Carotid Atherosclerosis Research Articles

A cross-sectional study of factors associated with carotid atherosclerosis.

The aim of this work was to study the relationship between carotid atherosclerosis (CAS) and several indexes and provide a basis for the prevention and treatment of cardiovascular and cerebrovascular diseases. There were 11,028 adults who underwent physical examination at the Guangzhou Cadre and Talent Health Management Center from January 2023 to December 2023 and were selected as research subjects. Retrospective analysis was used to understand the carotid atherosclerosis of the examined population and analyze its relationship with sex, age, blood pressure, blood glucose, blood lipids, renal function, 25-hydroxyvitamin D, neutrophil to lymphocyte count ratio (NLR), platelet to lymphocyte count ratio (PLR), systemic immune inflammation index (SII), monocyte count to high-density lipoprotein cholesterol ratio (MHR), triglyceride glucose body mass index (TyG-BMI), insulin resistance metabolic index (METS-IR), and other indicators. Among 11,028 subjects, the detection rate of carotid atherosclerotic thickening (CAT) was 12.00% and carotid atherosclerotic plaque (CAP) was 25.11%. The CAT and CAP detection rates in men were 13.32% and 28.78%, respectively, which were higher than the CAT detection rate of 8.28% and CAP detection rate of 14.80% in women, and the differences were statistically significant (both p < 0.001). Multivariate logistic regression analysis using TyG-BMI and METS-IR as two indicators was modeled separately, and the results showed that CAS was associated with men, increasing age, and systolic blood pressure. The area under the curve (AUC) was analyzed using the subject's work characteristic (ROC) curve in the descending order of METS-IR, TyG-BMI, and MHR. The combination of the three indexes of sex, age, and METS-IR predicted atherosclerosis with the highest AUC values. Carotid atherosclerosis is highly prevalent in men. Elevation of systolic blood pressure, fasting glucose, MHR, and TyG-BMI (or METS-IR) with age are independent influences on carotid atherosclerosis. The three indexes of MHR, TyG-BMI, and METS-IR, respectively, in combination with sex and age, can be used as a new and effective index to predict CAS.

Glucose-lowering medications and glucose levels as the major determinants of progression of carotid atherosclerosis in middle-aged adults and elders: a community-based prospective study.

Few prospective studies explored the incidence and determinant of carotid atherosclerosis (CA) progression (CAP). This community-based prospective study focused on the effects of diabetes mellitus (DM) treatments and glucose levels on CAP risks. We followed up a group of 657 CA-positive middle-aged adults and elders for CAP. CAP was defined as an increase in the total number of carotid plaque and/or an increase in diameter stenosis by at least 10%. After 4.05 years of followed-up, CAP was detected in 364 (55.4%) subjects. The multivariable-adjusted hazard ratios (HRs) were 1.805 (95% confidence interval [CI]: 1.374-2.358) and 0.694 (95% CI: 0.510-0.944) for elevated fasting plasma glucose (eFPG; FPG≥100 mg/dL) and glucose-lowering medications (GLM), respectively. As compared to GLM-negative+eFPG-positive subjects, the multivariable-adjusted HRs were 0.497 (95% CI: 0.373-0.662), 0.537(95% CI: 0.306-0.942), and 0.586 (95% CI: 0.412-0.833) for GLM-negative+eFPG-negative, GLM-positive+eFPG-negative, and GLM-positive+ eFPG-positive subjects, respectively. The multivariable-adjusted risks of CAP were similar between GLM-negative+eFPG-negative and GLM-positive+ eFPG-positive subjects (p=0.77). Stratified analyses showed that the multivariable-adjusted HRs per 5.0 mg/dL increase in FPG were significantly increased among GLM-negative subjects (HR=1.131; 95% CI: 1.094-1.171) and non-significantly decreased among GLM-positive subjects (HR=0.985; 95% CI: 0.957-1.013). We found that more than 50% of CA-positive subjects had CAP in 4 years and higher FPG significantly increased and GLM significantly decreased the risks of CAP. Additionally, GLM and FPG demonstrated an interactive effect on CAP risks. It seems possible that GLM may induce effects beyond lowering glucose levels and subsequently lowers CAP risks.

Deep Learning-Based Detection of Carotid Plaques Informs Cardiovascular Risk Prediction and Reveals Genetic Drivers of Atherosclerosis.

