Safety of endovascular therapy for symptomatic intracranial artery stenosis: a national prospective registry

IntroductionThe safety outcomes of endovascular therapy for intracranial artery stenosis in a real-world stetting are largely unknown. The Clinical Registration Trial of Intracranial Stenting for Patients with Symptomatic Intracranial Artery Stenosis (CRTICAS) was a prospective, multicentre, real-world registry designed to assess these outcomes and the impact of centre experience.Methods1140 severe, symptomatic intracranial arterial stenosis (ICAS) patients treated with endovascular therapy were included from 26 centres, further divided into three groups according to the annual centre volume of intracranial angioplasty and stent placement procedures over 2 years: (1) high volume for ≥25 cases/year; (2) moderate volume for 10–25 cases/year and (3) low volume for <10 cases/year.ResultsThe rate of 30-day stroke, transient ischaemic attack or death was 9.7% (111), with 5.4%, 21.1% and 9.7% in high-volume, moderate-volume and low-volume centres, respectively (p<0.05). Multivariable logistic regression confirmed high-volume centres had a significantly lower primary endpoint compared with moderate-volume centres (OR=0.187, 95% CI: 0.056 to 0.627; p≤0.0001), while moderate-volume and low-volume centres showed no significant difference (p=0.8456).ConclusionCompared with the preceding randomised controlled trials, this real-world, prospective, multicentre registry shows a lower complication rate of endovascular treatment for symptomatic ICAS. Non-uniform utilisation in endovascular technology, institutional experience and patient selection in different volumes of centres may have an impact on overall safety of this treatment.

Elevated Lipoprotein-Associated Phospholipase A2 is Associated with Intracranial Atherosclerosis

BackgroundLipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory factor in atherosclerotic plaque pathogenesis and is associated with an increased risk of ischemic stroke. Whether Lp-PLA2 is associated with the stenosis subtypes in acute ischemic stroke (AIS) has not been investigated. Methods126 eligible AIS patients were divided into four groups 1) no cerebral artery stenosis (NCS); 2) intracranial artery stenosis (ICAS); 3) extracranial artery stenosis (ECAS); and 4) combined intracranial and extracranial artery stenosis (IECS). The associations between serum Lp-PLA2 levels and the stenosis subtypes were statistically assessed. ResultsThe ICAS group had a lower frequency of dyslipidemia as compared with the NCS group and the IECS group (35.3% vs. 70% vs. 71.8%, P=0.001), and was more likely to be symptomatic than the ECAS group (76.5% vs. 43.8%, P=0.014). The Lp-PLA2 level in the ICAS group was 112.2±66.8 μg/L, which was higher than that in the NCS, ECAS and IECS groups (81.7±38.5, 106.1±57.8, 89.3±52.2 μg/L, respectively, P=0.025). In the 3rd and 4th quartiles of Lp-PLA2 level, stenosis occurred more frequently in the ICAS group than in the other three groups (3rd Q: 50.0% vs. 3.1% vs. 28.1% vs. 18.8%, P=0.002; 4th Q: 48.4% vs. 16.1% vs. 25.8% vs. 9.7%, P=0.014). The Lp-PLA2 level was higher in patients with more or severe stenosis in the ICAS group. ConclusionsElevated Lp-PLA2 level was differentially associated with increased risk in AIS patients with ICAS as compared to those with ECAS or no stenosis. Lp-PLA2 is a promising biomarker for ICAS and may be a potential therapeutic target for ICAS.

Blood biomarkers of progressive atherosclerosis and restenosis after stenting of symptomatic intracranial artery stenosis

In-stent restenosis (ISR) represents a major complication after stenting of intracranial artery stenosis (ICAS). Biomarkers derived from routine blood sampling including C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and mean platelet volume (MPV) have been associated with progressive atherosclerosis. We investigated the role of CRP, NLR, PLR and MPV on the development of intracranial ISR and recurrent stroke risk. We retrospectively included all patients who had undergone stenting of symptomatic ICAS at our university hospital between 2005 and 2016. ISR (≥ 50% stenosis) was diagnosed by regular Duplex sonography follow-up studies and confirmed by digital subtraction angiography or computed tomography angiography (mean follow-up duration: 5 years). Laboratory parameters were documented before stenting, at the time of restenosis and at last clinical follow-up. Of 115 patients (mean age: 73 ± 13 years; female: 34%), 38 (33%) developed ISR. The assessed laboratory parameters did not differ between patients with ISR and those without (p > 0.1). While ISR was associated with the occurrence of recurrent ischemic stroke (p = 0.003), CRP, NLR, PLR and MPV were not predictive of such events (p > 0.1). Investigated blood biomarkers of progressive atherosclerosis were not predictive for the occurrence of ISR or recurrent ischemic stroke after ICAS stenting during a 5-year follow-up.

