Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).

Cortico-limbic interactions and carotid atherosclerotic burden during chronic stress exposure.

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.

Impact of Carotid Siphon Calcification on the Course and Outcome of Patients With Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Carotid siphon calcification (CSC) serves as a marker of atherosclerosis and therefore may influence the outcome after subarachnoid hemorrhage (aSAH). We aimed to analyze the impact of CSC on neurological outcomes, ischemia, and vasospasm. METHODS: A total of 716 patients with aSAH were treated between December 2004 and June 2016 in our central European tertiary neurovascular care center in Essen, Germany. CSC was recorded using the Woodcock scale (grades 0-3) on a computed tomography scan. Study end points included an unfavorable outcome at 6 months post-aSAH (modified Rankin Scale score ≥4), vasospasm, and early cerebral ischemia (72 hours) and delayed cerebral ischemia (delayed cerebral ischemia; >72 hours) in the follow-up computed tomography scans. The associations were adjusted for patients' baseline characteristics and secondary complications. Finally, within a subgroup analysis, patients with and without daily aspirin intake after endovascular aneurysm occlusion were compared. RESULTS: Increasing grades of CSC were associated with lower rates of vasospasm in the anterior circulation. Severe CSC (grade 3) was independently related to the risk of an unfavorable outcome (adjusted odds ratio [aOR], 4.06 [95% CI, 1.98-8.33]; P<0.001) and early cerebral ischemia (aOR, 1.58 [95% CI, 1.03-2.43]; P=0.035) but not delayed cerebral ischemia (aOR, 1.08 [95% CI, 0.67-1.73]; P=0.763). In the aspirin subgroup analysis, the negative effect of severe CSC on functional outcome remained significant only in aSAH cases without aspirin (aOR, 5.47 [95% CI, 2.38-12.54]; P<0.001). In contrast, there was no association between severe CSC and unfavorable outcomes among individuals with daily aspirin intake (aOR, 0.84 [95% CI, 0.59-4.21]; P=0.603). CONCLUSIONS: Our data suggest CSC as a cerebrovascular risk factor resulting in higher rates of early cerebral ischemia and unfavorable outcomes after aSAH. However, by increasing arterial stiffness, CSC might lower the probability of vasospasm, which could explain the missing link between CSC and delayed cerebral ischemia. Additionally, aspirin intake seems to potentially mitigate the negative impact of CSC on aSAH outcome. Further investigations are needed to confirm the observations from the present study.

Combined Technique for Internal Carotid Artery Terminus or Middle Cerebral Artery Occlusions in the ASTER2 Trial.

BACKGROUND: The aim of this study was to report the results of a subgroup analysis of the ASTER2 trial (Effect of Thrombectomy With Combined Contact Aspiration and Stent Retriever vs Stent Retriever Alone on Revascularization in Patients With Acute Ischemic Stroke and Large Vessel Occlusion) comparing the safety and efficacy of the combined technique (CoT) and stent retriever as a first-line approach in internal carotid artery (ICA) terminus±M1-middle cerebral artery (M1-MCA) and isolated M1-MCA occlusions. METHODS: Patients enrolled in the ASTER2 trial with ICA terminus±M1-MCA and isolated M1-MCA occlusions were included in this subgroup analysis. The effect of first-line CoT versus stent retriever according to the occlusion site was assessed on angiographic (first-pass effect, expanded Treatment in Cerebral Infarction score ≥2b50, and expanded Treatment in Cerebral Infarction score ≥2c grades at the end of the first-line strategy and at the end of the procedure) and clinicoradiological outcomes (24-hour National Institutes of Health Stroke Scale, ECASS-III [European Cooperative Acute Stroke Study] grades, and 3-month modified Rankin Scale). RESULTS: Three hundred sixty-two patients were included in the postsubgroup analysis according to the occlusion site: 299 were treated for isolated M1-MCA occlusion (150 with first-line CoT) and 63 were treated for ICA terminus±M1-MCA occlusion (30 with first-line CoT). Expanded Treatment in Cerebral Infarction score ≥2b50 (odds ratio, 11.83 [95% CI, 2.32-60.12]) and expanded Treatment in Cerebral Infarction score ≥2c (odds ratio, 4.09 [95% CI, 1.39-11.94]) were significantly higher in first-line CoT compared with first-line stent retriever in patients with ICA terminus±M1-MCA occlusion but not in patients with isolated M1-MCA. CONCLUSIONS: First-line CoT was associated with higher reperfusion grades in patients with ICA terminus±M1-MCA at the end of the procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03290885.

