From the Department of Epidemiology, Johns Hopkins School of Hygiene and
Public Health, Baltimore, Md (M.D.); the Biomedical Program, University of
Alaska at Anchorage (M.D.); the Departments of Pathobiology, Epidemiology, and
Pathology, University of Washington, Seattle (C.-C.K., L.A.C., S.-P.W.,
J.T.G.); the State of Alaska, Epidemiology Section, Division of Public Health,
Anchorage (J.P.M.); the Department of Pathology, Louisiana State University
Medical School, New Orleans (W.P.N.); and the Department of Medicine, Alaska
Native Medical Center, Anchorage (J.C.F.).
Methods and Results—This retrospective investigation was
performed on premortem serum specimens and autopsy tissue from 60
indigenous Alaska Natives at low risk for coronary heart
disease, selected by the potential availability of their stored
specimens. Serum specimens were drawn a mean of 8.8 years (range, 0.7
to 26.2 years) before death, which occurred at a mean age of 34.1 years
(range, 15 to 57 years), primarily from
noncardiovascular causes (97%). Coronary
artery tissues were independently examined
histologically and, for C pneumoniae
organism and DNA, by immunocytochemistry (ICC) and polymerase chain
reaction (PCR) with species-specific monoclonal antibody and primers.
Microimmunofluorescence detected species-specific
IgG, IgA, and IgM antibody in stored serum. C
pneumoniae, frequently within macrophage foam cells,
was identified in coronary fibrolipid atheroma
(raised lesions, Stary types II through V) in 15 subjects (25%) and
early flat lesions in 7 (11%) either by PCR (14, 23%) or ICC (20,
33%). The OR for C pneumoniae in raised
atheroma after a level of IgG antibody
Conclusions—Serological evidence for C pneumoniae
infection frequently precedes both the earliest and more advanced
lesions of coronary atherosclerosis that harbor
this intracellular pathogen, suggesting a chronic infection and
developmental role in coronary heart disease.
Published reports on the seroepidemiology of
this agent and coronary heart disease in humans from 5 distinct
populations have used various study designs and generally support an
association.11 12 13 14 15 16 17 18 19 Prior infection has been
defined by combinations of C pneumoniae–specific IgG or IgA
antibody at various levels and circulating immune complexes of
chlamydial lipopolysaccharide.11 12 13 14 An
additional report from a multicenter US cohort study indicated an odds
ratio (OR) of 2.0 between IgG and asymptomatic carotid
atherosclerosis.18 Serum IgG
antibody levels
At present, the evidence for an association of C
pneumoniae and atherosclerosis does not constitute
causation. Data regarding whether infection precedes disease
(temporality) are circumstantial: the presence of IgG or IgA antibody
and absence of IgM antibody simultaneously with the
diagnosis of disease or the identification of the organism. Concern
persists that a finding of C pneumoniae antigen or DNA in
coronary atheroma or an immunologic response in
patients with advanced disease may reflect only a relatively late-onset
"passenger" role of the organism migrating within
macrophages to the site of disease, rather than playing an
early role in the endothelial injury hypothesized to
initiate atherosclerosis.21 22
Only the Helsinki Heart Study provided serological data suggesting that
infection does not represent a proclivity for C
pneumoniae to land in injured cardiac tissues or for myocardial
damage to reactivate a latent
infection.12
This study was designed to determine whether infection with C
pneumoniae, diagnosed by the host C
pneumoniae–specific antibody response, preceded any direct
evidence of this organism in coronary artery tissue from
low-risk subjects with early disease. We studied indigenous Alaska
Natives with a lower mortality rate from coronary heart disease
compared with whites both in Alaska and the rest of the United
States.23 24 A recent forensic autopsy study,
including 66% of subjects with a violent cause of death, demonstrated
a lower prevalence of raised atherosclerotic lesions in Alaska Natives
than in non-Natives.25 The basis of the
present report is the analysis of coronary artery
tissue specimens from Alaska Natives in that study and their stored
serum specimens obtained earlier for other reasons.
