NDT Advance Access published online on October 15, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm696
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Chlamydia pneumoniae accompanied by inflammation is associated with the progression of atherosclerosis in CAPD patients: a prospective study for 3 years*
Department of Internal Medicine, Yonsei University, College of Medicine The Institute of Kidney Disease, Seoul, Korea
Correspondence and offprint requests to: Correspondence and offprint requests to: Dae-Suk Han, Department of Internal Medicine, College of Medicine, Yonsei University, 134 Shinchon-dong, Seodaemoon-gu, Seoul, 120–752, Korea. Tel: +82-2-2228-1937; Fax: +82-2-393-6884; E-mail: dshan{at}yumc.yonsei.ac.kr
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Abstract |
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Background. The causes of accelerated atherosclerosis in end-stage renal disease (ESRD) patients are unknown, although recent studies have suggested that Chlamydia pneumoniae (Cp) infection and inflammation might be contributing factors. We aimed to evaluate the association of carotid atherosclerosis progression with Cp infection and inflammation in patients undergoing peritoneal dialysis (PD).
Methods. This is a prospective observational study. A total of 52 non-diabetic prevalent PD patients were included. The intima-media thickness of a common carotid artery (CCA-IMT) was measured at baseline and after 36 months by B-mode ultrasonography. Serum antibodies to Cp and inflammatory markers were obtained at the time of initial measurement of the CCA-IMT.
Results. CCA-IMT progressors (
CCA-IMT 
0.015 mm/year) had a higher prevalence of seropositivity for Cp IgA antibody, a higher level of Cp IgA antibodies indices, log IL-(interleukin-)6, and intercellular adhesion molecule-1 (ICAM-1) compared to the non-progressors (CCA-IMT < 0.015 mm/year). On multivariate analysis, Cp IgA index and log IL-6 were independent risk a factors for CCA-IMT progression. Also, Cp IgA index had independent positive correlation with the magnitude of annual CCA-IMT. Cp IgA antibody seropositive patients showed significantly higher mean annual CCA-IMT than seronegative patients. Moreover, patients with both positive Cp IgA antibodies and elevated IL-6 above the median level showed higher CCA-IMT than those with either factor alone.
Conclusions. Our data showed that Cp and inflammation were significant risk factors of CCA-IMT change in PD patients. This study strengthens evidence that Cp is involved in the pathogenesis of atherosclerosis and also suggests that the effect of Cp infection under high inflammatory status might be a risk factor for progression of atherosclerosis.
Keywords: atherosclerosis; Chlamydia pneumoniae; inflammation; intima-media thickness
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Introduction |
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Although continuous advances in dialysis and renal transplantation have significantly decreased the mortality rate from end-stage renal disease (ESRD) patients undergoing dialysis still have a higher mortality rate than the general population, and cardiovascular disease is the main contributor to this higher mortality. This phenomenon cannot be simply explained by the traditional cardiovascular risk factors such as hypertension, diabetes mellitus, cigarette smoking and dyslipidaemia. Therefore, much attention has recently been paid to on the non-traditional risk factors, such as chronic inflammation and infection.
Chlamydia pneumoniae (Cp) has been the most implicated micro-organism associated with atherosclerosis. It has been proposed that the organism infects the vessel wall, induces inflammatory mediators and promotes vascular smooth muscle proliferation [1]. A previous study has reported an increased prevalence of Cp seropositivity in ESRD patients compared with the general population [2]. Several reports have described a relationship between Cp and atherosclerosis in patients on haemodialysis [2–4]. While it is still under debate, Cp infection may be a risk factor for cardiovascular mortality in patients on continuous ambulatory peritoneal dialysis (CAPD) [5,6]. However, there has been no prospective study to evaluate the effect of Cp on the progression of atherosclerosis or morphological change of artery in CAPD patients.
Inflammatory processes play an important role in the pathogenesis of atherosclerosis, and elevated serum markers of vascular wall inflammation, such as IL- (interleukin-)6, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), C-reactive protein (CRP) and high sensitivity CRP (hsCRP) have been shown to predict cardiovascular events.
The measurement of the intima-media thickness of common carotid artery (CCA-IMT) assessed by high-resolution duplex ultrasonography has been used as a marker for subclinical atherosclerosis and predicting future cardiovascular disease [7].
We undertook this prospective study to investigate a possible association of Cp infection and markers of inflammation with changes in CCA-IMT.