Association of HIV and HCV Infection With Carotid Artery Plaque Echomorphology in the MACS/WIHS Combined Cohort Study.

BACKGROUND: HIV and hepatitis C virus (HCV) are associated with increased risk of carotid artery atherosclerotic plaque and stroke. We examined associations of HIV- and HCV-related factors with echomorphologic features of carotid artery plaque. METHODS: This cross-sectional study included participants from the MACS (Multicenter AIDS Cohort Study)/WIHS (Women's Interagency HIV Study) Combined Cohort Study who underwent high-resolution B-mode carotid artery ultrasound. Plaques were characterized from 6 areas of the right carotid artery. Poisson regression controlling for demographic and cardiometabolic risk factors determined adjusted prevalence ratios (aPRs) and 95% CIs for associations of HIV- and HCV-related factors with echomorphologic features. RESULTS: Of 2655 participants (65% women, median age 44 [interquartile range, 37-50] years), 1845 (70%) were living with HIV, 600 (23%) were living with HCV, and 425 (16%) had carotid plaque. There were 191 plaques identified in 129 (11%) women with HIV, 51 plaques in 32 (7%) women without HIV, 248 plaques in 171 (28%) men with HIV, and 139 plaques in 93 (29%) men without HIV. Adjusted analyses showed that people with HIV and current CD4+ count <200 cells/µL had a significantly higher prevalence of predominantly echolucent plaque (aPR, 1.86 [95% CI, 1.08-3.21]) than those without HIV. HCV infection alone (aPR, 1.86 [95% CI, 1.08-3.19]) and HIV-HCV coinfection (aPR, 1.75 [95% CI, 1.10-2.78]) were each associated with higher prevalence of predominantly echogenic plaque. HIV-HCV coinfection was also associated with higher prevalence of smooth surface plaque (aPR, 2.75 [95% CI, 1.03-7.32]) compared with people without HIV and HCV. CONCLUSIONS: HIV with poor immunologic control, as well as HCV infection, either alone or in the presence of HIV, were associated with different echomorphologic phenotypes of carotid artery plaque.

Abnormal vascular thickness and stiffness in young adults with type 1 diabetes: new insights from cutting-edge ultrasound modalities.

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/m2), 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.

Relationships of serum FGF23 and α-klotho with atherosclerosis in patients with type 2 diabetes mellitus.

BACKGROUND: Compelling evidence suggests that calcium/phosphorus homeostasis-related parameters may be linked to diabetes mellitus and cardiovascular events. However, few studies have investigated the association of fibroblast growth factor 23 (FGF23), α-klotho and FGF23/α-klotho ratio with atherosclerosis in patients with type 2 diabetes mellitus (T2DM). OBJECTIVE: This study was designed to evaluate whether FGF23, α-klotho and FGF23/α-klotho ratio are associated with T2DM and further to explore the relationships between these three factors and atherosclerosis in Chinese patients with T2DM. METHODS: Serum FGF23 and α-klotho levels were measured via an enzyme-linked immunosorbent assay (ELISA) kit, and the carotid intima-media thickness (CIMT) was assessed via high-resolution color Doppler ultrasonography. The associations of serum FGF23, α-klotho and FGF23/α-klotho ratio with atherosclerosis in T2DM patients were evaluated using multivariable logistic regression models. RESULTS: This cross-sectional study involved 403 subjects (207 with T2DM and 196 without T2DM), 41.7% of the patients had atherosclerosis, and 67.2% of the carotid intima were thickened to a thickness greater than 0.9 mm. Compared with those in the lowest tertile, higher tertiles of FGF23 levels and FGF23/α-klotho ratio were positively associated with T2DM after adjusting for covariates, and serum α-klotho concentration was inversely correlated with T2DM (all P values < 0.01). Moreover, elevated serum FGF23 levels and FGF23/α-klotho ratio were positively associated with CIMT and carotid atherosclerosis in T2DM patients (all P values < 0.01). Further spline analysis similarly revealed linear dose‒response relationship (all P values < 0.01). And there was still significant differences in CIMT and carotid atherosclerosis between the highest group of α-klotho and the reference group in T2DM patients (P values = 0.05). CONCLUSIONS: T2DM was positively linearly related to serum FGF23 concentration and FGF23/α-klotho ratio, and negatively correlated with serum α-klotho concentration. Furthermore, both FGF23 and FGF23/α-klotho ratio were positively correlated with CIMT and atherosclerosis in T2DM patients, while α-klotho was inversely correlated with both CIMT and atherosclerosis, although the associations were not completely significant. Prospective exploration and potential mechanisms underlying these associations remain to be further elucidated.

