Download Association Between Blood Pressure and C

Association Between Blood Pressure and C-Reactive Protein
Levels in Acute Ischemic Stroke
Mario Di Napoli, Francesca Papa
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Abstract—Among patients with acute stroke, high blood pressure (BP) and higher levels of circulating C-reactive protein
(CRP) at the entry are often associated with poor outcome, although the reason is unclear. If the link between BP and
stroke outcome is indeed mediated by inflammatory response, one would expect to see positive associations between
BP and CRP. In a prospective observational stroke data bank involving 535 first-ever ischemic stroke patients, we
studied the association between BP and baseline concentrations of CRP within 24 hours after stroke onset. The
association between BP components and the odds of having an elevated CRP level (ⱖ1.5 mg/dL) was assessed by
logistic regression analysis. An increase in systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), or
pulse pressure (PP) was significantly associated with an increase in the odds of having an elevated CRP level,
independent of other associated study factors. For each 10 mm Hg increase in SBP, DBP, MAP, or PP, the odds of
having a high CRP level increased by 72% (P⬍0.0001), 10% (P⬍0.0001), 21% (P⬍0.0001), and 10% (P⬍0.0001),
respectively. When the same model was rerun, adjusting for all considered BP components, only SBP significantly
increased the odds of an elevated CRP level by 77% (P⬍0.0001). Increased SBP was significantly associated with
elevated levels of circulating CRP in ischemic stroke patients. These findings support a possible role of acute
hypertension after stroke as an inflammatory stimulus contributing to ischemic brain inflammation. (Hypertension.
2003;42:1117-1123.)
Key Words: blood pressure 䡲 C-reactive protein 䡲 ischemia 䡲 stroke 䡲 risk factors
H
stroke have elevated BP at presentation, of which about half
have a history of hypertension.22 BP declines spontaneously
after stroke onset and returns to prestroke levels in two thirds
of patients within the first days.23 Most studies, although not
all, have found that high BP in the acute phase of stroke is
associated with a poor outcome.24 –26 An explanation for these
findings has not been given. High BP might promote early
recurrence, hemorrhagic transformation, or the formation of
cerebral edema.27 Both high and low BP were found to be
independent prognostic factors for poor outcome, relationships that appear to be mediated in part by increased rates of
early recurrence and death resulting from presumed cerebral
edema in patients with high BP and increased coronary heart
disease events in those with low BP.28 At the same time, a
stronger inflammatory response after stroke is associated with
a severe neurological deficit and a poor outcome with a
higher risk of new recurrent cardiovascular events.16,17 If the
link between BP and stroke outcome is indeed mediated by
inflammatory response, one would expect to see positive
associations between BP and markers of systemic inflammation, such as CRP. An exploratory analysis in the same stroke
cohort has suggested that elevated levels of systolic or
diastolic BP in the acute phase after an ischemic stroke are
associated with elevated levels of CRP.29 In the present study,
ypertension is a well-known risk factor for ischemic
stroke,1 and the effect of blood pressure–lowering treatment in preventing first stroke2 is well established, but the
pathologic and molecular mechanisms by which elevated
blood pressure (BP) leads to vascular disease are uncertain:
hypertension may promote endothelial expression of cytokines3,4 and stimulate inflammation.5,6 These data are particularly intriguing given that inflammation plays a critical role
in the pathogenesis of atherosclerosis.7
Prospective data demonstrate that inflammation, particularly C-reactive protein (CRP), appears to predict the risk of
cardiovascular events among healthy subjects,8,9 patients with
high vascular risk,10,11 those with stable and unstable angina,12–14 and stroke patients.15–17
Signs of an acute inflammatory response are also evident in
acute ischemic stroke.15–19 These acute-phase reactants, such
as cytokines and CRP may reflect inflammation related to the
pathobiology of ischemic stroke.19,20 However, many patients
(⬇25%) had normal levels of inflammation markers after
stroke, implying that ischemic lesion itself does not induce a
full-blown acute-phase response.15–17 The specific stimuli
that promote inflammatory response in acute ischemic stroke
have not been fully elucidated.
