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Longfei Wu, MD,*,1 Xiaoqin Huang, MD,*,1 Di Wu, MD,† Wenbo Zhao, MD,*
Chuanjie Wu, MD,* Ruiwen Che, MD,* Zhen Zhang, MD,* Fang Jiang, MD,*
Tingting Bian, MD,* Tingting Yang, MD,‡ Kai Dong, MD,* Qian Zhang, MD,*
Zhipeng Yu, MD,* Qingfeng Ma, MD,* Haiqing Song, MD,* Yuchuan Ding, MD,§
and Xunming Ji, MD, PhD‖
Background: The management of blood pressure (BP) for acute ischemic stroke
(AIS) patients undergoing thrombolysis is still under debate. The purpose of this
study was (1) to explore the association between post-thrombolysis BP and func-
tional outcome and (2) to examine whether post-thrombolysis BP can predict
functional outcome in Chinese AIS patients undergoing thrombolysis therapy. Methods:
From December 2012 to November 2016, AIS patients undergoing thrombolysis
were reviewed retrospectively in the Department of Neurology at Xuanwu Hos-
pital. The BP levels were measured before and immediately after thrombolysis.
Clinical outcomes, which comprised favorable outcome (modified Rankin Scale
score 0-2) and unfavorable outcome (modified Rankin Scale score 3-6) at 3 months,
were analyzed by logistic regression model. A receiver operating characteristic curve
was used to evaluate the predictive value of post-thrombolysis BP. Results: Patients
with unfavorable outcome at 3 months had a higher post-thrombolysis systolic
BP than those with favorable outcome (P = .015). Multivariate analysis showed
that post-thrombolysis systolic BP below 159.5 mm Hg was associated with fa-
vorable outcome. According to the receiver operating characteristic curve, post-
thrombolysis systolic BP was a predictor of functional outcome with an area under
the curve of .573 (95% confidence interval = .504-.642). Conclusions: Our study in-
dicated that post-thrombolysis systolic BP is a predictor of functional outcome
for Chinese AIS patients undergoing thrombolysis therapy. It is reasonable for AIS
From the *Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China; †China-America Institute of Neurosci-
ence, Xuanwu Hospital, Capital Medical University, Beijing, China; ‡Clinical Laboratory, Xuanwu Hospital, Capital Medical University, Beijing,
China; §Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan; and ‖Department of Neurosurgery, Xuanwu
Hospital, Capital Medical University, Beijing, China.
Received March 27, 2017; revision received April 21, 2017; accepted May 7, 2017.
Grant support: This study was supported by The National Science Fund for Distinguished Young Scholars (No. 81325007) and the Chang
Jiang Scholars Program (No. T2014251).
Address correspondence to Xunming Ji, MD, PhD, Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, No. 45,
Changchun Street, Xicheng District, Beijing 100053, China. E-mail: jixm@ccmu.edu.cn.
1
These authors contributed equally to this work.
1052-3057/$ - see front matter
© 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.05.011
Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2017: pp ■■–■■ 1
ARTICLE IN PRESS
2 L. WU ET AL.
patients to keep post-thrombolysis systolic BP below 159.5 mm Hg to obtain a
favorable outcome. Key Words: Post-thrombolysis—blood pressure—acute ischemic
stroke—functional outcome—intravenous thrombolysis.
© 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Baseline characteristics Favorable outcome (mRS score 0-2) Unfavorable outcome (mRS score 3-6) P value
Abbreviations: BMI, body mass index; BP, blood pressure; HCY, homocysteine; INR, international normalized ratio; IQR, interquartile
range; LDL, low-density lipoprotein; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; SD, standard
deviation; TIA, transient ischemic attack.
Results are expressed as percentages or mean ± SD and median (IQR).
*A P value less than .05 indicates statistical significance.
(148.60 ± 21.78 mm Hg vs 142.98 ± 18.93 mm Hg, P = .015; post-thrombolysis systolic BP, glucose, and internation-
Fig 1). al normalized ratio were statistically significant (P < .1,
In the univariate logistic regression analysis, age, Table 2). Multivariate analysis was done with the statis-
BMI, history of dyslipidemia, NIHSS score at baseline, tically significant factors previously mentioned. After
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POST-THROMBOLYSIS BLOOD PRESSURE AND OUTCOME 5
Table 2. Univariate and multivariate logistic regression analyses for functional outcome
Abbreviations: BMI, body mass index; BP, blood pressure; CI, confidence interval; HCY, homocysteine; INR, international normalized
ratio; LDL, low-density lipoprotein; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; TIA, transient ischemic attack.
*A P value less than .10 indicates statistical significance in the univariate analysis.
†A P value less than .05 indicates statistical significance in the multivariate analysis.
Figure 2. The receiver operating characteristic curve of predictors of functional outcome. BMI, body mass index; BP, blood pressure; NIHSS, National
Institutes of Health Stroke Scale.
Table 3. Logistic regression analysis for outcome by different values of post-thrombolysis systolic BP
≥159.5 mm Hg 1 — — 1 — —
<159.5 mm Hg .756 .654-.875 <.001* .751 .585-.964 .024*
Abbreviations: BMI, body mass index; BP, blood pressure; CI, confidence interval; NIHSS, National Institutes of Health Stroke Scale;
OR, odds ratio.