Atherosclerotic cardiovascular disease, the leading cause of global mortality, is driven by lipid accumulation and plaque formation within arterial walls. Carotid plaques, detectable via ultrasound, are a well-established marker of subclinical atherosclerosis. In this study, we trained a deep learning model to detect plaques in 177,757 carotid ultrasound images from 19,499 UK Biobank (UKB) participants (aged 47-83 years) to assess the prevalence, risk factors, prognostic significance, and genetic architecture of carotid atherosclerosis in a large population-based cohort. The model demonstrated high performance metrics with accuracy, sensitivity, specificity, and positive predictive value of 89.3%, 89.5%, 89.2%, and 82.9%, respectively, identifying carotid plaques in 45% of the population. Plaque presence and count were significantly associated with future cardiovascular events over a median follow-up period of up to 7 years, leading to improved risk reclassification beyond established clinical prediction models. A genome-wide association study (GWAS) meta-analysis of carotid plaques (29,790 cases, 36,847 controls) uncovered two novel genomic loci (p < 5×10 -8 ) with downstream analyses implicating lipoprotein(a) and interleukin-6 signaling, both targets of investigational drugs in advanced clinical development. Observational and Mendelian randomization analyses showed associations between smoking, low-density-lipoprotein (LDL) cholesterol, and high blood pressure and the odds of carotid plaque presence. Our study underscores the potential of carotid plaque assessment for improving cardiovascular risk prediction, provides novel insights into the genetic basis of subclinical atherosclerosis, and offers a valuable resource for advancing atherosclerosis research at the population scale.

Calculated whole blood viscosity in non-diabetic subjects with asymptomatic carotid atherosclerosis: How insulin resistance may affect blood viscosity.

Asymptomatic atherosclerosis is an important early marker of vascular damage and, among its risk factors, hemorheological alterations play an important role. In a cohort of 85 non-diabetic subjects with asymptomatic carotid atherosclerosis (ACA), we have measured whole blood viscosity (cWBV) according to the haematocrit and plasma fibrinogen level. The cWBV distinguish the subgroup of ACA subjects with 3-5 cardiovascular risk factors (CRFs) from that with 1-2 CRFs and the same behavior is present for haematocrit and plasma fibrinogen level. Therefore, we divided the whole group of ACA subjects according to the medians of the four surrogate indexes with an insulin resistance degree of TG/HDL-C, TyG, VAI and LAP. The analysis of the correlation between cWBV and each index of insulin resistance has shown that no correlation is present in the whole group and in the group of ACA subjects with 1-2 CRFs, while in the subgroup with 3-5 CRFs there is a positive correlation between cWBV with TG/HDL-C and TyG at a low degree of statistical significance. The date underline that subjects with this clinical condition have an unaltered evaluation of the cWBV compared to the other indices.

Citrullination Accompanies the Development of Carotid Atherosclerotic Plaques.

Citrullination represents a post-translational modification primarily mediated by peptidylarginine deiminase (PADI) 2 and 4 and resulting in the conversion of positively charged peptidylarginine to neutrally charged peptidylcitrulline. Molecular consequences of citrullination include the generation of neoepitopes which provoke the production of autoantibodies implicated in the development of autoimmune diseases. As citrullination initiates, promotes, and is enhanced by aseptic inflammation which plays a pivotal role in atherosclerosis, we proposed that citrullination might accompany the development of atherosclerotic vascular disease. To investigate features and patterns of citrullination in atherosclerotic plaques. We collected carotid atherosclerotic plaques (n = 14) and adjacent arterial segments (n = 14) which were pairwise excised during the carotid endarterectomy. The tissues were examined employing proteomic profiling (ultra-high performance liquid chromatography-tandem mass spectrometry analysis), haematoxylin and eosin staining, Western blotting and immunofluorescence staining for peptidylcitrulline, PADI2, and PADI4, and gene expression analysis. To better explore the mechanisms of citrullination in the neointima, we have also stained excised plaques for the extracellular vesicle markers (CD9 and CD81) and assessed co-localisation of PADI2 (a citrullination marker) with CD81 (an extracellular vesicle marker). In order to study the systemic response to citrullination in an atherosclerotic vascular disease setting, we measured the level of anti-citrullinated protein antibodies in the serum of patients with ischaemic stroke and healthy volunteers. Proteomic profiling found 213 plaque-specific and 111 intact arteria-specific proteins, as well as 46 proteins and 13 proteins which have been respectively upregulated or downregulated in plaques as compared with the adjacent intact segments. Among the top 20 upregulated proteins were atherogenic apolipoprotein B-100, iron-associated protein haptoglobin, and matrix metal-loproteinase-9, together indicating the advanced stage of plaque progression. In comparison with the intact arterial segments, plaques demonstrated protein signatures of innate immune response and oxidative stress, suggesting aseptic inflammation as a driver of atherosclerotic vascular disease. Both peptidylcitrulline and PADI2 have been abundant in the neointima but negligible in tunica media; further, the levels of peptidylcitrulline, PADI2, and PADI4 were elevated in plaque lysates in comparison with those from adjacent arterial segments (p = 0.025, 0.025, and 0.010, respectively). Notably, PADI2 and peptidylcitrulline were co-localised with the cells in the neointima and a considerable proportion of PADI2 was co-localised with CD81-positive extracellular vesicles (p = 0.003). Albeit citrullinated histone H3 and myeloperoxidase showed higher signal in the neointima than in tunica media (p = 0.048 and 0.023, respectively), we did not observe any signs of neutrophil extracellular traps (e.g., unwound chromatin or co-localisation of citrullinated histone H3 with neutrophil elastase) in the plaque tissue. Serum anti-citrullinated protein antibodies were not elevated in patients with ischaemic stroke (p = 0.71), suggesting that vascular citrullination likely does not trigger a generalised immune response. The development of carotid atherosclerosis is associated with citrullination, although it represents a local rather than systemic phenomenon in this clinical scenario.

