Risk stratification in symptomatic intracranial atherosclerotic disease with conventional vascular risk factors and cerebral haemodynamics

Background and purpose Symptomatic intracranial atherosclerotic stenosis(sICAS)is associated with a considerable risk of recurrent stroke despite contemporarily optimal medical treatment.Severity of luminal stenosis in sICAS and its haemodynamic significance quantified with computational fluid dynamics(CFD)models were associated with the risk of stroke recurrence.We aimed to develop and compare stroke risk prediction nomograms in sICAS,based on vascular risk factors and these metrics.Methods Patients with 50%-99%sICAS confirmed in CT angiography(CTA)were enrolled.Conventional vascular risk factors were collected.Severity of luminal stenosis in sICAS was dichotomised as moderate(50%-69%)and severe(70%-99%).Translesional pressure ratio(PR)and wall shear stress ratio(WSSR)were quantified via CTA-based CFD modelling;the haemodynamic status of sICAS was classified as normal(normal PR&WSSR),intermediate(otherwise)and abnormal(abnormal PR&WSSR).All patients received guideline-recommended medical treatment.We developed and compared performance of nomograms composed of these variables and independent predictors identified in multivariate logistic regression,in predicting the primary outcome,recurrent ischaemic stroke in the same territory(SIT)within 1 year.Results Among 245 sICAS patients,20(8.2%)had SIT.The D2H2A nomogram,incorporating diabetes,dyslipidaemia,haemodynamic status of sICAS,hypertension and age≥50 years,showed good calibration(P for Hosmer-Lemeshow test=0.560)and discrimination(C-statistic 0.73,95%CI 0.60 to 0.85).It also had better performance in risk reclassification and provided larger net benefits in decision curve analysis,compared with nomograms composed of conventional vascular risk factors only,and plus the severity of luminal stenosis in sICAS.Sensitivity analysis in patients with anterior-circulation sICAS showed similar results.Conclusions The D2H2A nomogram,incorporating conventional vascular risk factors and the haemodynamic significance of sICAS as assessed in CFD models,could be a useful tool to stratify sICAS patients for the risk of recurrent stroke under contemporarily optimal medical treatment.

Cerebral haemodynamics in symptomatic intracranial atherosclerotic disease:a narrative review of the assessment methods and clinical implications

Intracranial atherosclerotic disease(ICAD)is a common cause of ischaemic stroke and transient ischaemic attack(TIA)with a high recurrence rate.It is often referred to as intracranial atherosclerotic stenosis(ICAS),when the plaque has caused significant narrowing of the vessel lumen.The lesion is usually considered‘symptomatic ICAD/ICAS’(sICAD/sICAS)when it has caused an ischaemic stroke or TIA.The severity of luminal stenosis has long been established as a prognostic factor for stroke relapse in sICAS.Yet,accumulating studies have also reported the important roles of plaque vulnerability,cerebral haemodynamics,collateral circulation,cerebral autoregulation and other factors in altering the stroke risks across patients with sICAS.In this review article,we focus on cerebral haemodynamics in sICAS.We reviewed imaging modalities/methods in assessing cerebral haemodynamics,the haemodynamic metrics provided by these methods and application of these methods in research and clinical practice.More importantly,we reviewed the significance of these haemodynamic features in governing the risk of stroke recurrence in sICAS.We also discussed other clinical implications of these haemodynamic features in sICAS,such as the associations with collateral recruitment and evolution of the lesion under medical treatment,and indications for more individualised blood pressure management for secondary stroke prevention.We then put forward some knowledge gaps and future directions on these topics.

Genome sequencing reveals the role of rare genomic variants in Chinese patients with symptomatic intracranial atherosclerotic disease

Objectives The predisposition of intracranial atherosclerotic disease(ICAD)to East Asians over Caucasians infers a genetic basis which,however,remains largely unknown.Higher prevalence of vascular risk factors(VRFs)in Chinese over Caucasian patients who had a stroke,and shared risk factors of ICAD with other stroke subtypes indicate genes related to VRFs and/or other stroke subtypes may also contribute to ICAD.Methods Unrelated symptomatic patients with ICAD were recruited for genome sequencing(GS,60-fold).Rare and potentially deleterious single-nucleotide variants(SNVs)and small insertions/deletions(InDels)were detected in genome-wide and correlated to genes related to VRFs and/or other stroke subtypes.Rare aneuploidies,copy number variants(CNVs)and chromosomal structural rearrangements were also investigated.Lastly,candidate genes were used for pathway and gene ontology enrichment analysis.Results Among 92 patients(mean age at stroke onset 61.0±9.3 years),GS identified likely ICAD-associated rare genomic variants in 54.3%(50/92)of patients.Forty-eight patients(52.2%,48/92)had 59 rare SNVs/InDels reported or predicted to be deleterious in genes related to VRFs and/or other stroke subtypes.None of the 59 rare variants were identified in local subjects without ICAD(n=126).31 SNVs/InDels were related to conventional VRFs,and 28 were discovered in genes related to other stroke subtypes.Our study also showed that rare CNVs(n=7)and structural rearrangement(a balanced translocation)were potentially related to ICAD in 8.7%(8/92)of patients.Lastly,candidate genes were significantly enriched in pathways related to lipoprotein metabolism and cellular lipid catabolic process.Conclusions Our GS study suggests a role of rare genomic variants with various variant types contributing to the development of ICAD in Chinese patients.