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Subjects and methods |
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Study population
We initially performed baseline carotid duplex ultrasonography and biochemical analyses in 64 non-diabetic CAPD patients at a single dialysis unit of Severance hospital. We followed the patients for 36 months thereafter. During this period, 12 patients were excluded from the study, 5 were expired, 3 received kidney transplantation and 3 were switched to haemodialysis. Therefore, 52 (26 male, mean age 51.8 ± 10.8 years, range 32–74) out of 64 patients undertook follow-up carotid duplex ultrasonography after 36.0 ± 0.3 months of baseline ultrasonography. Causes of ESRD were chronic glomerulonephritis in 17 patients (32.7%), hypertension in 12 (23.1%), polycystic kidney disease in 2 (3.8%), and other (or unknown) causes in 21 (40.4%). Patients with diabetes mellitus, malignancy, autoimmune disease, general infection sign (fever, leukocytosis) and CAPD related infection (exit site infection, peritonitis) in the recent 6 months were excluded to avoid the potential confounding effects of these comorbid conditions. In addition, patients who had a history of coronary artery disease, cerebrovascular disease and/or peripheral vascular disease, and CAPD duration less than 6 months were not included. All patients received PD using a glucose-based lactate buffered solution. Informed consents were obtained from all study subjects.
Carotid ultrasonography
In all patients, both carotid arteries were examined with a duplex scanner (Toshiba, Tokyo, Japan) using a 7.5 MHz linear array transducer. All scans, both baseline and follow-up, were performed by the same trained sonographer.
Each subject was examined in the supine position in a semi-dark room. The far wall of the CCA-IMT, 0.5–1.0 cm proximal to the beginning of the carotid bulb, was used for measurements of CCA-IMT and lumen diameter. The CCA-IMT was defined as the distance between the leading edge of the lumen-intima echo and the leading edge of the media-adventitia echo. The lumen diameter was defined as the distance between the leading edge of the intima-lumen echo of the near wall and that of the lumen-intima echo of the far wall. The mean values of the CCA-IMT and lumen diameter were calculated from at least two measurements for each artery. A carotid plaque was defined as a localized intima-media thickening of greater than 1 mm with a minimum 100% increase in thickness compared with adjacent wall segments. The cross-sectional intima-media area (cIM area) of the artery was calculated using the following formula: 3.14 x [(lumen diameter/2 + CCA-IMT)2 – (lumen diameter/2)2] [8].
We measured the mean CCA-IMT at the onset and end of the study and evaluated the difference in the CCA-IMT over 36 months. For the assessment of factors that affect changes in CCA-IMT, the patients were divided into two groups, the progressors and non-progressors, based on the mean annual increment of CCA-IMT (CCA-IMT, mm/year). Progressors were defined as those with a mean annual CCA-IMT 0.015 mm/year, whereas non-progressors as those with a CCA-IMT < 0.015 mm/year according to the result of the meta-analysis which estimated the mean annual change in CCA-IMT among control groups from 13 published randomized placebo-controlled studies [7].
Biochemical analyses
A blood sample was drawn after a 12-h fast on the same day of the baseline carotid ultrasonography examination. Haemoglobin (g/dL), haematocrit (%), creatinine (mg/dL), albumin (g/dL), total cholesterol (mg/dL), triglyceride (mg/dL), high-density lipoprotein (HDL)-cholesterol (mg/dL), calcium (mg/dL) and phosphate (mg/dL) were measured. The enzymatic method was used to measure total cholesterol and triglyceride. The results were analyzed using a Hitachi 736–40 automated analyzer. HDL-cholesterol was measured by selective inhibition and the direct enzymatic method (Daichii, Tokyo, Japan) and low-density lipoprotein (LDL)-cholesterol was estimated by the Friedewald formula: LDL-cholesterol (mg/dL) = total cholesterol (mg/dL) – HDL-cholesterol (mg/dL) – triglyceride (mg/dL) / 5. CRP, hsCRP and IL-6 were measured as indicators of chronic inflammation. hsCRP was measured by a BNII nephelometer analyzer (Dade Behring Inc., Newark, DE, USA). Serum IL-6 (Pierce endogen, Rockford, Italy), ICAM-1 and VCAM-1 (R&D system Europe Ltd, Abingdon, UK) levels were measured by enzyme-linked immunosorbent assay (ELISA).
IgA and IgG antibodies to Cp were measured by ELISA (Bioclone, Sydney, Australia). The index value for distinguishing between positive and negative samples was calculated from the formula
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Seropositivity of IgG and IgA to Cp was defined as an index value > 1.10. The sensitivity and specificity of Cp IgG and IgA by ELISA compared to microimmunofluorescence (MIF) assay were as follows: The sensitivity was 90.4% for detecting IgG and 84.6% for IgA, and the specificity was 89.9% for detecting IgG and 86.7% for IgA [9].
