ARTICLE IN PRESS

Relationship between Post-Thrombolysis Blood Pressure and

Outcome in Acute Ischemic Stroke Patients Undergoing
Thrombolysis Therapy

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.

Introduction outcome and (2) to examine whether post-thrombolysis

Stroke is a major cause of death and disability around
the world, especially in developing countries.1,2 There are
2.5 million new stroke cases and 7.5 million stroke sur-
vivors each year in China.3 Stroke has brought a tremendous
burden on health-care expenditures. Intravenous throm-
bolysis with recombinant tissue plasminogen activator is
an approved method for acute ischemic stroke (AIS).4,5 AIS
patients could benefit from the intravenous thrombolysis
therapy. Nonetheless, some patients may still have poor
prognosis. The causes of this phenomenon are complicat-
ed. Nonideal management of blood pressure (BP) could
be a reason of poor prognosis.6
Over 60% of AIS patients experience an acute hyper-
tensive response within the first 24 hours of symptom onset.7
The mechanisms for acute hypertensive response differ.
Increased intracranial pressure, stress from critical illness
and hospitalization, elevated concentrations of circulating
plasma catecholamine and inflammatory cytokine, unrec-
ognized or uncontrolled pre-existing hypertension, the
Cushing phenomenon, dehydration, pain or discomfort,
nausea, and hypoxia are the potential pathogeneses or crit-
ical influences that contribute to the acute hypertensive
response.8-10 The elevated BP in AIS patients is considered
as a compensatory response that is beneficial for the per-
fusion of ischemic cerebral tissue and saving penumbra,
whereas excessively elevated BP will aggravate cerebral
edema and cause hemorrhagic transformation,11 especial-
ly for patients with thrombolysis therapy. On the other
hand, the decreased BP in AIS patients can reduce the risk
of hemorrhagic transformation but, at the same time, can
bring a poor prognosis by lowering the perfusion to the
penumbra area.12 American Heart Association and Amer-
ican Stroke Association guidelines recommend that a BP
goal of less than 185/110 mm Hg should be achieved before
thrombolysis therapy, and a BP goal of less than 180/
105 mm Hg should be achieved thereafter.12 Although these
recommendations have been suggested to limit the risk of
intracranial hemorrhage, we should know that no intra-
cranial hemorrhage does not indicate favorable outcome.
The optimal BP ranges for a favorable outcome have not
been determined.12 Actually, the BP targets are always based
on clinical judgment at present. Thus, it is necessary to
determine a proper BP range to obtain a favorable outcome
for AIS patients. Furthermore, in consideration of the ethnic
difference between Americans and Chinese, it is mean-
ingful to determine a threshold in the Chinese population.
The purpose of this study was (1) to explore the as-
sociation between post-thrombolysis BP and functional
BP can predict functional outcome in Chinese AIS pa-
tients undergoing thrombolysis therapy.
Methods
Patient Population
From December 2012 to November 2016, patients who
were diagnosed with AIS and underwent thrombolysis
therapy were admitted consecutively in the Department
of Neurology at Xuanwu Hospital. Inclusion criteria were
(1) patients who were diagnosed with AIS, defined ac-
cording to the World Health Organization13 and further
confirmed by computed tomography and magnetic res-
onance imaging scans;14,15 and (2) patients who received
a .9 mg/kg dose of intravenous recombinant tissue plas-
minogen activator within 4.5 hours from the stroke symptom
onset. Exclusion criteria were (1) patients with intracra-
nial hemorrhage, major ischemic infarction (those with
imaging evidence of ischemic injury involving more
than one third of the middle cerebral artery territory),12
or other diseases such as malignant tumor, epilepsy, and
autoimmune disease misdiagnosed as AIS; (2) patients
with contraindications for thrombolysis therapy; and
(3) patients who underwent endovascular treatment after
intravenous thrombolysis. The present study was con-
ducted in accordance with the American Heart Association
and American Stroke Association guidelines and was ap-
proved by the Ethics Committee of Xuanwu Hospital of
Capital Medical University.
Clinical Variables
At baseline, the following demographic and clinical data
were recorded: gender, age, body mass index (BMI), history
of hypertension (previous diagnosis, under antihyper-
tensive treatment, or BP of ≥140/90 mm Hg before stroke),
diabetes mellitus (previous diagnosis, under hypoglyce-
mic agents, fasting plasma glucose level of ≥7.0 mmol/L,
or random level of ≥11.1 mmol/L), dyslipidemia (previ-
ous diagnosis, under lipid-lowering therapy, fasting blood
cholesterol level of ≥5.18 mmol/L, triglyceride level of
≥1.70 mmol/L, low-density lipoprotein cholesterol level
of ≥3.37 mmol/L, or high-density lipoprotein cholester-
ol level of <1.04 mmol/L), coronary heart disease (previous
angina pectoris or myocardial infarction confirmed by cor-
onary angiography), atrial fibrillation (paroxysmal or
permanent atrial fibrillation confirmed by electrocardio-
gram), previous stroke (including ischemic stroke,
intracerebral hemorrhage, or subarachnoid hemorrhage
 ARTICLE IN PRESS