Specimens
Fifty-six subjects each had 1 accessible premortem serum specimen a
mean of 8.8 years (range, 0.7 to 26.2 years) before death, and 4
subjects had inadequate amounts of serum available. For 22 subjects, a
second serum specimen was available that was drawn a mean of 8.2 years
after the first and 11.9 years before death. All stored serum specimens
were collected for noncardiovascular health screening
programs, including hepatitis, and none were obtained for acute
respiratory disease investigations. Blood specimens at autopsy,
obtained by the prosector from either the vena cava, heart, or aorta,
were centrifuged, frozen, and available from only 45 subjects
for serum thiocyanate levels.
Analysis of Specimens
Polymerase Chain Reaction
Serology
Serum Thiocyanate
Statistical Analysis
Histopathology
Serological Testing
As presented in Table 2
As presented in Table 3
Other stratified univariate analyses included
examining the association of this threshold of IgG antibody,
Multivariate analysis permitted an adjustment
for the potential confounders of age, raised
histological lesion, interval from serum to death, and
smoking. Those produced statistically significant ORs of 3.65 and 9.40
for IgG antibody titers of
Persistence of seropositivity for C pneumoniae was
examined in 22 subjects with a second subsequent serum specimen
available before their death, but persistence was difficult to
correlate with infection at autopsy because only 5 subjects in this
subgroup had demonstrable organism. A total of 19 subjects had IgG
antibody (
A higher seroprevalence rate may be the driving force behind the high
levels of IgG antibody defining C pneumoniae
cardiovascular infection in the Alaska Native
population we studied. Prevalence rates of 77% and 49% for levels of
The finding in this study of C pneumoniae organism in
coronary arterial lesions described as adaptive
intimal thickening is consistent with previous reports that the
organism is never or rarely found in normal coronary
artery.1 2 3 4 5 6 Arterial locations of
intimal thickening correspond to regions of altered mechanical stress
and increased turnover of endothelial cells and smooth
muscle cells and increased concentrations of
LDLs.33 34 These areas have been referred to as
atherosclerosis-prone areas, and eccentric intimal
thickening indicates a region of increased susceptibility to plaque
formation.35 At the University of
Washington, C pneumoniae was previously demonstrated in 18%
(2/11) and 44% (7/16) of adaptive intimal thickening and fatty
streaks, respectively, in young adults.1 4 In the
present study, macrophage foam cells were present in
more than half of the specimens with only adaptive intimal thickening,
with and without C pneumoniae. A marked increase in the
prevalence of these progenitor atheromatous cells
characterized our subjects' specimens with C pneumoniae and
suggests the coexistence of this organism and early pathogenesis. The
recently reported replication of C pneumoniae within human
macrophages, endothelial cells, and vascular
smooth muscle cells gives biological plausibility to the concept of a
chronic intravascular infection that produces rather than follows an
immune response.22 Our finding of an associated
serological response to the presence of the organism in raised
coronary lesions supports this sequence of events.
The potential limitations of this study merit discussion. We are
aware of the criticism that "shopping" for optimal cut points in
continuous data of prognostic factors to obtain statistical
significance or a minimum P value for a threshold can
elevate the global error rate with
false-positives.36 However, our data were
ordinal, and our choice of thresholds was guided by the biological
basis of our reasoning that severe, persistent, or recurrent infections
more likely to generate a high level of antibody are most likely to be
associated with cardiovascular
disease.30 The earliest date of seropositivity
was determined only by the availability of the serum specimen and may
still not have preceded the biological onset of
atherosclerosis in these subjects. Because IgM was not
present, seropositivity most likely reflected an earlier
seroconversion. Moreover, a risk factor for this disease need not be
primordial. Early evidence of coronary
atherosclerosis in adolescence precedes exposure to
many of the acknowledged risk factors that occur only in
adulthood.37 Because small amounts of tissue were
examined by ICC staining, misclassification of tissues read as negative
was possible. However, the marked difference in accompanying
macrophage foam cells is consistent with our results.
