(Stroke. 1998;29:1495-1497.)
© 1998 American Heart Association, Inc.
Ambulatory Blood Pressure Monitoring and Stroke
More Questions Than Answers
Gregory Y. H. Lip, MD;
Christopher R. Gibbs, MRCP;
D. Gareth Beevers, MD
From the University Department of Medicine, City Hospital, Birmingham,
England.
Correspondence to Dr Gregory Y.H. Lip, University Department of Medicine, City Hospital, Birmingham B18 7QH, UK. E-mail greg{at}chtmedicine.demon.co.uk
Key Words: blood pressure monitoring, ambulatory • hypertension • stroke
The increasing use of
ambulatory blood pressure monitoring (ABPM) devices in the
investigation of hypertension has allowed detailed study of the
circadian rhythm of blood pressure variability, the assessment of
resistant hypertension, and the syndrome of "white coat"
hypertension. The relevance of ABPM to target-organ damage and the
complications of hypertension, such as heart attacks and strokes, has
only recently gained prominence.
There are more than 30 cross-sectional studies that have linked
ABPM to hypertensive target-organ damage, including left
ventricular hypertrophy
(LVH),1 2
microalbuminuria,3 hypertensive
retinal changes, and cerebrovascular disease.4
The majority of these studies have consistently reported that
patients with an absent or reduced fall in blood pressure at night
(referred to as "nondippers") have more severe target-organ damage,
including LVH5 and cerebrovascular
disease,4 6 when compared with patients who
demonstrate a normal nocturnal fall in blood pressure. For example,
Verdecchia et al,7 in a prospective cohort of
over 1100 hypertensive patients, reported higher mortality rates both
in nondippers and "reverse dippers" and higher
cardiovascular morbidity rates in female nondippers
compared with dippers.8 In addition, Yamamoto et
al9 recently reported that progressive
cerebrovascular disease, including silent ischemic lesions and
symptomatic stroke, was associated with a reduced nocturnal
blood pressure fall in patients with a history of lacunar infarction.
In a cross-sectional study of patients admitted with acute stroke
(ictus <12 hours), Lip at al10 reported that
such patients could generally be classed as nondippers, with higher
blood pressures recorded using ABPM (but not using casual manual
measurements) in black/Afro-Caribbean patients and also in patients
with hemorrhagic stroke. These studies therefore suggest the potential
usefulness of ABPM in epidemiological, cohort, or cross-sectional
studies and the assessment of ethnic differences, stroke subtypes, and
prognosis.
A nondipper status on ABPM may thus appear to be a potential predictor
of cardiovascular or cerebrovascular morbidity and
mortality. There are a number of potential problems that may complicate
such an assumption. Vascular disease itself could impair nocturnal
blood pressure falls through impairment of cardiovascular
reflexes.5 Furthermore, it remains uncertain
whether this nondipper status genuinely reflects a greater daily blood
pressure "load" or whether it merely means that the patient did not
sleep soundly, having been disturbed by the inflation of the blood
pressure cuff.11 This may particularly be the
case in an acutely unwell stroke patient who is unable to sleep
immediately after hospital admission. The association between nocturnal
blood pressure and the progression of cerebrovascular disease could be
complicated by the potential exacerbation of cerebral ischemia
by excessive falls in nocturnal blood pressure leading to reduced
cerebral blood flow12 13 or the reduction of
nocturnal blood pressure with antihypertensive
therapy.14
Blood pressure alterations following acute stroke, particularly a
reduction in the day-night difference and a transient elevation in
blood pressure after stroke, have been reported in a number of
studies.10 15 16 17 18 The interpretation of
the reduced day-night difference or nondipping is, however, complicated
by two factors. First, 20% of hypertensive patients exhibit
nondipping, which has also been described in medical conditions as
diverse as renal disease, diabetes with autonomic
neuropathy, heart failure, Cushing's disease, and severe
pre-eclampsia. Second, many studies have relied on arbitrary, fixed
thresholds for the definition of day and night, failing to account for
variable sleep patterns and the appreciable arousal from sleep in
some patients.11 Nevertheless, one plausible
explanation for the reduced day-night variation in poststroke patients
is the influence of stroke subtype (that is, cerebral infarct or
hemorrhage) and the extent or topographical location of
the cerebral lesion, perhaps with altered autonomic regulation leading
to pathological activation of the sympathetic nervous
system.19
Activation of the autonomic nervous system is well recognized as being
present in humans with essential hypertension. Indirect markers of
sympathetic tone, such as plasma norepinephrine, are
elevated in essential hypertension,20 and
sympathetic nerve activation to the skeletal muscle circulation is
increased in borderline hypertensive
individuals21 and further increased according to
the severity of the hypertension.22 Such
sympathetic activation may lead to alterations in cardiac and vascular
structure that are independent of the blood pressure
