Common and distinct risk profiles of asymptomatic extra- and intracranial atherosclerosis in the Nagahama cohort.

BACKGROUND AND PURPOSE: Atherosclerotic burden increases the risk of both extracranial internal carotid artery stenosis (ICS) and intracranial large artery disease (ICAD). However, the differences in risk profiles have not been thoroughly investigated. METHODS: Participants were recruited from the Nagahama study cohort in Japan. Individuals over 60 years old who underwent 1.5-T head and neck magnetic resonance angiography (MRA) between July 2013 and February 2017 were included. ICAD was defined as WASID ≥ 50 %, and ICS was defined as NSCET ≥ 30 %. The prevalence and association of risk factors, including proatherogenic and proinflammatory factors, and the p.R4810K variant in the RNF213 gene, were investigated. Multivariable logistic regression analyses were performed. RESULTS: A total of 3089 individuals participated in the study, with a mean age of 68.1 ± 5.3 years, and 36.0 % were males. Among them, 52 (1.7 %) had ICS, 119 (3.8 %) had ICAD, and 15 (0.49 %) had both conditions. Alopecia areata was an independent predictor for both ICS (Odds ratio [OR] 3.5; 95 % CI 1.3-8.3) and ICAD (OR 2.1; 95 % CI 1.0-3.9). Diabetes (OR 3.7; 95 % CI 2.0-7.0) and older age (OR 2.4; 95 % CI 1.2-4.5) were associated only with ICS, while the RNF213 variant was associated with only ICAD (OR 5.7; 95 % CI 1.6-16.0). ICS and ICAD were also independently associated with each other. CONCLUSIONS: In this MRA-based large scale study, alopecia areata, known as a systemic inflammatory disease, was shown to be a common risk factor for ICS and ICAD. While conventional atherosclerotic factors were associated with ICS, non-atherosclerotic factors appear to contribute to ICAD in Japan.

Development and validation of a clinical prediction model for ischemic stroke recurrence after successful stent implantation in symptomatic intracranial atherosclerotic stenosis.

OBJECTIVE: This study aimed to analyze the risk factors for recurrent ischemic stroke in patients with symptomatic intracranial atherosclerotic stenosis (ICAS) who underwent successful stent placement and to establish a nomogram prediction model. METHODS: We utilized data from a prospective collection of 430 consecutive patients at Jining NO.1 People's Hospital from November 2021 to November 2022, conducting further analysis on the subset of 400 patients who met the inclusion criteria. They were further divided into training (n=321) and validation (n=79) groups. In the training group, we used univariate and multivariate COX regression to find independent risk factors for recurrent stroke and then created a nomogram. The assessment of the nomogram's discrimination and calibration was performed through the examination of various measures including the Consistency index (C-index), the area under the receiver operating characteristic (ROC) curves (AUC), and the calibration plots. Decision curve analysis (DCA) was used to evaluate the clinical utility of the nomogram by quantifying the net benefit to the patient under different threshold probabilities. RESULTS: The nomogram for predicting recurrent ischemic stroke in symptomatic ICAS patients after stent placement utilizes six variables: coronary heart disease (CHD), smoking, multiple ICAS, systolic blood pressure (SBP), in-stent restenosis (ISR), and fasting plasma glucose. The C-index (0.884 for the training cohort and 0.87 for the validation cohort) and the time-dependent AUC (>0.7) indicated satisfactory discriminative ability of the nomogram. Furthermore, DCA indicated a clinical net benefit from the nomogram. CONCLUSIONS: The predictive model constructed includes six predictive factors: CHD, smoking, multiple ICAS, SBP, ISR and fasting blood glucose. The model demonstrates good predictive ability and can be utilized to predict ischemic stroke recurrence in patients with symptomatic ICAS after successful stent placement.

Association between BMI-based metabolic phenotypes and prevalence of intracranial atherosclerotic stenosis: a cross-sectional study.

