From the Departments of Thoracic Medicine (P.J.C., D.H.), Medicine
(G.Y.H.L., D.G.B.), and Microbiology (R.W.), City Hospital, Birmingham, and
School of Mathematics and Statistics, University of Birmingham (P.D.) (UK).
Correspondence to Dr P.J. Cook, Department of Medicine, Queen Elizabeth Medical Centre, Edgbaston, Birmingham B15, UK.
Methods—Antibodies to C pneumoniae were measured
in 176 patients with stroke or transient cerebral ischemia and
1518 control subjects with noncardiovascular,
nonpulmonary disorders. Acute infection or reinfection was
defined by IgG
Results—We found that 13.6% of stroke/transient ischemic
attack (TIA) patients and 5.7% of control subjects had antibody titers
suggesting acute C pneumoniae (re)infection, while
32.4% of stroke/TIA patients and 12.7% of control subjects had titers
suggesting previous infection (P<.05). Stroke/TIA
patients differed from control subjects in their levels of acute and
previous infection, with adjusted odds ratios of 4.2 (95% CI, 2.5 to
7.1) and 4.4 (95% CI, 3.0 to 6.5), respectively. These did not differ
notably between strokes resulting from major nonhemorrhagic infarcts,
small-vessel infarcts, or hemorrhage. Cholesterol,
triglyceride, fibrinogen, and von Willebrand factor
concentrations showed no apparent association with titers.
Conclusions—These data support the association of cerebral
vascular disease with previous C pneumoniae infection
and the association of stroke and transient cerebral ischemia
with recrudescence of infection.
Our study was designed to test the association of C
pneumoniae with stroke syndromes in the multiracial inner-city
population of west Birmingham, England, after adjustments for several
potential confounding variables. We subjected a proportion of
stroke patients to cerebral CT and carotid arterial
ultrasound examinations and measured blood concentrations of
cholesterol, triglyceride, fibrinogen, and von
Willebrand factor to elucidate the mechanism of any association
between C pneumoniae and cerebrovascular disease.
The World Health Organization definition of stroke was applied in this
study, ie, rapidly developing signs of focal or global
disturbance of cerebral function, with no apparent cause other
than cerebrovascular disease. In this setting, fully evolved strokes
were diagnosed when clinical neurological deficiency persisted for more
than 24 hours or led to death, and TIAs were diagnosed when it resolved
within 24 hours. Cases in which the diagnosis was uncertain, including
those in which neurological deficit had resolved by the time of
admission, were excluded. We also excluded all cases that were
complicated by clinical or electrocardiographic evidence of acute
myocardial ischemia or by clinical or radiological evidence of
active pulmonary disease. Because cardiac disease so commonly
accompanies cerebrovascular ischemia, we did not attempt to
exclude patients with chronic cardiac disease.
Control subjects were selected randomly from all admissions to the
emergency department with acute nonpulmonary,
noncardiovascular disorders, provided that there was no
evidence of active cardiac, vascular, or pulmonary disease;
thus, there is no reason to suspect that they were predisposed to
acquire C pneumoniae infection.
Blood was taken on admission (or within 12 to 24 hours, when immediate
venipuncture was impossible). All patients were asked to
return 2 to 3 months after discharge for convalescent blood sampling.
Fasting blood samples were taken within 24 hours for serum
cholesterol and triglyceride measurements, and
cerebral CT and Doppler ultrasound examinations of the carotid
arteries were performed within 10 days of admission. These
investigations, which were ordered by the admitting physician, were not
confined to any part of the study period or to any discernible subgroup
of patients. We also selected patients who presented within 12
hours of the onset of neurological symptoms (to avoid a significant
acute-phase response) for measurement of plasma fibrinogen and von
Willebrand factor.