Nomogram for predicting asymptomatic intracranial atherosclerotic stenosis in a neurologically healthy population

Asymptomatic intracranial atherosclerotic stenosis (aICAS) is a major risk factor for cerebrovascular events. The study aims to construct and validate a nomogram for predicting the risk of aICAS. Participants who underwent health examinations at our center from September 2019 to August 2023 were retrospectively enrolled. The participants were randomly divided into a training set and a testing set in a 7:3 ratio. Firstly, in the training set, least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were performed to select variables that were used to establish a nomogram. Then, the receiver operating curves (ROC) and calibration curves were plotted to assess the model’s discriminative ability and performance. A total of 2563 neurologically healthy participants were enrolled. According to LASSO-Logistic regression analysis, age, fasting blood glucose (FBG), systolic blood pressure (SBP), hypertension, and carotid atherosclerosis (CAS) were significantly associated with aICAS in the multivariable model (adjusted P < 0.005). The area under the ROC of the training and testing sets was, respectively, 0.78 (95% CI: 0.73–0.82) and 0.65 (95% CI: 0.56–0.73). The calibration curves showed good homogeneity between the predicted and actual values. The nomogram, consisting of age, FBG, SBP, hypertension, and CAS, can accurately predict aICAS risk in a neurologically healthy population.

POSSIBILITIES OF RADIOLOGICAL SCAN METHODS WITH POST-PROCESSING IMAGE RECONSTRUCTION IN THE ASSESSMENT OF ATHEROSCLEROTIC PLAQUES OF THE CAROTID ARTERIES

The aim. To establish the informativeness of the methods of computed tomography angiography, ultrasound diagnostics and magnetic resonance arteriography without contrast in patients with atherosclerosis of carotid arteries. Materials and methods. During July 2022 - July 2024, 82 male patients were examined on the basis of the Neurological Pathology Diagnostic Center of the KNP "Regional Clinical Hospital of the Ivano-Frankivsk Regional Council". Forty-six of them were included in the study group with clinical signs of atherosclerotic lesions of the carotid arteries. Thirty-six patients with asymptomatic course of the carotid arteries atherosclerosis were chosen as the control group. Patients of both groups were aged 51-79 years, and were homogeneous in terms of concomitant diseases, duration of smoking and lipidogram results. Exclusion criteria from both cohorts were: the presence of arrhythmia, radiation treatment of oncological processes in the projection of the head and neck, diagnosed Alzheimer's disease or Fara's disease, lack of written informed consent to participate in the study, impaired legal capacity of the person, when the written consent cannot be considered truly conscious. CTA was performed using a 160-slice computer tomograph Aquilion Prime Toshiba Scanner TSX-302A (Toshiba) with SUREPlaque software to analyze atherosclerotic plaques and vessels in the Carotid CTA fast scanning mode. MRI of the head and neck with non-contrast MR-arteriography was performed using a 1.5 Tesla Phillips Achieva device using blood flow imaging sequences: s3DI MC (three-dimensional time of flight MR-angiography). Ultrasound of the carotid arteries was performed using the Esaote MyLab9eXP device using B-mode, Doppler mapping and elastography. Atherosclerotic plaques were assessed according to the new imaging-based classification - Carotid Plaque-RADS from 2024. The results. According to the classification of Carotid Plaque-RADS, the following results were obtained according to visualization by ultrasound and CT methods: a combination of plaques of categories from Plaque-RADS 2 to Plaque-RADS 4, considering the types of each category, was detected in patients of both groups. There was no significant difference between the groups in the assessment of the structure of the atherosclerotic plaque (p=0.616). For the study group, the detection of the higher percentage of the stenotic lumen of the vessel was statistically different (median - 68.5% (interquartile range 9.75%)) compared to the control group (median - 60.0% (interquartile range 7.5%)) (p =0.048). A comparison of the degree of stenosis by ultrasound and CTA methods was carried out, where a direct correlation of very high strength according to the Chaddock scale was established (r=0.934 (confidence interval: 0.881 – 0.964), p˂0.001). Atherosclerotic lesions were characterized by indirect signs on MRI, namely: wall filling defects, which most likely correspond to plaques, increased bends of main arteries. Conclusions. Ultrasound diagnostics and reconstructive post-processing capabilities of computed tomography were practically equivalent in assessing the degree of stenosis with high correlation strength (r=0.934) and highly informative images of atherosclerotic masses of carotid arteries, while non-contrast magnetic resonance arteriography allowed to suspect atherosclerotic lesions as an area of ​​a filling defect without detailed tissue structures.