In addition, the BP response after an ischemic stroke is
variable21: three quarters of patients with acute ischemic
Received August 13, 2003; first decision September 8, 2003; revision accepted October 1, 2003.
From the Neurological Section, SMDN–Center for Cardiovascular Medicine and Cerebrovascular Disease Prevention, Sulmona (L’Aquila), Italy
Correspondence to Dr Mario Di Napoli, MD, Neurological Section, SMDN–Center for Cardiovascular Medicine and Cerebrovascular Disease
Prevention, Via Trento, 41, 67039, Sulmona (AQ), Italy. E-mail [email protected]
© 2003 American Heart Association, Inc.
Hypertension is available at http://www.hypertensionaha.org
DOI: 10.1161/01.HYP.0000100669.00771.6E
1117
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Hypertension
December 2003
Study flow diagram. Diagnosis of exclusion is also indicated. Concomitant disease includes major renal (n⫽13),
hepatic (n⫽13), and hematological disease (n⫽8). Ninety-two patients with
recent clinical infection had also a relevant comorbidity that was capable of
increasing acute-phase reactants.
Downloaded from http://hyper.ahajournals.org/ by guest on August 3, 2017
we sought to determine whether BP levels might contribute to
inflammatory response in acute ischemic stroke among ischemic stroke patients.
Methods
Study Design and Participants
The current study is based on data from the prospective hospitalbased Villa Pini Stroke Data Bank.15,16 The original inclusion criteria
were a diagnosis of first-ever ischemic stroke within 24 hours before
enrollment.15 We restricted our study to the 535 patients included
between March 1998 and March 2000, who were free of diseases that
might substantially affect their levels of CRP (recent clinical
infection, concurrent major renal hepatic or cancerous disease, recent
surgery or major trauma, acute osteoarthritis, or inflammatory
disease), and who had complete data on BP, CRP levels, and
covariates. Additional information on the design of the Villa Pini
Stroke Data Bank has been published elsewhere.15,16
Blood Pressure
BP was measured at the entry by a trained nurse. Two measurements
were taken on each arm. The lowest measurements on each arm were
averaged to obtain the systolic (SBP) and diastolic BP (DBP) values
that were recorded. The first and fifth Kortokoff sounds were
recorded and used to determine SBP and DBP, respectively. Mean
arterial pressure (MAP) was calculated as (SBP⫹2DBP)/3. Pulse
pressure (PP) was calculated as SBP⫺DBP.
C-Reactive Protein Assay
Blood samples were taken at admission, within 24 hours after
qualifying stroke, and at discharge. Levels of CRP were determined
with a commercially available, high-sensitivity, immunonephelometric, latex-enhanced assay (Dade Behring).15–17
Other Study Variables
Other factors included in this study were age, gender, body mass
index, cerebrovascular risk factors (cigarette smoking status, alcohol
abuse, hypercholesterolemia, hypertriglyceridemia, diabetes mellitus), cardiovascular comorbidity (arrhythmias and impulse conduction disorders, valvulopathies, left ventricular hypertrophy, coronary
heart disease, symptomatic internal carotid stenosis, peripheral
arterial disease), stroke subtypes (atherothrombotic, cardioembolic,
small-vessel occlusive (lacunar), or undetermined cause), neuroradiological findings (leukoaraiosis, single/multiple infarcts, large/
small infarcts, brain edema, hemorrhagic transformation). The Canadian Neurological Stroke Scale (CNSS) assessed initial stroke
severity. All definitions are previously given15–16 and definitions of
stroke subtypes and neuroradiological findings are summarized in
the Appendix of an online supplement (available at http://www.hypertensionaha.org). Information on current use of antihypertensive
medications was also obtained.
Statistical Analysis
Differences in proportions were evaluated by ␹2 analysis, unpaired t
test for continuous normally distributed variables, and MannWhitney U test for nonnormally distributed variables. A Pearson
correlation analysis was performed to assess any relationship between log-normalized levels of CRP and blood pressure at the entry.
