Redefining the exact roles and importance of carotid intima-media thickness and carotid plaque thickness in predicting cardiovascular events.

OBJECTIVE: The survey aimed to evaluate the precise roles and importance of carotid plaque thickness and carotid intima-media thickness measured in plaque-free areas (PF CC-IMTmean) in future cardiovascular risk prediction. MATERIAL AND METHODS: 188 respondents between the age of 46 and 87 divided into two groups (I group - 94 respondents without plaques with CIMT measurement and II Group 94 respondents with carotid plaques; 118 men and 70 women; mean age ± SD, 61.80 ± 5.49) were prospectively examined by the carotid ultrasound Doppler (carotid measurements included plaque thickness PT - nonstenotic plaques (carotid stenosis <50%) and stenotic culprit plaques (carotid stenosis ≥50%), mean CIMT and maximum CIMT). Subjects were followed for 36 months from the inclusion in the study (regular control examinations). Data were recorded on new cases of mortality (CV mortality) and adverse CV events (myocardial infarction - -MI, surgical or endovascular revascularization - coronary or stroke). RESULTS: In this study, CIMT values vary between 0.62 and 1.43 mm (mean CIMT = 1.21 ± 0.2 mm) while 52 subjects had nonstenotic plaques (14 respondents plaque ulceration, 22 type 2 diabetes mellitus, 38 arterial hypertension) and 38 subjects had stenotic culprit plaques (17 respondents plaque ulceration, 20 type 2 diabetes mellitus, 31 arterial hypertension). After 36 months of follow-up, 76 vascular events were noted (MI, transient ischaemic attack - TIA, stroke and cardiovascular angioplasty or surgery) in this period. CONCLUSION: Respondents with carotid plaques had higher cardiovascular events occurrence (p < .01, high statistical difference). Carotid plaques as a parameter have higher predictive vascular event value importance than CIMT. Of note, stenotic plaques, the presence of ulceration on the free surface of the plaque, type 2 diabetes mellitus and hypertension were connected with the highest events occurrence.

Cardiometabolic risk factors in MASLD patients with HCC: the other side of the coin.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) constitutes the commonest cause of chronic liver disorder worldwide, whereby affecting around one third of the global population. This clinical condition may evolve into Metabolic Dysfunction-Associated Steatohepatitis (MASH), fibrosis, cirrhosis and hepatocellular carcinoma (HCC), in a predisposed subgroup of patients. The complex pathogenesis of MASLD is severely entangled with obesity, dyslipidemia and type 2 diabetes (T2D), so far so nutritional and lifestyle recommendations may be crucial in influencing the risk of HCC and modifying its prognosis. However, the causative association between HCC onset and the presence of metabolic comorbidities is not completely clarified. Therefore, the present review aimed to summarize the main literature findings that correlate the presence of inherited or acquired hyperlipidemia and metabolic risk factors with the increased predisposition towards liver cancer in MASLD patients. Here, we gathered the evidence underlining the relationship between circulating/hepatic lipids, cardiovascular events, metabolic comorbidities and hepatocarcinogenesis. In addition, we reported previous studies supporting the impact of triglyceride and/or cholesterol accumulation in generating aberrancies in the intracellular membranes of organelles, oxidative stress, ATP depletion and hepatocyte degeneration, influencing the risk of HCC and its response to therapeutic approaches. Finally, our pursuit was to emphasize the link between HCC and the presence of cardiometabolic abnormalities in our large cohort of histologically-characterized patients affected by MASLD (n=1538), of whom 86 had MASLD-HCC by including unpublished data.

Plasma proteins associate with carotid plaques and predict incident atherosclerotic cardiovascular events.

