CLINICAL STUDY
Lack of association between Chlamydia pneumoniae seropositivity and aortic atherosclerotic plaques
A Population-Based transesophageal echocardiographic study
Yoram Agmon, MD*,
Bijoy K. Khandheria, MD, FACC*,*,
Irene Meissner, MD ,
Tanya M. Petterson, MS ,
W. Michael O’Fallon, PhD,
Teresa J. H. Christianson, BS,
David O. Wiebers, MD,
Thomas F. Smith, PhD ,
James M. Steckelberg, MD|| and
A. Jamil Tajik, MD, FACC*
* Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota, USA
|| Division of Infectious Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
Manuscript received April 23, 2002;
revised manuscript received January 16, 2003,
accepted January 24, 2003.
* Reprint requests and correspondence: Dr. Bijoy K. Khandheria, Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
khandheria{at}mayo.edu
 |
Abstract
|
|---|
OBJECTIVES: The objective of this study was to examine the relationship between Chlamydia pneumoniae seropositivity and aortic atherosclerotic plaques in the general population.
BACKGROUND: Seroepidemiologic studies suggest that C pneumoniae infection plays a role in the pathogenesis of atherosclerosis.
METHODS: Transesophageal echocardiography was performed in 385 subjects (median age 66 years, range 51 to 101 years; 53% men), a sample of the Olmsted County (Minnesota) population. The association between C pneumoniae immunoglobulin (Ig) G antibody titers and aortic atherosclerotic plaques was examined.
RESULTS: Chlamydia pneumoniae IgG antibodies (titers  1:16) were detected in 287 subjects (74.5%): low titers (1:16 to 1:32) in 58 (15.1%), intermediate titers (1:64 to 1:128) in 144 (37.4%), and high titers (1:256) in 85 subjects (22.1%). Antibody titers were not associated with the presence of aortic plaques after adjustment for age, gender, and smoking status (p = 0.64). Compared with titers <1:16, the adjusted odds ratios for aortic plaques were 1.46 (95% confidence interval [CI] 0.63 to 3.42) for low titers, 1.32 (95% CI 0.68 to 2.55) for intermediate titers, and 0.94 (95% CI 0.42 to 2.07) for high titers. Among the subgroup with plaques, antibody titers were not associated with the presence of plaques 4 mm thick (p = 0.99), plaques 6 mm (p = 0.49), or mobile debris (p = 0.71), after adjustment for age and smoking.
CONCLUSIONS: Chlamydia pneumoniae IgG antibody titers are not associated with the presence or severity of aortic atherosclerosis in the general population. These observations do not support a role for C pneumoniae infection in the initiation or progression of atherosclerosis.
|
Abbreviations and Acronyms
| | CI | = confidence interval | | hs-CRP | = high-sensitivity C-reactive protein | | Ig | = immunoglobulin | | OR | = odds ratio | | SPARC | = Stroke Prevention: Assessment of Riskin a Community | | TEE | = transesophageal echocardiography |
|
Inflammation plays a central role in the pathogenesis of atherosclerotic vascular disease and its atherothrombotic complications (1). It has been postulated that chronic infection with various pathogens may promote arterial inflammation, thereby contributing to the initiation and/or progression of atherosclerosis (2). Several large seroepidemiologic studies have observed an association between Chlamydia pneumoniae seropositivity and clinical coronary artery disease (3–5) and cerebrovascular disease (6), suggesting that chronic C pneumoniae may play a causal role in the atherosclerotic process. However, these observations are inconsistent with those of other studies (7–10). Thus, the importance of C pneumoniae infection in the pathogenesis of atherosclerotic vascular disease remains to be determined (11).
The Stroke Prevention: Assessment of Risk in a Community (SPARC) study is a National Institutes of Health-funded, population-based study designed to evaluate the prevalence of risk factors for stroke in the general population (12–14). Subjects were evaluated by transesophageal echocardiography (TEE), thereby allowing determination of the frequency and severity of aortic atherosclerosis in the population. The objective of the current study was to examine the relationship between seropositivity for C pneumoniae and anatomically defined atherosclerosis (aortic atherosclerotic plaques identified on TEE) in a sample of the general population, in an attempt to clarify the role of C pneumoniae infection in atherogenesis.
|
Methods
|
|---|
Study population.