Analyses were designed to assess the association of BP components
(SBP, DBP, MAP, and PP) with CRP levels after adjusting for the
other study variables. In our analyses, the BP components and other
study factors were independent variables, and CRP was the dependent variable. We analyzed CRP as a dichotomous outcome (CRP
⬍1.5 mg/dL or CRP ⱖ1.5 mg/dL) in logistic regression models. We
chose a cutoff point of 1.5 mg/dL because it has provided better
sensitivity and specificity for adverse outcome, based on the receiver
operator curves in a previous analysis in this stroke cohort.16
Individual BP component models assessed the effect of a single BP
component (SBP, DBP, MAP, or PP) on CRP, without adjustment
for other BP components. Dual BP component models assessed the
effects of MAP and PP on CRP after adjustment for one of the other
BP components (SBP and DBP). A final model assessed the effects
of all BP components (SBP, DBP, MAP, and PP) on CRP level.
Extended method and details on statistical plan can be found in an
online supplement available at http://www.hypertensionaha.org.
Results
Between March 1998 and March 2000, 881 potential firstever ischemic stroke patients were registered, and 535
(60.7%) were subsequently found to be eligible because they
fulfilled the inclusion criteria for the present study (Figure).
The exclusion criteria were mainly related to conditions
associated with increased levels of inflammation markers or a
not-confirmed diagnosis of first-ever ischemic stroke. The
mean (mean⫾SD) age of cohort was relatively old (72.7⫾9.1
years), and 309 (57.8%) subjects were women. The median
time from the onset of symptoms to BP measurement and
blood sample collection was 12 hours and 15 hours to CT
scan execution. At the entry, the average SBP, DBP, MAP,
and PP of the stroke cohort were 160⫾16 mm Hg,
94⫾13 mm Hg, 116⫾13 mm Hg, and 66⫾9 mm Hg, respectively. BP decreased on average by 11⫾25 mm Hg in
systolic, 14⫾14 mm Hg in diastolic, and 12⫾13 mm Hg in
Di Napoli and Papa
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mean during in-hospital stay; PP increased on average by
2⫾27 mm Hg.
Approximately 47% (n⫽250) of the cohort had a CRP
level of 1.5 mg/dL or higher, within 24 hours after stroke.
This percentage was reduced at 34% (n⫽182) at discharge
(12⫾5 days). Log-normalized concentration of CRP within
24 hours after stroke was significantly correlated, but modestly, with SBP (r⫽0.46; P⬍0.0001), DBP (r⫽0.46;
P⬍0.0001), and MAP (r⫽0.40; P⬍0.0001) at the entry. PP
was only poorly correlated (r⫽0.16; P⬍0.0001). While PAD
(r⫽0.49; P⬍0.0001) and MAP (r⫽0.46; P⬍0.0001) at discharge remained modestly and significantly correlated with
CRP levels at the entry, SBP was weakly (r⫽0.24;
P⬍0.0001), and PP was not more (r⫽0.07; P⫽0.350).
Patients without a history of arterial hypertension had significantly higher levels (median, 25th to 75th percentiles) of
CRP at the entry than patients with a documented history (2.0
[1.0 to 5.4] versus 1.0 [0.6 to 3.2] mg/dL; P⬍0.0001).
Table 1 shows the distribution of SBP, DBP, PP, and other
study measures according to CRP level. Those with a high
CRP level had higher mean SBP, DBP, MAP, and PP values.
Additionally, stroke patients with a high CRP level were
older male smokers with a higher prevalence of cardiovascular comorbidities and a more severe neurological deficit
resulting from a larger embolic infarct frequently complicated
by brain swelling and hemorrhagic transformation. Furthermore, they were less likely to be taking lipid lowering and
antihypertensive medications, such as calcium channel blockers and angiotensin-converting-enzyme inhibitors (ACE-I),
than were those with a low CRP level.