BACKGROUND: Obesity and metabolic syndrome (MetS) have been acknowledged to commonly co-exist and lead to increased risks of stroke, whereas the association between various BMI-based metabolic phenotypes and development of intracranial atherosclerotic stenosis (ICAS) remained controversial. METHODS: A total of 5355 participants were included from the Asymptomatic Polyvascular Abnormalities Community (APAC) study. Participants were categorized into six groups according to their body mass index (BMI) and MetS status. ICAS was assessed using transcranial Doppler (TCD) Ultrasonography. Logistic regression was employed to evaluate the association between BMI-based metabolic phenotypes and ICAS. RESULTS: 704 participants were diagnosed with ICAS. Compared to the metabolic healthy normal weight (MH-NW) group, the metabolic unhealthy normal weight (MUH-NW) group demonstrated a higher risk of ICAS (full-adjusted odds ratio [OR], 1.91; 95% confidence interval [CI], 1.42-2.57), while no significant association was observed in the metabolic unhealthy obesity (MUO) group (full-adjusted OR, 1.07; 95% CI, 0.70-1.65) and other metabolic healthy groups regardless of BMI. The results were consistent across gender, age, smoking, alcohol intake, and physical activity subgroups. CONCLUSION: The present study suggested that MUH-NW individuals had a significant association with increased risk of ICAS compared with MH-NW individuals.

Variants in 3p24.3 predicts the risk of early neurological deterioration in large artery atherosclerotic stroke.

The rate of early neurological deterioration (END) differs in different subtypes of ischaemic stroke. Previous studies showed PLCL2 gene is a novel susceptibility locus for the occurrence of atherosclerosis and thrombotic events. The objective of this research is to examine the efficacy that PLCL2 may have on the risk of END in large artery atherosclerotic (LAA) stroke. Tagged single nucleotide polymorphisms (SNPs) were identified by a strategy of fine-mapping. The genotyping of the selected SNPs was performed by SNPscan. The impact of PLCL2 on indicating the susceptibility of END in LAA patients was evaluated by binary logistic regression. The SNP-SNP interactions of PLCL2 for END was assessed by generalized multifactor dimensionality reduction (GMDR). A total of 1527 LAA stroke patients were recruited, 582 patients (38 %) experienced END. Compared to participants without END, participants experienced END were much older (P = 0.018), more likely to suffer pre-existing diabetes mellitus (P = 0.036), higher frequent in active tobacco users (P = 0.022) and had much higher median NIHSS on admission (P < 0.001). Rs4685423 was identified to be a predictor to the risk of END: the frequency of END in AA genotype patients is lower than that in AC or CC genotype patients (multivariate-adjusted, OR 0.63; 95 % CI 0.49-0.80; P < 0.001). The SNP-SNP interactions analysis indicates rs4685423 has the greatest impacton the risk of END for LAA patients. The time from admission diagnosis to END onset in AA genotype patients is much later than that in CA or CC genotype patients (log-rank, P = 0.005). In summary, the PLCL2 rs4685423 SNP is probably associated with the END risk in LAA stroke patients.

Clinico-radiological features of intracranial atherosclerosis-related large vessel occlusion prior to endovascular treatment.

The identification of large vessel occlusion with underlying intracranial atherosclerotic disease (ICAS-LVO) before endovascular treatment (EVT) continues to be a challenge. We aimed to analyze baseline clinical-radiological features associated with ICAS-LVO that could lead to a prompt identification. We performed a retrospective cross-sectional study of consecutive patients with stroke treated with EVT from January 2020 to April 2022. We included anterior LVO involving intracranial internal carotid artery and middle cerebral artery. We analyzed baseline clinical and radiological variables associated with ICAS-LVO and evaluated the diagnostic value of a multivariate logistic regression model to identify ICAS-LVO before EVT. ICAS-LVO was defined as presence of angiographic residual stenosis or a trend to re-occlusion during EVT procedure. A total of 338 patients were included in the study. Of them, 28 patients (8.3%) presented with ICAS-LVO. After adjusting for confounders, absence of atrial fibrillation (OR 9.33, 95% CI 1.11-78.42; p = 0.040), lower hypoperfusion intensity ratio (HIR [Tmax > 10 s/Tmax > 6 s ratio], (OR 0.69, 95% CI 0.50-0.95; p = 0.025), symptomatic intracranial artery calcification (IAC, OR .15, 95% CI 1.64-26.42, p = 0.006), a more proximal occlusion (ICA, MCA-M1: OR 4.00, 95% CI 1.23-13.03; p = 0.021), and smoking (OR 2.91, 95% CI 1.08-7.90; p = 0.035) were associated with ICAS-LVO. The clinico-radiological model showed an overall well capability to identify ICAS-LVO (AUC = 0.88, 95% CI 0.83-0.94; p < 0.001). In conclusion, a combination of clinical and radiological features available before EVT can help to identify an ICAS-LVO. This approach could be useful to perform a rapid assessment of underlying etiology and suggest specific pathophysiology-based measures. Prospective studies are needed to validate these findings in other populations.