Modulation of circulating levels of advanced glycation end products and its impact on intima-media thickness of both common carotid arteries: CORDIOPREV randomised controlled trial.

BACKGROUND: Increasing evidence supports the role of advanced glycation end products (AGEs) in atherosclerosis in both diabetic and non-diabetic patients, suggesting that therapeutic strategies targeting AGEs may offer potential benefits in this population. The Mediterranean diet is associated with improved biomarkers and anthropometric measurements related with atherosclerosis in addition to its ability to modulate AGE metabolism. Our aim was to determine whether the reduction in atherosclerosis progression (measured by changes in intima-media thickness of both common carotid arteries (IMT-CC)), observed after consumption of a Mediterranean diet compared to a low-fat diet, is associated with a modulation of circulating AGE levels in patients with coronary heart disease (CHD). METHODS: 1002 CHD patients were divided in: (1) Non-increased IMT-CC patients, whose IMT-CC was reduced or not changed after dietary intervention and (2) Increased IMT-CC patients, whose IMT-CC was increased after dietary intervention. Serum AGE levels (methylglyoxal-MG and Nε-Carboxymethyllysine-CML) and parameters related to AGE metabolism (AGER1 and GloxI mRNA and sRAGE levels) and reduced glutathione (GSH) levels were measured before and after 5-years of dietary intervention. RESULTS: The Mediterranean diet did not affect MG levels, whereas the low-fat diet significantly increased them compared to baseline (p = 0.029), leading to lower MG levels following the Mediterranean diet than the low-fat diet (p < 0.001). The Mediterranean diet, but not the low-fat diet, produced an upregulation of AGE metabolism, with increased AGER1 and GloxI gene expression as well as increased GSH and sRAGE levels in Non-increased IMT-CC patients (all p < 0.05). Although the Mediterranean diet increased MG levels in Increased IMT-CC patients, this increment was lower compared to the low-fat diet (all p < 0.05). CONCLUSIONS: Our results suggest that an improvement in modulation of AGE metabolism, which facilitates better management of circulating AGE levels, may be one of the mechanisms through which the Mediterranean diet, compared to a low-fat diet, reduces the progression of atherosclerosis in patients with CHD. Trial registration https://clinicaltrials.gov/ct2/show/NCT00924937 , Clinicaltrials.gov number, NCT00924937.

Plasma proteome association with coronary heart disease and carotid intima media thickness: results from the KORA F4 study.

BACKGROUND AND AIMS: Atherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with CHD and with carotid intima-media thickness (CIMT), as a surrogate measure of atherosclerosis. METHODS: The discovery phase included 1000 participants from the KORA F4 study, whose plasma protein levels were quantified using the aptamer-based SOMAscan proteomics platform. We evaluated the associations of plasma protein levels with CHD using logistic regression, and with CIMT using linear regression. For both outcomes we applied two models: an age-sex adjusted model, and a model additionally adjusted for body mass index, smoking status, physical activity, diabetes status, hypertension status, low density lipoprotein, high density lipoprotein, and triglyceride levels (fully-adjusted model). The replication phase included a matched case-control sample from the independent KORA F3 study, using ELISA-based measurements of galectin-4. Pathway analysis was performed with nominally associated proteins (p-value < 0.05) from the fully-adjusted model. RESULTS: In the KORA F4 sample, after Bonferroni correction, we found CHD to be associated with five proteins using the age-sex adjusted model: galectin-4 (LGALS4), renin (REN), cathepsin H (CTSH), and coagulation factors X and Xa (F10). The fully-adjusted model yielded only the positive association of galectin-4 (OR = 1.58, 95% CI = 1.30-1.93), which was successfully replicated in the KORA F3 sample (OR = 1.40, 95% CI = 1.09-1.88). For CIMT, we found four proteins to be associated using the age-sex adjusted model namely: cytoplasmic protein NCK1 (NCK1), insulin-like growth factor-binding protein 2 (IGFBP2), growth hormone receptor (GHR), and GDNF family receptor alpha-1 (GFRA1). After assessing the fully-adjusted model, only NCK1 remained significant (ß = 0.017, p-value = 1.39e-06). Upstream regulators of galectin-4 and NCK1 identified from pathway analysis were predicted to be involved in inflammation pathways. CONCLUSIONS: Our proteome-wide association study identified galectin-4 to be associated with CHD and NCK1 to be associated with CIMT. Inflammatory pathways underlying the identified associations highlight the importance of inflammation in the development and progression of CHD.