PURPOSE: Performing non-invasive carotid imaging is challenging, owing inter-operator variability and organizational barriers, but plasma proteomics can offer an alternative. We sought plasma proteins that associate with the presence of carotid plaques, their number and predict the incidence of clinically overt atherosclerotic cardiovascular events (ASCVD) above currently recognized risk factors in "apparently healthy" subjects. METHODS: We studied the plasma levels of 368 proteins in 664 subjects from the PLIC study, who underwent an ultrasound imaging screening of the carotids to check for the presence of plaques. We clustered, by artificial intelligence (A.I.), the proteins that associate with the presence, the number of plaques and that predict incident ASCVDs over 22 years (198 events were registered). FINDINGS: 299/664 subjects had at least 1 carotid plaque (1+) (77 with only one plaque, 101 with 2 plaques, 121 with ≥3 plaques (3+)). The remaining 365 subjects with no plaques acted as controls. 106 proteins were associated with 1+ plaques, but 97 proteins significantly predicted 3+ plaques only (AUC = 0.683 (0.601-0.785), p < 0.001), when considered alone. A.I. underscored 87 proteins that improved the performance of the classical risk factors both in detecting 3+ plaques (AUC = 0.918 (0.887-0.943) versus risk factors alone, AUC = 0.760 (0.716-0.801), p < 0.001) and in predicting the incident ASCVD (AUC = 0.739 (0.704-0.773) vs risk factors alone AUC = 0.559 (0.521-0.598), p < 0.001). The chemotaxis/migration of leukocytes and interleukins/cytokines signaling were biological pathways mostly represented by these proteins. DISCUSSION AND CONCLUSIONS: Plasma proteomics marks the number of carotid plaques and improve the prediction of incidence ASCVDs in apparently healthy subjects.

Serum Uric Acid, Hypertriglyceridemia, and Carotid Plaques: A Sub-Analysis of the URic Acid Right for Heart Health (URRAH) Study.

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ≥ 150 mg/dL. Higher levels of SUA (hSUA) were defined as ≥5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04-1.27], p < 0.001 and HR 1.25 [1.09-1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment. Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), and hSUA and hTG (38%) (Chi-square, 0.0001). Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1.341); p = 0.001], normal SUA and hTG [HR 1.305 (1.057 to 1.611); p = 0.001], and the combination of hUA and hTG [HR 1.539 (1.274 to 1.859); p = 0.001] were associated with a higher risk of plaque. Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single risk factors. The association between SUA and CVD events may be explained in part by a direct association of UA with carotid plaques.

A Radiomics-Based Nomogram Using Ultrasound Carotid Plaque Evaluation For Predicting Cerebro-Cardiovascular Events In Asymptomatic Patients.

RATIONALE AND OBJECTIVES: This study aims to assess whether a radiomics-based nomogram correlates with a higher risk of future cerebro-cardiovascular events in patients with asymptomatic carotid plaques. Additionally, it investigates the nomogram's contribution to the revised Framingham Stroke Risk Profile (rFSRP) for predicting cerebro-cardiovascular risk. MATERIALS AND METHODS: Predictive models aimed at identifying an increased risk of future cerebro-cardiovascular events were developed and internally validated at one center, then externally validated at two other centers. Survival curves, constructed using the Kaplan-Meier method, were compared through the log-rank test. RESULTS: This study included a total of 2009 patients (3946 images). The final nomogram was generated using multivariate Cox regression variables, including dyslipidemia, lumen diameter, plaque echogenicity, and ultrasonography (US)-based radiomics risk. The Harrell's concordance index (C-index) for predicting events-free survival (EFS) was 0.708 in the training cohort, 0.574 in the external validation cohort 1, 0.632 in the internal validation cohort, and 0.639 in the external validation cohort 2. The final nomogram showed a significant increase in C-index compared to the clinical, conventional US, and US-based radiomics models (all P < 0.05). Furthermore, the final nomogram-assisted method significantly improved the sensitivity and accuracy of radiologists' visual qualitative score of plaque (both P < 0.001). Among 1058 patients with corresponding 1588 plaque US images classified as low-risk by the rFSRP, 75 (7.1%) patients with corresponding 93 (5.9%) carotid plaque images were appropriately reclassified to the high-risk category by the final nomogram. CONCLUSION: The radiomics-based nomogram demonstrated accurate prediction of cerebro-cardiovascular events in patients with asymptomatic carotid plaques. It also improved the sensitivity and accuracy of radiologists' visual qualitative score of carotid plaque and enhanced the risk stratification ability of rFSRP. SUMMARY: The radiomics-based nomogram allowed accurate prediction of cerebro-cardiovascular events, especially ipsilateral ischemic stroke in patients with asymptomatic carotid atherosclerotic plaques. KEY RESULTS: The radiomics-based nomogram allowed accurate prediction of cerebro-cardiovascular events, especially ipsilateral ischemic stroke in patients with asymptomatic carotid atherosclerotic plaques. The radiomics-based nomogram improved the sensitivity and accuracy of radiologists' visual qualitative score of carotid plaque. The radiomics-based nomogram improved the discrimination of high-risk populations from low-risk populations in asymptomatic patients with carotid atherosclerotic plaques and the risk stratification capability of the rFSRP.