Frank’s Sign which is a Marker of Coronary Heart Disease

In today's clinical practice, the importance of a thorough clinical examination of the patient is emphasised in the article. There are 2 real-world instances of diagonal earlobe creases, commonly referred to as Frank's sign. The patients in both cases have ischemic heart disease, however they differ in terms of age and Frank's sign severity. Data from the literature are presented regarding the frequency of Frank's disease in various population groups, as well as its clinical importance and potential underlying pathophysiological causes. In the medical literature, the diagonal ear lobe crease (DELC) is termed as a substitute sign that can detect high-risk individuals with hidden atherosclerosis. However, there hasn't been any research on this subject in the dentistry or medical literature. Most clinical, angiography, and postmortem data are in favour of the idea that DELC is a useful extravascular physical marker that can determine individuals who are at risk of dying from coronary artery atherosclerosis. Some research findings have failed to support the theory linking DELC to certain health conditions. However, recent studies utilizing B mode ultrasonography have indicated a connection between DELC and the development of carotid artery atherosclerosis. Another study has also associated DELC with the existence of calcified carotid artery atheromas visible on panoramic radiographs. Notably, DELC is highly noticeable on head and neck oncology screening examinations. When the patient's vital signs, medical examination, and panoramic radiograph are combined, the results are DELC can aid to assess the patient's risk of atherosclerosis.

ADAMTS7 Promotes Smooth Muscle Foam Cell Expansion in Atherosclerosis.

Human genetic studies have repeatedly associated ADAMTS7 with atherosclerotic cardiovascular disease. Subsequent investigations in mice demonstrated that ADAMTS7 is proatherogenic and induced in response to vascular injury and that the proatherogenicity of ADAMTS7, a secreted protein, is due to its catalytic activity. However, the cell-specific mechanisms governing ADAMTS7 proatherogenicity remain unclear. To determine which vascular cell types express ADAMTS7, we interrogated single-cell RNA sequencing of human carotid atherosclerosis and found ADAMTS7 expression in smooth muscle cells (SMCs), endothelial cells (ECs), and fibroblasts. We subsequently created SMC- and EC-specific Adamts7 conditional knockout and transgenic mice. Conditional knockout of Adamts7 in either cell type is insufficient to reduce atherosclerosis, whereas transgenic induction in either cell type increases atherosclerosis. In SMC transgenic mice, this increase coincides with an expansion of lipid-laden SMC foam cells and decreased fibrous cap formation. RNA-sequencing in SMCs revealed an upregulation of lipid uptake genes typically assigned to macrophages. Subsequent experiments demonstrated that ADAMTS7 increases SMC oxLDL uptake through increased CD36 levels. Furthermore, Cd36 expression is increased due to increased levels of PU.1, a transcription factor typically associated with myeloid fate determination. In summary, Adamts7 expression in either SMCs or ECs promotes SMC foam cell formation and atherosclerosis. In SMCs, ADAMTS7 promotes oxLDL uptake via increased PU.1 and Cd36 expression, thereby increasing SMC foam cell formation and atherosclerosis.