Morning blood pressure surge and intracranial atherosclerotic plaque characteristics: a high-resolution magnetic resonance vessel wall imaging study.

OBJECTIVE: To investigate the relationship between morning blood pressure surge (MBPS) and intracranial atherosclerotic plaque burden and vulnerability. METHODS: A total of 267 ischaemic stroke patients were retrospectively analysed. Sleep-trough and prewaking MBPS were calculated from ambulatory blood pressure monitoring (ABPM). Plaque characteristics, including intraplaque haemorrhage (IPH), maximum wall thickness (max WT), and stenosis degree, were obtained from high-resolution MR vessel wall imaging (HR-vwMRI). Linear and logistic regression were used to detect the association. RESULTS: Subjects with the top tertile of sleep-trough MBPS (≥15.1 mmHg) had a lower prevalence (9.1% vs. 19.6%, P = .029) of severe stenosis (≥70%) than others. Subjects within the top tertile of prewaking MBPS (≥7.6 mmHg) had a lower percentage of IPH (27.3% vs. 40.4%, P = .035) than others. After adjusting for stroke risk factors (age, sex, diabetes, hyperlipidaemia, hyperhomocysteinaemia, smoking, and family stroke history) and 24-h mean systolic blood pressure, 10 mmHg sleep-trough MBPS increment was associated with 0.07mm max WT reduction, and the top tertile MBPS group was associated with a lower chance of severe stenosis (odd ratio = 0.407, 95% CI, 0.175-0.950). Additionally, an increased prewaking MBPS is associated with a lower incidence of IPH, with OR = 0.531 (95% CI, 0.296-0.952). Subgroup analysis demonstrated that the positive findings could only be seen in non-diabetic subjects. CONCLUSION: Increment of MBPS is negatively associated with intracranial atherosclerotic plaque burden and vulnerability, and this relationship remains significant in the non-diabetic subgroup. ADVANCES IN KNOWLEDGE: This study provided evidence that MBPS was associated with the intracranial atherosclerotic plaque burden and vulnerability on HR-vwMRI.

Hemodynamic assessment for intracranial atherosclerosis from angiographic images: a clinical validation study.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is one of the leading causes of ischemic stroke. Conventional anatomical analysis by CT angiography, MRI, or digital subtraction angiography can provide valuable information on the anatomical changes of stenosis; however, they are not sufficient to accurately evaluate the hemodynamic severity of ICAS. The goal of this study was to assess the diagnostic performance of the pressure ratio across intracranial stenoses (termed as fractional flow (FF)) derived from cerebral angiography for the diagnosis of hemodynamically significant ICAS defined by pressure wire-derived FF. METHODS: This retrospective study represents a feasible and reliable method for calculating the FF from cerebral angiography (AccuFFicas). Patients (n=121) who had undergone wire-based measurement of FF and cerebral angiography were recruited. The accuracy of the computed pressure ratio was evaluated using wire-based FF as the reference standard. RESULTS: The mean value of wire-based FF was 0.78±0.19, while the computed AccuFFicas had an average value of 0.79±0.18. Good correlation (Pearson's correlation coefficient r=0.92, P<0.001) between AccuFFicas and FF was observed. Bland-Altman analysis showed that the mean difference between AccuFFicas and FF was -0.01±0.07, indicating good agreement. The area under the curve (AUC) of AccuFFicas in predicting FF≤0.70, FF≤0.75, and FF≤0.80 was 0.984, 0.986, and 0.962, respectively. CONCLUSION: Angiography-based FF computed from cerebral angiographic images could be an effective computational tool for evaluating the hemodynamic significance of ICAS.