Our opportunity to correlate persistence of antibody with confirmed
infection was restricted by the limited availability of paired serum
specimens from individuals with demonstrable C pneumoniae at
autopsy. Although this study did not include control subjects, our
results permit comparisons between subjects with and without
demonstrated C pneumoniae and raised atheroma.
Although we did not use parallel assays in collaborating laboratories,
as others have recently done to confirm their findings of an
association of C pneumoniae and coronary
atherosclerosis,7 all of our
tissue specimens were uniformly examined independently by all assay
methods used. And finally, our conclusions offer no insights regarding
which of the several biological effects of chronic C
pneumoniae infections are the most likely pathogenic mechanisms
postulated for this bacterium in coronary
atherosclerosis.12 14 17 18
In this study of Alaska Natives, the evidence for infection preceding
or accompanying early asymptomatic lesions in young,
low-risk adults is consistent with the expectation that
exposure to risk factors for coronary
atherosclerosis should occur before or during the
earliest stages of disease development. This study also suggests some
additional evidence for the dose-response criterion of causality both
with respect to the grade of atherosclerotic lesion and the level of
C pneumoniae–specific antibody. Stored serum specimens
antedating the direct demonstration of the organism in
atheroma or confirmed coronary
atherosclerosis should be used in current
cardiovascular cohort studies with this resource and
well-documented clinical end points with access to coronary
artery tissue. Correlation of these data in individuals may indicate
where in the natural history of C pneumoniae infection the
primary prevention of cardiovascular disease might be
effected with antibiotics or vaccination, thereby demonstrating the
ultimate criterion of causality, the cessation of the exposure followed
by a reduction of disease.
Received December 2, 1997;
revision received March 18, 1998;
accepted April 20, 1998.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Confirmed Previous Infection With Chlamydia pneumoniae (TWAR) and Its Presence in Early Coronary Atherosclerosis
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
Background—Chlamydia
pneumoniae has been identified in coronary
atheroma, but concomitant serum antibody titers have been
inconsistently positive and unavailable before the detection of
early or advanced atherosclerotic lesions. 
1:256 >8 years
earlier was 6.1 (95% CI, 1.1 to 36.6) and for all coronary
tissues after adjustment for multiple potential confounding
variables, including tobacco exposure, was 9.4 (95% CI, 2.6 to
33.8).
Key Words: Chlamydia pneumoniae • coronary disease • atherosclerosis
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
In several
populations worldwide, Chlamydia pneumoniae TWAR, a recently
identified respiratory bacterial pathogen responsible for 
10% of
community-acquired pneumonia in adults, has been reported in
atherosclerotic lesions.1 2 3 4 5 6 7 8 Within
macrophages of atheroma resected from
coronary and carotid arteries, Chlamydia-specific
structures and antigen have been identified by electron microscopy and
immunocytochemistry (ICC), and species-specific nucleotide
sequences have been identified by polymerase chain reaction (PCR). The
organism is rarely found in vascular specimens from nonatherosclerotic
patients and those with nonatherogenic
arteriopathy.1 2 3 4 5 6 7 8 In addition, the agent has
recently been directly isolated from human
coronary7 and
carotid9 artery atherosclerotic plaque. After
rabbits received nasal inoculation of C pneumoniae, with
their subsequent seroconversion for organism-specific IgG antibody, the
organism was cultured from their early aortic atherosclerotic
plaque.10 1:64 conferred a 2- to 7-fold risk for concurrent
coronary artery disease, but neither the presence of serum
antibody nor its dose response has been associated with a finding of
C pneumoniae antigen or DNA in atherosclerotic
lesions.1 3 7 20
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
Cases
Sixty subjects were selected by matching all 103 Alaska Natives
previously autopsied and reported elsewhere25 to
a population-based serum bank of >300 000 Alaska Native specimens
maintained by the Centers for Disease Control and Prevention in
Anchorage, Alaska. Subjects selected were 75% male and included 47
Eskimos, 5 Aleuts, and 8 Indians residing in 40 communities
statewide. They died between February 1989 and December 1992 at a mean
age of 34.1 years (range, 15 to 57 years). Of these deaths, 97% were
considered not to be cardiovascular, 77% (46) were due
to accidents, 10% (6) due to alcohol, 3% (2) due to
cardiovascular disease, and 10% (6) due to other
causes.