Combining Computational Fluid Dynamics, Structural Analysis, and Machine Learning to Predict Cerebrovascular Events: A Mild ML Approach

Background/Objectives: Cerebrovascular events, such as strokes, are often preceded by the rupture of atherosclerotic plaques in the carotid arteries. This work introduces a novel approach to predict the occurrence of such events by integrating computational fluid dynamics (CFD), structural analysis, and machine learning (ML) techniques. The objective is to develop a predictive model that combines both imaging and non-imaging data to assess the risk of carotid atherosclerosis and subsequent cerebrovascular events, ultimately improving clinical decision-making. Methods: A multidisciplinary approach was employed, utilizing 3D reconstruction techniques and blood-flow simulations to extract key plaque characteristics. These were combined with patient-specific clinical data for risk evaluation. The study involved 134 asymptomatic individuals diagnosed with carotid artery disease. Data imbalance was addressed using two distinct approaches, with the optimal method chosen for training a Gradient Boosting Tree (GBT) classifier. The model’s performance was evaluated in terms of accuracy, sensitivity, specificity, and ROC AUC. Results: The best-performing GBT model achieved a balanced accuracy of 88%, with a ROC AUC of 0.92, a sensitivity of 0.88, and a specificity of 0.91. This demonstrates the model’s high predictive power in identifying patients at risk for cerebrovascular events. Conclusions: The proposed method effectively combines CFD, structural analysis, and ML to predict cerebrovascular event risk in patients with carotid artery disease. By providing clinicians with a tool for better risk assessment, this approach has the potential to significantly enhance clinical decision-making and patient outcomes.

Elevated Concurrent Carotid Atherosclerosis Rates in Patients with metabolic dysfunction-associated fatty liver disease (MAFLD) Compared to non-alcoholic fatty liver disease (NAFLD): A Cross-sectional Observational Study

Background and AimNon-alcoholic fatty liver disease (NAFLD) has been recognized as an independent risk factor for atherosclerotic cardiovascular disease. Recently, there has been a shift towards diagnosing metabolic dysfunction-associated fatty liver disease (MAFLD), offering simplified criteria and improved risk assessment. However, the association between MAFLD and carotid atherosclerosis remains poorly understood. Methods and ResultsThe study analyzed the association of concurrent carotid atherosclerosis between NAFLD and MAFLD patients with a retrospective cohort design. The study enrolled participants who underwent abdominal and carotid artery ultrasounds from a medical center in Taiwan. NAFLD and MAFLD were diagnosed based on imaging and specific criteria. Associations between NAFLD, MAFLD, and carotid atherosclerosis were analyzed using logistic regression.Among 11,194 participants, 57.1% were diagnosed with fatty liver disease, among which the NAFLD-MAFLD group comprised 4,689 individuals, with 900 in the NAFLD-only group and 669 in the MAFLD-only group. Significant demographic and clinical differences were observed between groups. Logistic regression showed that the MAFLD-NAFLD group and MAFLD-only group had significantly higher odds of concomitant carotid atherosclerosis. Among MAFLD patients, 65.5% had concurrent carotid arteriosclerosis with an odds ratio of 2.35 compared to non-MAFLD patients. The odds ratios for variables in MAFLD patients, such as diabetes mellitus, Fibrosis-4(FIB-4), number of FIB-4 > 1.3, and number of NAFLD fibrosis score > -1.455 were all greater than 2. ConclusionsMAFLD is associated with a higher prevalence of carotid atherosclerosis, compared to NAFLD. This suggests that MAFLD may serve as a significant risk factor for cardiovascular complications.

Intraplaque hemorrhage volume in patients with carotid atherosclerosis: How informative is it?

Background and purposeIntraplaque hemorrhage (IPH) of carotid atherosclerosis is an important feature in complex lesions preceding acute stroke events. The current study aimed to determine the role played by IPH volume compared to that of carotid stenosis or maximal wall thickness in patients with carotid IPH. Materials and methodsThis retrospective study included 233 patients who presented with carotid IPH on vessel wall imaging (VWI). We divided the patients into symptomatic or asymptomatic groups based on territorial acute focal infarction. The IPH volume, degree of stenosis, and maximal wall thickness on VWI were analyzed. ResultsOf the 233 included patients with carotid IPH, 51 (21.9%) patients showed initial clinical symptoms and positive territorial findings on diffusion-weighted imaging (DWI). Moreover, 154 (66.1%) patients had low-grade stenosis below 50% (n = 19: symptomatic groups). Overall, carotid IPH volume, degree of stenosis, and maximal wall thickness were all significantly higher in the symptomatic groups (p = 0.001). The degree of stenosis, in all patients and especially in those with high-grade stenosis above 50%, was significantly correlated with territorial acute focal infarction on multivariate analysis (p < 0.01). In patients with low-grade stenosis below 50%, maximal wall thickness was associated with territorial acute focal infarction (p = 0.48). ConclusionCarotid IPH volume was a risk factor for territorial acute focal infarction. However, in patients with high-grade stenosis, the degree of stenosis was significantly linked to acute stroke. By contrast, in patients with low-grade stenosis, maximal wall thickness exhibited a significant association with acute stroke.