Association between pulse pressure and carotid plaques in old adults with uncontrolled hypertension: results from a community-based screening in Hangzhou, China.

BACKGROUND: There is a broad pulse pressure (PP) and a high prevalence of carotid plaques in old adults. Previous studies have indicated that PP is strongly associated with carotid plaque formation. This study aimed to explore this association in old adults with uncontrolled hypertension. METHODS: 1371 hypertensive patients aged ≥ 60 years with uncontrolled hypertension were enrolled in a community-based screening in Hangzhou, China. Carotid plaques were assessed using ultrasonography. Logistic regression models were used to estimate the association between PP and carotid plaques by odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Carotid plaques were detected in 639 (46.6%) of subjects. Multiple plaques were found in 408 (63.8%) and soft plaques in 218 (34.1%). Elevated PP was associated with a high prevalence of carotid plaques. After adjusting for traditional risk factors, compared to patients within the lowest tertile of PP, those within the highest tertiles had an increased risk of carotid plaques (OR 2.061, CI 1.547-2.745). For each 1-SD increase, the risk increased by 40.1% (OR 1.401, CI 1.237-1.587). There was a nonlinear association between PP and carotid plaques (P nonlinearity = 0.039). The risk increased rapidly after the predicted PP level reached around 60 mmHg. The associations were stronger among participants with multiple and soft plaques. CONCLUSIONS: Our findings suggested that PP was independently associated with carotid plaques in old adults with uncontrolled hypertension who have an increased risk of atherosclerosis.

Improving radiomic modeling for the identification of symptomatic carotid atherosclerotic plaques using deep learning-based 3D super-resolution CT angiography.

Rationale and objectives: Radiomic models based on normal-resolution (NR) computed tomography angiography (CTA) images can fail to distinguish between symptomatic and asymptomatic carotid atherosclerotic plaques. This study aimed to explore the effectiveness of a deep learning-based three-dimensional super-resolution (SR) CTA radiomic model for improved identification of symptomatic carotid atherosclerotic plaques. Materials and methods: A total of 193 patients with carotid atherosclerotic plaques were retrospectively enrolled and allocated into either a symptomatic (n = 123) or an asymptomatic (n = 70) groups. SR CTA images were derived from NR CTA images using deep learning-based three-dimensional SR technology. Handcrafted radiomic features were extracted from both the SR and NR CTA images and three risk models were developed based on manually measured quantitative CTA characteristics and NR and SR radiomic features. Model performances were assessed via receiver operating characteristic, calibration, and decision curve analyses. Results: The SR model exhibited the optimal performance (area under the curve [AUC] 0.820, accuracy 0.802, sensitivity 0.854, F1 score 0.847) in the testing cohort, outperforming the other two models. The calibration curve analyses and Hosmer-Lemeshow test demonstrated that the SR model exhibited the best goodness of fit, and decision curve analysis revealed that SR model had the highest clinical value and potential patient benefits. Conclusions: Deep learning-based three-dimensional SR technology could improve the CTA-based radiomic models in identifying symptomatic carotid plaques, potentially providing more accurate and valuable information to guide clinical decision-making to reduce the risk of ischemic stroke.

ABO Blood Groups, RhD Factor and Their Association with Subclinical Atherosclerosis Assessed by Carotid Ultrasonography.