Demographic characteristics, medical history, smoking habit, drug
therapy, and physical signs were recorded by the admitting medical
staff; ethnic origin, smoking habit, and use of steroid medication were
later confirmed by postal questionnaires. Townsend scores of
socioeconomic deprivation were assigned to those subjects
who lived in the West Midlands conurbation by linking postal code
sectors to census enumeration districts. These scores, which include
items that reflect predominantly personal and family income, may be
considered to reflect the socioeconomic status of people living within
a particular locality.10 The higher the score
(ie, the more strongly positive), the greater was the degree of social
deprivation.
Serological Testing
Sera were tested by one investigator using Maxiscreen
Chlamydia MIF slides (IO International Ltd) and
fluorescein-conjugated anti-human immunoglobulins. Only an
even pattern of elementary body fluorescence was regarded as
positive. In every batch of slides tested, two control serum
preparations known to be positive for this organism and two negative
control subjects were each applied to two slides. All sera were
screened at a dilution of 1:8; thereafter, positive sera were tested at
dilutions of 1:8 to 1:1024.
Acute infection or reinfection just before entry into the study was
presumed to be indicated by titers of IgG
Rheumatoid factor was assayed in patients in whom connective tissue
diseases were suspected on clinical grounds, despite insufficient
evidence to exclude them from the study. C pneumoniae IgM
antibodies were discounted for serological classification when
rheumatoid factor was present because of nonspecific IgM
reactivity.
Analysis of Data
Finally, in the stroke/TIA patients only, we performed general linear
model analyses of variance on cholesterol,
triglyceride, fibrinogen, and von Willebrand factor
concentrations, stratifying data by all potentially associated factors.
Because cholesterol, triglyceride, and von
Willebrand factor levels had very skewed distributions, we used
their logarithmic (loge) transforms for these
analyses to stabilize variance.
The remaining 1518 patients (89.6%) were assigned to the control
group. In these patients, the primary indications for hospital
admission were abdominal pain in 460, for which causes were established
in 403 cases; chest pain, not suggestive of myocardial ischemia
and for which no cause was found, in 91; malignant disease in 85;
fractures of various bones in 77; urinary obstruction in 64;
complications of diabetes mellitus in 44; and other miscellaneous
medical and surgical diagnoses in 697.
The demographic characteristics of both groups are shown in Table 1
Thirty-one stroke/TIA and 282 control patients (17.6% and 18.6%,
respectively) returned for convalescent blood sampling within 160 days,
at a mean of 98.6 (SD 36.7) days after admission. After 160 days, we
judged that sera could no longer be regarded as convalescent, and we
discarded them. The demographic characteristics of these 313 patients
were broadly similar to those of the study groups that they
represented (Table 2
After patients with known connective tissue or other autoimmune disease
were excluded, there remained in the study 21 stroke/TIA patients and
133 control subjects in whom we suspected connective tissue diseases on
clinical grounds and whom we therefore tested for the presence of
rheumatoid factor. When this test was positive, in 4 stroke/TIA
patients and 24 control subjects, the finding of IgM antibodies was
discounted for the diagnosis of acute C pneumoniae
infection.
Acute infection was diagnosed solely from IgM titers in 14 stroke/TIA
patients and 30 control subjects, of whom 14 stroke/TIA patients and 22
control subjects would otherwise have been defined by their IgG titers
as previously infected. Nine stroke/TIA patients and 11 control
subjects were older than 60 years and therefore were within the age
group that has been associated with unsuspected rheumatoid factor
production.11
Fasting serum total cholesterol concentrations were
measured in 30 stroke and 421 control patients and fasting serum
triglyceride levels in 28 stroke and 419 control patients.
Plasma fibrinogen was measured in 71 stroke patients, and plasma von
Willebrand factor was measured in 69 stroke patients.
Seventy-five stroke patients underwent CT brain scanning, and 47
underwent carotid artery ultrasound examination.
Among the stroke/TIA patients, cerebral CT scans showed major
nonhemorrhagic infarcts in 26, small-vessel infarcts in 23,
intracerebral hemorrhage in 13, and no
abnormality in 13 (12 of whom had TIAs). Carotid artery ultrasound
examination showed arterial plaques in 35 stroke/TIA
patients (29 of whom had clinical evidence of cerebral infarction) and
was normal in 12.