Unseen threat: how subclinical atherosclerosis increases mortality risk in patients with type 1 diabetes.

BACKGROUND: Cardiovascular disease (CVD), particularly ischemic heart disease, remains the leading cause of death and morbidity in patients with type 1 diabetes. Detecting subclinical atherosclerosis could enhance cardiovascular risk stratification and enable individualised therapies. The aim of this study is to investigate the prevalence and predictors of subclinical atherosclerosis in patients with type 1 diabetes without overt cardiovascular disease (CVD) and to assess its impact on patient survival over a follow-up period of at least 5 years. METHODS: This observational study included 507 patients treated at the Diabetes Unit of the Hospital of Girona Doctor Josep Trueta between 2015 and 2023. The inclusion criteria for patients were as follows: those aged 18 and older with diabetes for a minimum of 10 years or those aged 40 and older with a diabetes for at least 5 years. Subclinical atherosclerosis was identified via ultrasound imaging of the carotid and femoral arteries. Clinical and biochemical evaluations were also conducted. Major cardiovascular events (MACE) and deaths from other causes were monitored, and survival analysis was performed using Kaplan‒Meier methods. RESULTS: Subclinical atherosclerosis was detected in 218 patients (43%). Multivariate analysis revealed that the male sex, diabetic nephropathy, tobacco exposure, higher HbA1c levels, older age, and longer diabetes duration were significant predictors. During a mean follow-up of 70.64 ± 27.08 months, 19 patients experienced MACE, and 13 died from any cause. The probability of MACE or death was greater in patients with subclinical atherosclerosis, with a hazard ratio (HR) of 25.1 (95% CI 5.81-108, p < 0.001) for MACE and an odds ratio (OR) of 7.57 (95% CI 1.97-53.9, p = 0.004) for death. CONCLUSION: Subclinical atherosclerosis is independently associated with increased overall mortality and MACE in patients with type 1 diabetes. Identifying clinical predictors can improve risk stratification and personalised therapeutic strategies to prevent MACEs in this high-risk population.

Pentoxifylline ameliorates subclinical atherosclerosis progression in patients with type 2 diabetes and chronic kidney disease: a randomized pilot trial.

BACKGROUND: Diabetic kidney disease (DKD) is associated with a higher risk of cardiovascular disease (CVD). Pentoxifylline (PTF), a nonselective phosphodiesterase inhibitor with anti-inflammatory, antiproliferative, and antifibrotic actions, has demonstrated renal benefits in both clinical trials and meta-analyses. The present work aimed to study the effects of PTF on the progression of subclinical atherosclerosis (SA) in a population of patients with diabetes and moderate to severe chronic kidney disease (CKD). METHODS: In this open-label, randomized controlled, prospective single-center pilot study the evolution of carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) were determined in 102 patients with type 2 diabetes mellitus and CKD assigned to PTF, aspirin or control groups during 18 months. We also determined the variations in the levels of inflammatory markers and Klotho (KL), a protein involved in maintaining cardiovascular health, and their relationship with the progression of SA. RESULTS: Patients treated with PTF presented a better evolution of CIMT, increased KL mRNA levels in peripheral blood cells (PBCs) and reduced the inflammatory state. The progression of CIMT values was inversely related to variations in KL both in serum and mRNA expression levels in PBCs. Multiple regression analysis demonstrated that PTF treatment and variations in mRNA KL expression in PBCs, together with changes in HDL, were significant determinants for the progression of CIMT (adjusted R2 = 0.24, P < 0.001) independently of traditional risk factors. Moreover, both variables constituted protective factors against a worst progression of CIMT [OR: 0.103 (P = 0.001) and 0.001 (P = 0.005), respectively]. CONCLUSIONS: PTF reduced SA progression assessed by CIMT variation, a beneficial effect related to KL gene expression in PBCs. TRIAL REGISTRATION: The study protocol code is PTF-AA-TR-2009 and the trial was registered on the European Union Drug Regulating Authorities Clinical Trials (EudraCT #2009-016595-77). The validation date was 2010-03-09.

