concentrations in essential hypertensive (EH) patients, and evaluated the association between sortilin, hypertension, and subclinical carotid atherosclerosis in hypertensive individuals.MethodsThis cross-sectional study included 336 individuals, including 186 newly diagnosed EH patients and 150 age-and-sex-matched normotensive healthy subjects (NT). Plasma sortilin and adiponectin (ADI) levels were measured using ELISA kits. In the EH group, high-resolution B-mode ultrasound was used to detect the existence of subclinical carotid atherosclerosis (subAS), which was defined as having a carotid intima–media thickness (cIMT) ≥ 1.0 mm and/or plaque on the carotid artery without any clinical manifestations.ResultsOur findings showed that plasma sortilin concentrations ranged from 3.34–11.34 ng/ml for all subjects. Sortilin levels were significantly higher in the EH group than in the NT group (8.10 ± 1.82 ng/ml vs. 6.37 ± 1.52 ng/ml, P < 0.001) and were further upregulated in the EH with subclinical carotid atherosclerosis (EH + subAS) group compared to the EH without subclinical carotid atherosclerosis (EH-subAS) group (8.42 ± 1.75 ng/ml vs. 7.79 ± 1.84 ng/ml, P < 0.05). In correlation analysis, sortilin was positively correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), white blood cell (WBC), endothelin-1 (ET-1), high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and cIMT (all P < 0.05) and negatively associated with NO and ADI (P < 0.001). Multiple linear regression analysis revealed that SBP, LDL-C, and ET-1 were independently associated with plasma sortilin levels. Increased sortilin levels were independently associated with the risk of EH (OR: 1.86, 95%CI: 1.56–2.20, P < 0.001) and EH + subAS (OR: 1.33, 95%CI: 1.07–1.66, P = 0.011), after adjustment for multiple risk factors. Restricted spline curve showed that elevated sortilin levels increase the odds of having EH.ConclusionElevated sortilin levels are associated with an increased risk of essential hypertension and subclinical carotid atherosclerosis in hypertensive patients.

MicroRNA and Hemostasis Profile of Carotid Atherosclerosis.

Carotid atherosclerosis (CA) is an important risk factor for ischemic stroke. We described the miRNA and hemostasis profile of patients with moderate and advanced stages of carotid atherosclerosis and elucidated potential correlations with hemostatic activation. A prospective case-control study included 61 patients with evidence of carotid atherosclerosis (via ultrasound). The study population was divided into groups depending on the degree of carotid artery stenosis: 60% or more (advanced) and <60% (moderate). All patients underwent the following blood tests: general blood test, hemostatic parameters and microRNA. Extraction of microRNA was performed using Leukocyte RNA Purification Kit (NORGEN Biotec Corp., Thorold, ON, Canada); miRNA quantification was performed via RT-PCR. Statistical analysis was performed in R programming language (v. 4.1.0) using RSudio. MicroRNA expression profile was different depending on CA degree. MiR-33a-5p/3p levels were higher in patients with ≥60% carotid stenosis (42.70 and 42.45 versus 38.50 and 38.50, respectively, p < 0.05). Almost complete separation can be visualized with the levels of miR-126-5p: 9.50 in the moderate CA group versus 5.25 in the advanced CA (p < 0.001). MiR-29-5p was higher in the moderate CA group: 28.60 [25.50;33.05] than in advanced CA group: 25.75 [24.38;29.50] (p = 0.086); miR-29-3p was also higher in the moderate CA group: 10.36 [8.60;14.99] than in advanced CA group: 8.46 [7.47;10.3] (p = 0.001). By-group pairwise correlation analyses revealed at least three clusters with significant positive correlations in the moderate CA group: miR-29-3p with factors V and XII (r = 0.53 and r = 0.37, respectively, p < 0.05); miR-21-5p with ADAMTS13, erythrocyte sedimentation rate and D-dimer (r = 0.42, r = 0.36 and r = 0.44, respectively, p < 0.05); stenosis degree with miR-33a-5p/3p and factor VIII levels (r = 0.43 (both) and r = 0.62, respectively, p < 0.05). Hemostasis parameters did not reveal significant changes in CA patients: the only statistically significant differences concerned factor VIII, plasminogen and (marginally significant) ADAMTS-13 and protein C. Down-regulation of miR-126-5p expression has been identified as a promising biomarker of advanced carotid atherosclerosis with high specificity and sensitivity. Correlation cluster analysis showed potential interplay between miRNAs and hemostatic activation in the setting of carotid atherosclerosis.

