(Stroke. 2000;31:1521.)
© 2000 American Heart Association, Inc.
Original Contributions |
Chlamydia pneumoniae and the Risk of First Ischemic Stroke
The Northern Manhattan Stroke Study
Presented in part in abstract form at the European Stroke Conference, Edinburgh, Scotland, May 1998, and published in abstract form (Cerebrovasc Dis. 1998;8[suppl 4]:4).
From the Department of Neurology, College of Physicians and Surgeons, Columbia University, and the Columbia-Presbyterian Medical Center of New York Presbyterian Hospital, New York, NY (M.S.V.E., R.L.S.); the Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY (M.S.V.E., R.L.S.); the Division of Biostatistics, Joseph P. Mailman School of Public Health, Columbia University, New York, NY (I.-F.L.); the Departments of Epidemiology and Pathobiology, School of Public Health and Community Medicine, University of Washington, Seattle (J.T.G.); and the Division of Epidemiology, Joseph P. Mailman School of Public Health, Columbia University, New York, NY (R.L.S.).
Correspondence to Mitchell S.V. Elkind, MD, Neurological Institute, 710 W 168th St, New York, NY 10032. E-mail mse13{at}columbia.edu
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Abstract |
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Background and Purpose—Serological evidence of infection with Chlamydia pneumoniae has been associated with cardiovascular disease in multiple epidemiological studies. The data on its association with ischemic stroke are limited. We sought to determine whether chronic C pneumoniae infection is associated with ischemic stroke in a multi-ethnic population.
Methods—The Northern Manhattan Stroke Study contains a
population-based, case-control study component. Cases had first
ischemic stroke and matched control subjects were derived
through random digit dialing. Titers of IgG, IgA, and IgM antibodies
specific for C pneumoniae were measured with the use of
microimmunofluorescence, and titers 
1:16 were
considered positive. Conditional logistic regression was used to
calculate odds ratios (ORs) and 95% confidence intervals (95% CIs)
after adjustment for medical, behavioral, and socioeconomic
factors.
Results—Eighty-nine cases and 89 control subjects were selected. Mean age among cases was 68.5±12.8 years; 53% were women and 15% of the subjects were white, 28% were black, and 54% were Hispanic. Elevated C pneumoniae IgA titers were significantly associated with risk of ischemic stroke after adjusting for other stroke risk factors (adjusted OR 4.51, 95% CI 1.44 to 14.06). IgG titers were less strongly associated with stroke risk (adjusted OR 2.59, 95% CI 0.87 to 7.75). The association of IgA with stroke risk was detected in both younger and older groups, in men and women, and in whites, blacks, and Hispanics. There was also a significant continuous increase in risk associated with the log-transformation of the titer for IgA (adjusted OR 1.32, 95% CI 1.05 to 1.66) but not IgG.
Conclusions—Serological evidence of chronic infection with C pneumoniae is associated with risk of ischemic stroke in an urban, multi-ethnic population. IgA titers may be a better marker of this risk than are IgG titers. This association is independent of other vascular disease risk factors. Further prospective epidemiological studies of the effect of this infection on stroke risk are warranted.
Key Words: atherosclerosis • cerebrovascular disorders • epidemiology • infection • risk factors
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Known risk factors for ischemic stroke fail to account for all cases. Chronic infection with Chlamydia pneumoniae, a common respiratory pathogen capable of infecting endothelium, arterial smooth muscle, and monocytes, is a recently proposed risk factor for atherosclerosis and coronary artery disease.1 2 Recent studies have also suggested a role for C pneumoniae in carotid atherosclerosis3 and cerebrovascular disease.4 5 We sought to determine whether serological evidence of infection with C pneumoniae is associated with first ischemic stroke in a case-control study in an elderly, multi-ethnic urban population.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The Northern Manhattan Stroke Study (NOMASS) is a population-based study designed to determine stroke incidence, risk factors, and prognosis in a multi-ethnic urban population. Northern Manhattan consists of the area north of 145th Street, south of 218th Street, bordered on the west by the Hudson River and on the east by the Harlem River. In 1990,
260 000 people lived in the community, with
40% aged >39 years and a race-ethnic mixture consisting of 20%
black, 63% Hispanic, and 15% white residents.6
Selection of NOMASS Cases and Control Subjects
Cases eligible for NOMASS were prospectively enrolled if they
met the following criteria: (1) diagnosed with first cerebral
infarction after July 1, 1993, (2) aged >39 years at onset of stroke,
and (3) resident in northern Manhattan in a household with a
telephone. Patients with intracerebral or
subarachnoid hemorrhage or transient ischemic
attack, defined as neurological deficits lasting <24 hours and no
ischemic infarct found on brain imaging, were excluded. Fatal
and nonfatal infarcts were enrolled. The methods of case detection in
NOMASS have been described previously.7 For this
analysis, 89 noncryptogenous cases were selected at random from
among the 711 stroke cases enrolled in NOMASS and matched by age, sex,
and race-ethnicity to 89 stroke-free community control subjects.