Table 2 presents the results of multivariable-adjusted
logistic regression models assessing the association of single
BP components with elevated CRP. Model 1 shows that, after
adjustment for other study factors, an increase in SBP was
significantly associated with an increase in the odds of having
an elevated CRP level. For each 10 mm Hg increase in SBP,
the odds of having an elevated CRP level increased by 72%
(odds ratio [OR], 1.72; 95% confidence interval [CI], 1.46 to
2.02; P⬍0.0001). Models 2, 3, and 4 show that, similarly to
SBP, an increase in DBP, MAP, or PP was significantly
associated with an increase in the odds of having an elevated
CRP level, independent of other study factors. For each
10 mm Hg increase in DBP, MAP, and PP, the odds of having
a high CRP level increased by 10% (OR, 1.10; 95% CI, 1.06
to 1.14; P⬍0.0001), 21% (OR, 1.21; 95% CI, 1.15 to 1.29;
P⬍0.0001), and 10% (OR, 1.10; 95% CI, 1.06 to 1.14;
P⬍0.0001), respectively. Next, we ran dual-component BP
models that assessed the association between SBP and DBP
with CRP after adjustment for MAP and PP and other study
factors (Table 3). In model 1 the dual effects of SBP and
MAP were considered. This model showed that MAP was no
longer associated with elevated CRP, whereas a 10 mm Hg
rise in SBP significantly increased the odds of an elevated
CRP level by 79% (P⬍0.0001). In model 2, the dual effects
of SBP and PP were considered. A 10 mm Hg increase in PP
was not related to CRP levels, but each 10 mm Hg increase in
SBP was associated with a significant 72% increase
(P⬍0.0001) in the odds of an elevated CRP. In models 3 and
4, when we compared the dual effects of DBP with MAP and
Blood Pressure and C-Reactive Protein in Stroke
1119
PP (Table 3), all components were significantly associated
with CRP levels. We then added all BP components in the
final model (Table 4); DBP, MAP, and PP were no longer
associated with elevated CRP, whereas a 10 mm Hg rise in
SBP significantly increased the odds of an elevated CRP level
by 77% (OR, 1.77; 95% CI, 1.48 to 2.11; P⬍0.0001). To
check whether our results were applicable, we repeated the
analyses with different cut-points of CRP level (0.5 mg/dL,
1.0 mg/dL, and 2.0 mg/dL). We found that only a 10 mm Hg
increase in SBP was associated with 14% (P⬍0.0001), 56%
(P⬍0.0001), and 72% (P⬍0.0001) increases, respectively, in
the odds of having an elevated CRP level in the model
adjusted for all BP components. In contrast, DBP, MAP, and
PP were not associated with CRP in this model. We then ran
2 subgroup analyses. First, we have previously reported that
the use of an ACE-I is associated with reduced levels of CRP
after stroke.30 Therefore, we examined the association between SBP and CRP in the group taking an ACE-I. We found
that in this group the association between SBP and CRP was
reduced and not more significant (OR, 1.01; 95%CI, 0.96 to
1.05; P⫽0.8136). Second, it has been reported that the
association of increasing SBP is stronger in older populations.28 Therefore, we sought to determine whether the
association between SBP and elevated CRP (ⱖ1.50 mg/dL)
differed according to age by constructing separate models
among persons ⬍70, 70 to 79, and ⱖ80 years of age. When
controlling for all BP components and other study factors,
there was some indication that the association between SBP
and CRP was strongest among older persons; a 10 mm Hg
increase in SBP among those ⬍70, 70 to 79, and ⱖ80 years
of age was associated with 0.6% (P⫽0.0017), 62%
(P⬍0.0001), and 37% (P⬍0.0001) increases, respectively, in
the odds of having an elevated CRP level.
Discussion
The primary finding of the present study was that an increase
in BP levels was associated with increased odds of having an
elevated CRP level (ⱖ1.5 mg/dL) among first-ever ischemic
stroke patients. This association was independent of a number
of other factors, including demographic factors, cardiovascular risk factors, and neuroradiological findings. Only SPB
showed a persistent, strong, significant association with CRP
when DBP, MAP, and PP were also taken into account. The
result persisted even when a different cut-off threshold of
CRP (0.5 mg/dL, 1.0 mg/dL, and 2.0 mg/dL) was used.
