Blood Pressure Evolution After Acute Ischemic Stroke in

Patients With and Without Sleep Apnea

Claudia Selic, MD*; Massimiliano M. Siccoli, MD*; Dirk M. Hermann, MD; Claudio L. Bassetti, MD

Background and Purpose—Sleep apnea (SA) is an independent risk factor for arterial hypertension and is present in 50%
to 70% of patients with ischemic stroke. The effects of SA on blood pressure (BP) and stroke outcome in the acute stroke
phase are essentially unknown.
Methods—We studied 41 consecutive patients admitted within 96 hours after stroke onset. Stroke severity on admission
(National Institutes of Health Stroke Scale [NIHSS]) and stroke outcome at discharge (modified Rankin Disability Scale
[mRS]) were assessed. Nocturnal breathing was assessed with an ambulatory device the first night after admission. SA
was defined by an apnea-hypopnea-index (AHI) ⱖ10/hour, and moderate-severe SA (MSSA) was defined by an AHI
⬎30/hour. BP monitoring was performed during the first 36 hours after admission. A nondipping status (NDS) was
defined by a ratio ⬎0.9 of mean systolic BP during nights 1 to 2/mean systolic BP during day 2.
Results—SA was found in 28 (68%) and MSSA in 11 (27%) of 41 patients. A correlation was found between AHI and
both NIHSS (r⫽0.331; P⫽0.035) and mRS (r⫽0.341; P⫽0.031). Patients with MSSA had higher systolic and diastolic
BP values during night 1 (P⫽0.003), day 2 (P⫽0.004), and night 2 (P⫽0.03). NDS was found in 26 (63%) patients.
Nondippers had a similar AHI but higher NIHSS (P⫽0.004) and mRS (P⫽0.005) than dippers. AHI and NDS were
confirmed to be independent predictors for both stroke severity and stroke outcome in a multiple stepwise linear
regression model.
Conclusions—SA severity is associated with high 24-hour BP values but only weakly with stroke severity and outcome.
Conversely, NDS is linked with a more severe stroke and a poorer evolution but not with SA severity. These data suggest
different, although overlapping, pathophysiological and clinical implications of circadian and nocturnal BP values in
acute stroke. (Stroke. 2005;36:2614-2618.)
Key Words: blood pressure 䡲 dipping/nondipping 䡲 ischemic stroke 䡲 sleep apnea 䡲 stroke outcome
Downloaded from http://ahajournals.org by on December 7, 2018

S leep apnea (SA) is a well-recognized independent risk factor

for cardiovascular morbidity and mortality.1,2 One possible
cause for this link is the association of SA with arterial
hypertension, which was found in several studies independently
of gender, body weight, age, and other cardiovascular risk
factors.3,4 The prevalence of SA in patients with arterial hyper-
tension is higher compared with the normal population,5 and
treatment with continuous positive airway pressure reduces
blood pressure (BP) in hypertensive SA patients.6,7 Finally, SA
is very frequent (50% to 70%) in patients with transient ischemic
attack and acute stroke8 –10 and may affect stroke outcome.11–13
Evolution of BP in acute stroke and its impact on outcome
has been addressed in several studies. Eighty percent of
patients with acute stroke are hypertensive on admission,
and elevated BP spontaneously declines over the following
days.14,15 Patients with both increased and decreased BP may
have an unfavorable prognosis, suggesting a bell-shaped
relationship between BP and stroke outcome.16,17 In addition,
an impairment of circadian BP modulation with loss of
physiological nocturnal BP dipping has been documented in
the first days after stroke.18 –21
Considering the strong association between SA and both
hypertension and stroke and the impact of elevated BP levels
on stroke outcome,19,22,23 it is surprising that the relationship
among BP, SA, and stroke was studied only once in the
literature.24 To test the hypothesis of a link between SA and
high BP in acute stroke, we correlated BP values with SA
severity and short-term outcome in 41 patients with acute
ischemic stroke.
Methods
Patients
Forty-five consecutive patients (ages 18 to 85 years) with acute
ischemic stroke admitted to our Department of Neurology were
prospectively included. The study design was approved by the local
ethical committee, and written informed consent was obtained from
each patient or relatives. Patients with very severe strokes (National
Institutes of Health Stroke Scale [NIHSS]25 ⬎20), intracerebral/sub-