Statistical analysis
All the statistics were performed with SPSS (Windows release 12.0) for personal computers. P-values less than 0.05 were considered statistically significant. Data were expressed as mean ± standard deviation. Differences between the two groups were analyzed by the Student's t-test and the Chi-square test and among three or more groups by ANOVA. A multiple regression analysis was used to examine the relationship between atherosclerotic change and select variables.
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Results |
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Demographic characteristics and biochemical data
Clinical and biochemical data from the study populations are shown in Table 1.
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Changes in carotid duplex ultrasonography parameters
A significant increase in the mean values of CCA-IMT (0.74 ± 0.11 versus 0.79 ± 0.12 mm, P < 0.001), and the cIM area (19.99 ± 4.57 versus 22.66 ± 5.12 mm2, P < 0.001) were noted between baseline and follow-up measurements. The mean annual
CCA-IMT was 0.015 ± 0.018 mm/year. The percentage of patients with carotid plaques did not change significantly (Table 2). To analyze factors that affect changes in CCA-IMT, patients were divided into two groups according to the change in CCA-IMT. In the progressors (annual CCA-IMT 0.015 mm/year, n = 31), the mean CCA-IMT significantly increased from 0.74 ± 0.12 mm to 0.82 ± 0.12 mm (P < 0.001) and the mean cIM area significantly increased from 20.00 ± 4.84 mm2 to 23.68 ± 5.06 mm2 (P < 0.001). The proportion of patients with carotid plaque increased, but was not statistically significant (Table 3). The mean annual CCA-IMT was significantly higher in the progressors than in the non-progressors (0.028 ± 0.010 versus –0.005 ± 0.001, P < 0.01).
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Clinical and biochemical parameters in the CCA-IMT progressors and non-progressors
There were no significant differences in age, sex, smoking, body mass index, mean arterial pressure, haemoglobin, haematocrit, albumin, calcium, phosphorus, intact parathyroid hormone, total cholesterol and triglyceride level between the progressors and the non-progressors. However, the progressors had lower HDL-cholesterol levels than the non-progressors (41.5 ± 11.8 versus 50.1 ± 16.7 mg/dL, P < 0.05). LDL-cholesterol was higher in the progressors, but was not statistically significant (P = 0.07). Among indicators of Cp infection and inflammation, CRP, hsCRP, IgG antibody index to Cp and VCAM-1 were higher in the progressors but not with statistical significance. However, log IL-6 (0.90 ± 0.69 versus 0.32 ± 0.43, P < 0.001), IgA antibody index to Cp (1.37 ± 0.64 versus 0.97 ± 0.33, P < 0.01) and ICAM-1 level (294.29 ± 96.81 versus 241.58 ± 79.09 ng/mL, P < 0.05) were significantly higher in the progressors than the non-progressors (Table 4). Also prevalence of seropositivity of IgA to Cp was significantly higher in the progressors (58.1 versus 28.6%, P < 0.05), whereas seropositivity of IgG to Cp was not different.
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On multiple logistic regression analysis adjusted for age, sex, log IL-6, Cp IgA antibody index, HDL-cholesterol and ICAM-1, the Cp IgA index [HR = 1.54 per 0.1 increase (1.07–2.22), P = 0.019] and log IL-6 [HR = 1.24 per 0.1 increase (1.04–1.54), P = 0.046] were independent risk factors of CCA-IMT progression, while ICAM-1, HDL-cholesterol and body mass index were not. When the Cp IgA antibody index was replaced by Cp IgA seropositivity, Cp IgA seropositivity [HR = 8.32 (1.28–54.14), P = 0.027] was the only independent risk factor of CCA-IMT progression (Table 5).
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Magnitude of CCA-IMT progression and traditional risk factors
The mean annual
CCA-IMT (m/year) showed a signifi- cant positive correlation with the initial body mass index (r = 0.320, P < 0.05) and LDL-cholesterol (r = 0.335, P < 0.05), and a negative correlation with HDL-cholesterol (r = –0.392, P < 0.01) (Figure 1). In contrast, there was no significant association between mean annual CCA-IMT and age, mean arterial pressure, haemoglobin, albumin, total cholesterol and triglyceride (data not shown).
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Magnitude of CCA-IMT progression and Cp infection, inflammatory markers
The annual
CCA-IMT was significantly correlated with the IgA antibody index to Cp (r = 0.392, P < 0.01), ICAM-1 (r = 0.347, P < 0.05) and log IL-6 (r = 0.400, P < 0.01) (Figure 2). However, no significant correlations were found between the mean annual CCA-IMT and CRP, hsCRP, IgG antibody index to Cp and VCAM-1 (data not shown). A stepwise multiple linear regression analysis showed that index of Cp IgA antibody and HDL-cholesterol were independently associated with the mean annual CCA-IMT (P < 0.05) after adjustment for age, body mass index, log IL-6, ICAM-1 and LDL-cholesterol (Table 6).
