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CICAS

Prevalence and Outcomes of Symptomatic Intracranial Large Artery Stenoses and Occlusions in China: The Chinese Intracranial Atherosclerosis Study

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Year of Publication: 2014

Authors: Yongjun Wang, Xingquan Zhao, Liping Liu, ..., for the CICAS Study Group

Journal: Stroke

Citation: Stroke. 2014;45:663-669.

Link: https://doi.org/10.1161/STROKEAHA.113.003508

PDF: https://www.ahajournals.org/doi/reader/1...EAHA.113.003508

Clinical Question

What is the prevalence, distribution, and 12-month recurrent stroke risk of symptomatic intracranial large artery occlusive disease among acute ischemic stroke and TIA patients across China?

Bottom Line

ICAS was present in 46.6% of 2,864 Chinese acute cerebral ischemia patients — the most common vascular lesion. At 12 months, recurrent stroke was 3.27% (no stenosis), 3.82% (50-69%), 5.16% (70-99%), and 7.27% (occlusion). The highest-risk subgroup — occlusion + ≥3 risk factors — had 19.05% recurrence. Seven independent predictors identified: stenosis severity (HR 1.29/grade), age (HR 1.03/year), family history (HR 2.01), prior cerebral ischemia (HR 2.37), heart disease (HR 1.98), complete circle of Willis (HR 2.36), and admission NIHSS (HR 1.05/point).

        Major Points
        ICAS prevalence 46.6% (1,335/2,864) in Chinese acute stroke/TIA — most common vascular etiology, far exceeding extracranial-only (4.9%).
Recurrent stroke graded by stenosis: 3.27% (none) → 3.82% (50-69%) → 5.16% (70-99%) → 7.27% (occlusion) at 12 months. Occlusion HR 2.39 (95% CI 1.62-3.54; P<0.001).
Highest-risk subgroup: occlusion + ≥3 risk factors → 19.05% recurrence at 12 months.
Rates substantially lower than SAMMPRIS (12.2%) and WASID (23% for ≥70%), likely due to MRA vs DSA and observational setting.
MCA most commonly affected: occlusion 14.18%, severe stenosis 6.04%, moderate 9.39%.
7 independent multivariate predictors: stenosis severity (HR 1.286/grade; P=0.0008), age >63 (HR 1.033/year; P=0.0007), family history (HR 2.008; P=0.0047), prior cerebral ischemia (HR 2.374; P=0.0015), heart disease (HR 1.981; P=0.0087), complete circle of Willis (HR 2.359; P=0.0145), NIHSS (HR 1.049/point; P=0.009).
Complete circle of Willis paradoxically increases risk (HR 2.36) — likely reflects hemodynamic compromise requiring collateral recruitment.
Posterior + bilateral ICAS distribution carries highest risk: anterior+posterior HR 2.88 (P<0.001).
96.2% received antithrombotics, 75.8% statins — yet recurrence remained high in severe stenosis groups.
Prospective, 22-center Chinese cohort with 93.9% follow-up at 12 months.

      

Design

Study Type: Prospective, multicenter, hospital-based observational cohort

Randomization:

Blinding: Central MRA readers blinded to clinical data; disagreements >10% resolved by third reader. Interrater κ=0.815.

Enrollment Period: October 2007 to June 2009

Follow-up Duration: 12 months (assessments at discharge, 3, 6, 12 months)

Centers: 22

Countries: China, Hong Kong

Sample Size: 2864

Analysis: Univariate and multivariate Cox proportional hazards regression. SAS 9.1.3.

Inclusion Criteria

Acute ischemic stroke or TIA.
Symptom onset <7 days before enrollment.
Age 18-80 years.
Able to undergo MR examination.

Exclusion Criteria

Clinically unstable or required close monitoring or moribund.
Disabled before admission (mRS >2).
Unable to comply with MR examination.
Severe comorbidity.
Known source of cardioembolism: AF history, valvular heart disease, valve replacement, AF/flutter on ECG/TEE/TTE/Holter.

Baseline Characteristics

Characteristic	Without ICAS (N=1,529)	With ICAS (N=1,335)
Male sex	1,048 (68.5%)	896 (67.1%)
Age (mean±SD)	61.5±11.2	62.4±11.3
Hypertension	1,161 (75.9%)	1,077 (80.7%)
Diabetes	464 (30.4%)	527 (39.5%)
Hyperlipidemia	1,161 (75.9%)	1,012 (75.8%)
Hyperhomocysteinemia	331 (21.7%)	419 (31.4%)
Current smoker	567 (37.1%)	482 (36.1%)
History of cerebral ischemia	1,047 (68.5%)	971 (72.7%)
NIHSS median (adjusted IQR)	3 (1-5)	5 (2-9)
Antithrombotic therapy	1,460 (95.5%)	1,296 (97.1%)
Statins	1,135 (74.2%)	1,035 (77.5%)

Arms

Field	Observational cohort
Intervention	Prospective registry of consecutive acute ischemic stroke/TIA patients. Grouped by stenosis severity: none/<50%, 50-69%, 70-99%, 100% occlusion. Treatment per local practice.
Duration	12-month follow-up

Outcomes

Outcome	Type	Control	Intervention	P-value
12-month recurrent stroke (ischemic or hemorrhagic)	Primary	No ICAS: 50/1,529 (3.27%)	Any ICAS: 80/1,335 (5.99%). By grade: 50-69%: 3.82%; 70-99%: 5.16%; Occlusion: 7.27%	<0.001
Total recurrent stroke	Secondary	130/2,864 (4.54%)	—
Nonfatal ischemic recurrence	Secondary	86/130 (66.2%)	—
Fatal stroke	Secondary	30/130 (23.1%)	—
Hemorrhagic recurrence	Secondary	19/130 (14.6%)	—
Observational study	Adverse		Prospective observational study of intracranial atherosclerotic stenosis - no intervention-related AE data

Subgroup Analysis

Recurrence by stenosis + risk factors: occlusion + ≥3 RF = 19.05%; <50% + 0 RF = 0.58%. By distribution: posterior only HR 2.07 (P=0.006); anterior+posterior HR 2.88 (P<0.001). Multiple ICAS HR 1.97 (P<0.001).

Criticisms

MRA used instead of DSA (gold standard) — TOF-MRA prone to flow artifacts; may over/underestimate stenosis.
Cannot fully exclude recanalized cardioembolic embolus mimicking in-situ stenosis.
No repeated MRA during follow-up to track stenosis progression.
BP and medication changes during follow-up not documented.
Did not exclude intracranial vasculitis.
Cannot determine if recurrent stroke was in territory of stenotic artery (no mandatory DWI at recurrence).
Different setting/imaging/ethnicity vs WASID/SAMMPRIS — not directly comparable.

Funding

Ministry of Science and Technology and Ministry of Health of the People's Republic of China. S.H. Ho Cardiovascular Disease and Stroke Center, Chinese University of Hong Kong.

Based on: CICAS (Stroke, 2014)