C pneumoniae and Cerebral Ischemia
Logistic regression analysis suggested statistically
significant associations of stroke/TIA with both acute and previous
C pneumoniae infection. After adjustment for ethnic origin,
age, sex, diabetes mellitus, and smoking habit, the ORs for stroke/TIA
were 4.2 (95% CI, 2.5 to 7.1) for acute (re)infection and 4.4 (95%
CI, 3.0 to 6.5) for previous infection. The variables that made the
largest contribution to the increase in ORs after this adjustment were
age and smoking habit; among young smokers, previous infection was more
common in the stroke/TIA group than in the control group.
With regard to CT scan findings (in 75 stroke/TIA patients),
serological results indicated acute (re)infection, previous infection,
and no infection in 26.9%, 26.9%, and 46.2% of patients with major
nonhemorrhagic infarcts; 17.4%, 43.4%, and 39.1% of those with
small-vessel infarcts; 23.1%, 46.2%, and 30.8% of those with
intracerebral hemorrhage; and 15.4%, 46.2%,
and 38.5% of those with no abnormality. There was no significant
variation among the four categories, individually (by
With regard to carotid artery ultrasound examination (in 47 stroke/TIA
patients), acute (re)infection, previous infection, and no infection
were found in 17.1%, 34.3%, and 48.6% of patients with
arterial plaques compared with 16.7%, 41.7%, and 41.7%,
respectively, of those without plaques. Again, there was no significant
difference between the two groups in this respect, but the small number
of cases limits the power to detect such a difference.
In stroke/TIA patients with serological evidence of acute
(re)infection, previous infection, and no infection, mean (95% CI)
fasting serum concentrations of cholesterol were 5.8 (5.0
to 6.6), 5.8 (5.2 to 6.4), and 5.5 (5.2 to 6.0) mmol/L, and mean
(95% CI) fasting serum concentrations of triglyceride
were 2.2 (1.7 to 2.9), 1.9 (1.6 to 2.3), and 1.9 (1.7 to 2.2)
mmol/L. Mean (95% CI) plasma concentrations of fibrinogen were
11.2 (9.7 to 12.3), 11.5 (10.3 to 12.6), and 12.1 (10.9 to 13.2)
µmol/L, and mean (95% CI) plasma concentrations of plasma von
Willebrand factor were 147 (127 to 167), 156 (139 to 172), and
150 (136 to 164) IU/dL, respectively. After adjustment by regression
analysis for variations in ethnic origin, age, sex, and smoking
habit, there were no significant differences in serum lipids, plasma
fibrinogen, or plasma von Willebrand factor between stroke/TIA
patients with acute C pneumoniae (re)infection, previous
infection, and no infection.
We found no noteworthy statistical interactions (ie, effect
modification) by ethnic origin, age, sex, smoking habit, diabetes
mellitus, or steroid use with the C pneumoniae–stroke/TIA
associations.
C pneumoniae and Cerebral Ischemia
It is noteworthy that we found substantial levels of acute and previous
infection in control subjects as well as stroke/TIA patients,
reflecting the high incidence of C pneumoniae infection in
our community. Nevertheless, the results of our study support an
association between cerebrovascular disease and C pneumoniae
infection and between acute cerebral ischemia and acute
recrudescence of infection. They therefore agree with the results of
Melnick et al,9 who reported a significant
cross-sectional association between previous C pneumoniae
infection and atherosclerosis in carotid arteries.
Since it is possible that any correlation between infection and strokes
might result from a common link to atherosclerosis, our
failure to distinguish ischemic from hemorrhagic strokes in
some patients might weaken the apparent association with C
pneumoniae. However, among those patients who underwent CT and
carotid ultrasound examinations, we could demonstrate no significant
differences in levels of C pneumoniae antibodies between
patients with major nonhemorrhagic infarcts, small-vessel infarcts,
intracerebral hemorrhage, and no abnormality;
nor could we demonstrate any significant differences between patients
with and without arterial plaques. There were too few
patients to allow differentiation between TIAs and fully evolved stroke
syndromes.