Adjusted for gender, age, BMI, history of hypertension, previous stroke, smoking, alcohol, oral antihypertensive agents, NIHSS score at
baseline, symptom onset-to-thrombolysis time, and prethrombolysis systolic BP.
*A P value less than .05 indicates statistical significance.
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POST-THROMBOLYSIS BLOOD PRESSURE AND OUTCOME 7
outcomes, which meant that both high BP and low BP the decreased systolic BP levels are related to the favor-
were associated with unfavorable outcome after AIS. The able outcome, early antihypertension for patients with
most favorable outcome was for systolic BP levels ranging thrombolysis therapy should not be conducted without
from 140 to 179 mm Hg on admission. The CHHIPS,20 a serious consideration because the BP levels tend to de-
multicenter, prospective, randomized, double-blind and crease spontaneously after the onset of stroke in most
placebo-controlled trial, suggested early antihyperten- patients.30 Besides, the decline of systolic BP levels is sig-
sive therapy. This trial revealed that early lowering of nificantly faster in patients with successful recanalization.31
BP with lisinopril and labetalol after acute stroke seemed Thus, to reduce the possibility of cerebral hypoperfusion
to be a promising approach to reduce mortality and po- caused by antihypertension, we should evaluate the risks
tential disability. Analogously, the ACCESS study,21 which sufficiently according to the practical situations before the
is a prospective, double-blind, placebo-controlled, ran- antihypertensive therapy and manage the BP levels cau-
domized, multicenter phase II study, suggested that, as tiously. Likewise, our study demonstrated that the post-
a safe therapeutic option, candesartan could reduce the thrombolysis systolic BP is an independent predictor of
cumulative 12-month mortality and the number of vas- functional outcome in Chinese AIS patients with intra-
cular events of the AIS patients. On the contrary, some venous thrombolysis therapy. Although the prediction of
studies disapproved of early antihypertensive therapy the post-thrombolysis systolic BP alone has not been proven
because it may bring an unfavorable outcome to AIS pa- to be highly efficient, the predictability could be im-
tients. An observational study found that BP reduction proved with the combination of BMI, NIHSS score at
in the first 24 hours of stroke onset is independently as- baseline, and glucose levels.
sociated with unfavorable outcome after 3 months.22 A Several limitations in our study should be considered.
randomized, placebo-controlled, double-blind trial named First, it was a single-center study. Thus, the enrolled pa-
SCAST23 concluded that the careful BP-lowering treat- tients may not be able to represent the whole AIS patients.
ment with candesartan leads to few benefits in patients Second, the loss of follow-ups with any reason may have
with acute stroke. If anything, the evidence suggested a caused some bias to the results. Third, the functional out-
harmful effect. Furthermore, 2 other trials, CATIS24 and comes of patients were evaluated at 3 months after the
ENOS,25 hold neutral opinions. These trials revealed that stroke. The condition of the patients may further improve
BP reduction with antihypertensive therapy did not reduce or aggravate. However, it has been suggested that func-
the likelihood of unfavorable outcome or improve the func- tional outcome at 3 months correlated well with functional
tional outcome. Thus, it can be concluded that BP reduction outcome at 1 year.32 Another limitation was that we did
in patients with chronic hypertension remains one of the not completely exclude patients with large-artery occlu-
most important factors in primary and secondary stroke sion. Recanalization is related to outcome.33 However, there
preventions, but the proper management strategy for acute was no evidence which proved that BP was an influence
hypertensive response of AIS has been a matter of debate.26 factor of recanalization. Further research is urgent. Finally,
Because of the lack of sufficient evidence and consis- the results of the present study could not be used to explain
tent conclusion, most recommendations for BP levels of to the outcomes of patients who did not meet the inclu-
AIS patients in the guidelines were based on expert sion criteria.
opinion. Moreover, the guidelines were not explicit on
the proper ranges of BP levels for AIS patients to obtain Conclusions
a more favorable outcome.12 The elevated BP is associ-
ated with an increased risk of intracranial hemorrhage In conclusion, our study indicated that post-thrombolysis
for AIS patients undergoing intravenous thrombolysis.27,28 systolic BP is a predictor of functional outcome for Chinese
Every 10 mm Hg elevation of systolic BP in the post- AIS patients undergoing thrombolysis therapy. It is rea-
thrombolysis period increased the odds of parenchymal sonable for AIS patients to keep the post-thrombolysis
hematoma by 59%,29 which always meant an unfavor- systolic BP below 159.5 mm Hg to obtain a favorable
able outcome. From this point of view, it seems that early outcome.
antihypertensive therapy in AIS patients with intrave-
nous thrombolysis therapy is reasonable. Acknowledgments: We thank the physicians, nurses, and
In our study, among the AIS patients undergoing in- patients who participated in our study and are grateful for
travenous thrombolysis, those who kept the post- the support from the Department of Neurology.
thrombolysis systolic BP below 159.5 mm Hg were
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