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Changes in carotid duplex ultrasonographic findings and differences of baseline risk factors between Cp IgA seropositive and seronegative patients
Cp IgA seropositive patients (n = 24) showed significantly higher mean annual
CCA-IMT (0.020 ± 0.019 versus 0.010 ± 0.016 mm/year, P < 0.05) and log IL-6 levels (0.80 ± 0.67 versus 0.49 ± 0.45, P < 0.05) than seronegative patients (Figure 3). The mean annual cIM area was higher in seropositive patients, but did not reach statistical significance. Among traditional and non-traditional risk factors, only log IL-6 was significantly higher in IgA seropositive patients (0.80 ± 0.69 versus 0.49 ± 0.45, P < 0.05). Moreover, when patients were stratified into four groups according to Cp IgA serology status and IL-6 levels (high log IL-6 0.455: median value of log IL-6; low log IL-6 < 0.455), the magnitude of the annual CCA-IMT was highest in the Cp IgA seropositive and high log IL-6 group (0.030 ± 0.009 mm/year, n = 14) (versus IgA seronegative and low log IL-6 group, n = 16, 0.008 ± 0.017 mm/year, P < 0.01; versus IgA seronegative and high log IL-6 group, n = 12, 0.013 ± 0.015 mm/year, P < 0.05; versus IgA seropositive and low log IL-6 group, n = 10, 0.006 ± 0.020 mm/year, P < 0.01) (Figure 4).
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P < 0.05 versus IgA seropositive and high log IL-6. IMT: intima-media thickness; Cp: Chlamydia pneumoniae; IL-6: interleukin-6. |
Discussion |
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Chronic persistent infection in dialysis patients, a non-traditional cardiovascular risk factor, could have rationale accounting for the atherogenic property of chronic inflammation. Many reports have suggested that infectious agents can evoke cellular and molecular changes that might cause or accelerate the atherosclerotic process. Among these pathogens, Cp, a Gram-negative obligate intracellular bacterium, has the strongest epidemiological evidence for an association with cardiovascular and cerebrovascular disease [1]. Cp is a common respiratory pathogen responsible for a wide range of chronic inflammatory conditions. It could be disseminated inside monocytes and macrophages from the respiratory tract to susceptible tissues including arteries. Indeed, local infection of Cp, as determined by the presence of chlamydial DNA, antigens or elementary bodies was found in 52% of atheromatous lesions but in only 5% of control samples [1]. In addition, there are several experimental evidences about initiation or progression of atherosclerosis by Cp infection. Cp infection in human monocytic cells induces various cytokines, such as tumor necrosis factor-
, IL-1 and IL-6 that are associated with the development of inflammation and atherosclerosis in an in vitro study [10]. Also, Kalayoglu et al. demonstrated that Cp lipopolysaccharide induced the foam-cell formation of macrophages that is one of the important processes of early atherosclerosis [11]. Moreover, Cp secretes a protease-like activity factor for degrading host cell transcription factors, which is required for major histocompatibility complex antigen expression. This mechanism may help the organism evade host immunity resulting in chronic persistent infection [12]. In addition to these in vitro studies, Cp infection was demonstrated to accelerate the complex atherosclerotic lesions in an in vivo study with Apo E3-leiden mice [13]. In spite of these quite strong experimental evidences, there have been controversies over seroepidemiological studies on ESRD patients and the general population regarding the atherogenic properties of Cp and its significance as a risk factor for cardiovascular morbidity and mortality. In ESRD patients, several prospective trials demonstrated higher cardiovascular morbidity and mortality rates in Cp seropositive patients compared to seronegative patients [5,6]. Moreover, Kato et al. have reported in a cross-sectional study that IgA antibody titer to Cp in patients on haemodialysis has a positive correlation with the maximal diameter of carotid artery plaques [3]. They later suggested IgA seropositivity to Cp as an independent risk factor for IMT progression in haemodialysis patients in a prospective study over 4 years [4]. The important or considerable role of Cp in atherosclerosis was further supported by the prospective study by Nishimura et al. They showed that Cp IgA seropositivity by the ELISA method is an independent risk factor for coronary artery stenosis on angiography in haemodialysis patients [14]. In accordance with these reports, our data clearly indicated that Cp IgA seropositivity is an independent risk factor for CCA-IMT progression, and the level of IgA antibody index to Cp has a significant positive correlation with the severity of CCA-IMT progression after adjustment for traditional risk factors and the levels of inflammatory markers. Cp IgA antibodies have a very short half-life; thus, IgA seropositivity is considered as a better marker for chronic infection or recent re-infection. A report of meta-analysis indicated that IgA seropositivity has a stronger association with coronary heart disease than IgG seropositivity [15]. On the other hand, a recent prospective observational study for patients