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Background: This study aimed to examine whether baseline atherosclerosis was associated with subsequent short-term domain-specific cognitive decline., Methods and Results: This research was based on the BRAVE (Beijing Research on Aging and Vessel) study, a population-based prospective cohort study of adults aged 40 to 80 years, free of dementia. At baseline (wave 1, 2019), cognitive assessments and atherosclerosis measures, including carotid intima-media thickness, carotid plaques, coronary artery calcification, and brachial-ankle pulse wave velocity were conducted. Cognitive function was reassessed in wave 2 (2022-2023) using linear mixed models for analysis. A total of 932 participants (63.7% women; mean age, 60.0±6.9 years) were included. Compared with the lowest tertile of carotid intima-media thickness, carotid plaques, and brachial-ankle pulse wave velocity, or a coronary artery calcification score=0, the highest tertile of carotid intima-media thickness (β=-0.065 SD/y [95% CI, -0.112 to -0.017]; P =0.008), carotid plaques (β=-0.070 SD/y [95% CI, -0.130 to -0.011]; P =0.021), and brachial-ankle pulse wave velocity (β=-0.057 SD/y [95% CI, -0.105 to -0.010]; P =0.018), and a coronary artery calcification score≥400 (β=-0.081 SD/y [95% CI, -0.153 to -0.008]; P =0.029) were significantly associated with a faster decline in semantic fluency after multivariable adjustment. Moreover, greater carotid intima-media thickness, coronary artery calcification, and brachial-ankle pulse wave velocity were significantly associated with a faster decline in global cognition., Conclusions: More significant atherosclerosis was associated with faster semantic fluency and global cognition declines.

This study investigates the influence of body physiology on the rupture risk of cerebral saccular aneurysms. Comprehensive hemodynamic analyses were conducted using computational fluid dynamics to assess the potential for aneurysm rupture under three physiological conditions: rest, normal activity, and exercise. Contours of wall shear stress, oscillatory shear index, and pressure were analyzed and compared to identify regions at high risk of rupture. Additionally, statistical analysis was performed to evaluate the rupture risk of aneurysms. Blood flow dynamics during the peak systolic phase were also examined under these conditions. Our findings indicate that the dome area, where blood pressure is highest and the incoming blood flow first contacts the aneurysm sac, is the critical region with a heightened risk of rupture., (© 2024. The Author(s).)

Carotid atherosclerosis is a major cause of stroke. Hemodynamic forces, such as shear stress and oscillatory shear, play an important role in the initiation and progression of atherosclerosis. The alteration of the immune microenvironment is the fundamental pathological mechanism by which diverse external environmental factors impact the formation and progression of plaques. However, Current research on the relationship between hemodynamics and immunity in atherosclerosis still lack of comprehensive understanding. In this study, we combined computational fluid dynamics (CFD) and Mass cytometry (CyTOF) technologies to explore the changes in the immune microenvironment within plaques under different hemodynamic conditions. Our results indicated that neutrophils were enriched in adverse flow environments. M2-like CD163+CD86+ macrophages were predominantly enriched in high WSS and low OSI environments, while CD163-CD14+ macrophages were enriched in low WSS and high OSI environments. Functional analysis further revealed T cell pro-inflammatory activation and dysregulation in modulation, along with an imbalance in M1-like/M2-like macrophages, suggesting their potential involvement in the progression of atherosclerotic lesions mediated by adverse flow patterns. Our study elucidated the potential mechanisms by which hemodynamics regulated the immune microenvironment within plaques, providing intervention targets for future precision therapies., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Menopausal vasomotor symptoms (VMS) are increasingly emphasized as a potentially important cardiovascular risk factor, but their role is still unclear. We assessed the association between VMS and subclinical atherosclerotic cardiovascular disease in peri- and postmenopausal women., Methods and Results: Using a cross-sectional study design, questionnaire data were collected from a population-based sample of women aged 50 to 64. The questionnaire asked whether menopause was/is associated with bothersome VMS. A 4-point severity scale was used: (1) never, (2) mild, (3) moderate, and (4) severe. The VMS duration and time of onset were also assessed. Associations with subclinical atherosclerotic cardiovascular disease, detected via coronary computed tomography angiography, coronary artery calcium score, and carotid ultrasound were assessed using the outcome variables "any coronary atherosclerosis," "segmental involvement score >3," "coronary artery calcium score >100," and "any carotid plaque," using logistic regression. Covariate adjustments included socioeconomic, lifestyle, and clinical factors. Of 2995 women, 14.2% reported ever severe, 18.1% ever moderate, and 67.7% ever mild/never VMS. Using the latter as reference, ever severe VMS were significantly associated with coronary computed tomography angiography-detected coronary atherosclerosis (multivariable adjusted odds ratio, 1.33 [95% CI, 1.02-1.72]). Corresponding results for ever severe VMS persisting >5 years or beginning before the final menstrual period were 1.50 (95% CI, 1.07-2.11) and 1.66 (95% CI, 1.10-2.50), respectively. No significant association was observed with segmental involvement score >3, coronary artery calcium score >100, or with any carotid plaque., Conclusions: Ever occurring severe, but not moderate, VMS were significantly associated with subclinical coronary computed tomography angiography-detected atherosclerosis, independent of a broad range of cardiovascular risk factors and especially in case of long durations or early onset.

Competing Interests: Disclosures None.

Purpose: Intraplaque haemorrhage (IPH) is a well-known risk factor for faster plaque progression (volume increase); however, its etiology is unclear. We aimed at determining what other local plaque- and systemic factors contribute to plaque progression and to the development and progression of IPH., Methods: We examined 98 asymptomatic participants with carotid plaque using serial multi-contrast magnetic resonance imaging. We measured the percent of wall volume (%WV=100 x [wall volume] / [total vessel volume]) and measured IPH and calcification volumes. We used generalized estimating equations-based regression to analyze predictors of %WV change and new IPH while accounting for covariates (sex, age and statin use), and multiple non-independent observations per participant., Results: Total follow-up was 1.8 ± 0.8 years on average. The presence of IPH (β: 0.6 %/y, p = 0.033) and calcification (β: 1.2 %/y, p = 0.028) were each associated with faster plaque progression. New IPH, detected on a subsequent scan in 4 % of arteries that did not initially have IPH, was associated with larger calcification (odds ratio [OR]: 2.6 per 1-SD increase, p = 0.038) and higher pulse pressure (OR: 2.3 per 1-SD increase, p = 0.016). Larger calcification was associated with greater increases in pulse pressure (β: 1.4 mm Hg/y per 1-SD increase, p = 0.040)., Conclusions: IPH and calcification are each independently associated with faster plaque progression. The association of carotid calcification to increased pulse pressure and new IPH development suggests a possible mechanism by which calcification drives IPH development and plaque progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The (embryonic lethal, abnormal vision, drosophila)-like protein 1 (ELAVL1) is a newly discovered protein associated with cerebral ischemic/reperfusion (I/R) injury. However, little is known of ELAVL1 in ischemic stroke patients., Objectives: To investigate the clinical significance of collateral circulation and serum ELAVL1 in patients with carotid atherosclerosis (CAS) and ischemic stroke., Material and Methods: The present prospective cohort investigation included 317 ischemic stroke patients and 300 CAS patients admitted between March 2020 and March 2022. Collateral circulation was measured using digital subtraction angiography (DSA) and graded using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading system. Enzyme-linked immunosorbent assays (ELISAs) were used to measure serum ELAVL1, C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). The serum levels of total cholesterol (TC), triglyceride (TG), high-density leptin cholesterol (HDL-C), and low-density leptin cholesterol (LDL-C) were also measured., Results: The serum levels of ELAVL1, CRP, IL-6, TNF-α, and LDL-C were all markedly higher, while HDL-C was significantly lower in ischemic stroke patients compared to the CAS patients. Serum ELAVL1 was markedly higher in ASITN/SIR grade 0-1 patients compared to grade 2-4 patients. Also, ELAVL1 correlated positively with serum CRP, IL-6, TNF-α, TC, and LDL-C, and negatively with HDL-C. Receiver operating characteristic (ROC) curves showed that ELAVL1 and collateral circulation have the potential to be used as biomarkers for the diagnosis of ischemic stroke. Meanwhile, CRP, IL-6, TNF-α, HDL-C, ASITN/SIR grading, and ELAVL1 were independent risk factors for ischemic stroke., Conclusions: We found that serum ELAVL1 was associated with clinical outcomes of ischemic stroke patients, while the combination of ELAVL1 and collateral circulation could be used as a potential biomarker for ischemic stroke diagnosis.