Received March 15, 2005; final revision received August 16, 2005; accepted September 12, 2005.
From the Neurology Department, University Hospital of Zurich, Zurich, Switzerland.
*Dr Selic and Dr Siccoli contributed equally to this work.
Correspondence to Claudio L. Bassetti, Neurologische Poliklinik, UniversitätsSpital Zürich, Frauenklinikstrasse 26, CH-8091 Zürich, Switzerland.
E-mail claudio.bassetti@usz.ch
© 2005 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org DOI: 10.1161/01.STR.0000189689.65734.a3

2614
 Selic et al BP, Stroke, and Sleep Apnea 2615

arachnoidal hemorrhage, hemorrhagic infarction, coma/stupor, and TABLE 1. Main Results of All Patients
life-threatening medical conditions were excluded.
Variable All Patients (n⫽41)
Clinical Evaluation Male/female (%) 33/8 (81/19)
Cardiovascular risk factors including family history, arterial hyper- Age, y 63⫾13 关25 to 83兴
tension (BP ⬎140/90 mm Hg measured ⱖ3 times before stroke), BMI, kg/m2 27⫾4 关21 to 39兴
diabetes (fasting glucose level ⬎140 mg/dL), smoking status, hyper-
cholesterinemia (cholesterol level ⬎250 mg/dL), adipositas (body NIHSS day 1 7⫾5 关1 to 20兴
mass index [BMI] ⱖ25 kg/m2), and previous history of coronary SSS day 1 41⫾13 关8 to 58兴
heart disease were recorded. Stroke side, right/left (%) 23/18 (56/44)
Stroke assessment included NIHSS and Scandinavian Stroke Scale
(SSS).26 Short-term stroke outcome was estimated by the modified Hemispheric/brainstem stroke (%) 38/3 (93/7)
Rankin Disability Scale (mRS)27 at hospital discharge. Latency S-R, h 37⫾25 关8 to 96兴
mRS at discharge 2⫾1.4 关0 to 5兴
Nocturnal Breathing Duration of hospital stay, days 12⫾7 关3 to 31兴
Overnight respirography was performed with an ambulatory device
AHI, /h 23⫾22 关0 to 101兴
(Autoset Embletta PDS; ResMed) during the first night after admis-
sion (night 1). This respirography has been validated before in AI, /h 11⫾16 关0 to 70兴
patients with stroke (C.L.B., et al, unpublished data, 2005). The OAI, /h 2⫾3 关0 to 15兴
analysis was performed automatically and corrected manually. Ap-
CAI, /h 8⫾15 关0 to 61兴
nea was defined by a cessation of oronasal airflow ⱖ10 seconds and
hypopnea by a reduction of oronasal airflow ⱖ10 seconds by ⱖ50% ODI, /h 14⫾15 关0 to 64兴
or ⱖ30% when associated with an oxygen desaturation ⱖ4%. CT90, % 10⫾20 关0 to 95兴
Apnea-hypopnea index (AHI) was defined by the mean number of No. of antihypertensive drugs (% of patients) 1⫾1 关0 to 3兴 (61)
apneas and hypopneas per hour and apnea index (AI) by the mean
number of apneas per hour between lights off and on. Moderate- History of arterial hypertension (%) 26 (63)
severe SA (MSSA) was defined by AHI ⬎30/hour, mild SA by AHI Positive family history for vascular diseases (%) 19 (46)
10 to 30/hour, and no SA by AHI ⬍10/hour. A differentiation Diabetes (%) 8 (20)
between obstructive (OAI) and central (CAI) AI was undertaken
Smoking (%) 28 (68)
according to standard criteria. The percentage of time with oxygen
saturation ⬍90%, as well as the oxygen desaturation-index (ODI) Hypercholesterinemia (%) 22 (54)
were calculated. The magnitude of the oxygen desaturation consid- BMI ⬎25 (%) 25 (61)
ered for ODI was ⱖ4%. Body position was not monitored.
Downloaded from http://ahajournals.org by on December 7, 2018