Characteristics and Correlations of Wall Shear Stress and Flow Turbulence in the Carotid Bifurcation Evaluated Using an Ultrasound Vector Flow Imaging.

INTRODUCTION: The aim of the study was to evaluate characteristics and provide the normal values of wall shear stress (WSS) and flow turbulence (Tur), and the relationship between them in the carotid bifurcation based on an ultrasound vector flow imaging (V Flow) in healthy adults. METHODS: Max and mean WSS and Tur values at three segments (initial segments of internal and external carotid arteries [IICA and IECA]; distal segment of common carotid artery [DCCA]), both in anterior and posterior walls, were successfully obtained in 56 healthy adults, using ultrasound V Flow function. Relationship between mean WSS and Tur was further explored. RESULTS: The mean WSS value was 0.71 Pa, 0.86 Pa, and 0.96 Pa at IICA, IECA, and DCCA, respectively (IICA < IECA < DCCA, p < 0.05). The mean Tur value was 13.85%, 5.46%, and 4.17% at IICA, IECA, and DCCA, respectively (IICA > IECA > DCCA, p < 0.05). A cutoff value (WSS = 0.4 Pa) was selected and Tur values were significantly higher in group with WSS cutoff value <0.4 Pa than group with WSS cutoff value ≥0.4 Pa (p < 0.01). CONCLUSION: WSS and Tur are moderately negatively correlated, which can be used in the quantitative evaluation of carotid bifurcation and could be a potential dual-parameter tool in the clinical research for early detection of carotid atherosclerosis.

Assessment for Carotid Atherosclerotic Plaque Using Vessel Wall Magnetic Resonance Imaging: A Multireader ROC Study to Determine Optimal Sequence for Detecting Vessel Wall Calcification.

INTRODUCTION: We aimed to compare conventional vessel wall MR imaging techniques and quantitative susceptibility mapping (QSM) to determine the optimal sequence for detecting carotid artery calcification. METHODS: Twenty-two patients who underwent carotid vessel wall MR imaging and neck CT were enrolled. Four slices of 6-mm sections from the bilateral internal carotid bifurcation were subdivided into 4 segments according to clock position (0-3, 3-6, 6-9, and 9-12) and assessed for calcification. Two blinded radiologists independently reviewed a total of 704 segments and scored the likelihood of calcification using a 5-point scale on spin-echo imaging, FLASH, and QSM. The observer performance for detecting calcification was evaluated by a multireader, multiple-case receiver operating characteristic study. Weighted κ statistics were calculated to assess interobserver agreement. RESULTS: QSM had a mean area under the receiver operating characteristic curve of 0.85, which was significantly higher than that of any other sequence (p < 0.01) and showed substantial interreader agreement (κ = 0.68). A segment with a score of 3-5 was defined as positive, and a segment with a score of 1-2 was defined as negative; the sensitivity and specificity of QSM were 0.75 and 0.87, respectively. CONCLUSION: QSM was the most reliable MR sequence for the detection of plaque calcification.

Relationship between nailfold videocapillaroscopic findings and cardiovascular risk factors.