Incidence of Carotid Wall Irregularities in Acute Ischemic Stroke Patients: A Descriptive Analysis.

Background Carotid wall abnormalities are significant predictors of cardiovascular events, including ischemic stroke. Identifying the clinical and biochemical risk factors associated with these abnormalities can aid in early intervention and prevention strategies. This study aimed to assess the association between lipid profiles, age, gender, smoking habits, hypertension, and carotid wall abnormalities in patients. Methodology A cross-sectional study was conducted on 60 patients, evaluating their clinical and biochemical profiles, including lipid levels, age, gender, smoking status, and the presence of hypertension. Carotid intima-media thickness was measured using ultrasound to identify carotid wall abnormalities. The data were analyzed to determine the associations between these factors and the presence of carotid wall abnormalities. Results Carotid wall abnormalities were present in 78.3% (n = 47) of the patients. Individuals with carotid wall irregularities exhibited markedly elevated total cholesterol concentrations (175 ± 35.0 mg/dl) compared to those without abnormalities (150 ± 31.0 mg/dl) (p = 0.007). The mean age was 64.0 ± 8.0 years in the abnormality group versus 56.0 ± 5.0 years in the non-abnormality group (p = 0.008). Males constituted 80.0% of the abnormality group, compared to 46.7% in the non-abnormality group (p = 0.03). This higher prevalence of carotid wall abnormalities in males could be related to gender-specific risk factors, such as higher rates of smoking and hypertension, both of which were more common in the abnormality group and are known contributors to vascular changes. Smoking (70% vs. 20%, p = 0.0005) and hypertension (85% vs. 40%, p = 0.0005) were significantly more prevalent in individuals with carotid wall abnormalities. Conclusions This study highlights the significant association between elevated total cholesterol, older age, male gender, smoking, and hypertension with carotid wall abnormalities. These findings emphasize the importance of early detection and management of these risk factors to prevent the progression of carotid atherosclerosis and reduce the risk of ischemic stroke and other cardiovascular events.

Chronic Ischemic Gastritis in a Patient With a History of Cancer and Atherosclerotic Disease

ABSTRACT Chronic mesenteric ischemia is an uncommon disease presenting with nonspecific symptoms. The large number of differential diagnoses may result in diagnostic delays and progression to acute mesenteric ischemia. A 74-year-old woman with a history of breast cancer and carotid atherosclerosis complained of postprandial abdominal pain, vomiting, and weight loss. Endoscopic examination showed active chronic gastritis Helicobacter pylori negative. Contrast-enhanced computed tomography revealed stenosis in the mesenteric arterial district. Chronic gastritis resistant to treatment in a patient complaining of postprandial abdominal pain and weight loss should be investigated for chronic mesenteric ischemia, although history of cancer could be a misleading factor.

Hand Osteoarthritis and Subclinical Cardiovascular Disease in Middle-Aged Women.

Objective: To determine subclinical cardiovascular disease (sCVD) in middle-aged women with clinically manifested hand osteoarthritis (HOA) and to improve the characterization of cardiovascular risk in this population. Design: We cross-sectionally evaluated the relationship between HOA and sCVD in 1,803 volunteers from the Mexican Teachers' Cohort. From 2012 to 2016, a subsample from Mexico City, the Northern state Nuevo León, and the Southern states Chiapas and Yucatán was invited for clinical evaluations, during which neurologists examined carotid arteries using ultrasound, and a standardized HOA questionnaire was also administered. HOA was defined as age ≥45 years, hand joint pain, and morning stiffness that lasted no longer than 30 minutes. sCVD was assessed using the intima-media thickness (IMT) and atherosclerotic plaques. Results: Among participants with a mean age of 51 years (±4), 18.4% met the criteria for HOA, and the prevalence of carotid atherosclerosis was 23.1%. After multivariable adjustment, women diagnosed with HOA had a 1.8% (95% confidence interval [CI] 0.3, 3.3) greater mean IMT than those without this joint disease. Similarly, women with HOA had 36% (95% CI 1.01, 1.84) higher odds of carotid atherosclerosis. Conclusions: HOA is associated with sCVD in middle-aged women. This relationship might be due to low-grade chronic inflammation; however, further research is required to clarify the underlying mechanisms.