POST-THROMBOLYSIS BLOOD PRESSURE AND OUTCOME
confirmed by imaging), previous transient ischemic attack
(a transient episode of neurological dysfunction caused
by focal brain, spinal cord, or retinal ischemia, without
corresponding acute infarction on diffusion-weighted
imaging), family history of stroke, smoking (current or
previous), alcohol (>50g a day for more than 1 year), oral
antihypertensive agents, antiplatelet agents, lipid-
lowering agents, National Institutes of Health Stroke Scale
(NIHSS) score (scores range from 0 to 42, with greater
scores indicating increasing severity), and symptom onset-
to-thrombolysis time. Auxiliary examinations included
blood routine, hematologic biochemistry, coagulation profile,
and electrocardiogram. Head computed tomography and
magnetic resonance imaging scans were performed in all
patients.
BP Measurements
The BP levels were measured before thrombolysis therapy
(prethrombolysis BP) and immediately after thromboly-
sis therapy (post-thrombolysis BP). BP measurements were
performed with validated, electronic, and automatic sphyg-
momanometers with patients lying in a supine position.
Patients with elevated BP higher than 185/110 mm Hg before
thrombolysis therapy were treated by intravenous pumping
of urapidil or nicardipine with the same protocol. After
the beginning of the BP-lowering therapy, we monitored
the BP every 5 minutes. We began our thrombolysis therapy
as soon as the BP was less than 185/110 mm Hg.12 Patients
with elevations of BP following thrombolysis therapy were
treated with either intravenous or oral antihypertensive
agents as clinically appropriate. The rest of the therapeu-
tic procedures followed current guideline recommendations.12
Outcome Assessment
Functional outcomes of AIS patients who underwent
intravenous thrombolysis therapy were assessed at 3
months after stroke onset according to the modified Rankin
Scale (mRS). A favorable outcome was defined as an mRS
score of 0-2 points, whereas an unfavorable outcome was
defined as an mRS score of 3-6 points.16 These assess-
ments were performed by experienced neurologists blinded
to the BP levels and the illness conditions of the pa-
tients during hospitalization. Follow-ups were conducted
by telephone interviews with patients or their relatives.
Statistical Analysis
We presented continuous variables as mean ± stan-
dard deviation or median with interquartile range (IQR),
and categorical variables as percentages. Values of the
measured parameters were checked if they were of normal
distribution or not, by means of the Kolmogorov–
Smirnov test before the statistical analysis. Baseline variables
on demographic and clinical data were compared by t-test
3
or the Mann–Whitney U-test for continuous variables
and chi-square test for categorical variables. To investi-
gate whether the post-thrombolysis BP allows prediction
of functional outcome in AIS patients, different statisti-
cal methods were used. First, we used the logistic
regression model. The univariate logistic regression anal-
ysis was performed to find variables that were accounted
for the favorable outcome. To adjust for confounding
factors, we undertook the multivariate logistic regres-
sion analysis. Second, a receiver operating characteristic
(ROC) curve was used to evaluate the predictive value
of post-thrombolysis BP and other predictors, and results
were reported as areas under the curve (AUCs).
Statistical significance was set for a P value less than
.05. Considering we may meet some concealed confound-
ers, statistical significance was set for a P value less than
.10 in the univariate analysis.17 All statistical analyses were
made using SPSS for Windows, version 23.0 (IBM Corp.,
Armonk, NY, USA).
Results
Of the 433 patients who underwent intravenous throm-
bolysis therapy during this study, 420 patients were enrolled
(4 patients underwent endovascular treatment after in-
travenous thrombolysis, and 9 patients were misdiagnosed
with AIS and were excluded) and 383 patients com-
pleted the 3-month follow-up eventually.
Baseline Data
Of all patients included in the present study, 253 pa-
tients (66.06%) had a favorable outcome and 130 patients
(33.94%) had an unfavorable outcome. The mean age was
60.94 years, and 73.37% were men. The mean NIHSS score
at baseline was 6.85 points, and the mean symptom onset-
to-thrombolysis time was 207.02 minutes. Twenty-nine
patients had an elevated prethrombolysis BP higher than
185/110 mm Hg. All of the BP levels were lowered to the
point below 185/110 mm Hg before thrombolysis. The mean
prethrombolysis BP after the BP-lowering therapy of these
29 patients was 175.21/93.79 mm Hg. In addition, the mean
post-thrombolysis systolic BP in AIS patients was
144.86 mm Hg. The baseline characteristics of the 383 pa-
tients are described in Table 1. Age, BMI, NIHSS score
at baseline, post-thrombolysis systolic BP, glucose, and
the international normalized ratio between the favor-
able and unfavorable outcome groups were significantly
different.
Post-Thrombolysis Systolic BP and 3-Month
Functional Outcome
In our study, post-thrombolysis systolic BP was sig-
nificantly higher in patients with an unfavorable outcome
at 3 months compared with those with a favorable outcome
 ARTICLE IN PRESS
4 L. WU ET AL.
Table 1. Baseline characteristics of patients