Background: The ABO blood group system has previously been associated with cardiovascular disease (CVD), where non-O blood group individuals have shown an increased risk. Studies assessing early atherosclerotic disease while also including RhD are few. We aimed to determine whether the ABO and RhD blood groups are associated with subclinical atherosclerosis in a healthy population. Methods: We included 3532 participants from the VIPVIZA trial with available carotid ultrasonography results to assess subclinical disease. Information about blood groups was obtained from the SCANDAT-3 database, where 85% of VIPVIZA participants were registered. Results: RhD- individuals aged 40 years showed increased carotid intima-media thickness (B 1.09 CI 95% 1.03; 1.14) compared to RhD+ individuals. For ABO, there were no differences in ultrasonography results when assessing the whole study population. However, 60-year-old individuals with heredity for CVD and a non-O blood group had decreased odds for carotid plaques (OR 0.54 CI 95% 0.33; 0.88). Conclusions: RhD blood group is associated with subclinical atherosclerosis in younger individuals, indicating a role as a mediator in the atherosclerotic process. In addition, a non-O blood group was associated with decreased subclinical atherosclerosis in individuals aged 60 and with heredity (corresponding to the group with the highest atherosclerotic burden).

Clinical effects of atorvastatin combined with conbercept in the treatment of patients with macular edema secondary to retinal vein occlusion and carotid plaque: study protocol for a prospective randomized controlled trial.

INTRODUCTION: Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs have been widely used in patients with macular edema (ME) secondary to retinal vein occlusion (RVO); however, recurrence is a major concern. This study aims to observe the clinical effects of atorvastatin and intravitreal therapy in the treatment of patients with branch or central RVO-ME and coexistent carotid plaques (CP). METHODS AND ANALYSIS: A prospective randomized controlled clinical trial will be conducted. Sixty-four patients diagnosed with branch or central RVO-ME and coexistent CP will be enrolled and randomly allocated in a 1:1 ratio to the control and experimental groups. The control group will be treated with intravitreal conbercept monthly for 3 months, followed by monthly evaluation and injection of pro re nata (PRN) for 12 months, while the experimental group will be treated with oral atorvastatin 20 mg daily combined with the control group treatment. If a drop of best-corrected visual acuity (BCVA) is more than five Early Treatment Diabetic Retinopathy Study (ETDRS) letters (one line) or an increment in central subfield thickness (CSFT) of 100 µm (or a 10% increment from the previous visit), intravitreal re-treatment will be performed. Outcome measurements include CSFT, BCVA, number of injections, and incidence of adverse events during the 12-month follow-up period. Differences between groups will be evaluated using Student's t-test, and comparisons between groups will be evaluated using repeated-measures analysis of variance. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board of Nanjing Lishui People's Hospital, Nanjing, China (approval number 2023KY0418-12, dated 18 April 2023), and has been registered on chictr.org.cn. Written informed consent will be collected from each patient and the results of this trial will be submitted to a peer-reviewed journal. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300071359. Registered on 12 May 2023.

Phthalate exposure and subclinical carotid atherosclerosis: A systematic review and meta-analysis.

Phthalates may be associated with an increased risk of cardiometabolic diseases by interfering with glucose and lipid metabolism and by promoting adipogenesis. This study aimed to perform a systematic review and meta-analysis of the association between phthalate exposure and subclinical carotid atherosclerosis, using surrogate markers such as carotid intima-media thickness (IMT) and carotid plaques. The literature search was performed using four databases (Web of Science, Medline, PubMed, and Scopus), and this systematic review includes all available observational studies until July 6th, 2023. The Joanna Briggs Institute critical appraisal tool was used to assess the risk of bias. Meta-analyses were performed, and random effects models were used. Six high-quality cross-sectional studies and 2570 participants aged 12 to 70 were included. Six phthalate metabolites showed significant associations with subclinical carotid atherosclerosis. Exposure to MBzP, ΣDEHP, and MnBP was associated with increased carotid IMT. Exposure to MEP was associated with a higher prevalence of carotid plaques, and MiBP was associated with a lower prevalence. Mixed results were observed for MMP in older adults. The meta-analyses showed a high degree of heterogeneity, and the results are based on single studies. This study accurately describes the evidence of this association to date, suggesting that phthalates are associated with increased carotid IMT and a higher prevalence of carotid plaques. Further research is needed to elucidate this association, as phthalates are still used in the manufacture of everyday products, humans continue to be exposed to them, and atherosclerosis is a public health concern.

Traditional Cardiovascular Risk Factors Are Stronger Related to Carotid Intima-Media Thickness Than to Presence of Carotid Plaques in People Living With HIV.