The study design and results of phase I of the SPARC study have been published recently in detail (12,13). The original study cohort consisted of 581 subjects, a random sample of Olmsted County (Minnesota) residents 45 years old, stratified by age and gender. Approximately four to five years (median 4.6 years, range 3.8 to 5.4 years) after their initial evaluation, eligible subjects were enrolled in phase II of the study. Of 504 subjects eligible for phase II (excluding 3 subjects from the original cohort lost to follow-up, 54 deceased, and 20 with severe medical disabilities precluding participation), 392 (78%) agreed to participate (14). Transesophageal echocardiography was repeated successfully in 388 subjects (99% of phase II participants), 385 of whom were included in the current analysis (two subjects were excluded because of incomplete echocardiographic data, and one subject was excluded because of positive immunoglobulin [Ig] M antibodies [titer 1:10] indicating acute C pneumoniae infection). The median age of the study population was 66 years (range 51 to 101 years); 53% were men. The study was approved by the Mayo Foundation Institutional Review Board. Written informed consent was obtained from all subjects.
Clinical and laboratory data.
Smoking status (current smoker, past smoker, or never smoked) was elicited by questionnaire. Previous clinical coronary artery disease and cerebrovascular disease were ascertained by questionnaire and abstracting of medical records at Mayo Clinic and Olmsted Medical Center, the two primary health care providers in Olmsted County.
Fasting blood samples were collected (on the day of TEE in 97% of subjects and within 20 days of TEE in the remaining subjects) and, using commercially available assays, were analyzed for the following infectious and inflammatory markers: - Chlamydia pneumoniae (TW 183) IgG and IgM antibody titers, with use of a microimmunofluorescence assay (MRL, Focus Technologies, Cypress, California). Seropositivity was defined as an IgG titer of 1:16 (7). Among seropositive subjects, antibody titers were defined as low (1:16 to 1:32), intermediate (1:64 to 1:128), or high (1:256).
- Blood counts, including white blood cell differential counts.
- Fibrinogen levels.
- High-sensitivity C-reactive protein (hs-CRP) levels, with use of a high-sensitivity, latex-enhanced, immunotubidimetric assay (Kamiya Biomedical, Seattle, Washington).
Tee.
Transesophageal echocardiography was performed using commercially available ultrasound instruments equipped with multiplane probes (Sequoia Ultrasound System, Acuson, Mountain View, California). The three segments of the thoracic aorta (ascending aorta, aortic arch, and descending thoracic aorta) were imaged in short- and long-axis views using high-frequency (7-MHz) ultrasonographic imaging. Atherosclerotic plaques were defined as irregular intimal thickening (at least 2 mm thick). The presence of plaques in the thoracic aorta (plaques of any degree in any aortic segment) was determined. Among subjects with plaques, the maximal plaque thickness and the presence of mobile aortic debris (in any segment of the aorta) were determined. For this analysis, plaque thickness was dichotomized arbitrarily at 4 mm (15) and 6 mm (detected in approximately 10% of the study population).
Statistical analysis.
Continuous data are summarized as medians and interquartile ranges (25% to 75%); categorical data are summarized as percentages. For continuous data, groups were analyzed using the Kruskal-Wallis nonparametric test. For categorical data, groups were analyzed using the chi-square statistic or Fisher exact test (when the expected number of subjects in a cell, under the null hypothesis, was <5).
Logistic regression was used to determine the relationship between C pneumoniae antibody titers and the odds of having aortic plaques (proportion of subjects with plaques of any degree divided by proportion without plaques). Among subjects with plaques, the odds of having plaques 4 mm thick (proportion with plaques 4 mm divided by proportion with plaques <4 mm), plaques 6 mm thick (proportion with plaques 6 mm divided by proportion with plaques <6 mm), and mobile debris (proportion with plaques with mobile debris divided by proportion with plaques without debris) were determined.
Univariate (unadjusted) odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated. Subsequently, ORs were estimated after adjustment for age, gender (for selected plaque variables), and smoking status (7,16) (7.0% of study participants were current smokers, 38.4% were past smokers, and 54.6% never smoked). Odds ratios were adjusted for gender for plaque variables with a large number of subjects (plaques of any degree and plaques 4 mm). Smoking was modeled as current smoker and past smoker (vs. never smoked) for plaque variables with a large number of subjects or as ever smoked (vs. never smoked) for plaque variables with a small number of subjects (plaques 6 mm and mobile debris).
|
Results
|
|---|
Aortic plaques (of any degree) were detected in 266 subjects (69.1% of subjects). Plaques were uncommon in the ascending aorta (23 subjects, 6.0%) but were common in the aortic arch (243 subjects, 63.1%) and descending thoracic aorta (210 subjects, 54.5%). Plaques 4 mm, plaques 6 mm, and plaques with mobile debris (in any segment of the aorta) were detected in 113, 41, and 20 subjects, respectively.