Baseline characteristics Favorable outcome (mRS score 0-2) Unfavorable outcome (mRS score 3-6) P value

Patients, n (%) 253 (66.06) 130 (33.94) —

Male, n (%) 192 (75.89) 89 (68.46) .119
Age (y) 60.04 ± 11.08 62.71 ± 12.31 .016*
61 (53-67) 64 (53.75-73.0)
BMI (kg/m2) 25.11 ± 3.15 25.94 ± 4.15 .048*
24.77 (22.86-27.16) 25.35 (23.52-28.55)
Hypertension, n (%) 164 (64.82) 95 (73.08) .113
Diabetes mellitus, n (%) 83 (32.81) 48 (36.92) .437
Dyslipidemia, n (%) 103 (40.71) 41 (31.54) .074
Coronary heart disease, n (%) 43 (17.00) 29 (22.31) .214
Atrial fibrillation, n (%) 32 (12.65) 19 (14.62) .602
Previous stroke, n (%) 58 (22.92) 32 (24.62) .743
Previous TIA, n (%) 5 (1.98) 4 (3.08) .756
Family history of stroke, n (%) 36 (14.23) 14 (10.77) .334
Smoking, n (%) 133 (52.57) 58 (44.62) .131
Alcohol, n (%) 96 (37.94) 43 (33.08) .334
Oral antihypertensive agents, n (%) 117 (46.25) 50 (38.46) .137
Oral antiplatelet agents, n (%) 36 (14.23) 23 (17.69) .383
Oral lipid-lowering agents, n (%) 24 (9.49) 13 (10) .881
NIHSS score at baseline (points) 5.39 ± 4.45 9.78 ± 6.20 <.001*
4 (2-7) 10 (4-13)
Onset-to-thrombolysis time (min) 205.38 ± 87.54 210.6 ± 81.29 .617
200 (136.0-257.5) 207 (157.5-267.25)
Prethrombolysis systolic BP (mm Hg) 147.31 ± 21.72 149.85 ± 22.61 .357
149 (130-160) 148 (137-168.25)
Post-thrombolysis systolic BP (mm Hg) 142.98 ± 18.93 148.60 ± 21.78 .015*
144 (130-155) 149 (132-160)
Hemoglobin (g/L) 140.26 ± 15.80 137.88 ± 18.46 .138
141 (132-151) 139 (126.25-149.75)
HCY (µmol/L) 17.16 ± 12.23 18.80 ± 15.68 .565
13.15 (10.825-17.9) 13.7 (10.8-17.6)
Glucose (mmol/L) 6.32 ± 2.40 7.34 ± 3.12 <.001*
5.53 (4.85,6.77) 6.175 (5.34,8.54)
Triglycerides (mmol/L) 1.71 ± 1.30 1.61 ± .94 .816
1.38 (.98-1.9925) 1.36 (.95-1.96)
Cholesterol (mmol/L) 4.33 ± .98 4.29 ± .85 .797
4.31 (3.535-4.91) 4.16 (3.65-4.91)
LDL (mmol/L) 2.76 ± .84 2.69 ± .78 .444
2.68 (2.2-3.27) 2.62 (2.18-3.13)
Albumin (g/L) 38.94 ± 3.72 39.28 ± 3.97 .418
39.01 (36.555-41.495) 39.52 (36.76-41.7425)
INR 1.05 ± .10 1.08 ± .17 .048*
1.03 (.99-1.09) 1.05 (.99-1.115)
Fibrinogen (g/L) 2.65 ± .66 2.78 ± .90 .117
2.605 (2.2825-2.95) 2.72 (2.305-3.215)