Understanding the Clinical Implications of Intracranial Arterial Calcification Using Brain CT and Vessel Wall Imaging

Background and Purpose: Intracranial arterial calcification (IAC) has been the focus of much attention by clinicians and researchers as an indicator of intracranial atherosclerosis, but correlations of IAC patterns (intimal or medial) with the presence of atherosclerotic plaques and plaque stability are still a matter of debate. Our study aimed to assess the associations of IAC patterns identified on computed tomography (CT) with the presence of plaque detected on vessel wall magnetic resonance imaging and plaque stability.Materials and Methods: Patients with stroke or transient ischemic attack and intracranial artery stenosis were recruited. IAC was detected and localized (intima or media) on non-contrast CT images. Intracranial atherosclerotic plaques were identified using vessel wall magnetic resonance imaging and matched to corresponding CT images. Associations between IAC patterns and culprit atherosclerotic plaques were assessed by using multivariate regression.Results: Seventy-five patients (mean age, 63.4 ± 11.6 years; males, 46) were included. Two hundred and twenty-one segments with IAC were identified on CT in 66 patients, including 86 (38.9%) predominantly intimal calcifications and 135 (61.1%) predominantly medial calcifications. A total of 72.0% of intimal calcifications coexisted with atherosclerotic plaques, whereas only 10.2% of medial calcifications coexisted with plaques. Intimal calcification was more commonly shown in non-culprit plaques than culprit plaques (25.9 vs. 9.4%, P = 0.008). The multivariate mixed logistic regression adjusted for the degree of stenosis showed that intimal calcification was significantly associated with non-culprit plaques (OR, 2.971; 95% CI, 1.036–8.517; P = 0.043).Conclusion: Our findings suggest that intimal calcification may indicate the existence of a stable form of atherosclerotic plaque, but plaques can exist in the absence of intimal calcification especially in the middle cerebral artery.

Glucose Fluctuation and Severe Internal Carotid Artery Siphon Stenosis in Type 2 Diabetes Patients

The impact of glucose fluctuation on intracranial artery stenosis remains to be elucidated. This study aimed to investigate the association between glucose fluctuation and intracranial artery stenosis. This was a cross-sectional study of type 2 diabetes mellitus (T2DM) patients equipped with the FreeStyle Libre Pro continuous glucose monitoring system (Abbott Laboratories) between February 2019 and June 2020. Glucose fluctuation was evaluated according to the standard deviation (SD) of blood glucose, coefficient of variation (%CV), and mean amplitude of glycemic excursions (MAGE). Magnetic resonance angiography was used to evaluate the degree of intracranial artery stenosis. Of the 103 patients, 8 patients developed severe internal carotid artery (ICA) siphon stenosis (≥70%). SD, %CV, and MAGE were significantly higher in the severe stenosis group than in the non-severe stenosis group (<70%), whereas there was no significant intergroup difference in the mean blood glucose and HbA1c. Multivariable logistic regression analysis adjusted for sex showed that SD, %CV, and MAGE were independent factors associated with severe ICA siphon stenosis. In conclusion, glucose fluctuation is significantly associated with severe ICA siphon stenosis in T2DM patients. Thus, glucose fluctuation can be a target of preventive therapies for intracranial artery stenosis and ischemic stroke.

Association between coexisting intracranial artery and extracranial carotid artery atherosclerotic diseases and ipsilateral cerebral infarction: a Chinese Atherosclerosis Risk Evaluation (CARE-II) study

BackgroundTo evaluate the association between coexisting intracranial and extracranial carotid artery atherosclerotic diseases and ipsilateral acute cerebral infarct (ACI) in symptomatic patients by using magnetic resonance (MR) vessel wall imaging.MethodsSymptomatic patients were recruited from a cross-sectional, multicentre study of Chinese Atherosclerosis Risk Evaluation (CARE-II). All patients underwent MR imaging for extracranial carotid arterial wall, intracranial artery and brain. Coexisting intracranial stenosis ≥50% and extracranial carotid artery mean wall thickness (MWT) ≥1 mm and plaque compositions at the same side were evaluated and the ipsilateral ACI was identified. The association between coexisting atherosclerotic diseases and ACI was evaluated using logistic regression.Results351 patients were recruited. Patients with ipsilateral ACI had significantly greater prevalence of coexisting intracranial stenosis ≥50% and carotid MWT ≥1 mm (20.5% vs 4.9%, p<0.001), calcification (15.1% vs 4.4%, p=0.001) and lipid-rich necrotic core (LRNC) (19.2% vs 7.8%, p=0.002) compared with those without. Coexisting intracranial artery stenosis ≥50% and carotid MWT ≥1 mm (OR 5.043, 95% CI 2.378 to 10.694; p<0.001), calcification (OR 3.864, 95% CI 1.723 to 8.664; p=0.001) and LRNC (OR 2.803, 95% CI 1.455 to 5.401; p=0.002) were significantly associated with ipsilateral ACI. After adjusting for confounding factors, the aforementioned associations remained statistically significant (intracranial stenosis ≥50% coexisting with carotid MWT ≥1 mm: OR 4.313, 95% CI 1.937 to 9.601, p<0.001; calcification: OR 3.606, 95% CI 1.513 to 8.593, p=0.004; LRNC: OR 2.358, 95% CI 1.166 to 4.769, p=0.017).ConclusionsCoexistence of intracranial artery severe stenosis and extracranial carotid artery large burden and intraplaque components of calcification and LRNC are independently associated with ipsilateral ACI.Trial registration numberhttps://www.clinicaltrials.gov/. Unique identifier: NCT02017756.