Background Cardiovascular disease is a major cause of morbidity and mortality in people living with HIV, who are at higher risk than the general population. We assessed, in a large cohort of people living with HIV, which cardiovascular, HIV-specific, and lipoproteomic markers were associated with carotid intima-media thickness (cIMT) and carotid plaque presence. We also studied guideline adherence on lipid-lowering medication in individuals with high and very high risk for cardiovascular disease. Methods and Results In 1814 individuals with a median (interquartile range) age of 53 (44-60) years, we found a carotid plaque in 909 (50.1%) and a median (interquartile range) intima-media thickness of 0.66 (0.57-0.76) mm. Ultrasonography was used for the assessment of cIMT and plaque presence. Univariable and multivariable regression models were used for associations with cIMT and presence of plaques. Age, Black race, body mass index, type 2 diabetes, and smoking (pack years) were all positively associated with higher cIMT. Levels of high-density lipoprotein cholesterol, specifically medium and large high-density lipoprotein subclasses, were negatively associated with higher cIMT. Only age and prior myocardial infarction were positively related to the presence of a carotid plaque. Lipid-lowering treatment was prescribed in one-third of people living with HIV, who are at high and very high risk for cardiovascular disease. Conclusions Traditional cardiovascular risk factors were significantly associated with higher cIMT but not with carotid plaques, except for age. HIV-specific factors were not associated with both ultrasound measurements. Future studies are needed to elucidate which factors contribute to plaque formation. Improvement of guideline adherence on prescription of lipid-lowering treatment in high- and very high-risk patients for cardiovascular disease is recommended. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03994835.

Computed tomography angiography-based radiomics model to identify high-risk carotid plaques.

Background: Extracranial atherosclerosis is one of the major causes of stroke. Carotid computed tomography angiography (CTA) is a widely used imaging modality that allows detailed assessments of plaque characteristics. This study aimed to develop and test radiomics models of carotid plaques and perivascular adipose tissue (PVAT) to distinguish symptomatic from asymptomatic plaques and compare the diagnostic value between radiomics models and traditional CTA model. Methods: A total of 144 patients with carotid plaques were divided into symptomatic and asymptomatic groups. The traditional CTA model was built by the traditional radiological features of carotid plaques measured on CTA images which were screened by univariate analysis and multivariable logistic regression. We extracted and screened radiomics features from carotid plaques and PVAT. Then, a support vector machine was used for building plaque and PVAT radiomics models, as well as a combined model using traditional CTA features and radiomics features. The diagnostic value between radiomics models and traditional CTA model was compared in identifying symptomatic carotid plaques by Delong method. Results: The area under curve (AUC) values of traditional CTA model were 0.624 and 0.624 for the training and validation groups, respectively. The plaque radiomics model and PVAT radiomics model achieved AUC values of 0.766, 0.740 and 0.759, 0.618 in the two groups, respectively. Meanwhile, the combined model of plaque and PVAT radiomics features and traditional CTA features had AUC values of 0.883 and 0.840 for the training and validation groups, respectively, and the receiver operating characteristic curves of combined model were significantly better than those of traditional CTA model in the training group (P<0.001) and validation group (P=0.029). Conclusions: The combined model of the radiomics features of carotid plaques and PVAT and the traditional CTA features significantly contributes to identifying high-risk carotid plaques compared with traditional CTA model.

The Association Between Hemoglobin Glycation Index and Carotid Artery Plaque in Patients With Coronary Heart Disease.

This study aimed to examine the association between the hemoglobin glycation index (HGI) and carotid artery plaque (CAP) in patients with coronary heart disease (CHD). We conducted a cross-sectional analysis of 10,778 patients with CHD. The participants were divided into three groups by HGI tertiles (T1 HGI<-0.44, T2 -0.44 ≤ HGI ≤ 0.15, T3 HGI>0.15). The presence of CAP was used to diagnose by carotid ultrasonography. Logistic regression analysis was used to analyze the association between the HGI and CAP. The association between HGI and CAP was also assessed according to sex, age, smoking status, and drinking status. We further assessed the association between HGI and the ultrasound characteristics of CAP. The baseline analysis showed substantial differences in relevant parameters between the three groups of patients with CHD according to the tertiles of the HGI. Multivariate logistic regression analysis showed that HGI was significantly associated with CAP (odds ratio [OR] 1.32; 95% confidence interval [CI] 1.26-1.39). The association between HGI and CAP exists among different sex, age, smoking, and drinking status. Furthermore, there was a significant and positive association between HGI and all four different echogenicities of the CAP.