Plaque features of the middle cerebral artery are associated with periprocedural complications of intracranial angioplasty and stenting.

PURPOSE: The identification of plaque features in the middle cerebral artery (MCA) may help minimize periprocedural complications and select patients suitable for percutaneous transluminal angioplasty and stenting (PTAS). However, relevant research is lacking. METHODS: We retrospectively included patients with symptomatic MCA stenosis who received PTAS. All patients underwent intracranial vessel wall MRI (VWMRI) before surgery. Periprocedural complications (PC) included ischemic and hemorrhagic stroke within 30 days. Stenosis location, MCA shape, plaque eccentricity and distribution, plaque thickness and length, and enhancement ratio were compared between patients with and without PC. RESULTS: Sixty-six patients were included in the study, of which 12.1% (8/66) had PC. Of the eight patients with PC, seven (87.5%) had superior wall plaques. In the non-PC group (n = 58), nine (17%) patients had superior wall plaques. Compared with patients without PC, those with PC had more frequent superior wall plaques (17% vs 87.5%, p < 0.001) and s-shaped MCAs (19% vs 50%, p = 0.071), different stenosis locations (p = 0.012), thicker plaques (1.58 [1.35, 2.00] vs 1.98 [1.73, 2.43], p = 0.038), and less frequent inferior wall plaques (79.2% vs 12.5%, p < 0.001). Multivariate analysis showed that only the presence of superior wall plaques (OR = 41.54 [2.31, 747.54]) was independently associated with PC. CONCLUSION: MCA plaque features were highly correlated with PC in patients with symptomatic MCA stenosis who underwent PTAS.

Association of Dental Infections with Intracranial Atherosclerotic Stenosis.

INTRODUCTION: Periodontal disease (PD) and dental caries are oral infections leading to tooth loss that are associated with atherosclerosis and cerebrovascular disease. We assessed the hypothesis that PD and caries are associated with asymptomatic intracranial atherosclerosis (ICAS) in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: Full-mouth clinical periodontal measurements (7 indices) collected at 6 sites per tooth from 6,155 subjects from the Dental Atherosclerosis Risk in Communities Study (DARIC) without prior stroke were used to differentiate seven PD stages (Periodontal Profile Class [PPC]-I to -VII) and dental caries on coronal dental surface (DS) and dental root surface (DRS). A stratified subset underwent 3D time-of-flight MR angiogram and 3D high isotropic-resolution black blood MRI. ICAS was graded according to the criteria established by the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial. We evaluated the relationship between PD stage and dental caries with asymptomatic ICAS, graded as no ICAS, <50% ICAS, and ≥50% ICAS. RESULTS: Among dentate subjects who underwent vascular imaging, 801 (70%) had no ICAS, 232 (20%) had <50% ICAS, and 112 (10%) had ≥50% ICAS. Compared to participants without gum disease (PPC-I), participants with mild-moderate tooth loss (PPC-VI), severe tooth loss (PPC-VII), and severe PD (PPC-IV) had higher odds of having <50% ICAS. Participants with extensive gingivitis (PPC-V) had significantly higher odds of having ≥50% ICAS. This association remained significant after adjusting for confounding variables: age, gender, race, hypertension, diabetes, dyslipidemia, 3-level education, and smoking status. There was no association between dental caries (DS and DRS) and ICAS <50% and ≥50%. CONCLUSION: We report significant associations between mild-moderate tooth loss, severe tooth loss, and severe PD with <50% ICAS as well as an association between extensive gingivitis and ≥50% ICAS. We did not find an association between dental caries and ICAS.

Immune Markers Are Associated With Asymptomatic Intracranial Large Artery Stenosis and Future Vascular Events in NOMAS.