Background: Various factors, including blood, inflammatory, infectious, and immune factors, can cause ischemic stroke. However, the primary cause is often the instability of cervical arteriosclerosis plaque. It is estimated that 18-25% of ischemic strokes are caused by the rupture of carotid plaque. 1 Plaque stability is crucial in determining patient prognosis. Developing a highly accurate, non-invasive, or minimally invasive technique to assess carotid plaque stability is crucial for diagnosing and treating stroke.Previous research by our group has demonstrated that the expression levels of CHOP (C/EBP homologous protein) and GRP78 (glucose-regulated protein 78) are correlated with the stability of atherosclerotic plaques. 2 OBJECT: This research assesses changes in GRP78 and CHOP expressions in human umbilical vein endothelial cells(HUVEC) following experiments within the hemodynamic influencing factors test system. Additionally, it includes conducting an empirical study on the impact of blood flow shear force on the stability of human carotid atherosclerotic plaques. The objective is to explore the implications of blood flow shear force on the stability of carotid atherosclerotic plaques., Method: The hemodynamic influencing factors test bench system was configured with low (Group A, 4 dyns/cm²), medium (Group B, 8 dyns/cm²), and high shear force groups (Group C, 12 dyns/cm²). Relative expression levels of GRP78 and CHOP proteins in human umbilical vein endothelial cells were measured using Western blot analysis, and quantitative analysis of GRP78 and CHOP mRNA was conducted using RT-qPCR. Meanwhile, plaques from 60 carotid artery patients, retrieved via Carotid Endarterectomy (CEA), were classified into stable (S) and unstable (U) groups based on pathological criteria. Shear force at the carotid bifurcation was measured preoperatively using ultrasound. Western blot and RT-qPCR were used to analyze the relative expression levels of GRP78 and CHOP proteins and mRNA, respectively, in the plaque specimens from both groups., Result: Expression levels of GRP78, CHOP proteins, and their mRNAs were assessed in groups A, B, and C via Western blot and RT-qPCR. Results showed that in the low-shear group, all markers were elevated in group A compared to groups B and C. Statistical analysis revealed significantly lower shear forces at the carotid bifurcation in group U compared to group S. In group U plaques, GRP78 and CHOP expressions were significantly higher in group U than in group S., Conclusion: Blood flow shear forces variably affect the expression of GRP78 and CHOP proteins, as well as their mRNA levels, in vascular endothelial cells. The lower the shear force and fluid flow rate, the higher the expression of GRP78 and CHOP, potentially leading to endoplasmic reticulum stress(ERS), which may destabilize the plaque., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Echogenicity of the carotid arterial wall, measured by gray scale median of the intima-media complex (IM-GSM), is a novel subclinical atherosclerosis marker with lower values indicating greater lipid deposition. Our longitudinal study investigated IM-GSM from childhood to adulthood and its associated risk factors., Methods and Results: A total of 240 participants from the Southern California CHS (Children's Health Study) underwent carotid artery ultrasounds in 2008 (mean age±SD): (11.2±0.6 years), and again around 2022 (24.2±1.6 years) to assess IM-GSM, carotid artery intima-media thickness, and carotid artery distensibility. Questionnaires and anthropometric and blood pressure measurements were completed by participants at both times. Mean and SD of IM-GSM were 108.2±24.6 in childhood and 75.6±15.8 in adulthood. Each 1-year increase in age was associated with -2.52 change in IM-GSM (95% CI, -2.76 to -2.27). Childhood and adulthood IM-GSMs were highly correlated (β=0.13 [95% CI, 0.05-0.22]). In childhood, Hispanic ethnicity, lower parental education levels and prenatal father smoking were significantly associated with lower IM-GSM. In adulthood, higher systolic blood pressure, carotid artery intima-media thickness, hypertension, and lower distensibility were significantly associated with lower IM-GSM. Weight status exhibited a consistent association with both childhood and adulthood IM-GSM. During the transition from childhood to adulthood, individuals who shifted from normal weight to overweight/obese or normal blood pressure to hypertension or experienced an increase in carotid artery intima-media thickness displayed lower levels of IM-GSM in adulthood., Conclusions: IM-GSM decreases with age. Maintaining healthy weight and blood pressure levels in children could potentially aid in preventing subclinical atherosclerosis.

Objective: This study utilized real-time shear wave elasticity imaging (SWE) and ultrafast pulse wave velocity (ufPWV) to assess carotid arterial stiffness, aiming to predict atherosclerosis risk in patients with metabolic syndrome (MS)., Methods: In this study, 181 patients with metabolic syndrome (MS group) were compared with 73 healthy adults. The MS group was divided into three groups: MS I group: CIMT was normal (CIMT < 1.0 mm, no plaque, n = 61); MS II group: CIMT thickening (1.0 mm ≤ CIMT<1.5 mm, no plaque, n = 39); MS III group: plaque group (CIMT ≥ 1.5 mm, plaque, n = 81). Concurrently, the group of 73 healthy individuals was designated as the control set (NC). Parameters assessed include carotid intima-media thickness (CIMT), elastic modulus values of the carotid artery's anterior and posterior walls (Mean, Max, Min), pulse wave velocity at systole's commencement (PWV-BS), and pulse wave velocity at systole's termination (PWV-ES). Differences, distribution characteristics, and correlations across these groups were analyzed., Results: A significant association was found between PWV-BS, PWV-ES, and arteriosclerosis severity, with these factors gaining importance as arteriosclerosis progressed. Notably, PWV-ES differences were significant across the four groups (p < 0.05). Both MS III and MS II groups exhibited higher PWV-ES values compared to the MS I group and controls. Statistically significant differences were observed between MS III, MS II, and MS I groups relative to the control group (p < 0.05). Additionally, the Mean, Max, and Min values of the anterior and posterior carotid walls in the MS III group surpassed those of the other groups., Conclusion: Real-time shear wave elasticity imaging and ultrafast pulse wave velocity are valuable tools for assessing atherosclerosis risk in MS patients. These non-invasive, safe, and reproducible imaging techniques can quantitatively evaluate the stiffness of the common carotid artery's wall, offering important insights into cardiovascular risk assessment., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To perform a correlation analysis on the structural and functional changes of the carotid artery in patients with H-type hypertension., Methods: Outpatients and inpatients with hypertension in our hospital between 2017 and 2018 were selected and divided into the H-type hypertension group (primary hypertension + plasma homocysteine ≥ 10 umol/l) ( n = 30) and the simple hypertension group (primary hypertension + plasma Hcy < 10 umol/l) ( n = 30) based on the plasma homocysteine (Hcy), and 30 healthy people were included in the control group. Thickness and stiffness parameters of the intima of the carotid artery (compliance coefficient [CC], stiffness index [β], and pulse wave velocity [PWV]) were measured for all study participants using ultrasound radiofrequency signal-based quality intima-media thickness (QIMT) and quantitative arterial stiffness (QAS) for contrast analysis., Results: Indexes such as QIMT, β, and PWV of the carotid artery were significantly higher, and the CC was significantly lower in the H-type hypertension group and simple hypertension group than the control group ( p < .05), and the difference was statistically significant; these indexes were significantly higher in the H-type hypertension group than in the simple hypertension group, and the CC was significantly lower than in the control group ( p < .05), and the difference was statistically significant., Conclusions: Hypertension can accelerate structural and functional changes of the carotid artery intima, with these changes being more significant in H-type hypertension. The ultrasound radiofrequency technique can be used to quantitatively evaluate the structure and function of the carotid artery in patients with H-type hypertension., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: The aim was to investigate the relationship between microvascular function, cardiovascular risk profile, and subclinical atherosclerotic burden., Methods and Results: The study enrolled 3809 individuals, 50-65 years old, participating in the population-based observational cross-sectional Swedish CArdioPulmonary bioImage Study. Microvascular function was assessed in forearm skin using an arterial occlusion and release protocol determining peak blood oxygen saturation (OxyP). Cardiovascular risk was calculated using the updated Systematic Coronary Risk Evaluation [SCORE2; 10-year risk of fatal and non-fatal cardiovascular disease (CVD) events]. The OxyP was compared with coronary artery calcification score (CACS) and to plaques in the carotid arteries. Individuals with OxyP values in the lowest quartile (Q1; impaired microvascular function) had a mean SCORE2 of 5.8% compared with 3.8% in those with the highest values of OxyP (Q4), a relative risk increase of 53%. The risk of having a SCORE2 > 10% was five times higher for those in Q1 (odds ratio: 4.96, 95% confidence interval: 2.76-8.93) vs. Q4 when adjusting for body mass index and high-sensitivity C-reactive protein. The OxyP was lower in individuals with CACS > 0 and in those with both carotid plaques and CACS > 0, compared with individuals without subclinical atherosclerotic burdens (87.5 ± 5.6% and 86.9 ± 6.0%, vs. 88.6 ± 5.8%, P < 0.01)., Conclusion: In a population without CVD or diabetes mellitus, impaired microvascular function is associated with cardiovascular risk profiles such as higher SCORE2 risk and CACS. We suggest that OxyP may serve as a microcirculatory functional marker of subclinical atherosclerosis and CVD risk that is not detected by structural assessments., Competing Interests: Conflict of interest: I.F. is part-time employed by Perimed, AB, which is developing products related to research described in this publication. None of the other authors have disclosable conflicts of interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Changes in arterial wall viscosity (AWW) and stiffness during type 2 diabetes (T2D) have been little investigated. We explored changes in carotid AWV considering change in arterial stiffness and loading conditions, in patients with T2D., Methods: This cross-sectional, monocentric study compared 19 middle-aged patients with T2D to 30 non-diabetic (ND) controls. The absolute viscosity (W V ) was determined as the area of the pressure-lumen cross-sectional area (P-LCSA) loop obtained by carotid tonometry and contralateral echo-tracking. The relative viscosity was determined as the ratio between W V and the elastic energy stored within the arterial wall (W V /W E ). Carotid geometry, midwall stress, distensibility and elastic modulus were also compared between groups., Results: T2D patients were older and more frequently had hypertension. Internal diameter, mean central and pulse blood pressure were higher in T2D patients but midwall stress was similar compared to ND controls. W V and W V /W E were higher in T2D patients when compared with ND controls (23 [16-41] vs. 11 [7-18] mm Hg.mm 2 , p=0.007 and 21% [17-25] vs. 12% [8-17], p < 0.001 respectively) even after adjustment on confounding factors. Carotid arterial stiffness was higher in T2D patients, but after adjustment this difference was only observed for the highest levels of midwall stress., Conclusions: Carotid AWV and stiffness are increased in T2D patients but only AWV is significantly increased after considering loading conditions. Whether this increase in energy dissipation within the arterial wall contributes to alter cardiovascular coupling in T2D remains to be established., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To observe the effect of acupuncture and moxibustion on arterial elasticity in patients with early carotid atherosclerosis., Methods: A total of 62 patients with early carotid atherosclerosis were randomly divided into a blank group (12 cases, 1 cases dropped-off), a sham-acupuncture group (25 cases, 5 cases dropped-off) and an acupuncture group (25 cases, 3 cases dropped-off). Patients in the acupuncture group received acupuncture treatment, including ①acupuncture：Baihui (GV20), Yintang (GV24 + ), Renying (ST9), Neiguan (PC6), Yanglingquan (GB34)；②moxibustion：Yinqiguiyuan (Zhongwan ［CV12］, Xiawan ［CV10］, Qihai ［CV6］, Guanyuan ［CV4］), Sihua (Geshu ［BL17］, Danshu ［BL19］)；③Intradermal needle：Xinshu (BL15), Danshu (BL19). Patients in the sham acupuncture group received placebo acupuncture, moxibustion, an intradermal needle, and the acupoints were the same as the acupuncture group. The above treatments were performed twice a week for 12 weeks. No intervention was given to the patients in the blank group. Diet and lifestyle education was given to the three groups. The ultrafast pulse wave velocity, including beginning-systolic pulse wave velocity (BS) and end-systolic pulse wave velocity (ES), was observed before treatment and 1, 2, 3 months after treatment in the three groups. The blood lipid level and platelet count (PLT) at each time point were observed. The safety of the treatments was also evaluated., Results: Compared with those before treatment, the BS and ES values of both sides in the acupuncture group decreased at 2 and 3 months after treatment ( P <0.05). Compared with the blank group, the bilateral ES of the acupuncture group were decreased at 2 months after treatment ( P <0.05), and the bilateral BS and ES were decreased at 3 months ( P <0.05). Compared with the sham-acupuncture group, the acupuncture group showed a decrease in left BS and left ES after 3 months of treatment ( P <0.05), and the overall decrease on the left side of the acupuncture group was better than that on the right side. There were no significant differences between three groups in the levels of blood lipid and PLT at each time point. No serious adverse safety events occurred in the three groups during the treatment., Conclusions: Acupuncture and moxibustion therapy can improve arterial elasticity in patients with early carotid atherosclerosis, and it is safe and effective.