Two hundred eighty-seven subjects (74.5%) were C pneumoniae seropositive (IgG titers 1:16). Low titers were present in 58 subjects (15.1%), intermediate titers in 144 subjects (37.4%), and high titers in 85 subjects (22.1%). Table 1 presents the distribution of C pneumoniae antibody titers in relation to the presence or absence of specific plaque variables. There was no significant difference in the distribution of C pneumoniae titers between subjects with and those without aortic plaques (of any degree). Among subjects with plaques, there were no significant differences in the distribution of C pneumoniae titers according to the presence or absence of severe plaque characteristics (plaques 4 mm, plaques 6 mm, and mobile debris).
View this table:
[in this window]
[in a new window]
|
Table 1 Distribution of Chlamydia pneumoniae Immunoglobin Antibody Titers in Relation to the Presence and Severity of Aortic Atherosclerotic Plaques
|
|
The ORs for aortic plaques in relation to C pneumoniae antibody titers are summarized in Table 2. Chlamydia pneumoniae titers were not associated with the presence of aortic plaques (of any degree), either univariately or after adjustment for age, gender, and smoking status. Among subjects with plaques, high titer was apparently associated with the presence of plaques 4 mm by univariate analysis (OR 2.05, compared with titers <1:16; 95% CI 1.00 to 4.21), but this association was not significant after adjustment for age, gender, and smoking status (adjusted OR 1.11; 95% CI 0.47 to 2.60). Moreover, the joint inclusion of all three levels of C pneumoniae antibody titers was not a significant addition to the unadjusted model (p = 0.20) or to the age-, gender-, and smoking-adjusted model (p = 0.99) of plaques 4 mm. Chlamydia pneumoniae titers were not associated with plaques 6 mm or with mobile debris, either univariately or after adjustment for age and smoking status.
View this table:
[in this window]
[in a new window]
|
Table 2 Association of Chlamydia pneumoniae IgG Antibody Titers With the Presence and Severity of Aortic Atherosclerotic Plaques
|
|
The associations between C pneumoniae antibody titers and all plaque variables remained nonsignificant after adjustment for additional aortic atherosclerotic risk factors (data not shown). Furthermore, the association between C pneumoniae titers and severe plaque features remained nonsignificant in an additional post hoc analysis, in which subjects with severe plaque characteristics were compared with the rest of the study population (i.e., compared with subjects with plaques of lesser severity or without plaques; data not shown).
The distribution of C pneumoniae antibody titers was not significantly different between subjects with and those without clinical coronary artery disease and cerebrovascular disease (Table 3). Blood cell counts (including white blood cell differential counts), fibrinogen levels, and hs-CRP levels were not significantly different among subjects with various C pneumoniae titers (Table 4).
View this table:
[in this window]
[in a new window]
|
Table 3 Distribution of Chlamydia pneumoniae IgG Antibody Titers in Relation to Frequency of Clinical Coronary Artery Disease and Cerebrovascular Disease
|
|
|
Discussion
|
|---|
This population-based TEE study shows that C pneumoniae seropositivity is not associated with the presence of aortic atherosclerotic plaques. Among subjects with plaques, C pneumoniae seropositivity is not associated with plaque severity, as defined by maximal plaque thickness or the presence of mobile debris. The lack of association between C pneumoniae seropositivity and clinical coronary artery disease or cerebrovascular disease in our study population supports our echocardiographic-anatomic observations.
C pneumoniae and atherosclerotic plaques.
Chlamydia pneumoniae, a common respiratory pathogen, is frequently detected in pathologic specimens of atherosclerotic plaques (17–21), but its presence in plaques is related inconsistently with plaque extent and severity (19,20,22,23). Using various imaging techniques, the relationship between C pneumoniae seropositivity and atherosclerosis has been examined in highly selected patients undergoing invasive angiographic studies (24,25) and in selected (26–28) and relatively nonselected (29–31) populations undergoing noninvasive ultrasonographic vascular imaging. Many of these studies have found positive associations (24,28,29,31), and two prospective studies have also shown an association between C pneumoniae seropositivity and the progression of carotid atherosclerosis (28,31). Nevertheless, these associations were not borne out in a large study of healthy individuals (30) or in our current study.