The possible correlation between serum GRB2 levels and carotid atherosclerosis in patients with type 2 diabetes mellitus.

Background and purposeGrowth factor receptor-bound protein 2(GRB2), a bridging protein. An animal study showed that downregulation of GRB2 inhibited the activation of PI3K/AKT/NF-kB pathway which improved lipid accumulation and inflammatory infiltration in rats with atherosclerosis (AS), resulting in an anti-AS effect. This was the first study to investigate blood GRB2 levels in type 2 diabetes mellitus(T2DM) patients with carotid atherosclerosis (CAS), exploring its relationship with various metabolic indicators, and further, examining whether GRB2 has an AS effect in patients with T2DM.MethodsA total of 203 participants were recruited in the study, including 69 T2DM patients without CAS (T2DM group), 67 T2DM patients with CAS (CAS group), and 67 in the age-sex-matched healthy subjects (Control group). Serum GRB2 levels were measured using enzyme-linked immunosorbent assay (ELISA) in 203 subjects who had received carotid ultrasonography. In addition, cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), glycosylated hemoglobin (HBA1c), fasting insulin (FINS), hypersensitive C-reactive protein (Hs-CRP), and Interleukin 6 (IL-6) were also tested. The correlation between serum GRB2 levels and other indexes was analyzed. Finally, we analyzed the risk factors affecting carotid intima-media thickness (CIMT) in T2DM patients.ResultsSerum GRB2 levels were increased in the T2DM group than in the control group, and further elevated in the CAS group (median 3.05 vs 4.40 vs 7.09 ng/ml, P<0.001). Spearman correlation analysis showed that GRB2 concentrations were negatively correlated with HDL-C, and positively associated with duration of diabetes, waist-to-hip ratio (WHR), TC, HBA1c, FPG, FINS, homeostasis model assessment-insulin resistance index (HOMA-IR), Hs-CRP, IL-6 and CIMT (P<0.01). Furthermore, serum GRB2 levels (P<0.001) remained independently related to CIMT after adjusting for the age, sex, duration of diabetes, and Body Mass Index (BMI) variables. Stepwise multiple linear regression analysis showed that IL-6, HDL-C, HBA1c, and CIMT are independent correlation factors of serum GRB2 (P<0.01). Univariate logistic regression suggested that disease duration, WHR, systolic blood pressure (SBP), TG, HDL-C, HBA1c, FPG, HOMA-IR, IL-6, Hs-CRP, and GRB2 independently associated with T2DM is combined with CAS(P<0.05). And multivariate logistic regression analysis showed that duration of diabetes, IL-6, and serum GRB2 levels were independent risk factors for T2DM combined with CAS (P<0.05), and serum GRB2 levels were a highly sensitive indicator of early AS (OR=1.405, 95% CI: 1.192-1.658 P<0.001). Moreover, the ROC curve AUC area of serum GRB2 expression levels was 0.80 (95%CI: 0.7291-0.8613, P < 0.001), with a sensitivity of 83.58% and specificity of 70.59%. The risk of CAS was substantially higher in patients with T2DM whose serum GRB2 concentration was >4.59 ng/ml.ConclusionsSerum GRB2 concentrations were significantly increased in T2DM combined with CAS, and serum GRB2 levels were linearly correlated with CIMT, suggesting that GRB2 may be involved in the occurrence and development of T2DM with CAS, which can be used as a predictor of whether T2DM is combined with CAS.

The influence of carotid atherosclerosis on surgical outcomes of patients with cervical spondylotic myelopathy: A retrospective study.