Association between soft drink consumption and carotid atherosclerosis in a large-scale adult population: The TCLSIH cohort study.

BACKGROUND AND AIMS: Carotid atherosclerosis indicates an increased risk for cardiac-cerebral vascular disease. Given the pattern of consumption in China, sugar-sweetened beverage is the main type of soft drink consumed. As soft drinks contain a high amount of fructose, they may be a risk factor of carotid atherosclerosis. A prospective cohort study was conducted to investigate the association between soft drink consumption and the incidence of carotid atherosclerosis in a Chinese adult population. METHODS AND RESULTS: A total of 3828 participants (men: 2007 and women: 1821) were included. Carotid atherosclerosis was measured by using ultrasonography and was defined by increased carotid intima-media thickness and/or carotid plaques. Soft drink consumption was assessed using a validated food frequency questionnaire. Cox proportional hazards regression analysis was used to assess the association of soft drink consumption categories with the incidence of carotid atherosclerosis. During a mean follow-up of 3.20 years, 1009 individuals of the 3828 eligible participants developed carotid atherosclerosis. After adjusting for potential confounding factors, we compared the higher levels to the lowest level of soft drink consumption in women, and we estimated the multivariable hazard ratios and 95% confidence intervals of incident carotid atherosclerosis to be 1.09 (0.80, 1.50), and 1.56 (1.14, 2.13) (P for trend <0.05). However, there was no significant association between soft drink consumption and the incidence of carotid atherosclerosis in men or total population. CONCLUSION: The result indicated that soft drink consumption was associated with a higher incidence of carotid atherosclerosis in women. TRIAL REGISTERED: UMIN Clinical Trials Registry. TRIAL REGISTRATION NUMBER: UMIN000027174. TRIAL REGISTRATION WEBSITE: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031137.

Increased circulating levels of MIP-1α and CD14 are associated with the presence of severe stenosis and hypoechoic plaques in patients with carotid atherosclerosis.

OBJECTIVE: Carotid atherosclerosis, a major cause of ischemic cerebrovascular events, is characterized by a pro-inflammatory and pro-oxidant vascular microenvironment. The current risk score models based on traditional risk factors for cardiovascular risk assessment have some limitations. The identification of novel blood biomarkers could be useful to improve patient management. The aim of the study was to evaluate the association of selected inflammation- and oxidative stress-related markers with the presence of severe stenosis and/or vulnerable plaques. METHODS: Circulating levels of soluble CD40 ligand, interleukin-10, macrophage inflammatory protein (MIP)-1α, endoglin, CD163, CD14, E-selectin, tumor necrosis factor-α, monocyte chemoattractant protein-1, C-Reactive protein, CD40 L + T lymphocytes, total antioxidant capacity, glutathione reductase activity, and protein carbonyl content were determined in patients with carotid atherosclerosis. RESULTS: Multiparametric analysis showed significantly higher levels of MIP-1α in patients with stenosis ≥70% than in patients with stenosis <70%, and significantly higher levels of CD14 in patients with hypoechoic (vulnerable) lesions compared to those with hyperechoic (stable) ones. The area under the curve obtained by the receiver operating characteristic curve analysis was 0.7253 for MIP-1α and 0.6908 for CD14. CONCLUSIONS: Our data suggest that circulating MIP-1α and CD14 levels are associated with the presence of advanced stenosis and of vulnerable carotid plaques.

Serum Urate Levels and Ultrasound Characteristics of Carotid Atherosclerosis across Obesity Phenotypes.