After forensic autopsy, the right coronary artery was
dissected from the heart, fixed in 10% buffered formalin, stained with
Sudan IV stain, and evaluated for lesions of the intimal surface as
described elsewhere.25 Slides were read by a
cardiovascular histopathologist, masked to any other
laboratory results, who used light microscopy and the classification of
Herbert Stary26 to grade
atherosclerosis, measure coronary intimal
thickness, and assess foam cells, lipid, and calcium within
atheroma.
Immunocytochemistry
Tissue sections sequential to those examined for histology were
stained by ICC with the genus-specific monoclonal antibody, CF-2, that
recognizes the lipopolysaccharide antigen of
Chlamydia species.4 Positive-staining
tissues were subsequently tested with the C
pneumoniae–specific monoclonal antibody, RR-402, with appropriate
controls of normal mouse ascitic fluids and HL cell monolayers infected
with C pneumoniae or C trachomatis. Slides were
read independently of other study results.
PCR was performed on DNA obtained from fixed tissue sections
16 mm thick with C pneumoniae–specific HL-1, HR-1
primer sets that amplified a 437-bp C pneumoniae–specific
DNA sequence.27 DNA was purified by boiling the
sections in a 5% suspension of Chelex 100 chelating resin (Sigma
Chemical Co) in sterile water. The resulting supernatants were
extracted with phenol/chloroform by standard methods and precipitated
with ethanol, and the DNA pellets were resuspended in 50 µL
Tris-ethanolamine buffer at pH 8. Mock extractions of buffer were done
and amplified to ensure that no contamination occurred. A control
consisting of PCR reagents without any specimen and various dilutions
of purified C pneumoniae DNA were done in each PCR run as
the negative and positive controls, respectively. Presumptive positives
and detection of products below the sensitivity of agarose gels
were confirmed by immunochemiluminescence as previously
described.1 When inhibition of PCR was observed,
drop dialysis against sterile water was performed and PCR was repeated
to detect a product and confirm true-negative status. Twenty-seven
specimens not yielding an amplification product were dialyzed and
reamplified, resulting in identification of C pneumoniae DNA
sequences in 4 additional subjects.
Serum was examined for IgG, IgM, and IgA antibody to C
pneumoniae with the microimmunofluorescence
test developed by the coauthors (S.-P.W.,
J.T.G.).28 Formalin-fixed whole elementary bodies
of C pneumoniae strain AR-39, a pharyngeal isolate obtained
in Seattle, were used as antigen to determine the presence of
species-specific antibodies in stored serum specimens. This assay is
not cross-reactive and is reproducible within a 2-fold variation. Serum
specimens were tested independently of all other results.
Serum thiocyanate levels were measured as in previous autopsy
studies.29 A smoker was defined as having a serum
thiocyanate level 90 µmol/L, a threshold previously
established in living smokers and
nonsmokers.29
Data were analyzed with univariate and
multivariate programs (SAS Institute). Geometric means
of IgG antibody were adjusted with multivariate linear
analysis. Specific levels of IgG antibody along with multiple
potentially confounding variables were entered into a
multivariate logistic model as independent
variables, with the response variable as C
pneumoniae organism demonstrated in coronary artery by
either ICC or PCR. Univariate analyses used
appropriate Student's t test and 
2
test.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
Detection of C pneumoniae
C pneumoniae organism was identified with PCR or ICC
staining in coronary arteries of 37% of all subjects (22/60).
Data in Table 1
indicate that ICC
staining was more often positive than PCR (20 versus 14 specimens,
respectively), and both techniques identified the organism in 55%
(12/22) of all positive subjects. Positive specimens included 35%
(14/40) of those with a raised atheroma and 39% (7/18) of
those with early flat lesions, including adaptive intimal thickening.
Among cases positive or negative for C pneumoniae organism,
there was a similar distribution of the established causes of death,
sex, and similar median ages.