BACKGROUND: Inflammation contributes to atherosclerosis but is incompletely characterized in intracranial large artery stenosis (ICAS). We hypothesized that immune markers would be associated with ICAS and modify the risk ICAS confers on future vascular events. METHODS: This study included a subsample of stroke-free participants in the prospective NOMAS (Northern Manhattan Study), who had blood samples analyzed with a 60-plex immunoassay (collected from 1993 to 2001) and ICAS assessment with time-of-flight magnetic resonance angiography (obtained from 2003 to 2008). We dichotomized ICAS as either ≥50% stenosis or not (including no ICAS). We ascertained post-magnetic resonance imaging vascular events. We used least absolute shrinkage and selection operator procedures to select immune markers independently associated with ICAS. Then, we grouped selected immune markers into a derived composite Z score. Using proportional odds regression, we quantified the association of the composite immune marker Z score, ICAS, and risk of vascular events. RESULTS: Among 1211 participants (mean age, 71±9 years; 59% women; 65% Hispanic participants), 8% had ≥50% ICAS. Using least absolute shrinkage and selection operator regression, we identified CXCL9 (C-X-C motif chemokine ligand 9), HGF (hepatocyte growth factor), resistin, SCF (stem cell factor), and VEGF-A(vascular endothelial growth factor A) to have the strongest positive relationships with ≥50% ICAS in fully adjusted models. Selected markers were used to derive a composite immune marker Z score. Over an average follow-up of 12 years, we found that each unit increase in immune marker Z scores was associated with an 8% (95% CI, 1.05-1.11), 11% (95% CI, 1.06-1.16), and 5% (95% CI, 1.01-1.09) increased hazard of death, vascular death, and any vascular event, respectively, in adjusted models. We did not find a significant interaction between immune marker Z scores and ICAS in their relationship with any longitudinal outcome. CONCLUSIONS: Among a diverse stroke-free population, selected serum immune markers were associated with ICAS and future vascular events. Further study is needed to better understand their role in the pathogenesis of ICAS and as a potential therapeutic target in stroke prevention.

Intracranial Atherosclerosis Increases the Risk of Postoperative Stroke After Cardiac Surgery: A Review and Meta-Analysis.

BACKGROUND: Postoperative stroke is a devastating complication of cardiac surgery with high morbidity, mortality, and health care cost. Extracranial carotid atherosclerosis (ECAS) is a known risk factor for stroke; however, the impact of intracranial atherosclerosis (ICAS) remains unclear. To our knowledge, this is the first literature review of ICAS in cardiac surgery. We aimed to assess the prevalence, association with postoperative stroke, and perioperative management of ICAS in cardiac surgery. METHOD: A search was performed to identify studies reporting rates of ICAS and stroke after cardiac surgery. Data extraction and primary outcomes for meta-analysis included the prevalence of preoperative ICAS and the association between ICAS and stroke. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled by random-effects modelling. RESULTS: Seventeen studies were reviewed and seven were included in the meta-analysis, comprising 4,936 patients. Prevalence of intracranial atherosclerosis (ICAS) among cardiac surgery patients was 21% (95% CI 13%-32%). Patients with ICAS were more likely to develop postoperative stroke (RR 3.61; 95% CI 2.30-5.67; p<0.001). ICAS was more closely associated with stroke than ECAS. Preoperative brain perfusion single-photon emission computed tomography with acetazolamide challenge, staged intracerebral revascularisation, or conversion to off-pump coronary artery bypass grafting are described management options for ICAS. CONCLUSION: Patients with ICAS are 3.61 times more likely to develop stroke after cardiac surgery. Known predictors for ICAS can be used to develop risk stratification screening tools. Further research with diverse cohorts is required to develop evidence-based guidelines for screening and management of ICAS in cardiac surgery.

Prevalence of intracranial artery stenosis in a general population using 3D-time of flight magnetic resonance angiography.