Background and Aims: Atherosclerosis is accompanied by pre-clinical vascular changes that can be detected using ultrasound imaging. We examined the value of such pre-clinical features in identifying young adults who are at risk of developing atherosclerotic cardiovascular disease (ASCVD)., Methods: A total of 2641 individuals free of ASCVD were examined at the mean age of 32 years (range 24-45 years) for carotid artery intima-media thickness (IMT) and carotid plaques, carotid artery elasticity, and brachial artery flow-mediated endothelium-dependent vasodilation (FMD). The average follow-up time to event/censoring was 16 years (range 1-17 years)., Results: Sixty-seven individuals developed ASCVD (incidence 2.5%). The lowest incidence (1.1%) was observed among those who were estimated of having low risk according to the SCORE2 risk algorithm (<2.5% 10-year risk) and who did not have plaque or high IMT (upper decile). The highest incidence (11.0%) was among those who were estimated of having a high risk (≥2.5% 10-year risk) and had positive ultrasound scan for carotid plaque and/or high IMT (upper decile). Carotid plaque and high IMT remained independently associated with higher risk in multivariate models. The distributions of carotid elasticity indices and brachial FMD did not differ between cases and non-cases., Conclusions: Screening for carotid plaque and high IMT in young adults may help identify individuals at high risk for future ASCVD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Carotid webs (CaWs) are fibromuscular projections in the internal carotid artery (ICA) that cause mild luminal narrowing (<50%), but may be causative in up to one-third of seemingly cryptogenic strokes. Understanding hemodynamic alterations caused by CaWs is imperative to assessing stroke risk. Time-Average Wall Shear Stress (TAWSS) and Oscillatory Shear Index (OSI) are hemodynamic parameters linked to vascular dysfunction and thrombosis., Purpose: To test the hypothesis: "CaWs are associated with lower TAWSS and higher OSI than mild atherosclerosis or healthy carotid bifurcation.", Study Type: Prospective study., Population: A total of 35 subjects (N = 14 bifurcations with CaW, 11F, age: 49 ± 10, 10 mild atherosclerosis 6F, age: 72 ± 9, 11 healthy 9F, age: 42 ± 13)., Field Strength/sequence: 4D flow/STAR-MATCH/3D TOF/3T MRI, CTA., Assessment: 4D Flow velocity data were analyzed in two ways: 1) 3D ROI in the ICA bulbar segment (complex flow patterns are expected) was used to quantify the regions with low TAWSS and high OSI. 2) 2D planes were placed perpendicular to the centerline of the carotid bifurcation for detailed analysis of TAWSS and OSI., Statistical Tests: Independent-samples Kruskal-Wallis-H test with 0.05 used for statistical significance., Results: The percent surface area where low TAWSS was present in the ICA bulb was 12.3 ± 8.0% (95% CI: 7.6-16.9) in CaW subjects, 1.6 ± 1.9% (95% CI: 0.2-2.9) in atherosclerosis, and 8.5 ± 7.7% (95% CI: 3.6-13.4) in healthy subjects, all differences were statistically significant (ƞ 2  = 0.3 [95% CI: 0.05-0.5], P-value CaW vs. healthy = 0.2). OSI had similar values in the CCA between groups (ƞ 2  = 0.07 [95% CI: 0.0-0.2], P-value = 0.5), but OSI was significantly higher downstream of the bifurcation in CaW subjects compared to atherosclerosis and normal subjects. OSI returned to similar values between groups 1.5 diameters distal to the bifurcation (ƞ 2  = 0.03 [95% CI: 0.0-0.2], P-value = 0.7)., Conclusion: Lower TAWSS and higher OSI are present in the ICA bulb in patients with CaW when compared to patients with atherosclerotic or healthy subjects., Evidence Level: 2 TECHNICAL EFFICACY: Stage 2., (© 2023 International Society for Magnetic Resonance in Medicine.)

Background: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in patients with Type 1 Diabetes (T1D). Early markers of CVD include increased carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), but these existing ultrasound technologies show limited spatial and temporal resolution in young adults. The purpose of this study is to evaluate the utility of high-resolution ultrasound modalities, including high frequency ultrasound CIMT (hfCIMT) and ultrafast ultrasound PWV (ufPWV), in young adults with Type 1 Diabetes., Methods: This is a prospective single-center observational cohort study including 39 participants with T1D and 25 age and sex matched controls. All participants underwent hfCIMT and ufPWV measurements. hfCIMT and ufPWV measures of T1D were compared with controls and associations with age, sex, BMI, A1c, blood pressure, and lipids were studied., Results: Mean age was 24.1 years old in both groups. T1D had a greater body mass index (27.7 [5.7] vs 23.1 [3.2] kg/m 2 ), LDL Cholesterol, and estimated GFR, and had a mean A1c of 7.4 [1.0] % (57 mmol/mol) and diabetes duration of 16.1 [3.7] years with 56% using insulin pumps. In T1D, hfCIMT was significantly increased as compared to controls (0.435 ± 0.06 mm vs 0.379 ± 0.06 mm respectively, p < 0.01). ufPWV measures were significantly increased in T1D (systolic foot PWV: 5.29 ± 0.23 m/s vs 5.50 ± 0.37 m/s, p < 0.01; dicrotic notch PWV = 7.54 ± 0.46 m/s vs 7.92 ± 0.41 m/s, p < 0.01). Further, there was an impact of A1c-measured glycemia on hfCIMT, but this relationship was not seen with ufPWV. No significant statistical correlations between hfCIMT and ufPWV measures in either T1D or healthy controls were observed., Conclusion: Young adults with T1D present with differences in arterial thickness and stiffness when compared with controls. Use of novel high-resolution ultrasound measures describe important relationships between early structural and vascular pathophysiologic changes and are promising tools to evaluate pre-clinical CVD risk in youth with T1D., Trial Registration: ISRCTN91419926., (© 2024. The Author(s).)

Background and Aims: Chronic stress associates with cardiovascular disease, but mechanisms remain incompletely defined. Advanced imaging was used to identify stress-related neural imaging phenotypes associated with atherosclerosis., Methods: Twenty-seven individuals with post-traumatic stress disorder (PTSD), 45 trauma-exposed controls without PTSD, and 22 healthy controls underwent 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). Atherosclerotic inflammation and burden were assessed using 18F-FDG PET (as maximal target-to-background ratio, TBR max) and MRI, respectively. Inflammation was assessed using high-sensitivity C-reactive protein (hsCRP) and leucopoietic imaging (18F-FDG PET uptake in spleen and bone marrow). Stress-associated neural network activity (SNA) was assessed on 18F-FDG PET as amygdala relative to ventromedial prefrontal cortex (vmPFC) activity. MRI diffusion tensor imaging assessed the axonal integrity (AI) of the uncinate fasciculus (major white matter tract connecting vmPFC and amygdala)., Results: Median age was 37 years old and 54% of participants were female. There were no significant differences in atherosclerotic inflammation between participants with PTSD and controls; adjusted mean difference in TBR max (95% confidence interval) of the aorta 0.020 (-0.098, 0.138), and of the carotids 0.014 (-0.091, 0.119). Participants with PTSD had higher hsCRP, spleen activity, and aorta atherosclerotic burden (normalized wall index). Participants with PTSD also had higher SNA and lower AI. Across the cohort, carotid atherosclerotic burden (standard deviation of wall thickness) associated positively with SNA and negatively with AI independent of Framingham risk score., Conclusions: In this study of limited size, participants with PTSD did not have higher atherosclerotic inflammation than controls. Notably, impaired cortico-limbic interactions (higher amygdala relative to vmPFC activity or disruption of their intercommunication) associated with carotid atherosclerotic burden. Larger studies are needed to refine these findings., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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., (© 2024. The Author(s).)

Carotid artery webs (CaW) are non-atherosclerotic projections into the vascular lumen and have been linked to up to one-third of cryptogenic strokes in younger patients. Determining how CaW affects local hemodynamics is essential for understanding clot formation and stroke risk. Computational fluid dynamics simulations were used to investigate patient-specific hemodynamics in carotid artery bifurcations with CaW, bifurcations with atherosclerotic lesions having a similar degree of lumen narrowing, and with healthy carotid bifurcations. Simulations were conducted using segmented computed tomography angiography geometries with inlet boundary conditions extracted from 2D phase contrast MRI scans. The study included carotid bifurcations with CaW (n = 13), mild atherosclerosis (n = 7), and healthy bifurcation geometries (n = 6). Hemodynamic parameters associated with vascular dysfunction and clot formation, including shear rate, oscillatory shear index (OSI), low velocity, and flow stasis were calculated and compared between the subject groups. Patients with CaW had significantly larger regions containing low shear rate, high OSI, low velocity, and flow stasis in comparison to subjects with mild atherosclerosis or normal bifurcations. These abnormal hemodynamic metrics in patients with CaW are associated with clot formation and vascular dysfunction and suggest that hemodynamic assessment may be a tool to assess stroke risk in these patients., (© 2024. The Author(s).)