View this table:
[in a new window]
Table 1. Demographic, Mortality, and Histopathological Data
of Alaska Native Subjects by Demonstration of C
pneumoniae TWAR Organism in Coronary Arteries at
Autopsy (n=60)
Raised fibrolipid plaques (Stary type III through V) were found in
coronary arteries in 40 individuals. Lower-grade lesions were
present in 18 subjects, including adaptive intimal thickening in 13
(Table 1
). Two specimens could not be graded. Macrophage foam
cells were identified in 77% of specimens that were positive for
C pneumoniae, compared with <8% with no organism
(P<0.0001). Foam cells were identified in 54% (7/13) of
specimens with only adaptive intimal thickening, including 3 of 5 with
C pneumoniae demonstrated. In specimens with C
pneumoniae, the mean thickness of the intima was 16% greater and
a lipid core within these atheroma was more common than in
specimens without the organism, although neither difference was
statistically significant (Table 1).
Premortem serum specimens were available for 95% of all subjects
who were positive for C pneumoniae organism and for 92% of
those who were negative, with similar time intervals between collection
of serum and death (Table 1). Among 56 subjects, the proportions with a
1:16 level of C pneumoniae–specific IgG, IgA, and IgM
antibody in serum specimens obtained 1 to 24 years before death were
84%, 57%, and 5%, respectively, and for a level of 1:128 they were
63%, 13%, and 0%, respectively. Although IgA antibody was detectable
more frequently at higher levels of IgG (82% at 1:256 IgG compared
with 68% for 1:16 IgG, P=0.05), IgA was not associated
with C pneumoniae in tissue. There was no sex-specific
difference in seropositivity; however, the power of the study to detect
this was only 55%. ,
the unadjusted serum geometric mean titer (GMT) of IgG antibody for
subjects with C pneumoniae–positive coronary
arteries, all ages combined, was 94.9, versus 54.9 (P=0.114)
for those with organism-negative specimens. Most of this difference
occurred in subjects >35 years of age who had an almost 5-fold higher
GMT preceding a finding of organism in tissue (P=0.024).
Although no difference was noted in younger subjects, interaction
between age and the presence or absence of C pneumoniae
did not achieve statistical significance. After adjustment for age,
smoking, and the interval between dates of serum acquisition and death,
the almost 2-fold difference in the GMTs of IgG antibody still did not
reach significance.
View this table:
[in a new window]
Table 2. Crude and Adjusted GMTs of Prior IgG Antibody by
C pneumonia (TWAR) Organism in Coronary Artery
at Autopsy by PCR or ICC and by Age at Death , the
unadjusted OR for C pneumoniae–specific IgG antibody and a
subsequent finding of this organism in the coronary artery is
significant for an antibody level of 1:256. The serum specimens with
this level of IgG antibody preceding this finding were obtained a mean
of 8.3 years (median, 6.6 years) before death. Serum specimens with
this level of antibody were followed by the absence of organism at
autopsy by a mean of 14.4 years (P=0.04 for the difference)
and median of 16.1 years (P=0.03). For lower thresholds of
IgG antibody, the presence of C pneumoniae in
coronary artery was not statistically significant.