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
 ARTICLE IN PRESS
POST-THROMBOLYSIS BLOOD PRESSURE AND OUTCOME 5
Table 2. Univariate and multivariate logistic regression analyses for functional outcome

Univariate analysis Multivariate analysis

Variables OR 95% CI P value OR 95% CI P value

Male 1.45 .907-2.317 .12 — — —

Age 1.021 1.002-1.04 .033* 1.022 .997-1.047 .085
BMI 1.068 1.005-1.134 .033* 1.086 1.005-1.174 .038†
Hypertension 1.456 .914-2.321 .114 — — —
Diabetes mellitus 1.192 .766-1.855 .437 — — —
Dyslipidemia .666 .426-1.042 .075* .642 .369-1.117 .117
Coronary heart disease 1.396 .824-2.365 .216 — — —
Atrial fibrillation 1.177 .638-2.17 .602 — — —
Previous stroke 1.087 .662-1.783 .743 — — —
Previous TIA 1.568 .414-5.943 .508 — — —
Family history of stroke .724 .375-1.397 .336 — — —
Smoking .721 .471-1.103 .131 — — —
Alcohol .803 .515-1.253 .334 — — —
Oral antihypertensive agents .722 .469-1.112 .139 — — —
Oral antiplatelet agents 1.392 .781-2.481 .263 — — —
Oral lipid-lowering agents 1.233 .596-2.551 .573 — — —
NIHSS score at baseline 1.168 1.115-1.223 <.001* 1.162 1.103-1.223 <.001†
Onset-to-thrombolysis time 1.001 .998-1.004 .616 — — —
Prethrombolysis systolic BP 1.005 .994-1.017 .356 — — —
Post-thrombolysis systolic BP 1.014 1.003-1.026 .016* 1.017 1.003-1.032 .017†
Hemoglobin .992 .979-1.004 .2 — — —
HCY 1.009 .993-1.025 .279 — — —
Glucose 1.143 1.055-1.238 .001* 1.13 1.016-1.256 .024†
Triglycerides .928 .765-1.127 .453 — — —
Cholesterol .953 .755-1.201 .681 — — —
LDL .901 .69-1.176 .443 — — —
Albumin 1.024 .967-1.084 .417 — — —
INR 7.295 1.247-42.692 .027* 5.169 .470-56.855 .179
Fibrinogen 1.27 .953-1.693 .103 — — —

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.