elevation,23 and this may be an important factor
in nondippers, who continue to demonstrate heightened nocturnal
sympathetic tone.24 Some experimental evidence
also suggests that increased 
-1 adrenergic receptor stimulation may
contribute to the persistently elevated blood pressure levels in
nondippers.16 Animal studies, rat models in
particular, have significantly contributed to our understanding of
autonomic modulation in acute stroke. For example, middle cerebral
artery occlusion (MCAO) in rats leads to consistent focal
cerebral ischemia, and this has proved to be a valuable model
for studying autonomic dysfunction and other
cardiovascular abnormalities in acute
stroke.25 Many studies have shown that MCAO leads
to an increase in renal sympathetic nerve discharge, an increase in
circulating norepinephrines, and associated myocardial
ischemia, subendocardial congestion, or subendocardial
hemorrage.25 26 27 28 Indeed, the sympathetic
activation is more marked after right MCAO, with involvement of the
insular cortex and amygdala.26 Because the latter
mediates cardiovascular responses to stress, the
neurochemical changes in the amygdala may thus be responsible for
stroke-induced cardiovascular
disturbances.27
Human studies have also attempted to determine the influence of
stroke subtype, the topographical location, the extent and laterality
of the infarction or hemorrhage, and the involvement of
structures such as the insular cortex on sympathetic nervous system
activation. For example, Sander and
Klingelhofer29 reported reduced day-night blood
pressure changes in patients with thromboembolic cerebral infarction
and that involvement of the insular cortex was associated with reverse
dipping and increased plasma norepinephrine levels. Right
hemisphere lateralization of autonomic control has also been
demonstrated in humans,30 31 with a reduction in
ipsilateral parasympathetic innervation after right hemisphere
stroke.32 33 It has even been postulated that
this relative increase in sympathetic tone could account for the
differential effects of cerebral infarction on cardiac
rhythm.34
Although the majority of clinical studies have not specifically
addressed the role of stroke subtype on the 24-hour blood pressure
profile, differential responses have been observed in a number of
studies. For example, Lip et al10 reported a
reduced day-night difference in all types of stroke, with a trend
toward reverse dipping in patients with primary
intracerebral hemorrhage (PICH). Similarly,
Yamamoto et al19 reported a significant reduction
in the proportional nighttime blood pressure fall in subcortical and
brain stem strokes, particularly after PICH. In this issue of
Stroke, the Leicester group35 report a
study using 24-hour ABPM to assess the diurnal blood pressure variation
in 98 stroke patients within 48 hours of ictus. Fifty patients had
cortical infarcts, 29 subcortical infarcts, and 19 PICH. Their patients
with cortical infarcts and PICH had significantly reduced diurnal
variation in systolic blood pressure, whereas subcortical
infarcts demonstrated only reduced percentage differences. Mean diurnal
differences in diastolic blood pressure were, however,
significantly reduced in all stroke groups. This article therefore
attempts to address the effect of stroke subtype on diurnal changes in
blood pressure, with the suggestion that autonomic regulation of blood
pressure is damaged, especially in cortical infarction and PICH,
leading to nondipping on ABPM. However, the numbers in each subgroup
are probably too small to draw precise conclusions about the effect of
the extent and laterality of the infarction or hemorrhage and
the involvement of structures involved in autonomic control. For
example, it would have been interesting to ascertain whether patients
with right MCAO, with involvement of the insular cortex and amygdala,
have more sympathetic activation, as was seen in animal
studies.26
The cynic would argue that the clinical and prognostic implications of
ABPM findings in acute stroke are unclear. The suggestion that
nondipping is associated with a poorer prognosis after stroke seems
plausible in view of the associations with target-organ damage and
complications of hypertension; however, if nondipping is detected in a
stroke patient in present-day clinical practice, our management is
still unlikely to differ. The use of cusums analysis is an
attempt to avoid the problems of day-night definition with ABPM
studies, but the clinical application of this complex statistical
method to clinical practice is uncertain; indeed, how many of us would
base our patient management on a cusum plot? Perhaps nondipping may
merely reflect a (very) large area of brain damage following a stroke,
whether ischemic or hemorrhagic. A larger and more
comprehensive series of well-characterized patients is therefore
needed, in which the analysis of the effect of different stroke
subtypes on blood pressure variation as a surrogate of autonomic
function would not only prove some clinical relationship to previous
animal work but also allow greater understanding of brain
anatomy and function and provide information on the prognostic
value of such measurements.
Footnotes
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
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