View this table:
[in a new window]
Table 3. Presence of C pneumoniae TWAR
Organism in Coronary Arteries of 56 Alaska Natives at Autopsy
in Relation to Level of IgG Antibody to C pneumoniae in
Serum Obtained a Mean of 8.7 Years Before Death 1:256,
and C pneumoniae organism in coronary artery by
grade of atheromatous lesion. This OR among subjects
with raised atheroma (Stary types III through V) was 6.08
(95% CI, 1.11 to 36.6; P=0.03), but the OR of 3.11 for
those with flat lesions (Stary types I or II), including adaptive
intimal thickening, did not achieve statistical significance (95% CI,
0.28 to 40.64; P=0.35). In addition, smoking status, defined
by a postmortem serum thiocyanate of 90 µmol/L, was unrelated
to either the presence of C pneumoniae organism in
coronary arterial tissue (OR, 0.64; 95% CI, 0.15
to 2.77) or to premortem serum IgG antibody of 1:256 (OR, 0.22; 95%
CI, 0.03 to 1.36). Smoking status was more commonly determined in
individuals with any atherosclerotic lesion compared with those with
only adaptive intimal thickening (OR, 7.78; 95% CI, 0.82 to 182), but
this difference was of marginal statistical significance
(P=0.06). 1:128 and 1:256, respectively. After the
backward elimination of statistically insignificant variables from
this full model, the only remaining covariate directly associated with
the presence of C pneumoniae in coronary arteries at
autopsy was an antemortem level of C pneumoniae–specific
IgG antibody of 1:256 (OR, 8.01; 95% CI, 2.46 to 25.99). The time
interval from this earliest identified seropositivity to death showed a
modest inverse relationship (OR, 0.86; 95% CI, 0.76 to 0.99). 1:8) in their first specimen, and 20 were positive in their
second serum. There was little trend over time for either IgG or IgA
antibody (r=0.255, P=0.265) compared with the
initial antibody levels, which were used in all primary
analyses. Persistent IgG and IgA antibody titers were 82% (18)
and 27% (6), respectively, including lower but present second
values of IgG in 56% (10) and of IgA in 50% (3) of those subjects
with both serum specimens positive. More than one fourth of subjects
with declining serum antibody levels, whether IgG (3/11) or IgA (2/7),
had a finding of C pneumoniae organism at autopsy. Of those
9 subjects with multiple serum specimens and initial IgG antibody
levels of 1:256, 78% (7/9) remained positive at the same level,
higher, or only 1 dilution less than the initial value. However, the
organism was not identified in tissue from 86% (6/7) of these subjects
with persistently high antibody levels.
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
This study provides direct evidence of infection with C
pneumoniae in coronary arteries obtained at autopsy and a
serological diagnosis of infection in the same individuals 5 to 14
years earlier, consistent with C pneumoniae playing
a role in the pathogenesis of atherosclerosis. This
significant relationship with organism-specific DNA or antigen appears
only with the highest levels of preexisting C
pneumoniae–specific IgG antibody established for the serological
diagnosis of respiratory infections.30 This
correlation of prior infection and subsequent molecular and immunologic
evidence of the organism in atheromatous tissue has not
been reported previously and strongly suggests a persistent or chronic
infection. In South African subjects,1 high
antibody titers were not correlated with the finding of C
pneumoniae organism in atheroma at autopsy, nor was
there any difference in the detection of C pneumoniae in
coronary atherectomy or carotid
endarterectomy specimens from US patients with
undetectable, low, or high IgG antibody
titers.3 8 Another study of explanted hearts
indicated seropositivity in patients both with and without demonstrable
organism and coronary
atherosclerosis.7 In a recent
trial, however, persistent seropositivity 1:64 during a 3-month
interval was related to secondary cardiovascular
events.31 After the administration of antibiotic
treatment directed at C pneumoniae, this level declined,
along with the cardiovascular event rate. 1:16 and 1:128, respectively, were noted in subjects in whom no
C pneumoniae was demonstrated in coronary tissue. In
other populations studied, lower antibody levels (1:8 to 1:64) defining
infection in patients with coronary
atherosclerosis have been accompanied by lower
seroprevalence rates in healthy control subjects, 42% to 59%, for a
titer of 1:16.14 15 17 18 It is noteworthy that
in Alaska Natives in 1994, pneumonia, usually nonbacteremic, persisted
as the third most common reason for hospitalization, consistent
with an undiagnosed burden of C pneumoniae respiratory
infection.32
Acknowledgments
This study was funded by the American Heart Association, grant
9306272S. We thank the Arctic Investigations Program, Center for
Infectious Diseases, Centers for Disease Control and Prevention for
providing stored serum; Dr Javier Nieto of The Johns Hopkins University
for critically reviewing the manuscript; Mark VanNatta, The Johns
Hopkins University, for advice; and Diane Ingle,
Epidemiology Section, State of Alaska and Dr
Dennis Fisher, University of Alaska at Anchorage, for
assistance.