Notably, carotid artery intima-medial thickness, the main measurement used in most ultrasonographic studies, is representative of the early stages of atherogenesis. By contrast, high-resolution, real-time TEE imaging allows visualization of the full range of aortic atherosclerotic plaques, from simple plaques to thick ("protruding") plaques (15) and mobile atherosclerotic debris, the echocardiographic hallmark of ruptured aortic plaque with superimposed thrombosis (32). Using TEE, we were able to examine the association between C pneumoniae seropositivity and both the presence and complexity of aortic plaques in a large sample of the general population and to conclude that previous (presumably chronic) infection with C pneumoniae, assessed serologically, does not appear to be involved in the atherosclerotic process in either its early or its more advanced stages.
An independent association between hs-CRP and aortic plaques has been demonstrated recently in the SPARC study population (33), an observation further supporting the systemic inflammatory nature of the atherosclerotic process (1). In our current analysis, C pneumoniae seropositivity was not associated with various markers of systemic inflammation. This observation, also made by other investigators (7,30), is consistent with the lack of association between C pneumoniae seropositivity and aortic atherosclerosis in our study population.
Study strengths and limitations.
The SPARC study is the only large-scale, population-based TEE study performed to date. Study participants were sampled from the adult population residing in a well-defined geographic area, are relatively free of selection bias, and are representative of the general population.
The following study limitations should be noted. First, this was a cross-sectional study, one lacking prospective follow-up data. However, data relating aortic plaque morphology, C pneumoniae serology, and inflammatory markers to future cardiovascular and cerebrovascular events will be available during long-term follow up of the study cohort.
Second, we examined the association between C pneumoniae IgG antibody titers and aortic atherosclerosis, assuming that the presence of IgG titers beyond a certain threshold (i.e., titers 1:16) is indicative of chronic C pneumoniae infection (7). Moreover, we examined the association between various levels of antibody titers and aortic atherosclerosis (4,7) and excluded one subject with positive C pneumoniae IgM antibodies, assuming that higher IgG titers are more likely to represent persistent C pneumoniae infection (in the absence of acute infection). Nevertheless, although widely studied (9) and widely available in clinical practice, C pneumoniae IgG antibody titers may not be the best serologic markers for assessing persistent infection, as suggested by the weak association between seropositivity and direct detection of C pneumoniae in atherosclerotic plaques (18,20,23) and by the apparently stronger relationship of C pneumoniae IgA titers (3,6,34,35), C pneumoniae immune complexes (3,34), and circulating C pneumoniae deoxyribonucleic acid (36) to atherosclerotic vascular disease.
Third, although we did not demonstrate any significant association between C pneumoniae seropositivity and aortic plaques, it is possible that the sample size of our study was underpowered for detecting minor associations. However, as shown in Table 2, the adjusted ORs for aortic plaques were close to 1.0 (many of them were <1.0), and there was no trend for increasing ORs with increasing titers (some ORs for higher titers were even lower than for lower titers). These findings suggest that a significant association between C pneumoniae seropositivity and aortic plaques is very unlikely and, if an association does exist, it is minor and of questionable clinical significance.
Finally, it has been postulated recently that the overall burden of pathogens (i.e., the effect of the combined presence of several infectious pathogens), not a specific pathogen, is the important factor in the development of atherosclerosis (37). Chlamydia pneumoniae was the only infectious agent examined in our study; therefore, we cannot reject the possibility that persistent C pneumoniae infection, in conjunction with other infectious pathogens, promotes the development of atherosclerosis.
Conclusions.
Seropositivity for C pneumoniae is not related to the presence or severity of aortic atherosclerotic plaques in the general population. These echocardiographic-anatomical findings do not support the hypothesis that C pneumoniae infection plays a role in the pathogenesis of atherosclerotic vascular disease. In acknowledgment of the potential limitations of seroepidemiologic assessment noted above, the negative results of our study and other studies (7–10) advocate that future studies should focus on nonserologic methods to address the possible role of C pneumoniae in atherogenesis.
|
Footnotes
|
|---|
Dr. Agmon is currently at the Rambam Medical Center, Haifa, Israel. This study was supported, in part, by research grant NS-06663 from the National Institute of Neurological Disorders and Stroke.