BACKGROUND: Nailfold Videocapillaroscopy (NVC) is a valuable tool in the differential diagnosis of Raynaud's phenomenon (RP), present in certain Rheumatic diseases (RD). Knowing that many people have cardiovascular risk factors (CVRF), the main objective was to demonstrate that CVRF and carotid plaques produce NVC alterations. METHODS: Cross-sectional unicentric study carried out from 2020 to 2023. Four groups were formed: subjects with RD and RP, participants with RD without RP, subjects with RP without RD and finally participants without RP or RD (study group). Each subject exhibiting CVRF presented only a single risk factor. The variables collected were: sociodemographic, CVRF (diabetes, tobacco, alcohol (ALC), obesity (OBE), dyslipidemia and arterial hypertension (AH)), diseases, RP, treatments, tortuosities and NVC alterations (ramified capillaries, enlarged capillaries, giant capillaries, haemorrhages and density loss) and carotid ultrasound (CU). RESULTS: 402 subjects were included (76 % women, mean age 51 ± 16 years), 67 % had CVRF, 50 % RP and 38 % RD. Tortuosities were present in 100 % of CVRF participants. A statistically significant association was found between the presence of CVRF and all the NVC alterations: ramified capillaries (OR = 95.6), enlarged capillaries (OR = 59.2), giant capillaries (OR = 8.32), haemorrhages (OR = 17.6) and density loss (OR = 14.4). In particular, an association was found between giant capillaries with AH (p = 0,008) and OBE (p ã€ˆ0,001), and haemorrhages and density loss with ALC and OBE (p < 0,001). On the other hand, 40 subjects presented CU plaques (9.9 %), associated with enlarged capillaries (OR = 8.08), haemorrhages (OR = 4.04) and ramified capillaries (OR = 3.01). The pathological intima-media thickness was also associated with haemorrhages (OR = 3.14). CONCLUSIONS: There is a clear association between CVRF and ultrasound atherosclerotic findings in carotid with NVC alterations. These findings are of special interest for a correct NVC interpretation and to avoid false positives in the diagnosis of primary and secondary RP.

Intracranial arterial calcification in patients with unruptured and ruptured intracranial aneurysms.

OBJECTIVES: Arterial calcification is thought to protect against rupture of intracranial aneurysms, but studies in a representative population of intracranial aneurysm patients have not yet been performed. The aim was to compare the prevalence of aneurysm wall calcification and intracranial carotid artery calcification (ICAC) between patients with an unruptured intracranial aneurysm (UIA) and a ruptured intracranial aneurysm (RIA). MATERIALS AND METHODS: We matched 150 consecutive UIA patients to 150 RIA patients on age and sex. Aneurysm wall calcification and ICAC were quantified on non-contrast enhanced computed tomography images with the modified Agatston score. We compared the prevalence of aneurysm wall calcification, ICAC, and severe ICAC (defined as a modified Agatston score in the fourth quartile) between UIA and RIA patients using univariate and multivariate conditional logistic regression models adjusted for aneurysm characteristics and cardiovascular risk factors. RESULTS: Aneurysm wall calcification was more prevalent in UIA compared to RIA patients (OR 5.2, 95% CI: 2.0-13.8), which persisted after adjustment (OR 5.9, 95% CI: 1.7-20.2). ICAC prevalence did not differ between the two groups (crude OR 0.9, 95% CI: 0.5-1.8). Severe ICAC was more prevalent in UIA patients (OR 2.0, 95% CI: 1.1-3.6), but not after adjustment (OR 1.0, 95% CI: 0.5-2.3). CONCLUSIONS: Aneurysm wall calcification but not ICAC was more prevalent in UIAs than in RIAs, which corresponds to the hypothesis that calcification may protect against aneurysmal rupture. Aneurysm wall calcification should be further assessed as a predictor of aneurysm stability in prospective cohort studies. CLINICAL RELEVANCE STATEMENT: Calcification of the intracranial aneurysm wall was more prevalent in unruptured than ruptured intracranial aneurysms after adjustment for cardiovascular risk factors. Calcification may therefore protect the aneurysm against rupture, and aneurysm wall calcification is a candidate predictor of aneurysm stability. KEY POINTS: Aneurysm wall calcification was more prevalent in patients with unruptured than ruptured aneurysms, while internal carotid artery calcification was similar. Aneurysm wall calcification but not internal carotid artery calcification is a candidate predictor of aneurysm stability. Cohort studies are needed to assess the predictive value of aneurysm wall calcification for aneurysm stability.

Aortic Stiffness Is Independently Associated with Intracranial Carotid Artery Calcification in Patients with Ischemic Stroke.