Previous studies have reported many independent factors
related to BP in the acute phase of stroke and their relationship with prognosis,23,28 but these studies did not consider
whether BP was associated with levels of CRP, a new and
up-and-coming prognostic factor of cardiovascular risk.16,17
Our study addresses the possible relationship between BP
levels and CRP in ischemic stroke. The present study is the
first to show that an increasing SBP is associated with an
elevated CRP level in the acute phase after stroke, independent of DBP, MAP, and PP. The present study also found
some indication that the association between an increasing
SBP and elevated CRP was stronger in older than in younger
persons.
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TABLE 1.
December 2003
Baseline Clinical Characteristics of Study Participants
CRP⬍1.5 mg/dL (n⫽285)
Variables
n.
CRPⱖ1.5 mg/dL (n⫽250)
(%)
n.
(%)
P
Blood Pressure, mm Hg
SBP, mean⫾SD
155⫾13
167⫾16
⬍0.0001
DBP, mean⫾SD
90⫾9
98⫾15
⬍0.0001
MAP, mean⫾SD
112⫾9
121⫾15
⬍0.0001
68⫾7
⬍0.0001
PP, mean⫾SD
64⫾10
Clinical
Age, ⬎70 y
Male
166
(58.2)
180
(72.0)
0.0009
96
(33.7)
130
(52.0)
⬍0.0001
Arterial hypertension
235
(82.5)
168
(67.2)
⬍0.0001
Diabetes mellitus
108
(37.9)
119
(47.6)
0.0234
Cholesterol level, ⬎5.0 mmol/L
161
(56.5)
114
(45.6)
0.0129
Triglycerides level, ⬎1.8 mmol/L
109
(38.2)
84
(33.6)
0.2642
0.0071
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Cigarette smoking
49
(17.2)
67
(26.8)
Alcohol abuse
86
(30.2)
55
(22.0)
0.0322
BMI, ⬎30 kg/m2
95
(33.3)
103
(41.2)
0.0601
Coronary heart disease
95
(33.3)
124
(49.6)
0.0001
Atrial fibrillation
62
(21.8)
94
(37.6)
0.0001
Mitral/aortic valve disease
122
(42.8)
94
(37.6)
0.2207
Peripheral arterial disease
50
(17.5)
54
(21.6)
0.2367
Left ventricular hypertrophy
85
(29.8)
62
(24.8)
0.1940
Symptomatic carotid stenosis (⬎50%)
58
(20.4)
71
(28.4)
0.0299
(3.0–6.0)
⬍0.0001*
Functional, at admission
CNSS, median (interquartile range)
7.5
(5.0–9.0)
5.0
⬍0.0001
Stroke subtypes
Atherothrombotic
108
(37.9)
104
(41.6)
Embolic
81
(28.4)
105
(42.0)
Lacunar
69
(24.2)
17
(6.8)
Other/uncertain
27
(9.5)
24
(9.6)
Neuroradiological findings
Ischemic lesions
0.0083
None
10
(3.5)
12
(4.8)
Single
137
(48.0)
150
(60.0)
(35.2)
Multiple
138
(48.4)
88
Leukoaraiosis
117
(41.1)
73
(29.2)
0.0043
Large infarct, ⬎1.5 cm
137
(48.1)
154
(61.6)
0.0017
Cortical infarct
119
(41.8)
120
(48.0)
0.1471
Brain swelling
54
(18.9)
97
(38.8)
⬍0.0001
Hemorrhagic transformation
32
(11.2)
69
(27.6)
⬍0.0001
Aspirin
149
(52.3)
125
(32.8)
0.6600
Statins
110
(38.6)
28
(11.2)
⬍0.0001
Calcium channel blockers
112
(39.3)
54
(21.6)
⬍0.0001
ACE-I
185
(64.9)
85
(34.0)
⬍0.0001
AT1 antagonist
49
(17.2)
43
(17.2)
0.9103
Diuretics
34
(11.9)
35
(14.0)
0.5595
Concomitant treatment, at admission
Antihypertensive drugs, at admission
SBP indicates systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; PP, pulse
pressure; CNSS, Canadian Neurological Stroke Scale; ACE-I, angiotensin-converting enzyme inhibitors; AT1,
angiotensin-1 receptor.