The appearance of atherosclerosis in the carotid artery may be suggest the possibility of atherosclerosis in the spinal cord artery, which can cause spinal cord ischemia and further lead to neural element damage.According to the inclusion and exclude standard, there are 137 patients with cervical spondylotic myelopathy (CSM) incorporating retrospective analysis. These patients were consecutively admitted into The Second Hospital- Cheeloo College of Medicine-Shandong University from January 2016 to December 2018 and have accepted surgical treatment. All patients were examined by color Doppler ultrasound to detect carotid atherosclerosis before surgery. All patients were divided into 2 groups according to the presence or absence of carotid atherosclerosis: carotid atherosclerosis group (n = 88) and noncarotid atherosclerosis group (n = 49). All patients were followed up for at least 12 months after surgery. Demographic and surgery-related data were collected and analyzed to identify potential factors that affect the surgical outcomes in CSM.The average age of carotid atherosclerosis group (51 males and 37 females), and noncarotid atherosclerosis group (24 males and 25 females) were 62.02 ± 10.34 years (range, 38–85 years) and 49.61 ± 10.28 years (range, 26–67 years), respectively.In carotid atherosclerosis group: pre and postoperative modify Japanese Orthopedic Association Scores (mJOA score) were 11.58 ± 1.82 and 14.36 ± 1.64; the recovery rate of mJOA score was 45.57% ± 13.28%. In noncarotid atherosclerosis group: pre and postoperative mJOA score were 12.00 ± 2.11 and 15.04 ± 1.70; the recovery rate of mJOA score was 53.90% ± 13.22%. Univariate logistic regression analysis demonstrated that gender (P = .004), age ≥65 years (P = .001), duration of symptoms ≥12 months (P = .040), smoking history (P < .001), preoperative mJOA score ≤11 (P = .007) and carotid atherosclerosis (P = .004) were related to poor surgical outcomes. Multivariate logistic regression analysis showed significant correlations between poor surgical outcomes and age ≥65 years (P = .047), smoking history (P = .010), preoperative mJOA score ≤11 (P = .008) or carotid atherosclerosis (P = .047).Carotid atherosclerosis may be a risk factor for poor surgical outcomes in CSM.

Gut Microbiome Alterations in Patients With Carotid Atherosclerosis.

Carotid atherosclerosis (CAS) is a reflection of systemic atherosclerosis and the main pathological processes of cardiovascular disease (CVD), namely, carotid intima–media thickening, carotid plaque formation, and carotid stenosis. Accumulating evidence indicates that the gut microbiota plays an important role in CVD and gut–brain disorders, but the associations of the composition and metabolites of the gut microbiome with CAS have not been studied comprehensively. We performed a gut microbiome genome-wide association study in 31 patients with CAS and 51 healthy controls using whole-genome shotgun sequencing. We found that several risk factors (waist circumference, body mass index, diastolic blood pressure, systolic blood pressure, fasting blood glucose, glycated hemoglobin A1c, total cholesterol, triglyceride, and low-density lipoprotein cholesterol) and inflammatory markers (white blood cell count and absolute value of neutrophils) were significantly higher in the CAS group than in the control group. In addition, 21 species and 142 pathways were enriched in the CAS group, and 10 species and 1 pathway were enriched in the control group. Specifically, Bacteroides eggerthii, Escherichia coli, and Klebsiella pneumoniae were the most abundant species in the CAS group, whereas Parabacteroides unclassified, Prevotella copri, Bacteroides sp 3_1_19, and Haemophilus parainfluenzae were the most abundant species in the control group. Finally, we found that most gut microbes and microbial pathways that were enriched in the CAS group had significant positive correlations with clinical characteristics, whereas the microbes and pathways enriched in healthy controls had significant negative correlations with clinical characteristics excluding high-density lipoprotein cholesterol. In addition, the associations between gut microbes and some microbial pathways (short-chain fatty acid, lipopolysaccharide, and menaquinol biosynthesis) were identified. Our results indicate the existence of a cyclic pathway that elevates the circulating concentrations of trimethylamine-N-oxide in patients with CAS but reduces its concentrations in healthy controls.

Associations between SNP83 of phosphodiesterase 4D gene and carotid atherosclerosis in a southern Chinese Han population: a case-control study.