INTRODUCTION: Intracranial carotid artery calcification (ICAC), as a strong contributor to the occurrence of ischemic stroke, might be present in the medial or intimal arterial layer. Traditional cardiovascular risk factors (CVRFs) are associated with ICAC; however, its association with new markers of vascular function is less understood. The paper aimed to evaluate the relationship between carotid-femoral pulse wave velocity (CF-PWV) and ICAC subtypes. METHODS: We enrolled 65 patients with ischemic stroke. CF-PWV, systolic, diastolic, mean blood pressure, and pulse pressure were measured within 6 ± 2 days after stroke onset, and CT was performed within 24 h. ICAC on the stroke site was classified by two methods: volume and score based. Tertiles of ICAC volume were determined, and low-grade ICAC (T1) was regarded as a reference. According to the score-based method, (dominant) medial and (dominant) intimal ICAC subtypes were determined. Data were analyzed with multivariate logistic regression. RESULTS: Medial and intimal ICAC subtypes were found in 34 (52%) and 24 (37%) patients, respectively. In 11% of patients, no ICAC calcifications were found. CF-PWV was higher in patients with high-grade ICAC (OR = 1.56, 95% CI = 1.03-2.35, p = 0.035). CF-PWV was higher in patients with the medial ICAC subtype (OR = 1.60, 95% CI = 1.00-2.55, p = 0.049) after adjustment for traditional CVRFs. CONCLUSION: Our study demonstrates that among patients with ischemic stroke, aortic stiffness is independently associated with ICAC and that medial ICAC, compared with intimal ICAC, is accompanied by more advanced aortic stiffness.

The Influence of Embolization of Internal Carotid Artery Aneurysms on Arterial Tortuosity: A Prospective Cohort Study.

PURPOSE: To measure changes in quantitative tortuosity descriptors of the internal carotid artery (ICA) after intracranial aneurysm embolization, and to determine possible factors associated with changes in tortuosity. MATERIALS AND METHODS: An analysis of 52 patients with embolized intracranial aneurysms was performed. ICA tortuosity was assessed by digital subtraction angiograms obtained prior to the embolization and after the first follow-up examination. For each patient, tortuosity descriptors were calculated: relative length (RL), sum of angle metrics (SOAM), triangular index, product of angle distance (PAD), and inflection count metric (ICM). To represent changes in tortuosity for each descriptor, delta (Δ) value was defined as value of the descriptor prior to embolization minus value of the descriptor on follow-up examination. RESULTS: In a median follow-up of 14 months, no statistically significant changes in tortuosity were observed on the nonembolized side. On the embolized side, SOAM (2.89 [SD ± 0.92] vs 2.38 [SD ± 0.94]; P < .001), PAD (5.01 [SD ± 1.83] vs 3.95 [SD ± 1.72]; P < .001), and ICM (12.18 [SD ± 4.55] vs 9.76 [SD ± 4.04]; P = .006) were significantly higher after embolization than before embolization. Median ΔRL (-0.02 [-0.045 to 0.002] vs -0.01 [-0.02 to 0.003]; P = .003), ΔPAD (0.84 [0.30-1.82] vs 0.10 [-0.001 to 1.10]; P < .001), and ΔICM (2.05 [0.42-3.50] vs 0.27 [0.02-2.16]; P = .004) were significantly higher on the embolized side. Tortuosity correlated with elapsed time after embolization. CONCLUSIONS: Tortuosity of the ipsilateral ICA increased after intracranial aneurysm embolization.

Association Between Serum Bilirubin, Lipid Levels, and Prevalence of Femoral and Carotid Atherosclerosis: A Population-Based Cross-Sectional Study.

BACKGROUND: Bilirubin may prevent lipid peroxidation and have important antiatherosclerotic effects. We determined associations of serum bilirubin and lipid with peripheral atherosclerosis. METHODS: We included 4290 participants (35% men; median age, 60 years) from the southeast China who underwent B-mode ultrasound examination. Increased intima-media thickness or a focal structure encroaching into the arterial lumen by at least 0.5 mm or >50% of the surrounding intima-media thickness value was regarded as having atherosclerosis. Fasting serum bilirubin and lipid levels were measured. Cholesterol/(HDL [high-density lipoprotein] cholesterol+bilirubin), and LDL (low-density lipoprotein cholesterol)/(HDL+bilirubin) ratios were calculated. Unconditional and multinomial logistic regression models were used to examine associations of bilirubin or lipid with prevalence of peripheral atherosclerosis. Mediation analyses were performed to assess the effect of bilirubin on atherosclerosis risk mediated via lipid. RESULTS: Compared with participants with the lowest levels of bilirubin, those with the highest tertile were less likely to have carotid or femoral atherosclerosis (odds ratios were 0.55-0.74). The highest levels of bilirubin significantly reduced the odds of concurrent carotid and femoral atherosclerosis by 35% to 45%. Participants with the highest levels of cholesterol, LDL, cholesterol/(HDL+bilirubin), and LDL/(HDL+bilirubin) ratios had 2.8- to 3.7-fold increased odds of concurrent carotid and femoral atherosclerosis. LDL accounted for 25.65% of the total bilirubin-atherosclerosis association. LDL and cholesterol mediated the associations between direct bilirubin and atherosclerosis (proportion: 20.40%, 9.67%, respectively). CONCLUSIONS: Increased serum bilirubin levels are inversely associated with the prevalence of carotid or femoral atherosclerosis. LDL and cholesterol may mediate these associations.