Coronary heart disease (%) 8 (20)

BP Values are mean⫾SD (range in brackets) unless indicated otherwise

BP and pulse rate were monitored with an ambulatory device (bp
one, Cardiette) over 36 hours in intervals of 30 minutes beginning
from night 1. Mean systolic and diastolic BP values and pulse rates
were calculated in all of the patients for each period of time (night 1,
day 2, and night 2, defined individually). NDS was defined as a ratio
⬎0.9 of mean systolic BP during nights 1 and 2/mean systolic BP
during day 2.18,28,29 The number of antihypertensive drugs used on
admission were recorded.
Statistics
Statistical analysis was performed with the SPSS software package.
Continuous data were presented as mean/SD and categorial variables
as numbers/percentage. Student unpaired t tests were used for
comparison of patients groups and for testing of continuous vari-
ables. Not normally distributed data were compared with the Mann–
Whitney test. Correlations were calculated using the Pearson coef-
ficient. A P⬍0.05 was considered to be statistically significant.
Multiple stepwise regression models (with entry value set to 0.05 and
removal value set to 0.1 in the univariate analysis) were tested using
stroke severity (SSS at day 1) and stroke outcome (mRS) as
dependent variables. Age, gender, number of cardiovascular risk
factors, BMI, history of arterial hypertension, diabetes, smoking
status, hypercholesterinemia, coronary heart diseases, adipositas,
mean systolic BP night 1/day/night 2, mean diastolic BP night
1/day/night 2, mean pulse night 1/day/night 2, number of antihyper-
tensive drugs, NDS, and AHI were candidate predictors.
Results
Forty-five patients were included, 41 completed the study,
and 4 had to be excluded. The main demographic and clinical
characteristics of these 41 patients are summarized in Table 1.
Latency S-R indicates latency from stroke onset to respirography; CT90,
percentage of time with oxygen saturation ⬍90%.
Sleep Breathing
The mean AHI was 23⫾22/hour (0 to 101), AI was 11⫾16/
hour (0 to 70), OAI was 2⫾3/hour (0 to 15), CAI was
8⫾15/hour (0 to 61), ODI was 14⫾15/hour (0 to 64), and
percentage of time with oxygen saturation ⬍90% was
10⫾20% (0 to 95). SA was found in 28 of 41 patients (68%).
Eleven patients (27%) had a MSSA (mean AHI, 50⫾21/hour
[31 to 101]; OAI, 5⫾5/hour [0 to 15]; and CAI, 24⫾23/hour
[1 to 61]). Seventeen patients had a mild SA (mean AHI,
20⫾7/hour [10 to 29]; OAI, 3⫾3/hour [0 to 9]; and CAI,
6⫾7/hour [0 to 20]). In 13 patients (32%), no SA was found
(mean AHI, 4⫾3/hour [0 to 8]; OAI, 1⫾1/hour [0 to 2]; and
CAI, 1⫾1/hour [0 to 3]).
Considering the entire group of patients (n⫽41), a weak but
statistically significant correlation between SA severity (AHI)
and stroke severity on admission (NIHSS day 1 [r⫽0.331;
P⫽0.035], SSS day 1 [r⫽⫺0.407; P⫽0.008]) and short-term
outcome (mRS at discharge [r⫽0.341; P⫽0.031]) was observed.
AHI remained significantly associated with both stroke severity
(P⫽0.015) and stroke outcome (P⫽0.031) in a multiple step-
wise linear regression model (Table 2).
When compared with patients without SA (n⫽13), patients
with MSSA (n⫽11) had a higher BMI (P⫽0.001), a lower
SSS on day 1 (P⫽0.046), and a longer duration of hospital-
ization (P⫽0.008). These and other results are shown in
Table 3.
 2616 Stroke December 2005