Strategies to take account of potential confounding variables are
essential in studies of C pneumoniae antibodies, which have
been associated with increasing age,24 male
sex,24 25 and smoking.24 26
In this study we found no noteworthy interactions of these factors—or
of ethnic origin, use of steroid medication, diabetes mellitus, or
Townsend score—with the association between C pneumoniae
and cerebral ischemia.
Several possible mechanisms have been proposed for a role of infection
in the pathogenesis of atheroma.12
Lipid metabolism is clearly
important27 ; for example, animal models have
shown that circulating monocytes adhere to and penetrate the
endothelium at an early stage in
atherogenesis28 and become engorged with oxidized
LDL, thereby producing the "foam cells" that are so characteristic
of atheroma.29 LDL, whose
concentration is increased in sepsis, becomes oxidized when free
superoxide radicals are released from endothelial cells
or monocyte-macrophages.30 Oxidized LDL
is a strong chemoattractant for monocytes31 and
may form a number of cytotoxic molecules important in vascular damage
and plaque evolution.32 In our study there was no
significant association of cholesterol or
triglyceride levels with C pneumoniae
antibodies, implying that a global dysregulation of lipid
metabolism plays no part in the association with cerebral
ischemia.
Thrombogenesis is intimately related to atherogenesis, and it is
widely believed that prothrombotic states predispose to atherosclerotic
vascular disease. Many factors may influence the development of these
conditions, among which fibrinogen is probably the most
important.33 34 High levels of this protein are
significantly associated with peripheral vascular disease,
in which they confer an increased risk of cardiac events and
mortality.35 Infection is known to increase blood
concentrations of plasma fibrinogen, and in a recent study an increased
plasma fibrinogen level was independently associated with
seropositivity for C pneumoniae.36
Fibrinogen and von Willebrand factor may be regarded as
possible markers for a prothrombotic state and for
endothelial damage, respectively. Neither was
significantly associated with C pneumoniae seropositivity in
our study, but since they were not measured in all patients, this
observation demands some caution.
As discussed above, other infectious agents have been also implicated
in atherosclerosis. We believe that the rise in
specific antibody levels that we have observed is disproportionate to
the nonspecific immunoglobulin increase that is associated with
"acute-phase reactions"; but even so, this rise does not prove a
causal role for C pneumoniae. The possibility that some of
our subjects had polymicrobial infections and that C
pneumoniae antibodies merely confound a more important association
has not been addressed. In this respect, the interactions of diverse
organisms may prove to be crucial and deserve to be investigated in
future research.
Serological Testing
The principle that a fourfold rise in specific IgG antibody titer
should constitute evidence of acute primary C pneumoniae
infection is generally accepted.41 However, the
rise may not be seen for 8 to 10 weeks42 and may
persist for several months43 ; we therefore
decided to set a time limit of 160 days on the interval between initial
and convalescent sera. In a single serum specimen, an IgG titer
Many authors have employed these serological
criteria,48 49 50 51 52 and a large study combining
serology with an examination of pharyngeal swabs by polymerase chain
reaction has provided evidence in support of
them.53 We chose to reject IgG titers <64 to
minimize the probability of false-positive
results.54 Our decision to include IgA is
justified by experimental evidence that it persists for more than 3
weeks in chronic infection.55 56
IgM is generally considered to signify acute primary
infection.38 A threshold titer of
Limitations of This Study
Fasting serum total cholesterol and
triglyceride were measured in only a third of all patients.
We did not attempt to differentiate between HDL and LDL
cholesterol, but we suggest that such a differentiation
might be informative. Furthermore, our approach does not address the
possibility of altered lipid metabolism or accumulation of
cholesteryl esters within cells.