Subclinical carotid atherosclerosis in gouty patients: relation to musculoskeletal ultrasonographic findings and serum sclerostin level

Objectives. To detect subclinical carotid atherosclerosis in gout patients and its relation to musculoskeletal ultrasound (MSK US) manifestations and serum sclerostin (SCL) levels. Patients and methods. Thirty Egyptian gouty patients were classified into two groups: Group A included 15 patients with diagnostic MSK US manifestations of gout (double contour sign), and Group B included 15 patients without MSK US findings. MSK US was done for both knees and the first MTP joints. Carotid duplex ultrasonography was done to evaluate carotid intima-media-thickness (CIMT) and serum SCL level was measured in all patients by ELISA technique. Results. Gouty patients with MSK US findings had a significantly higher increase in serum SCL levels than those without MSK US findings (p &lt;0.01). Group A patients had a significantly greater CIMT than patients of group B (p &lt;0.01). Serum uric acid and SCL levels were found to be significantly positively correlated. The ROC curve revealed that the optimal SCL cutoff value for detecting positive MSK US findings in gout patients was &gt;25.05 ng/ml. At this level, there was a significant difference between the patients with a CIMT &gt;0.9 mm and the patients with a CIMT ≤0.9 mm (p &lt;0.05). Conclusions. Patients with MSK US manifestations of gout are more liable to have subclinical carotid atherosclerosis than patients without these manifestations. SCL at a certain level &gt;25.05 ng/ml in gout patients might predispose patients to radiographic findings of MSK US of gout and subclinical atherosclerosis.

The Relationship Between NLRP3 Inflammasome and Its Downstream Inflammatory Factors in Obstructive Sleep Apnea Patients with Carotid Atherosclerosis Under Cigarette Exposure

Aim: To study the relationship between NLRP3 (nucleotide oligomerization domain [NOD]-, leucine-rich repeats [LRR]-, and pyrin domain-containing protein 3) inflammasome and its downstream inflammatory factors in obstructive sleep apnea (OSA) patients with carotid atherosclerosis (CAS) under cigarette exposure, further exploring the risk factors of CAS in OSA patients. Methods: A total of 109 adult males who underwent polysomnography and carotid artery ultrasonography in our hospital from October 2019 to December 2021 were selected. According to the detection results, they were divided into the OSA group, the CAS group, and the OSA combined CAS group; additionally, 29 healthy subjects who underwent a physical examination were also included. According to whether they were smoking, the groups were further divided into smoking and non-smoking groups. The age, body mass index (BMI), blood pressure, apnea-hypopnea index (AHI), lowest blood oxygen saturation (LSaO2), carotid intima-media thickness (CIMT), levels of blood sugar, blood low-density lipoprotein cholesterol (LDLc), and serum NLRP3, interleukin-1β (IL-1β), and interleukin-18 (IL-18) of all subjects were recorded. Results: The OSA combined CAS group had higher LDLc levels and AHI and lower LSaO2 than the OSA group and CAS group. The levels of serum NLRP3, IL-1β, and IL-18 in the OSA group were higher than those in the normal control group (P &lt; 0.05); and those in the OSA combined CAS group were higher than the OSA group and CAS group (P &lt; 0.05), regardless of cigarette exposure. Considering cigarette exposure, serum NLRP3, IL-1β, and IL-18 levels were higher in the OSA, CAS, and OSA combined CAS smoking groups than those in the non-smoking group (P &lt; 0.05). Under cigarette exposure, AHI, LDLc, NLRP3, IL-1β, and IL-18 were significantly positively correlated (P &lt; 0.05), and LSaO2 was negatively correlated with CAS in OSA (P &lt; 0.05). AHI, LSaO2, LDLc, NLRP3, and IL-1β are the risk factors for OSA combined with CAS. Conclusion: LSaO2, AHI, LDLc, NLRP3, and IL-1β are the important risk factors for OSA combined with CAS under cigarette exposure, and their levels can be used to predict the occurrence of CAS in OSA.

Relationships of Leg Ischemia Symptoms and Carotid Artery Atherosclerosis with Hypertensive-Disorders-of-Pregnancy-Associated Peptides in Patients with Lower Extremity Arterial Disease.

