Nonrelevant Cerebral Atherosclerosis is a Strong Prognostic Factor in Acute Cerebral Infarction
Background and Purpose—We investigated whether the presence of nonrelevant cerebral atherosclerosis (NRCA) had prognostic value in patients with acute stroke.
Methods—We compared prognosis in 780 consecutive patients with first-ever acute cerebral infarction who underwent cerebral angiography and diffusion-weighted MRI.
Results—NRCA was present in 267 patients (34.2%). Multivariate analysis demonstrated that the presence of NRCA was independently associated with less improvement in National Institute of Health Stroke Scale score during the first 7 days (P=0.004), and a poor functional outcome (modified Rankin Scale score >2) after 3 months (odds ratio, 2.51; 95% confidence interval, 1.55–4.07). An increase in burden count of NRCA was also associated with poor outcomes.
Conclusions—The presence and burden count of NRCA were associated with poor neurological outcomes in patients with acute cerebral infarction.
In cerebral infarction, the prognostic value of angiographic information is mainly focused on the steno-occlusive lesion of the symptomatic cerebral artery (relevant cerebral atherosclerosis [RCA]).1 Asymptomatic cerebral atherosclerosis (non-RCA [NRCA]) is also often found during cerebral angiography. Previous studies showed that the increase of total burden of cerebral atherosclerosis or RCA is associated with poor outcome.1–3 However, the prognostic value of NRCA is not well known. Therefore, we investigated whether the presence of NRCA also has a prognostic value in patients with acute cerebral infarction.
This was a retrospective, observational study on patients with acute cerebral infarction who were admitted to a neurology department within 72 hours of symptom onset between November 2008 and November 2011. We excluded patients with (1) high-risk potential cardiac sources of embolism on the basis of Trial of Org 10172 in Acute Stroke Treatment classification system because embolic occlusive lesions often cannot be differentiated from atherosclerotic lesions based on angiography, (2) rare causes of stroke, (3) history of previous stroke, (4) in-hospital stroke, (5) history of malignancy, and (6) patients who did not have a cerebral angiography or who had missing laboratory data used as covariates for analyses.
All patients underwent digital subtraction angiography, MR angiography, or computed tomography angiography. Cerebral atherosclerosis was defined when the artery showed ≥50% stenosis or occlusion. We divided the cerebral atherosclerosis into relevant and nonrelevant lesions (RCA and NRCA) on the basis of the arterial territory of acute infarction found on diffusion-weighted MR images. Figure I in the online-only Data Supplement shows examples of patients with NRCA. The burden count of NRCA was calculated in each patient.
Primary outcomes of this study were (1) early changes in the National Institute of Health Stroke Scale (NIHSS) scores during 7 days after admission and (2) functional outcome using the modified Rankin Scale (mRS) after 3 months from stroke onset. We collected NIHSS scores at admission (day 0), day 1, day 3, and day 7. If a patient was discharged between days 4 and 6, the NIHSS score at discharge was used as the score for day 7.
Statistical analyses were performed using SPSS for Windows (version 18.0, SPSS Inc, Chicago, IL). To evaluate the association between variables and early changes in NIHSS scores, we used a linear mixed model of repeated measures with unstructured covariances within subjects. We performed ordinal logistic regression to evaluate variables associated with mRS (0–6) and binary logistic regression on the basis of a dichotomized mRS (mRS≤2 versus mRS>2). Multivariate models were adjusted for sex, age, and those variables with P<0.10 in the univariate analysis. P<0.05 was considered statistically significant. Assessment for cerebral atherosclerosis and detailed statistical methods are shown in the online-only Data Supplement. The Institutional Review Board of Severance Hospital, Yonsei University Health System approved this study and waived the requirement for informed consent because of the retrospective and observational nature of the study.
There were 1564 candidates who were admitted during the study period. After excluding 784 patients according to the exclusion criteria, 780 patients were included. Among them, RCA was found in 285 patients (36.5%), and NRCA was present in 267 patients (34.2%). NRCA was most frequent in extracranial vertebral artery, followed by posterior and middle cerebral arteries (Table I in the online-only Data Supplement). Patients with NRCA were older, had higher high-sensitive C-reactive protein and glucose levels at admission than those without NRCA. The prevalence of RCA was not different between patients with NRCA and those without (Table II in the online-only Data Supplement).
The NIHSS score was assessed in all patients (100%) at day 0, 742 patients (95.1%) at day 1, 764 patients (97.9%) at day 3, and 696 patients (89.2%) at day 7. The NIHSS score at admission did not differ in patients with NRCA and those without NRCA. However, the NIHSS scores at day 1, day 3, and day 7 were higher in patients with NRCA than those without (Figure [A]). In multivariate linear mixed model, the presence and burden count of NRCA were positively associated with repeatedly measured NIHSS scores (Table). This finding means that there was less improvement in neurological deficits for 7 days in patients with NRCA than in those without NRCA.
An mRS score at 3 months after stroke onset was available in 749 patients (96.0%). An increase in burden count of NRCA was significantly associated with a worse functional outcome after 3 months (Figure [B]). In multivariate ordinal and binary logistic regression model, the presence and burden count of NRCA were independently associated with a worse functional outcome (Table). There was no significant interaction between the presence of RCA and NRCA in the multivariate models.
We performed further analysis by dividing patients into 4 groups according to the location of NRCA (no NRCA, only extracranial NRCA, only intracranial NRCA, and both intracranial and extracranial NRCA). Compared with the no NRCA group, patients with only intracranial NRCA showed less early improvement in neurological deficits and worse functional outcome. However, the presence of only extracranial NRCA was not a significant predictor in multivariate linear mixed model and ordinal logistic regression model (Table III in the online-only Data Supplement).
We demonstrated that the presence and burden count of NRCA are independent prognostic factors for short- and long-term neurological outcomes in patients with acute stroke. Our findings, together with previous evidence,3 indicate that advanced cerebral atherosclerosis, even though it is asymptomatic, may result in poor clinical outcomes. The presence of NRCA might affect the development and efficiency of the collateral vessels,2 and increase the risk of recurrent strokes, which could contribute to the poor outcome seen in these patients. Patients with asymptomatic cerebral atherosclerosis frequently have elevated inflammatory biomarkers,4 which are associated with recurrent stroke and further ischemic damage. The different prognostic effects of extracranial/intracranial NRCA might be because of relatively small number of patients with only extracranial NRCA in this study. This study has limitations. Because of the retrospective design, we could not present the data for stroke recurrence and the degree of collateral circulation according to the presence of NRCA. Some potential bias might be introduced by different diagnostic accuracy for cerebral atherosclerosis among digital subtraction angiography, computed tomography angiography and MR angiography, and interobserver variability in measuring cerebral atherosclerosis, NIHSS and mRS.
The presence and burden count of NRCA were associated with poor neurological outcomes in patients with acute cerebral infarction. Our findings suggest that further investigation is needed to the role of NRCA in stroke prognosis.
Sources of Funding
This work was supported by a grant from the Korea Healthcare Technology Research and Development Project, Ministry for Health, Welfare, and Family Affairs, Republic of Korea (A102065).
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.113.001111/-/DC1.
- Received February 7, 2013.
- Accepted March 29, 2013.
- © 2013 American Heart Association, Inc.
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