adjusting all the significant predictors in the univariate

Figure 1. Post-thrombolysis systolic BP between patients with favor-
able and unfavorable outcomes. The box–whisker plot indicates that post-
thrombolysis systolic BP was higher in patients with unfavorable outcome
compared with those with favorable outcome. P value refers to t-test for
difference between groups. A favorable outcome was defined as a modified
Rankin Scale score of 0-2 points, whereas unfavorable outcome was defined
as 3-6 points. BP, blood pressure.
logistic regression analysis, post-thrombolysis systolic BP
still remained statistically significant. Post-thrombolysis
systolic BP could be regarded as an independent prog-
nostic predictor of functional outcome with an adjusted
odds ratio (OR) of 1.017 (95% confidence interval
[CI] = 1.003-1.032). Other independent prognostic predic-
tors included BMI (OR = 1.086, 95% CI = 1.005-1.174), NIHSS
score at baseline (OR = 1.162, 95% CI = 1.103-1.223), and
glucose (OR = 1.13, 95% CI = 1.016-1.256). These prog-
nostic predictors are shown in Table 2.
Next, we found that 159.5 mm Hg was the cutoff point
of post-thrombolysis systolic BP as a predictor of functional
outcome by the ROC curve with an AUC of .573 (95%
CI = .504-.642). The NIHSS score at baseline showed a
greater discriminatory ability with an AUC of .74 (95%
CI = .681-.799) compared with BMI (AUC = .568, 95%
CI = .501-.636) and glucose (AUC=.617, 95% CI = .552-.682).
On further investigation, we discovered that the combination
 ARTICLE IN PRESS
6 L. WU ET AL.

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.

of the 4 independent prognostic predictors previously men- Discussion

tioned increased the discriminatory ability with an AUC
of .763 (95% CI = .707-.819). The ROC curve is shown in
Figure 2.
According to the different values of the post-thrombolysis
systolic BP, we classified patients into 2 groups with
the cutoff point of 159.5 mm Hg. Further, we investi-
gated the association between the 2 groups and functional
outcome with the logistic regression model. The lower
post-thrombolysis systolic BP (<159.5 mm Hg) indicated
a better prognosis with an unadjusted OR of .756 (95%
CI = .654-.875) and an OR of .751 (95% CI = .585-.964) after
adjusting for the possible confounders (Table 3).
In view of aging and other demographic changes world-
wide, it is likely that the burden of stroke will increase
substantially in the future.18 High BP (>140/90 mm Hg)
is very common (approximately 75% of patients) early
after ischemic stroke.19 Thus, it is critical for AIS pa-
tients to keep their BP levels in the appropriate ranges.
A few clinical trials have explored the relationship between
the BP levels and functional outcomes in AIS patients.
However, the results are diverse.
The International Stroke Trial11 showed a U-shaped re-
lationship between systolic BP levels and functional

Table 3. Logistic regression analysis for outcome by different values of post-thrombolysis systolic BP