Endovascular Management of Post-Irradiated Carotid Blowout Syndrome in Patients with Lower Neck Cancers.

OBJECTIVE: Lower neck cancers (LNCs) include specific tumour types and have some different vascular supply or collaterals from other head and neck cancers. This prospective study evaluated the outcome of endovascular management of post-irradiated carotid blowout syndrome (PCBS) in patients with LNC by comparing reconstructive management (RE) and deconstructive management (DE). METHODS: This was a single centre, prospective cohort study. Patients with LNC complicated by PCBS between 2015 and 2021 were enrolled for RE or DE. RE was performed by stent graft placement covering the pathological lesion and preventive external carotid artery (ECA) embolisation without balloon test occlusion (BTO). DE was performed after successful BTO by permanent coil or adhesive agent embolisation of the internal carotid artery (ICA) and ECA to common carotid artery, or ICA occlusion alone if the pathological lesion was ICA only. Cross occlusion included the proximal and distal ends of the pathological lesion in all patients. Re-bleeding events, haemostatic period, and neurological complications were evaluated. RESULTS: Fifty-nine patients (mean age 58.5 years; 56 male) were enrolled, including 28 patients undergoing RE and 31 patients undergoing DE. Three patients originally grouped to DE were transferred to RE owing to failed BTO. The results of RE vs. DE were as follows: rebleeding events, 13/28 (46%) vs. 10/31 (32%) (p = .27); haemostatic period, 9.4 ± 14.0 months vs. 14.2 ± 27.8 months (p = .59); neurological complication, 4/28 (14%) vs. 5/31 (16%) (p = .84); and survival time, 11.8 ± 14.6 months vs. 15.1 ± 27.5 months (p = .61). CONCLUSION: No difference in rebleeding risk or neurological complications was observed between the DE and RE groups. RE could be used as a potential routine treatment for PCBS in patients with LNC.

The prevalence and independent risk factors of elevated common carotid artery intima-media thickness and carotid plaque in patients with gout.

OBJECTIVES: Gout patients are at high risk of carotid atherosclerosis, which could be convincingly reflected by common carotid artery intima-media thickness (CCAIMT) and carotid plaque. The current study aimed to investigate the prevalence and risk factors of thick CCAIMT and carotid plaque in gout patients. METHODS: Comprehensive demographic characteristics, chronic comorbidities, disease features, and biochemical indexes (42 parameters) were obtained from 237 gout patients. CCAIMT and carotid plaque were evaluated by bilateral carotid artery ultrasound in gout patients and 80 healthy controls. RESULTS: The CCAIMT and carotid plaque percentage were increased in gout patients compared to healthy controls (both p<0.001). In detail, the prevalence of thick CCAIMT (>0.9 mm) and carotid plaque was 22.4% and 34.6% in gout patients, respectively. Forward-stepwise multivariate logistic regression model revealed that age (p<0.001, odds ratio (OR)=1.143], disease duration (p=0.001, OR=1.176), alkaline phosphatase (ALP) (p=0.002, OR=1.037), and low-density lipoprotein cholesterol (LDLC) (p=0.039, OR=2.144) were independently associated with elevated thick CCAIMT risk, while serum uric acid (SUA) (p=0.002, OR=0.992) exhibited an opposite trend; their combination well-identified thick CCAIMT risk [area under the curve (AUC)=0.910] by receiver operator characteristic (ROC) curve. Meanwhile, age (p<0001, OR=1.116), tophus (p=0.009, OR=3.523), and triglycerides (TG) (p=0.014, OR=1.323) were independently associated with a higher risk of carotid plaque, while SUA (p=0.008, OR=0.995) showed an opposite trend; their combination also well-identified carotid plaque risk (AUC=0.886) by ROC curve. CONCLUSIONS: Thick CCAIMT and carotid plaque are prevalent in gout patients, whose occurrence relates to age, disease duration, ALP, LDLC, SUA, TG, and tophus.