Cryptogenous stroke cases were excluded to allow study of a sample of
cases with well-defined causes of stroke.
The methods of control recruitment and enrollment have been described
in a previous publication.8 Random digit dialing of
16 000 households was performed by Audits and Surveys, Inc.
Community control subjects were enrolled if they (1) had never been
diagnosed with stroke, (2) were aged >39 years, and (3) resided in
Northern Manhattan for 3 months in a household with a telephone.
In-person evaluations were performed at the hospital or at home for
those who could not come in person. The telephone response rate was
94%, and 70% of those respondents participated in an in-person
evaluation. The study was approved by the institutional review boards
at Columbia-Presbyterian Medical Center and other primary
hospitals. All stroke cases and stroke-free control subjects gave
consent directly or through a surrogate when appropriate.
Index Evaluation of Cases and Control Subjects
Data were collected through interviews of cases and control
subjects by trained research assistants, medical record review,
physical and neurological examination by the study physicians,
in-person measurements, and fasting blood specimens for lipid and
glucose measurements, as described elsewhere.8 When
possible, data were obtained directly from subjects by use of the
standardized data collection instruments. When the subject was unable
to provide answers, a proxy knowledgeable about the subject’s history
was interviewed. Stroke-free controls were interviewed in person and
evaluated in the same manner as cases. Direct subject data were
obtained from 70% of cases and 99% of controls.
Standardized questions were adapted from the Behavioral Risk Factor
Surveillance System9 by the Centers for Disease Control
and Prevention regarding the following conditions: hypertension,
diabetes, hypercholesterolemia,
peripheral vascular disease, transient ischemic
attack, cigarette smoking, and cardiac conditions such as myocardial
infarction, coronary artery disease, angina, congestive heart
failure, atrial fibrillation, other arrhythmias, and
valvular heart disease. Standard techniques were used to
measure blood pressure, height, weight, and fasting glucose as
described in prior publications.10 Fasting lipid panels
(including total cholesterol, LDL, HDL, and
triglyceride) were measured with the use of a Hitachi 705
automated spectrometer (Boehringer). Hypertension was defined
as in prior publications,11 and diabetes mellitus was
defined by a fasting blood glucose level 127 mg/dL, the subject’s
self-report of such a history, or insulin or hypoglycemic use. The
definitions are noted in the legends. Because of concern that season in
which stroke occurred might influence the association with an infection
such as C pneumoniae, the date at which stroke occurred was
also classified as to season, and this was included as a covariate in
adjusted models. Strokes were classified as extracranial
atherosclerosis, intracranial
atherosclerosis, lacunar (small vessel), or
cardioembolic by a consensus of vascular neurologists, using the
results of the diagnostic evaluation.
Assessment of C pneumoniae Status
At the time of enrollment of cases and control subjects, blood
samples were obtained, centrifuged, and aliquoted into 1-mL
specimens. These were frozen at -70°C until the time of
analysis for C pneumoniae serology. Frozen sera
were analyzed for IgG, IgA, and IgM antibody titers to C
pneumoniae with the use of
microimmunofluorescence, the gold-standard
serological test for C pneumoniae, with the use of
techniques described elsewhere.12 Titers of IgG and
IgA were reported as 0, 2, 4, 8, 16, 32, 64, 128, 256, 512, and 1024,
based on serial dilutions. Titers of 1:16 were considered
positive.
Statistical Analyses
Statistical analyses were conducted with the use of SAS
computer software (SAS Institute). Means were calculated for continuous
variables and proportions for dichotomous variables, and
t tests were performed for comparisons of means and
2 tests for comparisons of proportions.