Objectives: We have proposed seven peptides with low molecular weights in blood as biomarkers for the diagnosis of hypertensive disorders of pregnancy (HDP). The purpose of this cross-sectional study was to investigate the relationships of the HDP-associated peptides with symptoms of leg ischemia and degree of atherosclerosis in patients with lower extremity arterial disease (LEAD). Methods: The subjects were 165 outpatients with LEAD (145 men and 20 women aged 74.3 ± 8.1 years [47-93 years]). Their symptoms of leg ischemia, leg arterial flow, and degree of atherosclerosis were evaluated using the Rutherford classification of Clinical Ischemia Category, ankle-brachial index (ABI) and the intima-media thickness (IMT) of carotid arteries, respectively. Serum concentrations of the HDP-related peptides were measured by mass spectrometry. Results: The grade of the Rutherford classification was positively associated with levels of the peptides with m/z 2091 and 2378 and was inversely associated with levels of the peptide with m/z 2081. The category of the Rutherford classification was inversely associated with ABI. There were no HDP-associated peptides that showed significant relationships with IMT. Conclusions: The peptides with m/z 2081, 2091, and 2378 are possible biomarkers of leg ischemia but are not associated with carotid atherosclerosis in LEAD patients.

Non-alcoholic fatty liver disease: A new predictor of recurrent ischemic stroke and transient ischemic attack in patients with carotid atherosclerosis

PurposeNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. This study focused on assessing the predictive significance of NAFLD for recurrent stroke and transient ischemic attack (TIA) risk to determine the value of NAFLD. MethodThis study included 742 participants (mean age: 64.26 ± 9.42 years, 497 males) with carotid atherosclerosis who underwent carotid CT angiography (CTA) between January 2013 and December 2021 in this retrospective study. NAFLD was diagnosed by non-enhanced abdominal CT. The clinical endpoint was a recurrent ischemic stroke or TIA. Cox proportional hazards and Kaplan-Meier analysis assessed whether NAFLD was associated with the endpoint. We accessed the predictive values of NAFLD, clinical, plaque characteristics, and combined model by the C statistics. The predictive performance of the combined model was assessed by receiver operating characteristic curve (ROC) analysis. ResultsA total of 742 participants (mean age: 64.26 ± 9.42 years, 497 males) were included. During 2.9 years of follow-up (interquartile range, 2.1–3.9), 166 patients reached the clinical endpoint. Multivariable cox analyses showed NAFLD was associated with recurrent stroke or TIA in all groups (all P<0.05). Patients with NAFLD had a lower event-free survival (EFS) rate than those without NAFLD (P<0.05). The combined model, including NAFLD, clinical data and plaque features, showed the best performance in predicting the clinical endpoint (AUC=0.79). ConclusionsNAFLD contributes to the prediction of recurrent ischemic stroke or TIA. NAFLD may be a novel imaging marker that offers a new perspective on preventing cardiovascular disease in the clinic.

&lt;i&gt;CDKN2B-AS1&lt;/i&gt; polymorphism rs1333049 is associated with advanced carotid artery atherosclerosis in a Slovenian population

Several studies have reported an association between the 9p21 region in the human genome and atherosclerosis. The rs1333049 polymorphism is a single nucleotide polymorphism (SNP) in CDKN2B-AS1, located in the 9p21 region. The aim of our study was to investigate the association between the rs1333049 polymorphism and advanced carotid atherosclerosis, as well as its effect on CDKN2B expression in endarterectomy sequesters. In our case-control study, we included 881 participants, divided into two groups. The case group comprised 308 participants with advanced atherosclerosis of the internal or common carotid artery (stenosis &gt; 75 %) who underwent a revascularization procedure. The control group included 573 participants without hemodynamically significant carotid atherosclerosis. We analyzed the rs1333049 polymorphism using the StepOne real-time polymerase chain reaction (PCR) and TaqMan SNP genotyping assay. We found a statistically significant association according to the co-dominant (P=0.014, OR=3.29, 95% CI: 1.32-8.91, and P=0.015, OR=2.50, 95% CI: 1.22-5.37) and dominant (P=0.006, OR=2.74, 95% CI: 1.36-5.71) models. We performed immunohistochemical analysis of CDKN2B expression on 26 endarterectomy sequesters. The C allele of rs1333049 was associated with a lower numerical area density of CDKN2B-positive cells in atherosclerotic plaques. In conclusion, the C allele of the rs1333049 SNP is associated with an increased risk of developing advanced carotid atherosclerosis and lower CDKN2B expression in the plaques.