*Mann-Whitney U test.
Di Napoli and Papa
TABLE 2. Logistic Regression Models Assessing the
Association Between Single Blood Pressure Components and
the Odds of Having an Elevated CRP Level
Models
Odds Ratio (95% CI)
for Elevated CRP
P
Model 1*
SBP
1.72 (1.46–2.02)
⬍0.0001
1.10 (1.06–1.14)
⬍0.0001
Model 2*
DBP
Model 3*
MAP
1.21 (1.15–1.29)
⬍0.0001
1.10 (1.06–1.14)
⬍0.0001
Blood Pressure and C-Reactive Protein in Stroke
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TABLE 4. Logistic Regression Models Assessing the
Association Between All Blood Pressure Components and the
Odds of Having an Elevated CRP
Odds Ratio (95% CI)
for Elevated CRP
P
SBP
1.77 (1.48–2.11)
⬍0.0001
DBP
0.97 (0.92–1.02)
NS
MAP
0.95 (0.88–1.03)
NS
PP
1.03 (0.98–1.09)
NS
Models
*Adjusted as described in Table 2. Odds ratios are given per 10 mm Hg
increase.
Model 4*
PP
CRP indicates C-reactive protein.
*Adjusted for all independent variables that showed a significant association
(P⬍0.05) with the dependent variable in Table 1. Odds ratios are given per
10 mm Hg increase.
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Increased BP may promote inflammation by modulation of
the biomechanical stimuli31: cyclic strain has been shown to
increase soluble intercellular adhesion molecule 1 (sICAM-1)
expression and mRNA expression and secretion of monocyte
chemotactic protein 1 (MCP-1).32–35 Ischemia in vivo and in
vitro have also been shown to upregulate the expression of
Ig-families of adhesion molecules in cerebral endothelial
cells and to facilitate leukocyte adhesion and transmigration
into the brain.36 These data suggest mechanisms by which the
increase in pulsatile load and cyclic wall stress imposed by
high SBP on the cerebral vasculature may facilitate and
increase ischemic brain inflammation.
Stimulation of human vascular smooth muscle cells by
angiotensin (Ang) II, a key regulator of BP, results in
inflammatory activation with dose-dependent increases in
expression and release of IL-6.5,6 Furthermore, cerebral ischemia induces the expression of IL-6 in neurons and
astrocytes, and ischemic brain tissues appear to be a major
source of IL-6 in stroke.18,19,37
TABLE 3. Logistic Regression Models Assessing the
Association Between Dual Blood Pressure Components and the
Odds of Having an Elevated CRP
Odds Ratio (95% CI)
for Elevated CRP
P
SBP
1.79 (1.48–2.16)
⬍0.0001
MAP
0.96 (0.89–1.05)
NS
SBP
1.72 (1.46–2.03)
⬍0.0001
PP
1.03 (0.97–1.081)
NS
DBP
0.31 (0.21–0.46)
⬍0.0001
MAP
5.51 (3.23–9.41)
⬍0.0001
DBP
1.72 (1.46–2.03)
⬍0.0001
PP
1.77 (1.48–2.11)
⬍0.0001
Models
Model 1*
Model 2*
Model 3*
Model 4*
*Adjusted as described in Table 2. Odds ratios are given per 10 mm Hg
increase. NS indicates not significant.
BP may also have a proinflammatory effect on the arterial
wall because of increased oxidative stress.38 In addition to its
effects on IL-6 expression,5,6 Ang II also stimulates increased
sICAM-1 expression and vascular infiltration by monocytes
and macrophages, which is reversible by ACE-I and Ang type
1 receptor blockade.39 It is possible that the lack of association between SBP and CRP levels in ACE-I–treated patients
may in part be due to anti-inflammatory effects mediated by
Ang II suppression.5,30
However, it is important to note that we had no information
on sICAM or reactive oxygen species or Ang II levels in the
present investigation. Explaining our results in terms of these
mechanisms is necessarily speculative, and other explanations are possible.