Conditional logistic regression was used to estimate the odds ratio for
matched case-control pairs before and after adjustment for potential
confounders. Subgroup analyses were performed in strata defined
by age, sex, and race-ethnicity. To determine whether a possible
dose-response effect of titer was present, log transformation of
IgG and IgA titers was performed, and a negative titer (0) was
considered to be equal to 1. Univariate and
multivariate regression analysis with the
log-transformed titers was then used to estimate odds ratios for
continuously increasing levels of titer for matched case-control pairs.
Subgroup analyses were performed in strata defined by age, sex,
and race-ethnicity. Statistical significance was determined at the
=0.05 level with use of 2-sided tests.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The mean age of the 89 ischemic stroke cases was 68.5±12.8 years. Cases were 54% Hispanic, 28% black, and 15% white; 53% were women. Cases were significantly more likely to be current smokers and to have hypertension and diabetes. Cases had a significantly lower mean total cholesterol level, but this may be due to their concurrent significantly lower mean HDL level. There were no significant differences in LDL levels. Controls were more likely to have a high school education (Table 1
). The stroke subtypes were
extracranial atherosclerosis (12%), intracranial
atherosclerosis (21%), lacunar (49%), and
cardioembolic (17%). Cryptogenous stroke cases were excluded by
design.
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The prevalence of elevated C pneumoniae titers in the
control population was high: IgG 83.2% and IgA 30.3% (Table 2). No subject had elevated IgM titers.
Among control subjects, a higher proportion of elevated titers was
found among those 65 years old and among men. The distribution of
titers was similar across race-ethnic groups (Table 2).
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Elevated IgG and IgA titers (1:16) were present in 81% and 46%
of cases, respectively. In conditional logistic regression
analysis (Table 3), elevated IgG
titers were not associated with overall odds of first ischemic
stroke in an unadjusted analysis (unadjusted OR 0.86, 95% CI
0.40 to 1.85). After adjustment for hypertension, diabetes, current
smoking, HDL, education, and season of enrollment, there was a trend
toward an increased odds of association (OR 2.59, 95% CI 0.87 to
7.75). Elevated IgA titers were significantly associated with risk of
ischemic stroke (unadjusted OR 2.27, 95% CI 1.12 to 4.62).
After adjustment for the above risk factors, the risk was increased
(adjusted OR 4.51, 95% CI 1.44 to 14.06). The association was
independent of cardiac disease, total cholesterol, LDL, and
leukocyte count. In an analysis performed with log-transformed
titers, there was a continuous increase in risk for each level of
antibody titer for IgA (adjusted OR 1.32, 95% CI 1.05 to 1.66) but not
IgG (Table 3). In a further analysis that used IgG
1:32 as the cutoff for an elevated IgG titer, the result was
virtually identical to that for the cutoff of 1:16 (Table 3).
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Subgroup analyses by age, sex, and race-ethnic group supported
the consistency of the association of IgA and stroke risk
in each subgroup, although numbers were not large enough to achieve
statistical significance in each subgroup (Table 4). Odds ratios were on the order of 2.0
to 3.0. Tests for interactions between C pneumoniae IgA and
the other risk factors revealed no significant interactions with any of
the other risk factors examined.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Our case-control study supports the previously described association between chronic C pneumoniae infection and risk of ischemic stroke and extends the observation to an elderly, multiethnic population, in whom the burden of stroke is greatest. This suggests that chronic C pneumoniae infection may be a risk factor for stroke in the elderly as well as the young. Because our study was restricted to incident stroke cases, it provides a more reliable estimate of the association between infection and stroke than earlier studies. Patients with prior stroke might be more susceptible to infection with C pneumoniae, and the inclusion of such patients could artificially elevate the prevalence of antibody titers among cases. Our data also suggest that there may be a continuous relationship between level of IgA but not IgG antibody titer and stroke risk.
Five studies besides our own have examined the role of C
pneumoniae in cerebrovascular disease. Wimmer et
al4 reported on a hospital-based case-control study
of 58 consecutive stroke or transient ischemic attack (TIA)
patients aged <50 years and 52 hospitalized control subjects. Among
controls and cases, 23.1% and 46.6% had elevated IgA antibody titers
(1:16) to C pneumoniae, respectively (adjusted OR 1.7,
95% CI 1.1 to 2.7). Elevated IgG levels were highly prevalent in both
cases (74.1%) and controls (77.0%) and were not associated with
stroke or TIA. Cook et al5 found in a case-control
study of 176 stroke/TIA and 1518 hospitalized controls that serological
evidence of previous infection was associated with risk of
cerebrovascular disease (OR 4.4). Patients ranged in age from 35 to 86
years. These studies examined the relation of C pneumoniae
to stroke in nonelderly populations, used both stroke and TIA patients,
and included recurrent as well as incident strokes. Our study found
similar results in a multi-ethnic, elderly population limited to
incident stroke (not TIA) patients.