Atherosclerosis was an important pathophysiological basis of atherothrombotic stroke, and phosphodiesterase 4D (PDE4D) polymorphism (SNP83/rs966221) was reported to be associated with the susceptibility to atherothrombotic stroke. Aim of the present study was to explore the potential association between SNP83 and carotid atherosclerosis (CAS). 204 southern Chinese Han participants were divided into two groups according to the carotid intima-media thickness (IMT) of the carotid artery: CAS group (carotid IMT ≥ 1.0mm) and non-CAS group (carotid IMT < 1.0mm). Carotid IMT was measured by color Doppler ultrasound. The PDE4D SNP83 polymorphism was determined by SNaPshot technique. Our study found that SNP83 was associated significantly with CAS susceptibility under the dominant, overdominant and codominant models. After adjusting for age, gender, low-density lipoprotein cholesterol, Hemoglobin A1c, cigarette smoking, hypertension history, and diabetes mellitus history, the association still remained significant (dominant model: crude OR = 2.373, 95% CI: 1.268-4.442, P = 0.007; adjusted OR = 3.129, 95% CI: 1.104-8.866, P = 0.032; overdominant model: crude OR = 1.968, 95% CI: 1.043-3.714, P = 0.037; adjusted OR = 2.854, 95% CI: 1.005-8.108, P = 0.049; codominant: crude OR = 2.102, 95% CI: 1.110-3.979, P = 0.023; adjusted OR = 2.984, 95% CI: 1.047-8.502, P = 0.041). Carotid IMT of carriers with CT + CC genotypes was higher than carriers with TT genotype (P = 0.016). Our results indicated that the SNP83/rs966221 located on PDE4D gene was significantly associated between CAS susceptibility and carotid IMT independently of conventional risk factors in a southern Chinese Han population.

The Proinflammatory Soluble CD40 Ligand Is Associated with the Systemic Extent of Stable Atherosclerosis.

Background and objectives: Polyvascular atherosclerosis is frequent and associated with a high cardiovascular risk, although the mechanisms regulating the atherosclerosis extent to single or multiple arterial territories are still poorly understood. Inflammation regulates atherogenesis and soluble CD40 ligand (sCD40L) is an inflammatory mediator associated with the presence of single-territorial atherosclerosis. We assessed whether the sCD40L expression is associated with the atherosclerosis extent to single or multiple arterial territories and with the atherosclerosis severity in different territories. Materials and Methods: We prospectively enrolled 94 participants with no atherosclerosis (controls, n = 26); isolated coronary atherosclerosis (group 1, n = 20); coronary and lower extremity (LE) atherosclerosis (group 2, n = 18); coronary and carotid atherosclerosis (group 3, n = 12); and coronary, LE, and carotid atherosclerosis (group 4, n = 18). Serum sCD40L levels were quantified. Results: The sCD40L levels (ng/mL, mean (standard deviation)) were 4.0 (1.5), 5.6 (2.6), 7.2 (4.2), 5.9 (3.7), and 5.1 (2.4) in controls and groups 1 to 4, respectively (ANOVA p = 0.012). In nonrevascularized patients, the sCD40L levels were significantly higher in group 2 than in group 1 and were correlated with the number of LE diseased segments. Prior LE bypass surgery was associated with lower sCD40L levels. Coexistence of coronary and LE atherosclerosis was independently associated with the sCD40L levels. Conclusions: The sCD40L levels were increased in stable atherosclerosis, particularly in polyvascular coronary and LE atherosclerosis. The number of LE diseased segments and prior LE revascularization were associated with sCD40L expression. To our knowledge, these are novel data, which provide insights into the mechanisms underlying multi-territorial atherosclerosis expression. sCD40L may be a promising noninvasive tool for refining the stratification of the systemic atherosclerotic burden.

Comparison of the Characteristics and Risk Factors of Carotid Atherosclerosis in High Stroke Risk Populations Between Urban and Rural Areas in North China.