BACKGROUND: Data on prevalence of intracranial artery stenosis (ICAS) in Western populations is sparse. The aim of the study was to assess the prevalence and risk factors for ICAS in a mainly Caucasian general population. METHODS: We assessed the prevalence of ICAS in 1847 men and women aged 40 to 84 years who participated in a cross-sectional population-based study, using 3-dimensional time-of-flight 3 Tesla magnetic resonance angiography. ICAS was defined as a focal luminal flow diameter reduction of ≥50 %. The association between cardiovascular risk factor levels and ICAS was assessed by multivariable regression analysis. RESULTS: The overall prevalence of ICAS was 6.0 % (95 % confidence interval (CI) 5.0-7.2), 4.3 % (95 % CI 3.1-5.7) in women and 8.0 % (95 % CI 6.3-10.0) in men. The prevalence increased by age from 0.8 % in 40-54 years age group to 15.2 % in the 75-84 years age group. The majority of stenoses was located to the internal carotid artery (52.2 %), followed by the posterior circulation (33.1 %), the middle cerebral artery (10.8 %) and the anterior cerebral artery (3.8 %). The risk of ICAS was independently associated with higher age, male sex, hypertension, hyperlipidemia, diabetes mellitus, current smoking and higher BMI. CONCLUSIONS: The prevalence of ICAS in a general population of Caucasians was relatively high and similar to the prevalence of extracranial internal carotid artery stenosis in previous population-based studies.

Extracranial-Intracranial Bypass and Risk of Stroke and Death in Patients With Symptomatic Artery Occlusion: The CMOSS Randomized Clinical Trial.

Importance: Prior trials of extracranial-intracranial (EC-IC) bypass surgery showed no benefit for stroke prevention in patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), but there have been subsequent improvements in surgical techniques and patient selection. Objective: To evaluate EC-IC bypass surgery in symptomatic patients with atherosclerotic occlusion of the ICA or MCA, using refined patient and operator selection. Design, Setting, and Participants: This was a randomized, open-label, outcome assessor-blinded trial conducted at 13 centers in China. A total of 324 patients with ICA or MCA occlusion with transient ischemic attack or nondisabling ischemic stroke attributed to hemodynamic insufficiency based on computed tomography perfusion imaging were recruited between June 2013 and March 2018 (final follow-up: March 18, 2020). Interventions: EC-IC bypass surgery plus medical therapy (surgical group; n = 161) or medical therapy alone (medical group; n = 163). Medical therapy included antiplatelet therapy and stroke risk factor control. Main Outcomes and Measures: The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization. There were 9 secondary outcomes, including any stroke or death within 2 years and fatal stroke within 2 years. Results: Among 330 patients who were enrolled, 324 patients were confirmed eligible (median age, 52.7 years; 257 men [79.3%]) and 309 (95.4%) completed the trial. For the surgical group vs medical group, no significant difference was found for the composite primary outcome (8.6% [13/151] vs 12.3% [19/155]; incidence difference, -3.6% [95% CI, -10.1% to 2.9%]; hazard ratio [HR], 0.71 [95% CI, 0.33-1.54]; P = .39). The 30-day risk of stroke or death was 6.2% (10/161) in the surgical group and 1.8% (3/163) in the medical group, and the risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2.0% (3/151) and 10.3% (16/155), respectively. Of the 9 prespecified secondary end points, none showed a significant difference including any stroke or death within 2 years (9.9% [15/152] vs 15.3% [24/157]; incidence difference, -5.4% [95% CI, -12.5% to 1.7%]; HR, 0.69 [95% CI, 0.34-1.39]; P = .30) and fatal stroke within 2 years (2.0% [3/150] vs 0% [0/153]; incidence difference, 1.9% [95% CI, -0.2% to 4.0%]; P = .08). Conclusions and Relevance: Among patients with symptomatic ICA or MCA occlusion and hemodynamic insufficiency, the addition of bypass surgery to medical therapy did not significantly change the risk of the composite outcome of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01758614.

Association between Urine Albumin-to-creatinine Ratio and Intracranial Atherosclerotic Plaque in Chinese Adults - Results from the PRECISE Study.