The Atherosclerosis Risk in Communities (ARIC) Study Investigators3 reported a similar magnitude of association of C pneumoniae IgG antibodies with asymptomatic carotid atherosclerosis assessed by ultrasound imaging (adjusted OR 2.0, 95% CI 1.2 to 3.4). Patients were aged 45 to 64 years, but IgA levels were not reported. A prospective study13 that examined a combined exposure of elevated IgG and/or IgA antibody titers in patients with hypertension and another cardiovascular risk factor also found an elevated relative risk for stroke (8.58). Another prospective study,14 a nested case-control study from Sweden, found no association of IgG or IgA titers and stroke risk. This latter study may have been influenced, however, by selection bias and a recent epidemic of C pneumoniae.
In our study, IgA titers were more strongly associated with risk of stroke than were IgG titers. This may reflect the possibility that IgA antibodies, which last only 3 to 5 days in the circulation, are a marker of persistent, chronic infection, whereas IgG antibodies, which are produced for 3 to 5 years, are a marker of remote, completed infection. Evidence from studies of IgA in other chlamydial diseases, including chronic bronchitis associated with C pneumoniae15 16 and pelvic inflammatory disease associated with Chlamydia trachomatis,17 support this hypothesis. In addition, IgA is associated with persistent infection in other chronic bacterial diseases, including yersinial reactive arthritis18 and Pseudomonas aeruginosa in cystic fibrosis.19 20 Changing the criterion for a positive IgG titer to 1:32 did not materially affect our results. Another potential reason for the discrepancy between the association of IgG and IgA as stroke risk markers could be due to the high prevalence of IgG in our elderly population.
We found consistency in the association between
ischemic stroke and C pneumoniae serology in both
young and old, men and women, and in each of the 3 race-ethnic groups.
Because our sample size was small, there was insufficient power to
detect statistically significant associations after adjustment for
other risk factors, and any subgroup analyses of this data must
be viewed with caution. We did find odds ratios ranging between 1.7 and
3.0 in the different subgroups, and these were statistically
significant among those aged 65 years and among women in unadjusted
models. We did not find a difference in the prevalence of C
pneumoniae among the different race-ethnic groups in northern
Manhattan. Differences in prevalence according to race and
socioeconomic status have been reported by
others.21 22 Our population, though racially and
ethnically diverse, shares a common environment that may minimize
differences in infectious disease history. Our results, moreover,
should be generalizable to most urban, multi-ethnic populations in the
United States.
Our study is limited by its inclusion of patients only with defined stroke subtypes (extracranial atherosclerosis, intracranial atherosclerosis, cardioembolic, and lacunar). We chose not to include cryptogenous strokes to enrich our sample for strokes with atherosclerosis as the underlying mechanism. Almost 50% of our cases were thought to have small-vessel disease as the mechanism of stroke, and an additional 33% had either intracranial or extracranial atherosclerosis. Because small-vessel disease may share pathophysiological mechanisms with large-artery atherosclerotic disease, it is likely that our sample is weighted toward atherosclerotic mechanisms. Our numbers were too small to draw conclusions about the association of C pneumoniae titers with individual stroke subtypes and in particular in nonatherosclerotic subtypes, but an ongoing study in the northern Manhattan population is investigating this issue.
Because of the retrospective design of this case-control study, we cannot be certain that stroke itself did not cause the antibody titers to rise in the case population. Patients with stroke could be more susceptible to C pneumoniae infection, but this would not be expected to occur immediately. Alternatively, C pneumoniae antibody levels could rise after stroke because of immune response to common epitopes in C pneumoniae and infarcted brain tissue (ie, "molecular mimicry") or because of nonspecific immunological activation. The majority (71%) of the samples in NOMASS were drawn within 48 hours of admission, however, which should minimize the possibility of poststroke changes in serology. We did not measure serial antibody titers at intervals after stroke, which might help to resolve this issue, nor did we measure antibody titers to other organisms. In addition, although we attempted to adjust in our analysis for the major stroke risk factors, there still could be residual confounding in this case-control study by other risk factors that were not measured.