BACKGROUND: Existing evidence suggests a close link among high levels of serum urate (SU), obesity and carotid atherosclerosis. The aim of the present study was to evaluate the interrelations between SU levels and carotid atherosclerosis in subjects with different obesity phenotypes. METHODS: In this study, a total of 2076 subjects (mean age 48.1 ± 13.1 years; 1307 women) were recruited: 59 with general obesity, 616 with central obesity, 715 with mixed (general-central) obesity and 686 non-obese. Anthropometric measurements, vascular risk factors, blood biochemistry analysis (including SU levels), and carotid ultrasound were performed. Ultrasound assessment included evaluation of intima-media thickness (IMT) and plaque characteristics, including number, total area and type (vulnerable vs. stable) of plaques. RESULTS: After adjustment for potential confounders, the highest levels of SU were observed in subjects with mixed obesity, followed by subjects with central obesity, general obesity and the non-obese (309.4 ± 82.2 vs. 301.2 ± 73.1 vs. 272.9 ± 61.8 vs. 234.2 ± 59.8 µmol/L, respectively; F = 149.2, post hoc p < 0.001). Similarly, subjects with mixed and central obesity presented higher values of IMT compared to subjects with general obesity and the non-obese (0.68 ± 0.16 vs. 0.67 ± 0.16 vs. 0.62 ± 0.14 vs. 0.57 ± 0.13 mm, respectively; F = 54.2, post hoc p < 0.001). No difference in number, total area and type of plaques among obesity groups were attested (all p > 0.05). Significantly higher IMT values were observed in subjects with increased SU levels compared to subjects with normal SU levels (0.70 ± 0.10 vs. 0.62 ± 0.14 mm, p = 0.02) only within the central obesity group. Increasing levels of SU were associated with a higher frequency of increased IMT only in subjects with central obesity (OR 1.033, 95% CI 1.025-1.041). Similarly, SU levels yielded a satisfactory performance in detecting subjects with increased IMT (AUC 0.65, 95% CI 0.50-0.73, subjects with carotid plaques (0.62, 95% CI 0.55-0.68) and subjects with vulnerable plaque types (0.68, 0.59-0.76) only within the central obesity group. CONCLUSIONS: Among the studied obesity types, the association between SU levels and markers of carotid atherosclerosis was of particular significance in subjects with central obesity.

A Comparative Study on the Presence and Reversibility of Subclinical Arterial Damage in HCV-Infected Individuals and Matched Controls.

Background: The arterial pathology and mechanisms of increased cardiovascular disease (CVD) risk in HCV-infected individuals are not yet clear. The aim of this study was to identify types of arterial pathology in treatment-naive chronic HCV patients and to test their reversibility after successful treatment. Methods: Consecutive, never-treated, HCV-infected patients were compared with age and CVD-related risk factors, matched controls, healthy individuals (HI), patients with rheumatoid arthritis (RA) and people living with HIV (PLWH), in terms of arterial stiffening by pulse wave velocity, arterial atheromatosis/hypertrophy by carotid plaques/intima-media thickness and impaired pressure wave reflections by augmentation index. After three months of sustained virological response (SVR) administered using direct-acting antivirals, vascular examination was repeated in HCV-infected patients to test drug and viral-elimination effect in subclinical CVD. Results: Thirty HCV patients were examined at baseline; fourteen of them were re-examined post-SVR. Compared with HI, HCV patients had significantly more plaques, which is similar to that of RA patients and the PLWH group. No other differences were found in all other vascular biomarkers, and regression among HCV patients also revealed no differences 3 months post-SVR. Conclusions: Accelerated atheromatosis, rather than arterial stiffening, arterial remodeling and peripheral impaired hemodynamics is the underlying pathology leading to increased CVD risk in HCV patients.

Sex differences in the association between stroke risk factors and pre-clinical predictors of stroke in the childhood determinants of Adult Health study.

BACKGROUND AND AIMS: It is unclear why blood pressure (BP), metabolic markers and smoking increase stroke incidence in women more than men. We examined these associations with carotid artery structure and function in a prospective cohort study. METHODS: Participants in the Australian Childhood Determinants of Adult Health study at ages 26-36 years (2004-06) were followed-up at 39-49 years (2014-19). Baseline risk factors included smoking, fasting glucose, insulin, systolic and diastolic BP. Carotid artery plaques, intima-media thickness [IMT], lumen diameter and carotid distensibility [CD] were assessed at follow up. Log binomial and linear regression with risk factor × sex interactions predicted carotid measures. Sex-stratified models adjusting for confounders were fitted when significant interactions were identified. RESULTS: Among 779 participants (50% women), there were significant risk factor × sex interactions with baseline smoking, systolic BP and glucose associated with carotid measures in women only. Current smoking was associated with incidence of plaques (RRunadjusted 1.97 95% CI 1.4, 3.39), which reduced when adjusted for sociodemographics, depression, and diet (RRadjusted 1.82 95% CI 0.90, 3.66). Greater systolic BP was associated with lower CD adjusted for sociodemographics (ßadjusted -0.166 95% CI -0.233, -0.098) and hypertension with greater lumen diameter (ßunadjusted 0.131 95% CI 0.037, 0.225), which decreased when adjusted for sociodemographics, body composition and insulin (ßadjusted 0.063 95% CI -0.052, 0.178). Greater glucose (ßunadjusted -0.212 95% CI -0.397, -0.028) was associated with lower CD, which decreased when adjusted for sociodemographics, BP, depression and polycystic ovary syndrome (ßadjusted -0.023 95% CI -0.249, 0.201). CONCLUSIONS: Smoking, SBP and glucose affect carotid structure and function more in women than men with some of this risk due to co-occurring risk factors.