Microglia, the main immunocompetent cells of the brain, regulate neuronal function, but their contribution to cerebral blood flow (CBF) regulation has remained elusive. Here, we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion. Microglia establish direct, dynamic purinergic contacts with cells in the neurovascular unit that shape CBF in both mice and humans. Surprisingly, the absence of microglia or blockade of microglial P2Y12 receptor (P2Y12R) substantially impairs neurovascular coupling in mice, which is reiterated by chemogenetically induced microglial dysfunction associated with impaired ATP sensitivity. Hypercapnia induces rapid microglial calcium changes, P2Y12R-mediated formation of perivascular phylopodia, and microglial adenosine production, while depletion of microglia reduces brain pH and impairs hypercapnia-induced vasodilation. Microglial actions modulate vascular cyclic GMP levels but are partially independent of nitric oxide. Finally, microglial dysfunction markedly impairs P2Y12R-mediated cerebrovascular adaptation to common carotid artery occlusion resulting in hypoperfusion. Thus, our data reveal a previously unrecognized role for microglia in CBF regulation, with broad implications for common neurological diseases., Competing Interests: Disclosures: D. Máthé reported grants from European Union H2020 HCEMM-739593 and from NRDIO, Hungary, TKP-BIOImaging-2020-4.1.1-TKP2020 during the conduct of the study. D. Máthé is CEO and stakeholder of CROmed Ltd. Z. Lenkei reported personal fees from Iconeus outside the submitted work. No other disclosures were reported., (© 2022 Császár et al.)

Background: Evidence suggests marginal superiority of static aortic systolic blood pressure (aSBP) compared with brachial SBP (bSBP) regarding the association with organ damage and prognosis of cardiovascular disease (CVD). The noninvasive 24-hour aSBP assessment is feasible and associates better with presence of left ventricular hypertrophy compared with 24-hour bSBP. We aimed at comparing the association of 24-hour aSBP and 24-hour bSBP with indices of arterial damage and examining the role of 24-hour SBP amplification variability (within-subjects' SD) in this association., Methods: Consecutive subjects referred for CVD risk assessment underwent 24-hour aortic and brachial ambulatory BP monitoring using a validated oscillometric device (Mobil-O-Graph). Arterial damage was assessed by carotid intima-media thickness (IMT) and detection of carotid and femoral atheromatosis (plaque presence)., Results: Cross-sectionally 501 individuals (aged 54±13 years, 57% men, 80% hypertensives) were examined. Multivariable analysis revealed superiority of 24-hour aSBP regarding the association with IMT, carotid hypertrophy and carotid-but not femoral-atheromatosis. In receiver operator characteristics analysis, 24-hour aSBP displayed a higher discriminatory ability-compared to 24-hour bSBP-for the detection of both carotid hypertrophy (area under the curve, 0.662 versus 0.624, P <0.05) and carotid atheromatosis (area under the curve, 0.573 versus 0.547, P <0.05). This effect was more prominent in individuals with above-median 24-hour SD of SBP amplification., Conclusions: Our results suggest that 24-hour aSBP assessment may be of significant value in clinical practice to detect site-specific arterial damage on the basis of pressure amplification variability and should be prospectively examined in clinical trials.

Aims: Atherosclerotic cerebrovascular disease underlies the majority of ischaemic strokes and is a major cause of death and disability. While plaque burden is a predictor of adverse outcomes, plaque vulnerability is increasingly recognized as a driver of lesion rupture and risk for clinical events. Defining the molecular regulators of carotid instability could inform the development of new biomarkers and/or translational targets for at-risk individuals., Methods and Results: Using two independent human endarterectomy biobanks, we found that the understudied glycoprotein, chitinase 3 like 1 (CHI3L1), is up-regulated in patients with carotid disease compared to healthy controls. Further, CHI3L1 levels were found to stratify individuals based on symptomatology and histopathological evidence of an unstable fibrous cap. Gain- and loss-of-function studies in cultured human carotid artery smooth muscle cells (SMCs) showed that CHI3L1 prevents a number of maladaptive changes in that cell type, including phenotype switching towards a synthetic and hyperproliferative state. Using two murine models of carotid remodelling and lesion vulnerability, we found that knockdown of Chil1 resulted in larger neointimal lesions comprised by de-differentiated SMCs that failed to invest within and stabilize the fibrous cap. Exploratory mechanistic studies identified alterations in potential downstream regulatory genes, including large tumour suppressor kinase 2 (LATS2), which mediates macrophage marker and inflammatory cytokine expression on SMCs, and may explain how CHI3L1 modulates cellular plasticity., Conclusion: CHI3L1 is up-regulated in humans with carotid artery disease and appears to be a strong mediator of plaque vulnerability. Mechanistic studies suggest this change may be a context-dependent adaptive response meant to maintain vascular SMCs in a differentiated state and to prevent rupture of the fibrous cap. Part of this effect may be mediated through downstream suppression of LATS2. Future studies should determine how these changes occur at the molecular level, and whether this gene can be targeted as a novel translational therapy for subjects at risk of stroke., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Objectives: Circulating Endothelial Progenitor Cells (EPCs) predict cardiovascular outcomes in patients with coronary disease. However, the predictive value of EPCs after ischemic stroke is not well established. We aimed to study the prognostic role of EPCs in patients with acute ischemic stroke and carotid atherosclerosis, focusing on post-stroke functional outcome and stroke recurrences., Materials and Methods: We studied consecutive adult patients with an acute (<7 days) anterior circulation ischemic stroke and carotid atherosclerosis. Cardioembolic strokes were excluded. We measured circulating EPCs by flow cytometry (CD34+/CD133+/KDR+) at inclusion (7±1 days after stroke) and at one year of follow-up. At three months and at one year we registered the modified Rankin Scale score, stroke recurrences and coronary syndromes during the follow-up., Results: We studied 80 patients with a mean age of 74.3±10.4 years. We divided the population in tertiles according to the EPCs count. At three months we observed a favorable outcome in 25/36 (69.4%) patients in the lowest, 19/22 (86.4%) in the medium and 21/22 (95.5%) in the highest tercile (p=0.037). In the multivariable analysis a higher EPCs count was associated with favorable functional outcome after adjusting for age and baseline NIHSS score (OR=3.61, 95%CI 1.34-9.76; p=0.011). This association persisted at one year of follow-up. We did not find association between counts of EPCs and stroke recurrence., Conclusions: In patients with acute ischemic stroke and carotid atherosclerosis, a higher count of EPCs was associated with favorable functional outcome in the mid and long-term follow-up. Counts of EPCs did not predict stroke recurrences., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To determine differences in outcomes among patients undergoing ipsilateral carotid bypass with hostile or normal neck anatomy., Methods: Single-center retrospective review of all ipsilateral extracranial carotid bypasses performed between 1998 and 2018., Results: Forty-eight patients underwent ipsilateral carotid bypass from the common carotid artery to either the internal carotid artery or carotid bifurcation during the study period. Seven patients were excluded owing to either a lack of follow-up or missing data. The indications for intervention included infected patches, aneurysmal degeneration, symptomatic and asymptomatic stenosis or restenosis, carotid body tumors, neck malignancy, and trauma. In 25 procedures (61%), there was a hostile neck anatomy defined as a prior history of external beam neck irradiation or neck surgery. Among this group, 12 pectoralis muscle flaps were performed for reconstructive coverage. Conduits included polytetrafluorethylene (n = 21), great saphenous vein (n = 9), superficial femoral artery (n = 7) and arterial homograft (n = 4). All superficial femoral artery conduits were used in the hostile neck group (P = .03). The overall mean time of follow-up was 22 months, with all bypasses remaining patent with no significant clinical stenosis. The 30-day ipsilateral stroke and myocardial infarction rates were 4.88% each, all within the hostile neck group, with no 30-day mortalities for the entire cohort. One-third of the muscle flaps were performed in the setting of infected patches (P = .02) with no significant differences in perioperative outcomes with use. The overall median hospital length of stay was significantly increased in patients receiving muscle flap coverage (3.0 vs 7.0 days; P = .04)., Conclusions: In patients with a complex carotid pathology, ipsilateral carotid bypass is an effective solution for carotid reconstruction. Different conduits should be used depending on the indication. Muscle flap coverage should be considered in hostile settings when primary wound closure is not feasible., (Published by Elsevier Inc.)

Background: Hemodynamic disturbances cause half of the perioperative strokes following carotid endarterectomy (CEA). Guidelines strongly recommend strict pre- and postoperative blood pressure (BP) monitoring in CEA patients, but do not provide firm practical recommendations. Although in the Netherlands 50 centres perform CEA, no national protocol on perioperative hemodynamic, and cerebral monitoring exists. To assess current monitoring policies of all Dutch CEA-centres, a national survey was conducted., Methods: Between May and July 2017 all 50 Dutch CEA-centres were invited to complete a 42-question survey addressing perioperative hemodynamic and cerebral monitoring during CEA. Nonresponders received a reminder after 1 and 2 months. By November 2017 the survey was completed by all centres., Results: Preoperative baseline BP was based on a single bilateral BP-measurement at the outpatient-clinic in the majority of centres (n = 28). In 43 centres (86%) pre-operative monitoring (transcranial Doppler (TCD, n = 6), electroencephalography (EEG, n = 11), or TCD + EEG (n = 26)) was performed as a baseline reference. Intraoperatively, large diversity for type of anaesthesia (general: 45 vs. local [LA]:5) and target systolic BP (>100 mm hg - 160 mm hg [n = 12], based on preoperative outpatient-clinic or admission BP [n = 18], other [n = 20]) was reported. Intraoperative cerebral monitoring included EEG + TCD (n = 28), EEG alone (n = 13), clinical neurological examination with LA (n = 5), near-infrared spectroscopy with stump pressure (n = 1), and none due to standard shunting (n = 3). Postoperatively, significant variation was reported in standard duration of admission at a recovery or high-care unit (range 3-48 hr, mean:12 hr), maximum accepted systolic BP (range >100 mm hg - 180 mm Hg [n = 32]), postoperative cerebral monitoring (standard TCD [n = 16], TCD on indication [n = 5] or none [n = 24]) and in timing of postoperative cerebral monitoring (range directly postoperative - 24 hr postoperative; median 3 hr)., Conclusions: In Dutch centres performing CEA the perioperative hemodynamic and cerebral monitoring policies are widely diverse. Diverse policies may theoretically lead to over- or under treatment. The results of this national audit may serve as the baseline dataset for development of a standardized and detailed (inter)national protocol on perioperative hemodynamic and cerebral monitoring during CEA., (Copyright © 2021. Published by Elsevier Inc.)