We believe that our strategy for preventing interference by rheumatoid
factor in IgM measurement has allowed us to make a valid interpretation
of the results. However, in the future we would recommend the routine
absorption of sera with anti-human IgG, as advocated by Verkooyen et
al.11
Conclusions
Received August 12, 1997;
revision received November 18, 1997;
accepted November 18, 1997.
© 1998 American Heart Association, Inc.
Original Contributions
Chlamydia pneumoniae Antibody Titers Are Significantly Associated With Acute Stroke and Transient Cerebral Ischemia
The West Birmingham Stroke Project
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and Purpose—Several
studies have implied an association between Chlamydia
pneumoniae and atherosclerosis. Our research
was designed to investigate the association of this organism with
strokes and transient cerebral ischemia. 
512 or IgM 8 or fourfold rise in IgG, and previous
infection was defined by IgG 64 to 256 or lgA 8. Logistic regression
was used to examine the influences of ethnic origin, age, sex, smoking
habit, diabetes mellitus, steroid medication, and social
deprivation on antibody levels. Some patients underwent CT
and carotid ultrasound examinations and cholesterol,
triglyceride, fibrinogen, and von Willebrand factor
estimations.
Key Words: cerebral ischemia, transient • infection • stroke, ischemic
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Chlamydia pneumoniae was first
described in 1986.1 Serological studies indicate that it is
one of the most prevalent infectious agents worldwide,2 3 4
with a wide range of clinical manifestations, chiefly affecting the
respiratory tract.5 Serological associations have also been
demonstrated with coronary artery disease 6 7 8 and
asymptomatic carotid
atherosclerosis.9
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Study Subjects and Investigations
Approval for this project was obtained from the hospital
ethical committee at the City Hospital, Birmingham. Subjects were older
than 16 years, all were admitted to this hospital through the emergency
department, and all gave informed consent to participate. All adult
patients were initially considered to be eligible; recruitment was
prospective and continued at a steady rate, so that subjects were
admitted consecutively throughout a 24-month period (March 1993 through
March 1995). Exclusion criteria were known immunodeficiency,
hypergammaglobulinemia, connective tissue disease, and other autoimmune
disease.
In every case, 2 to 5 mL of serum was obtained by
centrifugation within 6 hours and stored at -20°C
until analysis; testing of admission and convalescent sera was
deferred until both specimens were available. Each blood sample was
labeled only with a serial number; thus, the investigator was blind to
all patient data at the time of testing and remained so until
statistical analysis of the results. 512, IgM8, or—in patients
who provided convalescent samples—IgG rising fourfold between initial
and convalescent sampling. Titers indicating previous infection without
recrudescence were presumed to be IgG 64 to 256 or IgA8, provided
that IgM could not be detected and there was no significant rise in
IgG.
We compared raw frequencies of acute (re)infection and previous
infection between the stroke/TIA and control groups by simple
univariate analyses, using 
2
tests. We used a logistic regression modeling method, as implemented in
the EGRET statistical package, to explore possible influences of ethnic
origin (Caucasian, Asian, or Afro-Caribbean), age, sex, smoking habit
(current or previous versus never), diabetes mellitus, steroid use, and
Townsend score on any association of antibody levels with stroke/TIA.
Therefore, we derived ORs expressing the associations of stroke/TIA
with acute C pneumoniae (re)infection and previous
infection, adjusted for potential confounding factors.
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Study Subjects and Investigations
Twenty-six stroke/TIA patients and 312 potential control
subjects were excluded by the criteria stated above, and 53 control
subjects refused to participate. We recruited 1694 patients. One
hundred seventy-six (10.4%) had been admitted with acute neurological
dysfunction; fully evolved stroke syndromes were eventually diagnosed
in 164 patients and TIAs in 12. 