Objective: To study the characteristics and risk factors of carotid atherosclerosis in populations at high risk of stroke in urban and rural areas of North China.Methods: A cross-sectional study was conducted to investigate high stroke risk populations in representative urban and rural areas sampled from 12 regions of China. A pre-designed questionnaire, ultrasound, and laboratory examinations were performed to evaluate risk factors.Results: A total of 30,175 patients were included in the study. The overall prevalence of carotid atherosclerosis was 54.53%, among which intimal thickening and plaque were 39.22 and 41.25%, respectively. The prevalence of carotid atherosclerosis in the urban group was higher than in the rural group. Multivariate logistic regression analysis revealed that male gender, age, smoking, hypertension, dyslipidemia, stroke, atrial fibrillation, systolic blood pressure, and levels of fasting blood glucose, total cholesterol, and low-density lipoprotein cholesterol were the common independent risk factors for carotid atherosclerosis in both groups. Higher education, high salt consumption, passive smoking, family history of stroke, and transient ischemic attack were unique independent risk factors, and high-density lipoprotein cholesterol was a protective factor for carotid atherosclerosis in the urban population.Conclusion: This study suggests that risk factors for carotid atherosclerosis differ between urban and rural populations in North China.

Advanced glycation end product levels were correlated with inflammation and carotid atherosclerosis in type 2 diabetes patients.

Diabetes mellitus with atherosclerosis (AS) adds to the social burden. This study aimed to investigate whether advanced glycation end product (AGE) levels were correlated with inflammation and carotid AS (CAS) in type 2 diabetes mellitus (T2DM) patients. A total of 50 elderly T2DM patients and 50 age-matched senior healthy subjects were recruited in this study. T2DM patients were classified into two groups based on the intima–media thickness (IMT) of the carotid artery from color Doppler ultrasonography. Patients with IMT > 1 mm were classified into the T2DM + CAS group (n = 28), and patients with IMT < 1 mm were assigned as the T2DM + non-atherosclerosis (NAS) group (n = 22). The plasma levels of AGEs, receptor for AGE (RAGE), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) of all subjects were measured by enzyme-linked immunosorbent assay. The T-lymphocyte subsets were analyzed by a flow detector. T2DM + CAS patients showed significantly higher concentrations of AGEs, RAGE, TNF-α, and IFN-γ in the peripheral blood. The highest levels of CD4+ T cells were observed in the T2DM + CAS group. The AGE level was positively correlated with the concentrations of RAGE, TNF-α, IFN-γ, and CD4+. In summary, the results showed that the levels of AGEs may be correlated with the inflammatory status in T2DM patients with CAS.

Differentiation of Pontine Infarction by Size.

PurposeWe hypothesized that the current criteria may be unsuitable for lacunar pontine infarctions (LPI) diagnosis and that size criteria may indicate different stroke mechanisms.MethodsA total of 102 patients with isolated pontine infarctions were divided into a parent artery disease (PAD) and non-PAD groups according to stenosis of basilar artery. Further, 86 patients from the non-PAD group were divided into paramedian pontine infarction (PPI) and LPI groups. Data were collected from the three groups. The “golden” criterion for LPI was established based on the location of the infarction. A receiver operating characteristic (ROC) curve were used to evaluate the optimal cutoff value to use as an LPI diagnostic indicator.ResultsThere was a high prevalence of patients with PAD in both asymptomatic carotid atherosclerosis (ACAS) and PPI groups. Patients with PPI had a higher prevalence in diabetes and ACAS than those with LPI. Based upon the ROC curve, the optimal lesion size cutoff value for use as an LPI diagnostic indicator was 11.8 mm.ConclusionsDiffusion weighted imaging (DWI) cutoff points for predicting LPI may differ from that of the middle cerebral artery territory. The diameter of LPI may also indicate different stroke mechanisms.

Association of serum 3-nitrotyrosine with carotid atherosclerosis in newly diagnosed type 2 diabetic patients