The motive of this article is to present the case study of patients to investigate the association between the ultrasonographic findings of lower extremity vascular disease (LEAD) and plaque formation. Secondly, to examine the association between the formation of coronary artery and carotid artery atherosclerosis in patients with type 2 diabetes mellitus. 124 patients with type 2 diabetes (64 males and 60 females with the age group 25-78 years) are considered for the research studies who have registered themselves in the Department of Endocrinology and Metabolism from April 2017 to February 2019. All participants have reported their clinical information regarding diabetes, alcohol consumption, smoking status, and medication. The blood samples from subjects are collected for measurement of HbA 1c , total cholesterol, triglycerides, HDL-c, and LDL-c levels. Two-dimensional ultrasound has been used to measure the inner diameter, peak flow velocity, blood flow, and spectral width of the femoral artery, pop artery, anterior iliac artery, posterior tibial artery, and dorsal artery and to calculate the artery stenosis degree. Independent factors of atherosclerosis are determined by multivariate logistic regression analysis. The results are evaluated within the control group and it is found that there is no significant impact of gender, age, and body mass index ( P > 0.05) on the lower extremity vascular diseases. Those with smoking, alcohol consumption, hypertension, and dyslipidemia have higher positive rate ( P < 0.05). The type 2 diabetes mellitus group has higher diastolic blood pressure and lower triglyceride ( P < 0.05). Diastolic blood pressure, HbA 1C , total cholesterol, HDL-c, and LDL-C are not remarkably dissimilar between the type 2 diabetes mellitus group and the control group ( P > 0.05). Compared with the control group, the type 2 diabetes mellitus group has higher frequency of lower extremity vascular diseases in the dorsal artery than in the pop artery ( P < 0.05). The blood flow of type 2 diabetes mellitus group is found to be lower than that of the control group, especially in the dorsal artery ( P < 0.05). The blood flow velocity of the dorsal artery is accelerated ( P < 0.01). Among 117 patients of type 2 diabetes mellitus (94.35%) with a certain degree of injury, there are 72 cases of type I carotid stenosis (58.06%), 30 cases of type II carotid stenosis (24.19%), and 15 cases of type III carotid stenosis (12.10%). Out of 108 subjects in the control group, there are 84 cases of type 0 carotid stenosis (77.78%), 19 cases of type I carotid stenosis (17.59%), 5 cases of type II carotid stenosis (4.63%), and 0 case of type III carotid stenosis (0.00%). Compared with the control group, carotid stenosis is more common in patients with type 2 diabetes mellitus ( P < 0.05). Age, smoking, duration of diseases, systolic blood pressure, and degree of carotid stenosis are found to be associated with atherosclerosis. The findings suggest that the color Doppler ultrasonography can give early warning when applied in patients with carotid and lower extremity vascular diseases to delay the incidence of diabetic macroangiopathy and to control the development of cerebral infarction, thus providing an important basis for clinical diagnosis and treatment., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Zheng Yang et al.)

Introduction: The optimal treatment strategy for patients with concomitant carotid and cardiac disease remains controversial. Transcarotid artery revascularization stenting with reversed flow protection (TCAR) has achieved results equivalent to carotid endarterectomy (CEA) in high risk patients., Methods: A retrospective review of all patients at a single center who received staged TCAR prior to cardiac intervention was performed., Results: 37 patients underwent 42 TCAR procedures prior to cardiac intervention (25 requiring open cardiac surgery and 12 requiring percutaneous intervention). There were no myocardial or neurological complications following TCAR prior to cardiac intervention. Three patients (8%) developed a neck hematoma which required evacuation., Conclusion: A staged approach to combined carotid and cardiac pathology with TCAR prior to cardiac intervention appears to be a safe and effective strategy.

Objectives: During carotid artery stenting (CAS), hemodynamics may be affected by the carotid sinus reflex in some cases. Although general anesthesia has been reported to stabilize intraoperative hemodynamics, the patient's neurological condition must be assessed indirectly. Therefore, we investigated the changes in intraoperative hemodynamics and perioperative complications of CAS under general anesthesia and evaluated the efficacy of somatosensory evoked potential (SEP) monitoring in detecting a reduction in perfusion during CAS., Materials and Methods: From April 2011 to August 2016,57 consecutive patients who underwent CAS under general anesthesia were evaluated. The follow-up period ranged from 3 to 8 years. During CAS, anesthesiologists monitored and managed the hemodynamics. SEP monitoring was performed during the CAS procedure in all patients., Results: Intraoperative hypotension (systolic blood pressure ≤ 100 mmHg) was evident in 16 patients (28.1%), and 13 patients (22.8%) experienced intraoperative bradycardia; however, all of these cases were promptly managed under general anesthesia. None of the patients showed systolic blood pressure < 50 mmHg from baseline. Regarding perioperative complications, none of the patients exhibited myocardial infarction or postoperative hyperperfusion symptoms, and there was no mortality. Among 21 patients (36.8%) with a decrease in the intraoperative SEP, 3 (5.3%) exhibited transient ischemic symptoms and 1 (1.8%) had postoperative infarction., Conclusions: CAS under general anesthesia is a safe and effective management option in terms of intraoperative hemodynamic stability. In addition, our findings indicate that SEP monitoring could be helpful in evaluating transient postoperative cerebral ischemia or cerebral infarction after CAS., Competing Interests: Declarations of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cerebral cortical microinfarcts (CMI) are small ischemic lesions that are associated with cognitive impairment and probably have multiple etiologies. Cerebral hypoperfusion has been proposed as a causal factor. We studied CMI in patients with internal carotid artery (ICA) occlusion, as a model for cerebral hemodynamic compromise. We included 95 patients with a complete ICA occlusion (age 66.2 ± 8.3, 22% female) and 125 reference participants (age 65.5 ± 7.4, 47% female). Participants underwent clinical, neuropsychological, and 3 T brain MRI assessment. CMI were more common in patients with an ICA occlusion (54%, median 2, range 1-33) than in the reference group (6%, median 0; range 1-7; OR 14.3; 95% CI 6.2-33.1; p <.001). CMI were more common ipsilateral to the occlusion than in the contralateral hemisphere (median 2 and 0 respectively; p <.001). In patients with CMI compared to patients without CMI, the number of additional occluded or stenosed cervical arteries was higher ( p =.038), and cerebral blood flow was lower (B -6.2 ml/min/100 ml; 95% CI -12.0:-0.41; p =.036). In conclusion, CMI are common in patients with an ICA occlusion, particularly in the hemisphere of the occluded ICA. CMI burden was related to the severity of cervical arterial compromise, supporting a role of hemodynamics in CMI etiology.

Objective: We aimed to evaluate the association between the shift of metabolic status and future risk of carotid artery plaque (CAP) in community-based Chinese adults., Methods: The current study included 9836 Chinese adults (4085 males and 5751 females, mean age 35.8 years) with metabolically healthy status at baseline (2013). Metabolically healthy status was defined as no self-reported history of metabolic diseases and cancer, and normal blood pressure, fasting blood glucose, glycated hemoglobin A1c level, and lipid profiles. Metabolically unhealthy status was defined if any of the following metabolic abnormalities were confirmed twice during follow up: high blood pressure, impaired glucose regulation, high triglycerides, high total cholesterol, high low-density lipoprotein cholesterols, or low high-density lipoprotein cholesterols. The transition was confirmed if participants' metabolic status shifted from baseline healthy to unhealthy status during follow up (2014-2018)., Results: We have identified 133 incident cases of CAP during follow up. Compared to those who remained metabolically healthy, the transition to high blood pressure, high total cholesterol, and high low-density lipoprotein cholesterols, were associated with high risk of developing carotid artery plaque (Hazards ratios (HRs) ranged from 1.69 to 2.34; p < 0.05 for all). The transition to impaired glucose regulation, high total triglycerides, and low high-density lipoprotein cholesterols, were associated with high risk of carotid artery plaque only in participants with metabolically healthy overweight at baseline (HR ranged from 1.95 to 4.62; p < 0.05 for all)., Conclusion: The transition from baseline metabolically healthy status to unhealth status was associated with high risk of incident CAP., (© 2021. The Author(s).)

Recent studies have supported the relationship between periodontitis and carotid artery calcification (CAC), but still uncertain. This systematic review is aimed at evaluating the association between periodontitis and CAC. The search was conducted in four electronic databases: PubMed, EMBASE, Web of Science, and The Cochrane Library, supplemented by checking references of included articles and related review articles. Eligibility assessment and data extraction were conducted independently. The quality assessment and publication bias analysis were performed. The association between periodontitis and CAC was presented in odd ratio (OR) with 95% confidence interval (CI). Additional outcomes included the percentage of alveolar bone loss in CAC versus non-CAC. Twelve studies were included, and 10 were performed quantity analysis. Periodontitis with secure definition (OR = 2.02, 95%CI = 1.18 - 3.45) and insecure definition (OR = 10.78, 95%CI = 4.41 - 26.34) was associated with CAC. And a higher average percentage of alveolar bone loss (weighted mean difference = 10.84%; 95%CI = 6.40 - 15.48) was also observed in CAC patients compared to non-CAC patients. No significant publication bias was found. The results of this systematic review and meta-analysis revealed a significant relationship between periodontitis and CAC., Competing Interests: The authors report no conflicts of interest related to this study., (Copyright © 2021 Wenxuan Wang et al.)