. They were broadly similar with respect
to ethnic origin and sex. The stroke/TIA group had a higher mean age, a
higher proportion of diabetics, more current and previous smokers, and
more steroid users (although data on smoking habit and steroid use were
incomplete). These potential confounding variables were taken into
account by the logistic regression analysis.
View this table:
[in a new window]
Table 1. Demographic Characteristics of Stroke/TIA and
Control Groups ).
View this table:
[in a new window]
Table 2. Demographic Characteristics of Patients Who Gave
Convalescent Sera
Of the 176 patients in the stroke/TIA group, 24 (13.6%) had
serological evidence of acute (re)infection, 57 (32.4%) previous
infection, and 95 (54.0%) no infection. In the control group of 1518
subjects, 87 (5.7%) had evidence of acute (re)infection, 193 (12.7%)
previous infection, and 1238 (81.6%) no infection. On
2 analysis, there was a statistically
significant difference (P<.05) between the stroke/TIA and
control groups in the distribution of the three possible serological
classifications—acute (re)infection, previous infection, and no
infection. The crude ORs for stroke/TIA were 3.6 (95% CI, 2.2 to 5.9)
for acute (re)infection and 3.9 (95% CI, 2.7 to 5.5) for previous
infection. These analyses would change very little if we
ignored IgM antibody titers from the 9 stroke/TIA patients and 11
control subjects older than 60 years who were not tested for rheumatoid
factor and in whom we detected acute C pneumoniae infection
solely on the basis of IgM. 2 analysis) or in pairs, in their
distributions of acute (re)infection, previous infection, and no
infection. In this comparison, however, the small number of cases
limits the power of such tests to detect variation.
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Case Definition
We decided to include both fully evolved stroke syndromes and TIAs
in this study, recognizing the fact that their differentiation
(depending on whether clinical neurological deficit persisted for >24
hours) is somewhat arbitrary and that there are no a priori
reasons to assume that different pathological processes apply in the
pathogenesis of these two conditions. The World Health Organization
definitions, used in this study, are widely accepted.
The notion that infections may be partly responsible for vascular
occlusive disease is not new.12 Many workers have
proposed a role in atherosclerosis for Coxsackie
viruses,13 14 and cytomegalovirus infection is
strongly associated with rapidly progressive coronary
atherosclerosis in cardiac transplant
recipients.15 16 Other putative associations of
coronary artery disease include Helicobacter
pylori17 and dental
sepsis.18 However, the strongest infectious
contender for a role in the pathogenesis of atheroma is
C pneumoniae. Both in chronic coronary artery
disease and in acute myocardial infarction, several workers have
demonstrated high levels of antibodies to C
pneumoniae.6 19 Inclusions reacting with C
pneumoniae–specific antibodies have been reported in
coronary arterial fatty streaks and fibrolipid
atheromatous plaques,20 21 and
C pneumoniae DNA has been demonstrated in plaques by the
polymerase chain reaction.22 23
Various techniques are available to detect C pneumoniae
antibodies.37 The best and most widely used is
the MIF assay,38 which is time-consuming and
subject to some operator variation but is sensitive and
species-specific and reliably detects IgG, IgM, and
lgA.39 The kit that we used has been employed in
several studies2 40 and performs similarly to
other MIF assays. 512
can be interpreted as evidence of acute primary
infection44 or—particularly in older
people—reinfection or recrudescence of chronic or latent
infection.45 IgG titers 
256 may persist for
many months46 and have generally been accepted
(in a single serum specimen) as evidence of previous
infection,47 provided that there is no rise in
IgM antibodies. In our study patients who had IgG titers 512 in the
first serum and who gave convalescent samples invariably showed a fall
in titers between the two sera, but some who had initial titers of 64
to 256 maintained them. 16 has been
proposed, with titers of 8 indicating "probable acute
infection,"57 but we found no difference in the
proportions of patients with IgM antibodies at these two titers in a
pilot study and therefore saw no merit in drawing a distinction between
such low levels of antibody production. It has been
suggested58 that rheumatoid factor may make the
measurement of IgM antibodies unreliable, particularly in elderly
patients.11 For this reason, we excluded from the
study all patients with known connective tissue or other autoimmune
disease and measured rheumatoid factor in other cases in which such
diseases were considered possible, discounting IgM antibodies when it
was present. (The presence of connective tissue disease per se was
not considered to be an important confounding variable. We
therefore did not measure other markers of such diseases, such as
antinuclear antibodies, which are not reported to interfere
significantly with IgM assays.) As demonstrated above, ignoring IgM
titers from the remaining patients older than 60 years would not have
significantly altered the relationships of stroke/TIA to acute and
chronic C pneumoniae infections.