|
References
|
|---|
1. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med. 1999;340:115–126[Free Full Text]
2. Epstein SE, Zhou YF, Zhu J. Infection and atherosclerosis: emerging mechanistic paradigms. Circulation. 1999;100:e20–28[Abstract/Free Full Text]
3. Saikku P, Leinonen M, Tenkanen L, et al. Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study. Ann Intern Med. 1992;116:273–278[Abstract/Free Full Text]
4. Siscovick DS, Schwartz SM, Corey L, et al. Chlamydia pneumoniae, herpes simplex virus type 1, and cytomegalovirus and incident myocardial infarction and coronary heart disease death in older adults: the Cardiovascular Health Study. Circulation. 2000;102:2335–2340[Abstract/Free Full Text]
5. Roivainen M, Viik-Kajander M, Palosuo T, et al. Infections, inflammation, and the risk of coronary heart disease. Circulation. 2000;101:252–257[Abstract/Free Full Text]
6. Elkind MS, Lin IF, Grayston JT, Sacco RL. Chlamydia pneumoniae and the risk of first ischemic stroke: the Northern Manhattan Stroke Study. Stroke. 2000;31:1521–1525[Abstract/Free Full Text]
7. Ridker PM, Kundsin RB, Stampfer MJ, Poulin S, Hennekens CH. Prospective study of Chlamydia pneumoniae IgG seropositivity and risks of future myocardial infarction. Circulation. 1999;99:1161–1164[Abstract/Free Full Text]
8. Nieto FJ, Folsom AR, Sorlie PD, Grayston JT, Wang SP, Chambless LE. Chlamydia pneumoniae infection and incident coronary heart disease: the Atherosclerosis Risk in Communities Study. Am J Epidemiol. 1999;150:149–156[Abstract/Free Full Text]
9. Danesh J, Whincup P, Walker M, et al. Chlamydia pneumoniae IgG titres and coronary heart disease: prospective study and meta-analysis. BMJ. 2000;321:208–213[Abstract/Free Full Text]
10. Wald NJ, Law MR, Morris JK, Zhou X, Wong Y, Ward ME. Chlamydia pneumoniae infection and mortality from ischaemic heart disease: large prospective study. BMJ. 2000;321:204–207[Abstract/Free Full Text]
11. Epstein SE, Zhu J. Lack of association of infectious agents with risk of future myocardial infarction and stroke: definitive evidence disproving the infection/coronary artery disease hypothesis? Circulation. 1999;100:1366–1368[Free Full Text]
12. Meissner I, Whisnant JP, Khandheria BK, et al. Prevalence of potential risk factors for stroke assessed by transesophageal echocardiography and carotid ultrasonography: the SPARC study: Stroke Prevention: Assessment of Risk in a Community. Mayo Clin Proc. 1999;74:862–869[Abstract]
13. Agmon Y, Khandheria BK, Meissner I, et al. Independent association of high blood pressure and aortic atherosclerosis: a population-based study. Circulation. 2000;102:2087–2093[Abstract/Free Full Text]
14. Agmon Y, Khandheria BK, Meissner I, et al. Aortic valve sclerosis and aortic atherosclerosis: different manifestations of the same disease? Insights from a population-based study. J Am Coll Cardiol. 2001;38:827–834[Abstract/Free Full Text]
15. Amarenco P, Cohen A, Tzourio C, et al. Atherosclerotic disease of the aortic arch and the risk of ischemic stroke. N Engl J Med. 1994;331:1474–1479[Abstract/Free Full Text]
16. Hahn DL, Golubjatnikov R. Smoking is a potential confounder of the Chlamydia pneumoniae-coronary artery disease association. Arterioscler Thromb. 1992;12:945–947[Abstract/Free Full Text]
17. Grayston JT, Kuo CC, Coulson AS, et al. Chlamydia pneumoniae (TWAR) in atherosclerosis of the carotid artery. Circulation. 1995;92:3397–3400[Abstract/Free Full Text]
18. Chiu B, Viira E, Tucker W, Fong IW. Chlamydia pneumoniae, cytomegalovirus, and herpes simplex virus in atherosclerosis of the carotid artery. Circulation. 1997;96:2144–2148[Abstract/Free Full Text]
19. Thomas M, Wong Y, Thomas D, et al. Relation between direct detection of Chlamydia pneumoniae DNA in human coronary arteries at postmortem examination and histological severity (Stary grading) of associated atherosclerotic plaque. Circulation. 1999;99:2733–2736[Abstract/Free Full Text]