Carotid intima-media thickness and atherosclerotic plaques are associated with renal function decline: a 14-year longitudinal population-based study.

BACKGROUND: Chronic kidney disease (CKD) leads to increased morbidity and mortality. The underlying causes of CKD are often similar to those of atherosclerosis. We investigated whether carotid atherosclerotic parameters are associated with renal function decline. METHODS: Within the population-based Study of Health in Pomerania (SHIP), Germany, 2904 subjects were observed over 14 years. The carotid intima-media thickness (cIMT) as well as carotid plaques were measured by standardized B-mode ultrasound protocol. CKD is defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and albuminuria as urinary albumin-creatinine ratio (ACR) ≥30 mg/g. eGFR was calculated by the full age spectrum (FAS) equation and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Mixed models were applied to associate carotid parameters with change in renal function longitudinally and adjusted for confounding. RESULTS: The age range of the study sample was 25-86 years with a median of 54 years at baseline. In longitudinal analyses, subjects with high cIMT and the presence of plaques at baseline showed a greater decrease in eGFR (cIMT: FAS-eGFR: P < .001, CKD-EPI-eGFR: P < .001; plaques: FAS-eGFR: P < .001, CKD-EPI-eGFR: n.s.) as well as an increased risk of developing CKD during the follow-up (cIMT: FAS-eGFR: P = .001, CKD-EPI-eGFR: P = .04; plaques: FAS-eGFR: P = .008, CKD-EPI-eGFR: P = .001). There was no association between atherosclerotic parameters and the risk of developing albuminuria. CONCLUSIONS: cIMT and carotid plaques are associated with renal function decline as well as CKD in a population-based sample. Furthermore, the FAS equation adapts best to this study population.

Comparison of Parameters for Assessment of Carotid Stiffness and Their Association with Carotid Atherosclerosis in Rural Australian Adults: A Pilot Study.

Carotid stiffness has been associated with the development and progression of carotid artery disease and is an independent factor for stroke and dementia. There has also been a lack of comparison of different ultrasound-derived carotid stiffness parameters and their association with carotid atherosclerosis. This pilot study aimed to investigate the associations between carotid stiffness parameters (derived via ultrasound echo tracking) and the presence of carotid plaques in Australian rural adults. In cross-sectional analyses, we assessed forty-six subjects (68 ± 9 years; mean ± SD) who underwent carotid ultrasound examinations. Carotid stiffness was assessed by a noninvasive echo-tracking method, measuring and comparing multiple carotid stiffness parameters, including stroke change in diameter (ΔD), stroke change in lumen area (ΔA), ß- stiffness index, pulse wave velocity beta (PWV-ß), compliance coefficient (CC), distensibility coefficient (DC), Young's elastic modulus (YEM), Peterson elastic modulus (Ep), and strain. Carotid atherosclerosis was assessed bilaterally by the presence of plaques in the common and internal carotid arteries, while carotid stiffness was assessed at the right common carotid artery. ß-stiffness index, PWV-ß, and Ep were significantly higher (p = 0.006, p = 0.004, p = 0.02, respectively), whilst ΔD, CC, DC, and strain were lower among subjects with carotid plaques (p = 0.036, p = 0.032, p = 0.01, p = 0.02, respectively) comparing to subjects without carotid plaques. YEM and ΔA did not significantly differ among the groups. Carotid plaques were associated with age, history of stroke, coronary artery disease, and previous coronary interventions. These results suggest that unilateral carotid stiffness is associated with the presence of carotid plaques.