TABLE 2. Independent Predictors of Stroke Severity (SSS Day 1) TABLE 3. Comparison of Patients Without SA (AHI<10/h) and
Patients With MSSA (AHI>30/h)
Variable Estimate SE t P Value
Stroke Severity, SSS day 1 AHI⬍10/h AHI⬎30/h P
Variable (n⫽13) (n⫽11) Value
AHI, /h ⫺0.209 0.081 ⫺2.587 0.015
Male/female (%) 8/5 (62/38) 10/1 (91/9) NS
NDS ⫺14.040 3.804 ⫺3.691 0.001
Age, y 57⫾17 67⫾12 NS
Stroke outcome, mRS
BMI, kg/m2 25⫾3 29⫾2 0.001
AHI, /h 0.021 0.009 2.265 0.031
NIHSS day 1 6⫾5 9⫾5 NS
NDS 1.124 0.441 2.551 0.016
SSS day 1 47⫾12 35⫾14 0.046
Full model for SSS day 1: F⫽10.89, P⬍0.001, R2⫽0.413; Full model for
mRS: F⫽6.428, p⫽0.005, R2⫽0.300. Latency S-R, h 46⫾27 33⫾20 NS
mRS at discharge 1.7⫾1.6 2.5⫾1.6 NS
BP Duration of hospitalization, 8⫾3 16⫾8 0.008
History of arterial hypertension was present in 26 of 41 day
patients (63%). Twenty-five (61%) patients were treated with AHI, /h 4⫾3 50⫾21 (⬍0.0001)
antihypertensive drugs. The mean BP during night 1 was AI, /h 1⫾1 29⫾24 (0.022)
140⫾25 (100 to 239)/87⫾16 (63 to 147) mm Hg, during day OAI, /h 1⫾1 5⫾5 NS
2 it was 153⫾24 (117 to 220)/97⫾15 (72 to 138) mm Hg, CAI, /h 1⫾1 24⫾23 0.036
and during night 2 it was 144⫾31 (86 to 209)/90⫾20 (51 to
ODI, /h 3⫾3 34⫾18 0.003
129) mm Hg. Patients with MSSA had higher systolic and
CT90, % 4⫾10 7⫾6 NS
diastolic BP values during night 1, day 2, and night 2 than
patients without SA (Table 3; Figure). Diabetes (%) 3 (23) 0 (0) NS
Twenty-six patients (63%) were nondippers. Nondippers Smoking (%) 8 (62) 9 (82) NS
had more severe strokes (NIHSS day 1, P⫽0.004; SSS day 1, Hypercholesterinemia (%) 7 (54) 5 (45) NS
P⫽0.003), worse outcome (mRS, P⫽0.005), and also a lower Coronary heart disease (%) 3 (23) 3 (27) NS
number of antihypertensive drugs on admission (P⫽0.009). History of arterial 7 (54) 8 (73) NS
NDS remained significantly associated with both stroke hypertension (%)
severity (P⫽0.001) and stroke outcome (P⫽0.016) in a No. antihypertensive drugs 1⫾0.5 (46) 1⫾0.5 (64) NS
multiple-stepwise linear regression model (Table 2). (% of patients)
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Conversely, there were no significant differences between Nondippers (%) 9 (69) 8 (73) NS
dippers and nondippers regarding history of hypertension and Systolic BP night 1, mm Hg 129⫾18 157⫾19 0.003
respiratory parameters. A reverse dipping (BP night⬎BP day)
Systolic BP day 2, mm Hg 136⫾16 166⫾24 0.004
was found in 7 patients (17%), 3 of whom had MSSA. These
Systolic BP night 2, mm Hg 131⫾26 162⫾32 0.03
and other results are shown in Table 4.
Diastolic BP night 1, mm Hg 80⫾12 98⫾13 0.005
Discussion Diastolic BP day 2, mm Hg 87⫾11 104⫾15 0.009
We investigated the evolution of BP in the acute stroke phase Diastolic BP night 2, mm Hg 82⫾17 99⫾19 0.029
and its relationship to SA and stroke outcome. Our main Pulse night 1, beats/min 67⫾9 66⫾15 NS
results can be summarized as follows: (1) SA was found in Pulse day 2, beats/min 75⫾10 69⫾12 NS
69% of patients, and its severity was associated with higher
Pulse night 2, beats/min 67⫾11 66⫾12 NS
24-hour BP values but only weakly with stroke severity and
stroke outcome; and (2) a NDS was observed in 63% of NS indicates no significant difference; latency S-R, latency from stroke onset
to respirography; CT90, percentage of time with oxygen saturation ⬍90%.
patients and was linked to a more severe stroke and a worse
stroke outcome but not with SA severity.
have, to our best knowledge, never been reported before in
SA, BP, and Stroke Outcome stroke victims. Turkington et al24 found an increased BP
The high frequency of SA (69%) and MSSA (27%) in stroke variability (expressed as 10 and 15 mm Hg dips in BP) in 7
victims is in line with previous reports.8 –10 Our study also patients with SA (AHI⬎10/h), as compared with 5 patients
confirms the high proportion of hypopneas and central apneas without SA but did not provide data on absolute BP values.
in the first few nights after stroke (mean latency to sleep Several mechanisms may explain higher BP values in
recording, 37⫾25 h),10 which contrasts with the predomi- stroke patients with SA including oscillations in cardiac
nance of obstructive and apneic events thereafter.8,9,30 The output and heart rate, increased sympathetic activity, and
pathophysiological mechanisms involved therein remain un- impaired baroreceptor control.31,32 Considering the observa-
clear at this point. tion of a similar BP evolution in patients with and without
In patients with SA, we found significantly higher systolic SA, sleep disordered breathing appears to be a factor contrib-
and diastolic BP values than in patients without SA. Further- uting to the overall poststroke increase of BP.
more, a linear, dose-response relationship between SA sever- We observed only a weak relationship between SA severity
ity (AHI) and BP levels was observed, similar to what has and both stroke severity and short-term stroke outcome. Several
been reported in the general SA population.3 These findings previous studies also failed to find any significant link between
 Selic et al BP, Stroke, and Sleep Apnea 2617