Footnotes
Reprint requests to Michael Davidson, MD, MPH, Center for Clinical Trials, Johns Hopkins University, Rm 5010, 615 N Wolfe St, Baltimore, MD 21205.
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
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R. Tavendale, D. Parratt, S.D. Pringle, R. A'brook, and H. Tunstall-Pedoe Serological markers of Chlamydia pneumoniae infection in men and women and subsequent coronary events. The Scottish Heart Health Study Cohort Eur. Heart J., February 2, 2002; 23(4): 301 - 307. [Abstract] [Full Text] [PDF]
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 J. Boman and M. R. Hammerschlag Chlamydia pneumoniae and Atherosclerosis: Critical Assessment of Diagnostic Methods and Relevance to Treatment Studies Clin. Microbiol. Rev., January 1, 2002; 15(1): 1 - 20. [Abstract] [Full Text]
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D. Sander, K. Winbeck, J. Klingelhofer, T. Etgen, and B. Conrad Enhanced Progression of Early Carotid Atherosclerosis Is Related to Chlamydia pneumoniae (Taiwan Acute Respiratory) Seropositivity Circulation, March 13, 2001; 103(10): 1390 - 1395. [Abstract] [Full Text] [PDF]
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 F Schiele, M K Batur, M F Seronde, N Meneveau, P Sewoke, A Bassignot, G Couetdic, F Caulfield, and J-P Bassand Cytomegalovirus, Chlamydia pneumoniae, and Helicobacter pylori IgG antibodies and restenosis after stent implantation: an angiographic and intravascular ultrasound study Heart, March 1, 2001; 85(3): 304 - 311. [Abstract] [Full Text]
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P. Vehmaan-Kreula, M. Puolakkainen, M. Sarvas, H. G. Welgus, and P. T. Kovanen Chlamydia pneumoniae Proteins Induce Secretion of the 92-kDa Gelatinase by Human Monocyte- Derived Macrophages Arterioscler. Thromb. Vasc. Biol., January 1, 2001; 21 (1): e1 - e8. [Abstract] [Full Text] [PDF]
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 S A Morre, W Stooker, W K Lagrand, A J C van den Brule, and H W M Niessen Microorganisms in the aetiology of atherosclerosis J. Clin. Pathol., September 1, 2000; 53(9): 647 - 654. [Abstract] [Full Text] [PDF]
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P. Liuba, P. Karnani, E. Pesonen, I. Paakkari, A. Forslid, L. Johansson, K. Persson, T. Wadstrom, and R. Laurini Endothelial Dysfunction After Repeated Chlamydia pneumoniae Infection in Apolipoprotein E-Knockout Mice Circulation, August 29, 2000; 102(9): 1039 - 1044. [Abstract] [Full Text] [PDF]
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 S. D. Wright, C. Burton, M. Hernandez, H. Hassing, J. Montenegro, S. Mundt, S. Patel, D. J. Card, A. Hermanowski-Vosatka, J. D. Bergstrom, et al. Infectious Agents Are Not Necessary for Murine Atherogenesis J. Exp. Med., April 18, 2000; 191(8): 1437 - 1442. [Abstract] [Full Text] [PDF]
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C. Bartels, M. Maass, G. Bein, N. Brill, J. F. M. Bechtel, R. Leyh, and H.-H. Sievers Association of Serology With the Endovascular Presence of Chlamydia pneumoniae and Cytomegalovirus in Coronary Artery and Vein Graft Disease Circulation, January 18, 2000; 101(2): 137 - 141. [Abstract] [Full Text] [PDF]
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 D. Taylor-Robinson, B. J Thomas, L. von Hertzen, R. Isoaho, S.-L. Kivelä, and P. Saikku Relation of C pneumoniae antibodies to ischaemic heart disease BMJ, December 11, 1999; 319(7224): 1575 - 1575. [Full Text]
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 Y.-k. Wong, K. D. Dawkins, and M. E. Ward Circulating chlamydia pneumoniae DNA as a predictor of coronary artery disease J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1435 - 1439. [Abstract] [Full Text] |