First, we cannot exclude the possibility that the relationship
between CRP and BP levels is only an epiphenomenon. The
present study was based on observational data, and confounding from factors that were not controlled for and/or residual
confounding from factors that we did control for, but that
were imperfectly measured, may be an alternative explanation for our results. The presence of a selection bias is also
plausible because this is not a randomized controlled trial;
both CRP and SBP may be markers for something involved in
the selection bias. One cannot definitively rule out chance as
an explanation for the findings of this study; the large number
of variables entered into the univariable analysis and a
borderline modeling technique make it possible, suggesting
that, without internal or external validation, our results should
be considered as hypothesis generating.
Second, our analyses are based on single measurements of
BP and inflammatory markers, which may not reflect these
relationships over time, making it impossible to determine the
temporal ordering of the association that we observed between SBP and CRP. Cross-sectional independent association
of high BP and plasma levels of CRP have been reported.40,41
Although the evidence noted above suggests that increases in
SBP would enhance inflammation, the nature of our data
could leave open different possibilities in the relationship
between BP and the acute phase response after stroke. One
important possibility is that inflammation, reflected by the
levels of CRP, is not playing a role in the development of
high BP even before the ischemic stroke occurs. However, in
our cohort, an acute increase of BP more than a history of
arterial hypertension was associated with higher levels of
CRP after stroke. Probably the levels of BP after an ischemic
stroke are one of the underlying processes related to inflam-
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mation that are relevant in the inflammatory response in
ischemic stroke patients, more so than a history of arterial
hypertension. Furthermore, the consistency of the association
between SBP and CRP across different models and different
definitions of CRP elevation indicates that our results may
not simply be due to chance.
Several theories have been offered as to why an elevated
BP may be a predictor of poor outcome after stroke. High BP
might promote early recurrence, hemorrhagic transformation,
or the formation of cerebral edema, thus increasing the risk of
death or new cardiovascular events.25–28 The present study
suggests another explanation as to why SBP may be predictive of poor outcome. Our study shows that increasing levels
of BP were associated with higher odds of having an elevated
CRP level, a higher BP, more specifically SBP, thus facilitating or increasing an inflammatory response after stroke,
which influences the prognosis of ischemic stroke patients as
previously demonstrated.16,17 However, low BP was also
found to be an independent prognostic factor for poor
outcome in patients with ischemic stroke, and this observation is apparently in contrast with the relationship between
SBP and CRP that is suggested by our results.28 The relationship between CRP and SBP is probably more complex than
we realize. Given the observational nature of our study, our
results should not be taken as evidence of a causal relationship and should be interpreted with caution. Patients with
high CRP in acute brain ischemia might have a predisposition
to the activation of inflammation in response to triggering
stimuli in cardiovascular events. Acute brain ischemia increases BP, and ischemia may induce brain inflammation
separately.
In conclusion, we found that increased SBP was significantly associated with elevated levels of circulating CRP in
ischemic stroke patients. These findings support a possible
role of acute hypertension after stroke as an inflammatory
stimulus contributing to ischemic brain inflammation.
Perspectives
Future studies need to clarify whether or not an elevated BP
leads to increased inflammatory response after stroke,
whether this effect is more or less pronounced in certain
subgroups such as the elderly, and whether the association
between BP and inflammation helps to explain why SBP has
been associated with outcome in stroke. Probably, the levels
of BP after an ischemic stroke are one of underlying processes related to inflammation, and they are relevant in the
inflammatory response after an ischemic stroke. From this
point of view, because higher CRP levels are an independent
prognostic factor after stroke16 and high BP is apparently
associated with higher CRP levels, the current approach to the
treatment of acute hypertension27 after stroke probably should
be revisited from different perspectives.
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Association Between Blood Pressure and C-Reactive Protein Levels in Acute Ischemic
Stroke
Mario Di Napoli and Francesca Papa
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Hypertension. 2003;42:1117-1123; originally published online November 3, 2003;
doi: 10.1161/01.HYP.0000100669.00771.6E
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