Mean systolic and diastolic BP values

during night 1, day 2, and night 2 in
patients without SA (AHI⬍10/h), with
mild SA (10/hⱕAHIⱕ30/h), and with
MSSA (AHI⬎30/h). Values are
mean⫾SD. SBP, systolic BP; DBP, dia-
stolic BP. *P⬍0.05 compared with
patients without SA (AHI⬍10/h).

stroke severity and SA.8 –10,12 Data on SA and short-term stroke
outcome are scarce and contradictory. In 1 study, worsening of
neurological deficits in the acute phase was observed in patients
with SA in the absence, however, of any detrimental effect on
short-term stroke outcome.12 Conversely, Kaneko et al33 re-
TABLE 4. Comparison of Patients With and Without Nocturnal
BP Dipping (See Text for Definition)
Dippers Nondippers
Variable (n⫽15) (n⫽26)
Downloaded from http://ahajournals.org by on December 7, 2018
ported, as we did in the present study, an association between SA
severity and duration of hospitalization.
The only weak association found between SA severity (as
estimated by the AHI) and short-term stroke outcome could
be related not only to the size of the present study, but also to
the high frequency of central apneas recorded in our patients
in the very acute phase of stroke. In fact, central respiratory
events are known to have less detrimental effects (eg, on
cerebral blood flow) than obstructive respiratory events.34 In
P addition, a spontaneous improvement of central respiratory
Value events can often be observed in the subacute phase of