AIMS: Intracranial plaque may cause stroke in the absence of luminal stenosis. Although urine albumin-to-creatinine ratio (ACR) has been proved an established risk factor for cardiovascular disease, stroke and carotid atherosclerosis, little is known on the relationship between urine ACR and intracranial plaque. METHODS: Subjects with history of stroke or coronary heart disease (CHD) were excluded in the PRECISE study. The intracranial plaque was assessed by vessel wall magnetic resonance imaging (MRI). Subjects were stratified according to ACR tertiles. Logistic regression and ordinal regression were performed to analyze the association between ACR and the presence of intracranial plaque or sum of the stenosis score for each artery. RESULTS: 2962 individuals were included with the mean age of 61.0±6.6 years. The median ACR was 11.7mg/g (interquartile range 7.0-22.0 mg/g), and the mean estimated glomerular filtration rate (eGFR) based on combination of creatinine and cystatin C was 88.5±14.8 ml/min·1.73m2. 495 (16.7%) participants had intracranial plaque. The highest ACR tertile with ACR ＞16.00mg/g was independently associated with the presence of intracranial plaque (OR 1.38, 95% CI: 1.05-1.82, p=0.02) and the odds of higher intracranial plaque burden (common OR 1.39, 95% CI: 1.05-1.83, p=0.02) after adjustment of confounding factors. No significant association was observed between eGFR and intracranial plaque presence or intracranial plaque burden. CONCLUSIONS: Among a low-risk community-dwelling population without prior stroke or CHD in China, ACR was independently associated with intracranial plaque presence and plaque burden measured by vessel wall MRI.

The incomplete circle of Willis is associated with vulnerable intracranial plaque features and acute ischemic stroke.

BACKGROUND: The circle of Willis (CoW) plays a significant role in intracranial atherosclerosis (ICAS). This study investigated the relationship between different types of CoW, atherosclerosis plaque features, and acute ischemic stroke (AIS). METHODS: We investigated 97 participants with AIS or transient ischemic attacks (TIA) underwent pre- and post-contrast 3T vessel wall cardiovascular magnetic resonance within 7 days of the onset of symptoms. The culprit plaque characteristics (including enhancement grade, enhancement ratio, high signal in T1, irregularity of plaque surface, and normalized wall index), and vessel remodeling (including arterial remodeling ratio and positive remodeling) for lesions were evaluated. The anatomic structures of the anterior and the posterior sections of the CoW (A-CoW and P-CoW) were also evaluated. The plaque features were compared among them. The plaque features were also compared between AIS and TIA patients. Finally, univariate and multivariate regression analysis was performed to evaluate the independent risk factors for AIS. RESULT: Patients with incomplete A-CoW showed a higher plaque enhancement ratio (P = 0.002), enhancement grade (P = 0.01), and normalized wall index (NWI) (P = 0.018) compared with the patients with complete A-CoW. A higher proportion of patients with incomplete symptomatic P-CoW demonstrated more culprit plaques with high T1 signals (HT1S) compared with those with complete P-CoW (P = 0.013). Incomplete A-CoW was associated with a higher enhancement grade of the culprit plaques [odds ratio (OR):3.84; 95% CI: 1.36-10.88, P = 0.011], after adjusting for clinical risk factors such as age, sex, smoking, hypertension, hyperlipemia, and diabetes mellitus. Incomplete symptomatic P-CoW was associated with a higher probability of HT1S (OR:3.88; 95% CI: 1.12-13.47, P = 0.033), after adjusting for clinical risk factors such as age, sex, smoking, hypertension, hyperlipemia, and diabetes mellitus. Furthermore, an irregularity of the plaque surface (OR: 6.24; 95% CI: 2.25-17.37, P < 0.001), and incomplete symptomatic P-CoW (OR: 8.03, 95% CI: 2.43-26.55, P = 0.001) were independently associated with AIS. CONCLUSIONS: This study demonstrated that incomplete A-CoW was associated with enhancement grade of the culprit plaque, and incomplete symptomatic side P-CoW was associated with the presence of HT1S of culprit plaque. Furthermore, an irregularity of plaque surface and incomplete symptomatic side P-CoW were associated with AIS.