To investigate the association of serum 3-nitrotyrosine (3-NT) with carotid atherosclerosis in newly diagnosed type 2 diabetic patients. 96 patients with newly diagnosed type 2 diabetes mellitus treated in the department of endocrinology of Tangshan Gongren Hospital were recruited, and were divided into two groups depending on their carotid atherosclerosis status as carotid atherosclerosis group (CAS group, n=54) and non-carotid atherosclerosis group (NCAS group, n=42); while 51 healthy subjects without type 2 diabetes mellitus from the medical examination center were recruited as normal control group (NC group, n=51). Demographic and clinical data of all subjects were collected. Serum 3-NT levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA). (1) The levels of 3-NT in CAS group and NCAS group were all higher than those in NC group, and the level of 3-NT in CAS group was higher than that in NCAS group (all P<0.05); (2) In type 2 diabetic patients, 3-NT was positively correlated with HbA1C and low density lipoprotein-cholesterol (both P<0.05); (3) Logistic regression analysis showed that age (OR=1.271, P=0.023), HbA1C (OR=1.812, P=0.005) , Hcy (OR=1.194, P=0.019), and 3-NT (OR=1.593, P=0.011) were risk factors of CAS in type 2 diabetic patients. Serum 3-NT was closely correlated with carotid atherosclerosis in newly diagnosed type 2 diabetic patients, suggesting that serum 3-NT may be involved in the carotid atherosclerosis of newly diagnosed type 2 diabetic patients. Key words: 3-nitrotyrosine; Newly diagnosed; Diabetes mellitus, type 2; Carotid atherosclerosis

Effects of Cervical Rotatory Manipulation on Internal Carotid Artery in Hemodynamics Using an Animal Model of Carotid Atherosclerosis: A Safety Study.

BackgroundSpinal manipulation, particularly in cervical rotatory manipulation (CRM), has become increasingly popular in physical therapies, with satisfying effect. However, it is still unclear whether CRM affects internal carotid arteries (ICA) with mild carotid atherosclerosis (CAS), especially in hemodynamics.Material/MethodsNine cynomolgus monkeys were randomly divided into 3 groups: the CAS-CRM, the CAS, and the blank control groups. CAS models were developed in the left ICA in the CAS-CRM and the CAS groups. The monkeys in the CAS-CRM group underwent CRM intervention for 3 weeks. Histology and hemodynamics were measured, including peak systolic velocity (PSV), end-diastolic velocity (EDV), time average velocity (TAV), resistance index (RI), and pulsatility index (PI). Measurements were made separately at 3 different rotation angles (0°, 45°, and 90°).ResultsIn the 3 groups, with the increase of rotation angle, the decreasing tendency of PSV, EDV, and TAV and the increasing tendency of RI and PI were statistically significant. At each angle, the monkeys in the CAS-CRM and the CAS groups had lower levels of PSV, EDV, and TAV and higher levels of RI and PI compared with the blank control group. No significant difference in hemodynamics was found between the CAS-CRM and the CAS groups.ConclusionsBoth the rotational angle and the atherosclerotic disease can affect the blood flow of the ICA. However, CRM does not cause adverse effects on hemodynamics in cynomolgus monkeys with mild CAS, and appears to be a relatively safe technique.

A3543 Relationship between different morning blood pressure surge and carotid atherosclerosis in patients with hypertension

Objectives: To investigate the relationship between carotid atherosclerosis and different morning blood pressure surge in patients with hypertension. Methods: 251 patients with hypertension were monitored with 24 h dynamic blood pressure monitoring and color Doppler ultrasonography. Patients were divided into carotid atherosclerosis group (IMT ≥ 1.2 mm) (n = 182) and non carotid atherosclerosis group (n = 69). BP morning surge is classified as Sleep-trough Surge, Preawakening Surge and Rising Surge. The blood pressure variability and BP morning surge of two groups were analyzed. Results: In Carotid atherosclerosis group, age, TC, LDL-C were higher than those in non carotid atherosclerosis group (p < 0.05). No difference of BMI, FPG, TG, HDL-C was found between two groups (p > 0.05). Compared with non carotid atherosclerosis group,24hSBPSD, nSBPSD, Sleep-trough Surge were higher in carotid atherosclerosis group (14.5 ± 3.0 vs 13.6 ± 2.8 mmHg, P < 0.05; 12.9 ± 3.9 vs 11.7 ± 3.6 mmHg, P < 0.05; 19.9 ± 15.3 vs 13.9 ± 11.4 mmHg, P < 0.05). No differences of Preawakening Surge and Rising Surge were found between two groups. Multiple regression analysis showed that TC and Sleep-trough Surge were the risk factors of IMT (OR:1.280 and 1.150, P < 0.001). Conclusion: Patients with carotid atherosclerosis have higher BPV, MBPS and TC. The Sleep-trough Surge can better reflect the relationship between MBPS and carotid atherosclerosis.