Male/female (%) 11/4 (73/27) 22/4 (85/15) NS stroke.10 Additional studies are, however, needed to test the
Age, y 62⫾15 63⫾12 NS hypothesis that obstructive SA persisting beyond the very
BMI, kg/m2 28⫾4 27⫾3 NS acute phase after stroke may have a more significant, detri-
NIHSS day 1 5⫾3 9⫾5 0.004 mental effect on its short-term outcome.
SSS day 1 49⫾9 36⫾13 0.003
Dipping Status, SA, and Stroke Outcome
Latency S-R, h 45⫾24 32⫾24 NS We confirm that NDS, observed in 63% of patients, is a
mRS at discharge 1.3⫾0.9 2.5⫾1.5 0.005 frequent phenomenon in acute ischemic stroke. This obser-
AHI, /h 21⫾14 24⫾25 NS vation was made first by Sander and Klingelhofer.35 In a
AI, /h 10⫾12 11⫾18 NS series of 86 patients with acute stroke, Lip et al18 found mean
OAI, /h 3⫾4 2⫾3 NS day-night differences in systolic and diastolic BP ⬍10%,
CAI, /h 7⫾13 10⫾17 NS
demonstrating that NDS was a common finding in this stage.
Jain et al21 reported a NDS in 88% of 50 patients examined in
ODI, /h 14⫾13 14⫾17 NS
the first 120 hours after stroke. In 58%, the mean nocturnal
CT90, % 11⫾26 9⫾14 NS
BP was even higher than daytime BP (reverse dipping).
History of arterial hypertension (%) 12 (80) 14 (54) NS Our data also suggest that loss of physiological nocturnal BP
No. of antihypertensive drugs 1.5⫾1 (87) 1.0⫾1 (42) 0.009 dipping is a stronger predictor for a worse stroke outcome than
(% of patients) increased circadian BP values. Similar to us, Bhalla et al19 found
Systolic BP night 1, mm Hg 127⫾20 148⫾25 0.011 that a decrease in day-night BP difference was associated with
Systolic BP day 2, mm Hg 151⫾24 154⫾25 NS poor outcome in 72 patients 1 week after stroke. In hypertensive
Systolic BP night 2, mm Hg 125⫾28 153⫾29 0.009 patients, Verdecchia et al36 reported that the number of com-
Diastolic BP night 1, mm Hg 78⫾11 93⫾16 0.005 bined fatal and nonfatal cardiovascular events per 100 patient-
Diastolic BP day 2, mm Hg 95⫾14 97⫾16 NS
years was higher in patients with reduced nocturnal BP variation
(4.99 in nondippers; 1.79 in dippers). Size and design of our
Diastolic BP night 2, mm Hg 78⫾17 96⫾19 0.009
study do not allow us to test the hypothesis of a link between
Pulse night 1, beats/min 59⫾6 68⫾13 0.011 stroke outcome and increased BP variability,24 BP values at both
Pulse day 2, beats/min 67⫾7 73⫾13 NS extremes of its spectrum,17 or hypotensive BP values after the
Pulse night 2, beats/min 60⫾7 67⫾13 NS first 24 hours.16
NS indicates no significant difference; latency S-R, latency from stroke onset NDS is thought to arise from an imbalance between sympa-
to respirography; CT90, percentage of time with oxygen saturation ⬍90%. thetic and parasympathetic tone. This may be because of an
 2618 Stroke December 2005
increased, stroke-related catecholamine and cortisol release,
possibly reflecting the cerebral response to a decreased perfusion
in the ischemic penumbra but also changes in the sleep-wake
cycle and the acute stress of hospitalization. Based on our data,
stroke severity and use of antihypertensive drugs at stroke onset,
but not SA, influence the dipping status of acute stroke patients.
Other studies have suggested a role also of stroke topography
(cortical versus noncortical) and stroke etiology (hemorrhagic
versus ischemic).18 –21 Obviously, we cannot exclude, based on
our data, the possibility that, in larger size studies including more
patients, an association between NDS and SA of obstructive type
could be found.
Conclusions
SA severity is associated with elevated circadian BP levels
but only weakly with stroke severity and outcome. NDS
predicts the presence of more severe stroke and poorer
outcome but is not linked with SA severity. These data
suggest that elevated circadian BP values and NDS have
different, although overlapping, pathophysiological and clin-
ical implications in acute ischemic stroke.
Acknowledgments
Prof Wilhelm Vetter, Department of Internal Medicine, University
Hospital of Zurich, provided helpful comments on blood pressure
results. Dr Esther Werth and Sabrina Döring, Department of Neu-
rology, University Hospital of Zurich, assisted in the recording and
scoring of respirographies. We thank Dr Valentin Rousson for
statistical advice.
Downloaded from http://ahajournals.org by on December 7, 2018
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