Macrophage polarization is of great importance in the formation of atherosclerotic plaque. Homeobox A5 (HOXA5), one of the homeobox transcription factors, has been revealed to be closely associated with macrophage phenotype switching. This study aims to investigate the role of HOXA5 in carotid atherosclerosis (CAS). Herein, the role of HOXA5 was explored in polarized RAW264.7 macrophages in vitro and ApoE -/- mice in vivo. Interestingly, compared with that in M0 macrophages, both the mRNA and protein expression levels of HOXA5 were decreased in lipopolysaccharide (LPS)/interferon (IFN)-γ-induced M1 macrophages, while increased in IL-4-induced M2 macrophages. In addition, in the presence of IL-4, HOXA5-overexpressing RAW264.7 cells preferred to polarizing toward M2 phenotypes. Furthermore, we found that HOXA5 bound to the promoter region and activated the expression of mediator subunit 1 (MED1), a gene known to regulate macrophage differentiation. Knocking MED1 down inhibited HOXA5-enhanced M2 macrophage polarization. In vivo, the CAS model was induced in ApoE -/- mouse fed with a Western-type diet and placed a perivascular carotid collar. Decreased mRNA and protein expressions of HOXA5 were observed in carotid arteries of CAS mice. Forced overexpression of HOXA5 reduced intimal hyperplasia and lipid accumulation in carotid vessels, and it also promoted the polarization of macrophages to M2 subtypes. The expression of MED1 was decreased in atherosclerotic carotid vessels, while HOXA5 overexpression restored its change. Collectively, HOXA5 in carotid arteries is involved in the macrophage M1/M2 switching in atherosclerotic plaque, which may be associated with its transcriptional regulation of MED1., (© 2021 International Union of Biochemistry and Molecular Biology.)

Purpose: Obstructive sleep apnea-hypopnea syndrome (OSAHS) may affect cerebrovascular reactivity (CVR), representing cerebrovascular endothelial function, through complex cerebral functional changes. This study aimed to evaluate the change of CVR after 1-month and 6-month mandibular advancement device (MAD) treatment of patients with carotid atherosclerosis (CAS) combined with OSAHS., Methods: Patients with carotid atherosclerosis combined with OSAHS who voluntarily accepted Silensor-IL MAD therapy were prospectively enrolled. All patients underwent polysomnographic (PSG) examinations and CVR evaluation by breath-holding test using transcranial Doppler ultrasound at baseline (T0), 1 month (T1), and 6 months (T2) of MAD treatment., Results: Of 46 patients (mean age 54.4 ± 12.4 years, mean body mass index [BMI] 27.5 ± 4.5 kg/m 2 ), 41 patients (responsive group) responded to the 1-month and 6-month treatment of MAD, an effective treatment rate of 89%. The remaining 5 patients (non-responsive group) were younger (47.4 ± 13.5 years) and had a higher BMI (35.8 ± 1.8 kg/m 2 ). The responsive group had an improvement of apnea-hypopnea index (AHI) (events/h) from 33.0 ± 25.0 (T0) to 12.4 ± 10.4 (T1) and 8.7 ± 8.8 (T2), P < 0.001; minimum arterial oxygen saturation (minSpO 2 ) (%) increased from 79.8 ± 9.1 (T0) to 81.8 ± 9.4 (T1) and 85.2 ± 5.4 (T2), P < 0.01; longest apnea (LA) (s) decreased from 46.5 ± 23.1 (T0) to 33.3 ± 22.7 (T1) and 29.4 ± 18.5 (T2), P < 0.001; T90 (%) decreased from 10.3 ± 14.9 (T0) to 6.1 ± 11.8 (T1) and 3.3 ± 7.5 (T2), P < 0.05. Sleep architecture of these patients also improved significantly. The responsive group had a significant increase in left, right, and mean breath-holding index (BHI): left BHI(/s) from 0.52 ± 0.42 (T0) to 0.94 ± 0.56 (T1) and 1.04 ± 0.64 (T2), P < 0.01; right BHI(/s) from 0.60 ± 0.38 (T0) to 1.01 ± 0.58 (T1) and 1.11 ± 0.60 (T2), P < 0.01; mean BHI(/s) from 0.56 ± 0.38 (T0) to 0.97 ± 0.55 (T1) and 1.07 ± 0.59 (T2), P < 0.01), suggesting improved CVR., Conclusion: Effective MAD therapy is beneficial for restoring cerebrovascular endothelial function in patients with CAS and OSAHS in a short period (1 month and 6 months)., Trial Registration: Clinical trial registration number: NCT03665818. September 11, 2018., (© 2021. Springer Nature Switzerland AG.)

Aim: Resistive index of ophthalmic artery (RI-OA) is associated with atherosclerotic diseases. The aim of this study was to evaluate the association of RI-OA and hypertension-related vascular and kidney damage. Materials and methods: Two-hundred and eighty hypertensive patients underwent evaluation of RI-OA, carotid atherosclerosis and level of 24 h albuminuria. Results: Albuminuria and carotid atherosclerosis were positively associated with RI-OA independently of other cardiovascular risk factors. Receiver-operating characteristic curve analysis allowed us to calculate a cut-off value of RI-OA >0.625, which would be suspicious about the existence of atherosclerotic disease. Conclusion: The ophthalmic vascular circulation allows to study connections between macro- and microcirculation in vivo . RI-OA could be a useful marker for a better stratification of the risk of developing kidney and cardiovascular disease.

Background: The development of metabolic syndrome (MS) augments risk for atherosclerotic cardiovascular disease (CVD), but pathophysiological mechanisms of this relation are still under discussion. Overlapping CVD risk factors make it difficult to assess the importance of individual elements. This study aimed to analyze subclinical atherosclerosis based on arterial structure and function parameters in patients with MS and different triglycerides levels., Methods: Patients (aged 40-65 years) were divided into two groups: patients with MS and with or without hypertriglyceridemia (hTG). Noninvasive assessment of vascular parameters-aortic augmentation index adjusted for heart rate 75 bpm (AIxHR75), pulse wave velocity (PWV), and common carotid artery intima-media thickness (cIMT) were performed., Results: Carotid-femoral PWV (cfPWV) and carotid-radial PWV (crPWV) were significantly higher in patients with hTG. After adjusting for age, gender, waist circumference, fasting glucose, smoking status, cardiovascular family history and mean arterial pressure, crPWV (OR 1.150; CI 95% 1.04-1.28), cfPWV (OR 1.283; CI 95% 1.14-1.42) and cIMT (OR 1.13; CI 95% 1.02-1.25) were significantly associated with hTG (p < 0.05), while AIxHR75 did not show significant association., Conclusion: Increased triglycerides are independently associated with a cfPWV, crPWV, and cIMT and may modify CVD risk in patients with MS., (© 2021. The Author(s).)

Aims: To define the prevalence, progression, and the relationship between carotid and subclavian artery atherosclerosis and to identify factors associated with disease progression in a population of asymptomatic patients., Methods: Among all consecutive patients without a history of cardiovascular disease admitted to our hospital for duplex ultrasound examinations of the supra-aortic arteries, from January to December 2012, we retrospectively identified 530 patients with two evaluations at least 3 years apart. Each artery was graded according to stenosis degree, as absent or less than 20%, 20-49%, 50-69%, 70-99% and total occlusion. Disease progression was defined for any class increase at any time interval. Patients were grouped according to the presence of a more than 20% stenosis of the supra-aortic district at baseline, as controls, without atherosclerosis: n = 111, 21%; isolated carotid artery disease: n = 390, 74%; concomitant subclavian artery-carotid artery disease: n = 29, 5%. There were no cases with isolated subclavian artery atherosclerosis., Results: The mean time-lapse between the two evaluations was 3.1 ± 0.3 years; we documented disease progression in 32 patients (6%), all limited to the carotid artery (P = 0.009 vs. controls, with no differences between isolated carotid artery disease and concomitant carotid and subclavian artery disease). Hypertension was significantly (P < 0.001) associated with disease progression, regardless of the single or double district involvement., Conclusion: The subclavian artery is far less prone to atherosclerosis than the carotid artery, and features lesser disease progression. Understanding factors for the different susceptibility to atherosclerosis in these two close arterial districts provides insight into local factors prompting vascular disease., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

As asthma and atherosclerosis have similar pathophysiological mechanisms and risk factors, asthmatic patients may have an increased risk of atherosclerosis. This study aimed to determine the possibility of a higher risk of atherosclerosis in asthma patients compared with healthy controls by measuring carotid elasticity and distensibility. This was a cross-sectional study on 326 participants including 221 patients (129 [58.37%] females) with persistent asthma, aged 46.47±11.58 years, body mass index (BMI) of 29.74±3.99, and 105 healthy control subjects (60 [57.14%] females) aged 46.08±11.35 years, and BMI of 29.42±3.76. Of the 221 patients with asthma, 75 (33.93%) had mild, 74 (33.48%) had moderate and 72 (32.57%) had severe asthma. The carotid distensibility and elasticity were recorded and compared in both patients and control groups. There was no statistically significant difference between the patients and healthy control groups in terms of age, BMI and gender (p=0.775, p=0.482, and p=0.834, respectively). A statistically significant difference was determined between the patient and control groups in respect of both distensibility and elasticity (10.93±1.64 vs. 11.5±1.31, p=0.002 and 0.21±0.03 vs. 0.22±0.04, p=0.001, respectively). Statistically significant differences were determined between the control group and the asthma subgroups in respect of distensibility and elasticity (p<0.001, for both comparisons). The results showed that the difference was mainly due to the patients with severe asthma. Carotid distensibility and elasticity were decreased in asthmatic patients, and the main reason for this decrease was the patients in the severe asthma group. These results may suggest that the risk of subclinical carotid atherosclerosis is increased in patients with asthma, especially those with severe asthma.