Not all stroke patients underwent cerebral CT and carotid artery
ultrasound examinations and estimations of plasma fibrinogen and plasma
von Willebrand factor, and no control subjects did so. Only
limited conclusions can be drawn from these measurements.
These data support the association of cerebrovascular disease with
previous C pneumoniae infection and the association of acute
stroke and TIAs with acute recrudescence of infection. We believe that
more research to elucidate the mechanism(s) of these associations is
warranted and that particular attention should be paid to dysregulation
of thrombogenesis and lipid metabolism.
Selected Abbreviations and Acronyms
CI
=
confidence interval
MIF
=
microimmunofluorescence
OR
=
odds ratio
TIA
=
transient ischemic attack
Acknowledgments
This study was supported by the Peel Medical Research Trust, the
British Heart Foundation, and the Stroke Association (P.J.C.). We wish
to acknowledge the advice of Richard Matthews (Virology Laboratory,
City Hospital, Birmingham). We thank Dr Andrew Blann for assistance
with plasma fibrinogen and von Willebrand factor measurements.
The advice and support of Dr John Treharne (Senior Lecturer in
Virology, University of London) are also gratefully acknowledged. We
wish to thank IO International Ltd, London, for their generous help. We
also thank the referees of an earlier draft of this paper for their
helpful comments and suggestions.
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
This article has been cited by other articles:
 |
|
 |
|
  S Alamowitch, J Labreuche, P-J Touboul, F Eb, P Amarenco, and for the GENIC Investigators Chlamydia pneumoniae seropositivity in aetiological subtypes of brain infarction and carotid atherosclerosis: a case control study J. Neurol. Neurosurg. Psychiatry, February 1, 2008; 79(2): 147 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. B. Goldstein, R. Adams, M. J. Alberts, L. J. Appel, L. M. Brass, C. D. Bushnell, A. Culebras, T. J. DeGraba, P. B. Gorelick, J. R. Guyton, et al. Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline. Circulation, June 20, 2006; 113(24): e873 - e923. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. B. Goldstein, R. Adams, M. J. Alberts, L. J. Appel, L. M. Brass, C. D. Bushnell, A. Culebras, T. J. DeGraba, P. B. Gorelick, J. R. Guyton, et al. Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline. Stroke, June 1, 2006; 37(6): 1583 - 1633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S.V. Elkind, M. L. C. Tondella, D. R. Feikin, B. S. Fields, S. Homma, and M. R. Di Tullio Seropositivity to Chlamydia pneumoniae Is Associated With Risk of First Ischemic Stroke Stroke, March 1, 2006; 37(3): 790 - 795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Njamnshi, K. N. Blackett, J. N. Mbuagbaw, F. Gumedze, S. Gupta, and C. S. Wiysonge Chronic Chlamydia pneumoniae Infection and Stroke in Cameroon: A Case-Control Study Stroke, March 1, 2006; 37(3): 796 - 799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. C. Worm, G. H. Wirnsberger, A. Mauric, and H. Holzer High prevalence of Chlamydia pneumoniae infection in cyclosporin A-induced post-transplant gingival overgrowth tissue and evidence for the possibility of persistent infection despite short-term treatment with azithromycin Nephrol. Dial. Transplant., July 1, 2004; 19(7): 1890 - 1894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L M. Grimaldi, A Pincherle, F Martinelli-Boneschi, M Filippi, F Patti, A Reggio, D Franciotta, L Allegra, G Comi, and F Blasi An MRI study of Chlamydia pneumoniae infection in Italian multiple sclerosis patients Multiple Sclerosis, October 1, 2003; 9(5): 467 - 471. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Kamath and G.Y.H. Lip Fibrinogen: biochemistry, epidemiology and determinants QJM, October 1, 2003; 96(10): 711 - 729. [Full Text] [PDF]