Cerebral hemodynamics in symptomatic anterior circulation intracranial stenosis measured by angiography-based quantitative flow ratio: association with CT perfusion.

OBJECTIVES: Cerebral hemodynamics is important for the management of intracranial atherosclerotic stenosis (ICAS). This study aimed to determine the utility of angiography-based quantitative flow ratio (QFR) to reflect cerebral hemodynamics in symptomatic anterior circulation ICAS by evaluating its association with CT perfusion (CTP). METHODS: Sixty-two patients with unilateral symptomatic stenosis in the intracranial internal carotid artery or middle cerebral artery who received percutaneous transluminal angioplasty (PTA) or PTA with stenting were included. Murray law-based QFR (µQFR) was computed from a single angiographic view. CTP parameters including cerebral blood flow, cerebral blood volume, mean transit time (MTT), and time to peak (TTP) were calculated, and relative values were obtained as the ratio between symptomatic and contralateral hemispheres. Relationships between µQFR and perfusion parameters, and between µQFR and perfusion response after intervention, were analyzed. RESULTS: Thirty-eight patients had improved perfusion after treatment. µQFR was significantly correlated with relative values of TTP and MTT, with correlation coefficients of -0.45 and -0.26, respectively, on a per-patient basis, and -0.72 and -0.43, respectively, on a per-vessel basis (all p < 0.05). Sensitivity and specificity for µQFR to diagnose hypoperfusion at a cut-off value of 0.82 were 94.1% and 92.1%, respectively. Multivariate analysis revealed that µQFRpost (adjusted odds ratio [OR], 1.48; p = 0.002), collateral score (adjusted OR, 6.97; p = 0.01), and current smoking status (adjusted OR, 0.03; p = 0.01) were independently associated with perfusion improvement after treatment. CONCLUSIONS: µQFR was associated with CTP in patients with symptomatic anterior circulation ICAS and may be a potential marker for real-time hemodynamic evaluation during interventional procedures. KEY POINTS: • Murray law-based QFR (µQFR) is associated with CT perfusion parameters in intracranial atherosclerotic stenosis and can differentiate hypoperfusion from normal perfusion. • Post-intervention µQFR, collateral score, and current smoking status are independent factors associated with improved perfusion after treatment.

Recurrence risk in symptomatic intracranial stenosis treated medically in the real world.

BACKGROUND: The risk of early recurrence in medically treated patients with intracranial atherosclerotic stenosis (ICAS) may differ in clinical trials versus real-world settings. Delayed enrollment may contribute to lower event rates in ICAS trials. We aim to determine the 30-day recurrence risk in a real-world setting of symptomatic ICAS. METHODS: We used a comprehensive stroke center stroke registry to identify hospitalized patients with acute ischemic stroke or TIA due to symptomatic 50-99% ICAS. The outcome was recurrent stroke within 30 days. We used adjusted Cox regression models to identify factors associated with increased recurrence risk. We also performed a comparison of 30-day recurrent stroke rates in real world cohorts and clinical trials. RESULTS: Among 131 hospitalizations with symptomatic 50-99% ICAS over 3 years, 80 hospitalizations of 74 patients (mean age 71.6 years, 55.41% men) met the inclusion criteria. Over 30 days, 20.6 % had recurrent stroke; 61.5% (8/13) occurred within first 7 days. The risk was higher in patients not receiving dual antiplatelet therapy (HR 3.92 95% CI 1.30-11.84, p = 0.015) and hypoperfusion mismatch volume >3.5 mL at a T max>6 s threshold (HR 6.55 95% CI 1.60-26.88, p < 0.001). The recurrence risk was similar to another real world ICAD cohort (20.2%), and higher than that seen in clinical trials (2.2%-5.7%), even in those treated with maximal medical treatment or meeting inclusion criteria for trials. CONCLUSIONS: In patients with symptomatic ICAS, the real-world recurrence of ischemic events is higher than that seen in clinical trials, even in subgroups receiving the same pharmacological treatment strategies.