Background: Poststent ballooning/angioplasty (post-SB) have been shown to increase the risk of stroke risk after transfemoral carotid artery stenting. With the advancement of transcarotid artery revascularization (TCAR) with dynamic cerebral blood flow reversal, we aimed to study the impact of post-SB during TCAR., Methods: Patients undergoing TCAR in the Vascular Quality Initiative between September 2016 and May 2019 were included and were divided into three groups: those who received prestent deployment angioplasty only (pre-SB, reference group), those who received poststent deployment ballooning only (post-SB), and those who received both prestent and poststent deployment ballooning (prepost-SB). Patients who did not receive any angioplasty during their procedure (n = 367 [6.7%]) were excluded because these represent a different group of patients with less complex lesions than those requiring angioplasty. Primary outcome was in-hospital stroke or death. Analysis was performed using univariable and multivariable logistic regression models., Results: Of 5161 patients undergoing TCAR, 34.7% had pre-SB only, 25% had post-SB only, and 40.3% had both (prepost-SB). No differences in the rates of in-hospital and 30-day stroke, death, and stroke/death were observed among the three groups; in-hospital stroke/death in the pre-SB group was 1.4% (n = 25), post-SB 1.2% (n = 16), and prepost-SB 1.4% (n = 29; P = .92). However, patients undergoing post-SB and prepost-SB had higher rates of in-hospital transient ischemic attacks (TIA) (post-SB, 0.9%; prepost-SB, 1% vs pre-SB, 0.2%, P < .01) and postprocedural hypotension (16.6% and 16.8% vs 13.1%, respectively; P < .001). Post-SB also had longer operative times, as well as flow reversal and fluoroscopy times. On multivariable analysis, no association was seen between post-SB and the primary outcome of in-hospital stroke/death (post-SB odds ratio [OR], 0.88; 95% confidence interval [CI], 0.44-1.73; prepost-SB OR, 0.98; 95% CI, 0.57-1.70). Similarly, no significant differences were noted in terms of postprocedural hemodynamic instability and 30-day outcomes. However, post-SB and prepost-SB were associated with four times the odds of in-hospital TIA compared with pre-SB alone (post-SB OR, 4.24 [95% CI, 1.51-11.8]; prepost-SB OR, 4.76 [95% CI, 1.53-14.79]; P = .01). Symptomatic patients had higher rates of in-hospital stroke/death compared with their asymptomatic counterparts; however, there was no significant interaction between symptomatic status and ballooning in predicting the primary outcome., Conclusions: Post-SB was used in 65.3% of TCAR patients. This maneuver seems to be safe without an increase in the odds of postoperative in-hospital stroke/death. However, the increased rates of TIA associated with post-SB requires further investigation., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: To quantitatively evaluate changes in vascular elasticity and intima-media thickness (IMT) of the common carotid artery (CCA) with Ultrasound radiofrequency (RF)-data technology in asymptomatic patients with type-2 diabetes mellitus (T2DM) and controls., Materials and Methods: Thirty-seven T2DM patients and 39 controls were enrolled. Arterial elasticity and CCA-IMT were quantitatively assessed by RF-data technology. The CCA diameters in the diastolic and systolic phases, carotid distensibility (CD), IMT, values of stiffness (β) and local pulse wave velocity (PWVβ) were measured and compared between the two groups., Results: The T2DM group had significantly larger CCA diastolic and systolic diameter, lower CD values, higher IMT measurements (all p < 0.001), and higher values of β and PWVβ (all P < 0.05) than the controls. Significant differences were not revealed in the mean values of IMT, β, PWVβ and CD across both sides of the CCA (all P > 0.05)., Conclusions: Higher IMT measurement and lower arterial elasticity of the CCA are significantly pronounced in asymptomatic T2DM patients and may suggest atherosclerotic changes, and the ultrasound RF-data technique may be used as a potential approach for detection of early-stage atherosclerosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background Increased carotid intima-media thickness, interadventitial diameter, presence of carotid plaque, and lower distensibility are predictors for cardiovascular disease. These indices likely relate to cerebrovascular disease, and thus may constitute a form of vascular contributions to dementia and Alzheimer disease-related dementia. Therefore, we assessed the relationship of carotid measurements and arterial stiffness with incident dementia in the ARIC (Atherosclerosis Risk in Communities) study. Methods and Results A total of 12 459 ARIC participants with carotid arterial ultrasounds in 1990 to 1992 were followed through 2017 for dementia. Dementia cases were identified using in-person and phone cognitive status assessments, hospitalization discharge codes, and death certificate codes. Cox proportional hazards models were used to estimate the hazard ratios (HRs) for incident dementia. Participants were aged 57±6 at baseline, 57% were women, and 23% were Black individuals. Over a median follow-up time of 24 years, 2224 dementia events were ascertained. After multivariable adjustments, the highest quintile of carotid intima-media thickness and interadventitial diameter in midlife was associated with increased risk of dementia (HR [95% CIs], 1.25 [1.08-1.45]; and 1.22 [1.04-1.43], respectively) compared with its respective lowest quintile. Presence of carotid plaque did not have a significant association with dementia (HR [95% CI], 1.06 [0.97-1.15]). Higher distensibility was associated with lower risk of dementia (HR [95% CI] highest versus lowest quintile, 0.76 [0.63-0.91]). Conclusions Greater carotid intima-media thickness, interadventitial diameter, and lower carotid distensibility are associated with an increased risk of incident dementia. These findings suggest that both atherosclerosis and carotid stiffness may be implicated in dementia risk.

Introduction: Like other autoimmune diseases, systemic sclerosis (SSc) has been described to be associated with accelerated atherosclerosis (ATS). Before clinical manifestations of cardiovascular disease (CVD) occur, subclinical ATS can be investigated in different ways., Aim: To evaluate the presence of subclinical ATS in a group of patients with SSc, and to identify different risk profiles among patients., Methods: Subclinical ATS was reviewed in 43 SSc patients and 27 healthy controls, using 2 methods: carotid ultrasound and flow mediated dilation (FMD) of the brachial artery., Results: Plaques were statistically more frequent in SSc patients than in controls (65% vs 30%, P = .006); intima-media thickness of common carotid artery (CCA-IMT) resulted in statistically higher (median value 0.8 mm vs 0.55 mm; P < .0001) while FMD was significantly lower (median value 9% vs 14%; P = .0086) in patients compared to healthy controls. Among the SSc patients, thickening of CCA-IMT was significantly associated with the presence of diastolic dysfunction of left ventricle (absence of diastolic dysfunction: odds ratio [OR] 0.2, 95% CI 0.04-0.92, P = .038) and with a higher Framingham score (OR 1.3, 95% CI 1.03-1.6], P = .024). The diffuse cutaneous form was slightly protective against pathological FMD (OR 0.12, 95% CI 0.022-0.71, P = .019)., Conclusions: This study confirms the involvement of macrocirculation in SSc patients, detecting the presence of subclinical ATS markers more frequently in patients compared to healthy controls. Framingham score, diastolic dysfunction of left ventricle and limited cutaneous form of the disease appeared to be associated with a higher risk of developing ATS., (© 2020 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Currently, there are various types of patches available on the market for carotid endarterectomy (CEA) with enlargement angioplasty, prosthetic, and biological patches including bovine pericardial patches. Despite the increasing use of these biological patches, there are little data in the literature comparing the results of these 2 types of patch. The purpose of this study is to compare the short- and long-term results of bovine pericardium patches (BPPs) with prosthetic patches (PPs) in carotid thromboendarterectomy., Methods: This study presents a retrospective analysis of all CEAs performed at Montpellier and Nîmes University Hospitals (France) in 2014 and 2015. Patients who underwent eversion were excluded. Preoperative, peroperative, and postoperative clinical and Doppler ultrasound results were collected and analyzed. The primary end point was the comparison of the restenosis rate between the BPP and the PP group. Secondary end points were the analysis of restenosis risk factors (type of patch, gender, renal failure, smoking, diabetes, arterial hypertension, dyslipidemia, and redo surgery were analyzed); the comparison of morbidity-mortality and infection between the BPP and the PP group and the comparison of morbidity-mortality between symptomatic and asymptomatic stenosis., Results: In total, 342 CEAs were performed: 168 (49%) with BPP and 174 (51%) with PP. Median follow-up was 30 months (interquartile range = 24). The stroke rate at day 30 was 3.22% and mortality at day 30 was 1.86%. There was no significant difference between groups concerning anyone of the variables of interest. At the end of follow-up, the restenosis rate >50% was 7.31% (6.45% for the BPP group vs. 8.22% for the PP group, P = 0.55). The severe restenosis rate (>70%) was 4.65% (5.16% for the BPP group vs. 4.11% for the PP group, P = 0.79). The univariate analysis identified renal failure (odds ratio = 2.69) as the main risk factor. The postoperative infection rate was 1.17% (0.59% for the BPP group vs. 1.75% for the PP group, P = 0.62)., Conclusions: The rates of stroke and postoperative death, bleeding, infection, and restenosis are comparable between BPPs and PPs in our study. The use of prosthetic or biological patches seems to deliver comparable outcomes. Further studies on larger samples are required., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: To determine whether macrovascular disease assessed by carotid ultrasonography and arterial stiffness by pulse wave velocity are independently associated with diabetic retinopathy in type 2 diabetes., Methods: A random subgroup of surviving participants with type 2 diabetes from the Fremantle Diabetes Study Phase II were invited to take part in this sub-study in 2018-2019. In addition to standardized questionnaires, a physical examination and fasting biochemical tests, each underwent dilated colour fundus photography, carotid arterial ultrasonography with measurement of the intima-media thickness (IMT) and quantification of the degree of stenosis, and pulse wave analysis calculation of the carotid-femoral pulse wave velocity (cfPWV). The cross-sectional association between arterial disease parameters and diabetic retinopathy was assessed using generalized estimating equation models which enabled both eyes to be included in the analysis., Results: Some 270 participants [mean ± sd age 72 ± 9 years, 153 (57%) men and median (IQR) diabetes duration 15 (11-22) years] were included in analysis. Of 524 assessable eyes, 82 (16%) had diabetic retinopathy. In multivariable analysis, significant independent associates of diabetic retinopathy were age at diabetes diagnosis (inversely), HbA 1c , insulin treatment and urinary albumin to creatinine ratio (all P ≤ 0.022), as well as cfPWV [odds ratio (OR) 1.13, 95% confidence interval (CI) 1.03, 1.23 per 1 m/s increase; P = 0.008] and common carotid artery (CCA) IMT ≥1 mm (OR 2.95, 95% CI 1.21, 7.23; P = 0.018)., Conclusions: The association between diabetic retinopathy and CCA IMT suggests that carotid disease may share cardiovascular risk factors with diabetic retinopathy. The association between diabetic retinopathy and cfPWV may reflect the consequences of altered intravascular haemodynamics., (© 2020 Diabetes UK.)