Univariate analysis Multivariate analysis

Post-thrombolysis systolic BP OR 95% CI P value OR 95% CI P value

≥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.
 ARTICLE IN PRESS
POST-THROMBOLYSIS BLOOD PRESSURE AND OUTCOME
outcomes, which meant that both high BP and low BP
were associated with unfavorable outcome after AIS. The
most favorable outcome was for systolic BP levels ranging
from 140 to 179 mm Hg on admission. The CHHIPS,20 a
multicenter, prospective, randomized, double-blind and
placebo-controlled trial, suggested early antihyperten-
sive therapy. This trial revealed that early lowering of
BP with lisinopril and labetalol after acute stroke seemed
to be a promising approach to reduce mortality and po-
tential disability. Analogously, the ACCESS study,21 which
is a prospective, double-blind, placebo-controlled, ran-
domized, multicenter phase II study, suggested that, as
a safe therapeutic option, candesartan could reduce the
cumulative 12-month mortality and the number of vas-
cular events of the AIS patients. On the contrary, some
studies disapproved of early antihypertensive therapy
because it may bring an unfavorable outcome to AIS pa-
tients. An observational study found that BP reduction
in the first 24 hours of stroke onset is independently as-
sociated with unfavorable outcome after 3 months.22 A
randomized, placebo-controlled, double-blind trial named
SCAST23 concluded that the careful BP-lowering treat-
ment with candesartan leads to few benefits in patients
with acute stroke. If anything, the evidence suggested a
harmful effect. Furthermore, 2 other trials, CATIS24 and
ENOS,25 hold neutral opinions. These trials revealed that
BP reduction with antihypertensive therapy did not reduce
the likelihood of unfavorable outcome or improve the func-
tional outcome. Thus, it can be concluded that BP reduction
in patients with chronic hypertension remains one of the
most important factors in primary and secondary stroke
preventions, but the proper management strategy for acute
hypertensive response of AIS has been a matter of debate.26
Because of the lack of sufficient evidence and consis-
tent conclusion, most recommendations for BP levels of
AIS patients in the guidelines were based on expert
opinion. Moreover, the guidelines were not explicit on
the proper ranges of BP levels for AIS patients to obtain
a more favorable outcome.12 The elevated BP is associ-
ated with an increased risk of intracranial hemorrhage
for AIS patients undergoing intravenous thrombolysis.27,28
Every 10 mm Hg elevation of systolic BP in the post-
thrombolysis period increased the odds of parenchymal
hematoma by 59%,29 which always meant an unfavor-
able outcome. From this point of view, it seems that early
antihypertensive therapy in AIS patients with intrave-
nous thrombolysis therapy is reasonable.
In our study, among the AIS patients undergoing in-
travenous thrombolysis, those who kept the post-
thrombolysis systolic BP below 159.5 mm Hg were
associated with an increased probability of 3 months’ fa-
vorable outcome, compared with those with a post-
thrombolysis systolic BP over 159.5 mm Hg. This finding
indicated a remarkable significance for patients to un-
dertake thrombolysis therapy with electrocardiograph
monitoring to monitor the BP levels at any time. Although
7
the decreased systolic BP levels are related to the favor-
able outcome, early antihypertension for patients with
thrombolysis therapy should not be conducted without
serious consideration because the BP levels tend to de-
crease spontaneously after the onset of stroke in most
patients.30 Besides, the decline of systolic BP levels is sig-
nificantly faster in patients with successful recanalization.31
Thus, to reduce the possibility of cerebral hypoperfusion
caused by antihypertension, we should evaluate the risks
sufficiently according to the practical situations before the
antihypertensive therapy and manage the BP levels cau-
tiously. Likewise, our study demonstrated that the post-
thrombolysis systolic BP is an independent predictor of
functional outcome in Chinese AIS patients with intra-
venous thrombolysis therapy. Although the prediction of
the post-thrombolysis systolic BP alone has not been proven
to be highly efficient, the predictability could be im-
proved with the combination of BMI, NIHSS score at
baseline, and glucose levels.
Several limitations in our study should be considered.
First, it was a single-center study. Thus, the enrolled pa-
tients may not be able to represent the whole AIS patients.
Second, the loss of follow-ups with any reason may have
caused some bias to the results. Third, the functional out-
comes of patients were evaluated at 3 months after the
stroke. The condition of the patients may further improve
or aggravate. However, it has been suggested that func-
tional outcome at 3 months correlated well with functional
outcome at 1 year.32 Another limitation was that we did
not completely exclude patients with large-artery occlu-
sion. Recanalization is related to outcome.33 However, there
was no evidence which proved that BP was an influence
factor of recanalization. Further research is urgent. Finally,
the results of the present study could not be used to explain
to the outcomes of patients who did not meet the inclu-
sion criteria.
Conclusions
In conclusion, our study indicated that post-thrombolysis
systolic BP is a predictor of functional outcome for Chinese
AIS patients undergoing thrombolysis therapy. It is rea-
sonable for AIS patients to keep the post-thrombolysis
systolic BP below 159.5 mm Hg to obtain a favorable
outcome.
Acknowledgments: We thank the physicians, nurses, and
patients who participated in our study and are grateful for
the support from the Department of Neurology.
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2. Kim JY, Yenari MA. Hypothermia for treatment of stroke.
Brain Circ 2015;1:14-25.
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