At the present time, serology with the microimmunofluorescence technology used in our study remains the gold standard for the clinical diagnosis of C pneumoniae infection. Serologies are known to correlate poorly with presence of C pneumoniae in vascular specimens with the use of immunohistochemistry and other pathological techniques.23 Other postulated markers of infection, such as polymerase chain reaction and flow cytometry, are currently under investigation but are not yet standardized for general use.24 Whether these techniques will provide a more reliable marker of C pneumoniae infection remains under active investigation.
Prospective studies of the relationship between C pneumoniae and ischemic stroke as well as between reliable markers of other chronic infections and stroke are needed. Recent prospective studies have not confirmed that serological evidence of C pneumoniae infection is associated with heart disease.25 26 27 These studies did not measure IgA antibody titers, however. Studies of the relationship between infection and atherosclerotic heart disease, moreover, may not reflect the relationship between infection and stroke. In northern Manhattan, atherosclerosis accounts for only 10% to 20% of ischemic stroke.28 The role of chlamydial infection as a risk factor for stroke caused by nonatherosclerotic mechanisms, such as small-vessel disease caused by lipohyalinosis or hypercoagulability, remains unknown. Future studies will therefore need to evaluate associations within different subtypes of stroke as well as to carefully measure and control for other potential risk factors that may confound the association.
In summary, our study supports an association between chronic C pneumoniae infection and ischemic stroke. Evidence from pilot clinical trials of anti-chlamydial agents in patients with coronary artery disease27 29 30 31 as well as animal studies32 already suggest that the risk of atherosclerotic disease associated with C pneumoniae may be modifiable. Corroboration from larger, prospective studies of the role of C pneumoniae in stroke would indicate the potential for clinical trials of anti-chlamydial therapy to prevent incident or recurrent stroke and could lead to further efforts to identify other organisms that may play a role in the atherosclerotic process.
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Acknowledgments |
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This work was supported by grants from the National Institute of Neurological Disorders and Stroke (R01-NS-27517 and R01-NS-29993 to Dr Sacco and T32-NS-07153 to Dr Elkind), the General Clinical Research Center (2-M01-RR00645), an American Heart Association Scientist Development Grant (Dr Elkind), and Centers for Disease Control Cooperative Agreement (Dr Elkind). We acknowledge the support of Dr J.P. Mohr, Director of Cerebrovascular Research, Neurological Institute, Columbia University, and Drs Lisa A. Jackson and San Pin Wang, University of Washington.
Received December 22, 1999; revision received March 27, 2000; accepted April 7, 2000.
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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]
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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]
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J. Oliveira-Filho, L. C. Viana, R. M. Vieira-de-Melo, F. Faical, J. A. Torreao, F. A.G.A. Villar, and F. J.F.B. Reis Chagas Disease Is an Independent Risk Factor for Stroke: Baseline Characteristics of a Chagas Disease Cohort Stroke, September 1, 2005; 36(9): 2015 - 2017. [Abstract] [Full Text] [PDF]
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 J G Ray, M M Mamdani, and W H Geerts Giant cell arteritis and cardiovascular disease in older adults Heart, March 1, 2005; 91(3): 324 - 328. [Abstract] [Full Text] [PDF]
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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]
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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]
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 E. Lalla, I. B. Lamster, M. A. Hofmann, L. Bucciarelli, A. P. Jerud, S. Tucker, Y. Lu, P. N. Papapanou, and A. M. Schmidt Oral Infection With a Periodontal Pathogen Accelerates Early Atherosclerosis in Apolipoprotein E-Null Mice Arterioscler. Thromb. Vasc. Biol., August 1, 2003; 23(8): 1405 - 1411. [Abstract] [Full Text] [PDF]