20. Ericson K, Saldeen TG, Lindquist O, Paulson C, Mehta JL. Relationship of Chlamydia pneumoniae infection to severity of human coronary atherosclerosis. Circulation. 2000;101:2568–2571[Abstract/Free Full Text]
21. Rassu M, Cazzavillan S, Scagnelli M, et al. Demonstration of Chlamydia pneumoniae in atherosclerotic arteries from various vascular regions. Atherosclerosis. 2001;158:73–79[CrossRef][Medline]
22. Vink A, Poppen M, Schoneveld AH, et al. Distribution of Chlamydia pneumoniae in the human arterial system and its relation to the local amount of atherosclerosis within the individual. Circulation. 2001;103:1613–1617[Abstract/Free Full Text]
23. LaBiche R, Koziol D, Quinn TC, et al. Presence of Chlamydia pneumoniae in human symptomatic and asymptomatic carotid atherosclerotic plaque. Stroke. 2001;32:855–860[Abstract/Free Full Text]
24. Thom DH, Wang SP, Grayston JT, et al. Chlamydia pneumoniae strain TWAR antibody and angiographically demonstrated coronary artery disease. Arterioscler Thromb. 1991;11:547–551[Abstract/Free Full Text]
25. Burian K, Kis Z, Virok D, et al. Independent and joint effects of antibodies to human heat-shock protein 60 and Chlamydia pneumoniae infection in the development of coronary atherosclerosis. Circulation. 2001;103:1503–1508[Abstract/Free Full Text]
26. Espinola-Klein C, Rupprecht HJ, Blankenberg S, et al. Are morphological or functional changes in the carotid artery wall associated with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, or herpes simplex virus infection? Stroke. 2000;31:2127–2133[Abstract/Free Full Text]
27. Schmidt C, Hulthe J, Wikstrand J, et al. Chlamydia pneumoniae seropositivity is associated with carotid artery intima-media thickness. Stroke. 2000;31:1526–1531[Abstract/Free Full Text]
28. Sander D, Winbeck K, Klingelhofer J, Etgen T, Conrad B. Enhanced progression of early carotid atherosclerosis is related to Chlamydia pneumoniae (Taiwan acute respiratory) seropositivity. Circulation. 2001;103:1390–1395[Abstract/Free Full Text]
29. Atherosclerosis Risk in Communities (ARIC) Study InvestigatorsMelnick SL, Shahar E, Folsom AR, et al. Past infection by Chlamydia pneumoniae strain TWAR and asymptomatic carotid atherosclerosis. Am J Med. 1993;95:499–504[CrossRef][Medline]
30. Markus HS, Sitzer M, Carrington D, Mendall MA, Steinmetz H. Chlamydia pneumoniae infection and early asymptomatic carotid atherosclerosis. Circulation. 1999;100:832–837[Abstract/Free Full Text]
31. Mayr M, Kiechl S, Willeit J, Wick G, Xu Q. Infections, immunity, and atherosclerosis: associations of antibodies to Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus with immune reactions to heat-shock protein 60 and carotid or femoral atherosclerosis. Circulation. 2000;102:833–839[Abstract/Free Full Text]
32. Vaduganathan P, Ewton A, Nagueh SF, Weilbaecher DG, Safi HJ, Zoghbi WA. Pathological correlates of aortic plaques, thrombi and mobile "aortic debris" imaged in vivo with transesophageal echocardiography. J Am Coll Cardiol. 1997;30:357–363[Abstract]
33. Agmon Y, Khandheria BK, Meissner I, et al. C-reactive protein levels are associated with the presence and severity of aortic atherosclerotic plaques in the population (abstr). J Am Soc Echocardiogr. 2001;14:431
34. Wimmer ML, Sandmann-Strupp R, Saikku P, Haberl RL. Association of chlamydial infection with cerebrovascular disease. Stroke. 1996;27:2207–2210[Abstract/Free Full Text]
35. Strachan DP, Carrington D, Mendall MA, et al. Relation of Chlamydia pneumoniae serology to mortality and incidence of ischaemic heart disease over 13 years in the Caerphilly Prospective Heart Disease Study. BMJ. 1999;318:1035–1039[Abstract/Free Full Text]
36. Wong YK, Dawkins KD, Ward ME. Circulating Chlamydia pneumoniae DNA as a predictor of coronary artery disease. J Am Coll Cardiol. 1999;34:1435–1439[Abstract/Free Full Text]
37. Zhu J, Nieto FJ, Horne BD, Anderson JL, Muhlestein JB, Epstein SE. Prospective study of pathogen burden and risk of myocardial infarction or death. Circulation. 2001;103:45–51[Abstract/Free Full Text]
|
Top
Abstract
Methods