Background: To propose a protocol for the routine clinical use of duplex ultrasound (DUS) assessment after transcarotid artery revascularization (TCAR) procedures, with its specific point of vascular access, based on DUS data from routine clinical practice., Methods: DUS data were retrospectively collected at 2 centers from a total of 97 patients who underwent a TCAR procedure with at least 30-day and up to 12-month follow-up. Peak systolic velocity (PSV), end diastolic velocity (EDV), and the internal carotid artery (ICA)/common carotid artery (CCA) PSV ratio were collected at baseline (≤30 days after the procedure) and compared with subsequent measurements., Results: Baseline data were established within 30 days after the procedure. There were no access site stenoses, pseudoaneurysms, or dissections detected in follow-up. Average hemodynamics measurements at 12 months after the procedure (36% of patients reached this time point to date) were PSV 167 ± 153 cm/sec, EDV 51 ± 55 cm/sec, and ICA/CCA PSV 2.3 ± 1.9. Five patients (5.2%) exhibited velocities indicative of ≥80% in-stent restenosis (ISR) at 12 months after the procedure. Two patients (2.1%) underwent repeat intervention for ISR based on high velocities and before significant clinical consequence. The other 3 patients (3.1%) were asymptomatic and are being managed medically and monitored for neurological symptoms. One intraprocedural stroke (1.0% of total treated) was observed., Conclusions: This protocol not only illustrates the utility of using the CCA for the arterial access sheath for carotid stenting, but also successfully identifies patients with clinically significant restenosis >80%-99%. A surveillance regimen of baseline at ≤30 days after the procedure, followed by assessment at 6 and 12 months, and yearly thereafter appears to be a safe and effective protocol, based on the data available to date. A PSV >340 cm/sec and ICA/CCA ratio >4.15 is consistent with an 80-99% restenosis after TCAR. Although a small number, this study serves as a starting point for those who perform TCAR to specifically look at the CCA access site to rule out these potential pitfalls which did occur in the early trials., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The glucose-lowering independent effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on arterial wall function has not yet been clarified. This study aims to assess whether SGLT2i treatment can attenuate endothelial dysfunction related to type 2 diabetes mellitus (T2D) compared with glucose-lowering equivalent therapy., Methods: In a prospective, open-label, single-center, randomized clinical trial, 98 patients with T2DM and carotid intima-media thickness above the 75th percentile were randomized 1:1 to 12 weeks of therapy with dapagliflozin or glibenclamide in addition to metformin in glucose-lowering equivalent regimens. The coprimary endpoints were 1-min flow-mediated dilation (FMD) at rest and 1-min FMD after 15 min of ischemia followed by 15 min of reperfusion time (I/R)., Results: Ninety-seven patients (61% males, 57 ± 7 years) completed the study. The median HbA1c decreased by - 0.8 (0.7)% and -0.7 (0.95)% following dapagliflozin and glibenclamide, respectively. The first coprimary endpoint, i.e., rest FMD changed by + 3.3(8.2)% and - 1.2(7.5)% for the dapagliflozin and glibenclamide arms, respectively (p = 0.0001). Differences between study arms in the second coprimary endpoint were not significant. Plasma nitrite 1 min after rest FMD was higher for dapagliflozin [308(220) nmol/L] than for glibenclamide (258[110] nmol/L; p = 0.028). The resistive indices at 1 min [0.90 (0.11) vs. 0.93 (0.07); p = 0.03] and 5 min [0.93 (0.07) vs. 0.95 (0.05); p = 0.02] were higher for the glibenclamide group than for the dapagliflozin group. Plasma biomarkers for inflammation and oxidative stress did not differ between the treatments., Conclusions: Dapagliflozin improved micro- and macrovascular endothelial function compared to glibenclamide, regardless of glycemic control in patients with T2DM and subclinical carotid atherosclerotic disease.

The goal of this meta-analysis is to investigate whether carotid intraplaque neovascularization (IPN) on contrast-enhanced ultrasound (CEUS) correlates with past cardiovascular events (CVEs) and prognosis. The present meta-analysis included 22 studies involving 3232 patients. The pooled analysis revealed that the presence of IPN was significantly associated with a higher incidence of future CVEs (pooled relative risk = 3.28, 95% confidence interval [CI]: 2.28-4.73) and a lower event-free probability (pooled hazard ratio = 2.51, 95% CI: 1.48-4.27). The presence of IPN was significantly associated with higher rates of past cardiac events (odds ratio = 4.25, 95% CI: 2.48-7.29) and past cerebrovascular accidents (odds ratio = 4.83, 95% CI: 2.66-8.78). Our results suggest that carotid IPN on CEUS significantly correlates with past cardiac events and cerebrovascular accidents and can predict future CVEs. Carotid CEUS is useful in CVE risk stratification., Competing Interests: Conflict of interest disclosure The authors declare no competing interests., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Sarcoidosis is a multisystemic chronic inflammatory disease that the specific etiology is not known clearly. The aim of this study is, to investigate the presence of subclinical atherosclerosis and endothelial dysfunction by using carotid intima-media thickness and flow-mediated dilatation measurements, measuring the copeptin values, which is a stress marker, and interpreting the association of copeptin values with these two variables in sarcoidosis patients without conventional risk factors for coronary artery disease. Seventy-four patients (50 f, 24 m) with histopathological diagnosis of sarcoidosis and 60 healthy volunteers (35 f, 25 m) with similar sociodemographic characteristics were included in this study. CIMT, FMD, and serum copeptin levels of all participants were measured. The values of CIMT and Copeptin in sarcoidosis patients were significantly higher (p = 0.001, p < 0.001 respectively), and FMD was significantly lower (p = 0.01) than the control group. In sarcoidosis patients not significant correlation found among CIMT with copeptin (r: 0.16, p = 0.18) and FMD with copeptin (r: 0.01, p = 0.96). With the demonstration of the presence of subclinical atherosclerosis and endothelial dysfunction, we suggest; sarcoidosis patients may be followed more closely in terms of cardiovascular diseases. And new studies are needed to investigate the pathophysiology and the effects of high copeptin levels in sarcoidosis patients.

Background: Coronary artery disease is the primary cause of death in patients with carotid artery disease and silent ischemia is a marker for adverse coronary events. A new noninvasive cardiac diagnostic test, coronary computed tomography-derived fractional flow reserve (FFR CT ) can reliably identify ischemia-producing coronary stenosis in patients with coronary artery disease and help to select patients for coronary revascularization. The purpose of this study is to determine the prevalence of silent coronary ischemia in patients undergoing carotid endarterectomy (CEA) and to evaluate the usefulness of FFR CT in selecting patients for coronary revascularization to decrease cardiac events and improve survival., Methods: Patients with no cardiac history or symptoms admitted for elective CEA were enrolled in a prospective, open-label, institutional review board-approved study and underwent preoperative coronary computed tomography angiography (CTA) and FFR CT with results available to physicians for patient management. Lesion-specific coronary ischemia was defined as FFR CT of 0.80 or less distal to a focal coronary stenosis with an FFR CT of 0.75 or less, indicating severe ischemia. Primary end point was incidence of major adverse cardiovascular events (MACE; defined as cardiovascular death, myocardial infarction, or stroke) at 30 days and 1 year., Results: Coronary CTA and FFR CT was performed in 90 CEA patients (age 67 ± 8 years; male 66%). Lesion-specific coronary ischemia was found in 51 patients (57%) with a mean FFR CT of 0.71 ± 0.14. Severe coronary ischemia was present in 39 patients (43%), 26 patients had multivessel ischemia, and 5 had left main disease. CEA was performed as scheduled in all patients with no postoperative deaths or myocardial infarctions. There were no MACE events at 30 days. After recovery from surgery, 36 patients with significant lesion-specific ischemia underwent coronary angiography with coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) in 30 patients (33%). Survival at 1 year was 100% and freedom from MACE was 98%., Conclusions: Patients undergoing CEA have a high prevalence of unsuspected (silent) coronary ischemia, which may place them at risk for coronary events. Preoperative diagnosis of silent ischemia using CTA and FFR CT can identify high-risk patients and help to guide patient management. Selective postoperative coronary revascularization of patients with significant ischemia may decrease the risk of cardiac events and improve survival, but longer follow-up is needed and prospective, controlled trials are indicated., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

MRI can assess plaque composition and has demonstrated an association between some atherosclerotic risk factors (RF) and markers of plaque vulnerability in naive patients. We aimed at investigating this association in medically treated asymptomatic patients. This is a cross-sectional interim analysis (August 2013-September 2016) of a single center prospective study on carotid plaque vulnerability (MAGNETIC study). We recruited patients with asymptomatic carotid atherosclerosis (US stenosis > 30%, ECST criteria), receiving medical treatments at a tertiary cardiac rehabilitation. Atherosclerotic burden and plaque composition were quantified with 3.0 T MRI. The association between baseline characteristics and extent of lipid-rich necrotic core (LRNC), fibrous cap (CAP) and intraplaque hemorrhage (IPH) was studied with multiple regression analysis. We enrolled 260 patients (198 male, 76%) with median age of 71-y (interquartile range: 65-76). Patients were on antiplatelet therapy, ACE-inhibitors/angiotensin receptor blockers and statins (196-229, 75-88%). Median LDL-cholesterol was 78 mg/dl (59-106), blood pressure 130/70 mmHg (111-140/65-80), glycosylated hemoglobin 46 mmol/mol (39-51) and BMI 25 kg/m 2 (23-28); moreover, 125 out of 187 (67%) patients were ex-smokers. Multivariate analysis of a data-set of 487 (94%) carotid arteries showed that a history of hypercholesterolemia, diabetes, hypertension or smoking did not correlate with LRNC, CAP or IPH. Conversely, maximum stenosis was the strongest independent predictor of LRNC, CAP and IPH (p < 0.001). MRI assessment of plaque composition in patients on treatment for asymptomatic carotid atherosclerosis shows no correlation between plaque vulnerability and the most well-controlled modifiable RF. Conversely, maximum stenosis exhibits a strong correlation with vulnerable features despite treatment.