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 Y. Agmon, B. K. Khandheria, I. Meissner, T. M. Petterson, W. M. O'Fallon, T. J. H. Christianson, D. O. Wiebers, T. F. Smith, J. M. Steckelberg, and A. J. Tajik Lack of association between Chlamydia pneumoniae seropositivity and aortic atherosclerotic plaques: A Population-Based transesophageal echocardiographic study J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1482 - 1487. [Abstract] [Full Text] [PDF]
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 A. Slepenkin, V. Motin, L. M. de la Maza, and E. M. Peterson Temporal Expression of Type III Secretion Genes of Chlamydia pneumoniae Infect. Immun., May 1, 2003; 71(5): 2555 - 2562. [Abstract] [Full Text] [PDF]
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 T. D. Read, G. S. A. Myers, R. C. Brunham, W. C. Nelson, I. T. Paulsen, J. Heidelberg, E. Holtzapple, H. Khouri, N. B. Federova, H. A. Carty, et al. Genome sequence of Chlamydophila caviae (Chlamydia psittaci GPIC): examining the role of niche-specific genes in the evolution of the Chlamydiaceae Nucleic Acids Res., April 15, 2003; 31(8): 2134 - 2147. [Abstract] [Full Text] [PDF]
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 G. Falck, J. Gnarpe, L.-O. Hansson, K. Svardsudd, and H. Gnarpe Comparison of Individuals With and Without Specific IgA Antibodies to Chlamydia pneumoniae: Respiratory Morbidity and the Metabolic Syndrome Chest, November 1, 2002; 122(5): 1587 - 1593. [Abstract] [Full Text] [PDF]
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M. S.V. Elkind, R. Sciacca, B. Boden-Albala, S. Homma, and M. R. Di Tullio Leukocyte Count Is Associated With Aortic Arch Plaque Thickness Stroke, November 1, 2002; 33(11): 2587 - 2592. [Abstract] [Full Text] [PDF]
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 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]
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 B. Wizel, B. C. Starcher, B. Samten, Z. Chroneos, P. F. Barnes, J. Dzuris, Y. Higashimoto, E. Appella, and A. Sette Multiple Chlamydiapneumoniae Antigens Prime CD8+ Tc1 Responses That Inhibit Intracellular Growth of This Vacuolar Pathogen J. Immunol., September 1, 2002; 169(5): 2524 - 2535. [Abstract] [Full Text] [PDF]
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K. Kohara, Y. Tabara, Y. Yamamoto, M. Igase, and T. Miki Chlamydia pneumoniae Seropositivity Is Associated With Increased Plasma Levels of Soluble Cellular Adhesion Molecules in Community-Dwelling Subjects: The Shimanami Health Promoting Program (J-SHIPP) Study Stroke, June 1, 2002; 33(6): 1474 - 1479. [Abstract] [Full Text] [PDF]
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 C. Stollberger and J. Finsterer Role of Infectious and Immune Factors in Coronary and Cerebrovascular Arteriosclerosis Clin. Vaccine Immunol., March 1, 2002; 9(2): 207 - 215. [Full Text] [PDF]
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J. Danesh, P. Whincup, S. Lewington, M. Walker, L. Lennon, A. Thomson, Y.-K. Wong, X. Zhou, and M. Ward Chlamydia pneumoniae IgA titres and coronary heart disease. Prospective study and meta-analysis Eur. Heart J., March 1, 2002; 23(5): 371 - 375. [Abstract] [Full Text] [PDF]
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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]
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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]
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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]
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D. Virok, Z. Kis, L. Karai, L. Intzedy, K. Burian, A. Szabo, B. Ivanyi, E. Gonczol, and M. S. Elkind Chlamydia pneumoniae in Atherosclerotic Middle Cerebral Artery Editorial Comment Stroke, September 1, 2001; 32(9): 1973 - 1976. [Abstract] [Full Text] [PDF]
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 R. L. Sacco Newer risk factors for stroke Neurology, September 1, 2001; 57(90002): S31 - 34. [Abstract] [Full Text]
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M. S. Elkind, J. Cheng, B. Boden-Albala, M. C. Paik, and R. L. Sacco Elevated White Blood Cell Count and Carotid Plaque Thickness : The Northern Manhattan Stroke Study Stroke, April 1, 2001; 32(4): 842 - 849. [Abstract] [Full Text] [PDF]
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R. LaBiche, D. Koziol, T. C. Quinn, C. Gaydos, S. Azhar, G. Ketron, S. Sood, and T. J. DeGraba Presence of Chlamydia pneumoniae in Human Symptomatic and Asymptomatic Carotid Atherosclerotic Plaque Stroke, April 1, 2001; 32(4): 855 - 860. [Abstract] [Full Text] [PDF]
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