|
|
|
|
|
|
P. J. Lindsberg and A. J. Grau Inflammation and Infections as Risk Factors for Ischemic Stroke Stroke, October 1, 2003; 34(10): 2518 - 2532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. G. Butchart, A. Ionescu, N. Payne, J. Giddings, G. L. Grunkemeier, and A. G. Fraser A New Scoring System to Determine Thromboembolic Risk After Heart Valve Replacement Circulation, September 9, 2003; 108(90101): II-68 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yoneda, K. Miura, H. Matsushima, K. Sugi, T. Murakami, K. Ouchi, K. Yamashita, H. Itoh, T. Nakazawa, M. Suzuki, et al. Aspirin inhibits Chlamydia pneumoniae-induced NF-{kappa}B activation, cyclo-oxygenase-2 expression and prostaglandin E2 synthesis and attenuates chlamydial growth J. Med. Microbiol., May 1, 2003; 52(5): 409 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Spence and J. Norris Infection, Inflammation, and Atherosclerosis Stroke, February 1, 2003; 34(2): 333 - 334. [Full Text] [PDF]
|
|
|
|
 |
|
 J.A. Erkens, O.H. Klungel, R.M.C. Herings, R.P. Stolk, J.A. Spoelstra, D.E. Grobbee, and H.G.M. Leufkens Use of fluorquinolones is associated with a reduced risk of coronary heart disease in diabetes mellitus type 2 patients Eur. Heart J., October 2, 2002; 23(20): 1575 - 1579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Vainas, H. A.J.M. Kurvers, W. H. Mess, R. d. Graaf, R. Ezzahiri, J. H.M. Tordoir, G.-W. H. Schurink, C. A. Bruggeman, and P. J.E.H.M. Kitslaar Chlamydia pneumoniae Serology Is Associated With Thrombosis-Related but Not With Plaque-Related Microembolization During Carotid Endarterectomy Stroke, May 1, 2002; 33(5): 1249 - 1254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. B. Gorelick Stroke Prevention Therapy Beyond Antithrombotics: Unifying Mechanisms in Ischemic Stroke Pathogenesis and Implications for Therapy: An Invited Review Stroke, March 1, 2002; 33(3): 862 - 875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ciervo, P. Visca, A. Petrucca, L. M. Biasucci, A. Maseri, and A. Cassone Antibodies to 60-Kilodalton Heat Shock Protein and Outer Membrane Protein 2 of Chlamydia pneumoniae in Patients with Coronary Heart Disease Clin. Vaccine Immunol., January 1, 2002; 9(1): 66 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Elkind, J. Cheng, B. Boden-Albala, T. Rundek, J. Thomas, H. Chen, L. E. Rabbani, R. L. Sacco, and A. G. Thrift Tumor Necrosis Factor Receptor Levels Are Associated With Carotid Atherosclerosis * Editorial Comment Stroke, January 1, 2002; 33(1): 31 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. U. Heuschmann, D. Neureiter, M. Gesslein, B. Craiovan, M. Maass, G. Faller, G. Beck, B. Neundoerfer, and P. L. Kolominsky-Rabas Association Between Infection With Helicobacter pylori and Chlamydia pneumoniae and Risk of Ischemic Stroke Subtypes: Results From a Population-Based Case-Control Study Stroke, October 1, 2001; 32(10): 2253 - 2258. [Abstract] [Full Text] [PDF]
|
|
|
|