on haemodialysis showed that Cp seropositivity does not increase all-cause and cardiovascular mortality [16]. In addition, in a univariate analysis Zoccali et al. reported that Cp IgA seropositivity is associated with higher cardiovascular mortality and morbidity in patients on haemodialysis, but this effect lost its statistical significance after adjustment for conventional risk factors, such as age, smoking, diabetes and hypercholesterolaemia [17]. These two studies implied that serologic assessment by the detection of Cp antibody might not have clinical availability for the risk factor of atherosclerosis in patients maintaining haemodialysis. However, these results cannot refute the capability of Cp to induce atherosclerosis as proven by in vitro and in vivo experimental studies [10–13]. This might be due to the methodological limitation of the serologic assay alone to detect vascular Cp infection. Because this organism is difficult to culture and neither pathologic diagnosis from arterial tissue nor Cp DNA detection by polymerase chain reaction (PCR) in cultured peripheral blood mononuclear cells is possible for clinical application, antibody detection by serologic assay is currently the only clinically available method and routine approach to identify Cp infection. However, several reports suggested that this method has a higher prevalence of positive results than other methods of Cp identification, such as DNA detection by PCR and culture in the general population as well as in ESRD patients. Also, there is a lack of evidence for an association between local vascular infection and positive serology [18]. Although serologic assay of Cp alone could be considered less valid based on these conflicting reports, Cp seropositivity limited to high inflammatory status could obtain clinical significance with the hypothesis that Cp infection leads to the pathogenesis of atherosclerosis by causing chronic inflammation. In addition, seroepidemiological studies for ESRD patients found a positive correlation between Cp IgA titer and IL-6 level, which is the most potent atherogenic pro-inflammatory cytokine and a growth factor for vascular smooth muscle cell [3]. Higher IL-6 levels were also observed in IgA seropositive patients compared with negative patients [19]. Our results showed that IL-6 is significantly higher in Cp IgA seropositive patients in accordance with the previous reports. CCA-IMT progression was highly enhanced in Cp IgA seropositive patients, especially in high inflammatory status assessed by IL-6 but not in patients with low inflammatory status. These findings suggest that Cp may trigger the production of this pro-inflammatory, atherogenic cytokine resulting in the aggravation of atherosclerosis or at least it can be speculated that this organism accelerates the process of atherosclerosis only in the case of high inflammatory status. Thus, it is possible that the serologic assay of Cp combined with the measurement of inflammatory markers especially IL-6 could be of help in predicting the progression of atherosclerosis in patients undergoing CAPD. The limitations of this study should be considered. First, we used an ELISA method to detect antibodies of Cp, not a MIF assay. Although the MIF method is recommended for serologic assays because of its high sensitivity and specificity, the interpretation of the results can be time consuming, subjective and have poor reproducibility [20]. On the other hand, the ELISA method is relatively simple, more objective, reproducible and clinically applicable due to the photometrical interpretation method used to detect Cp. Second, we relied on a single blood sample from each patient and thus cannot account for a possible variation in IgA seropositivity and IgA antibody index to Cp over time. However, we excluded the patients who had symptoms and signs of acute infection. Therefore, initial IgA antibody seropositivity and index were not related to acute infection of Cp, but reflect a chronic persistent infection. Third, only 52 patients were studied and our data need to be confirmed in a larger group.
In conclusion, the present study showed that Cp IgA seropositivity in high inflammation status might be an important clinical risk factor for atherosclerosis in patients undergoing CAPD, and the Cp serologic test by the ELISA method in combination with a test for IL-6 level could be a useful predictor of future atherosclerosis.
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Acknowledgments |
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Conflict of interest statement. None declared.
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Notes |
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* The results presented in this paper have not been published previously in whole or part, except in abstract form.
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References |
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- Danesh J, Collins R, Peto R. Chronic infections and coronary heart disease: is there a link? Lancet (1997) 350:430–436.[CrossRef][Web of Science][Medline]
- Wszola M, Kwiatkowski A, Nosek R, et al. Chlamydia pneumoniae infection and ischemic heart disease in hemodialysis patients. Transplant Proc (2006) 38:31–34.[CrossRef][Web of Science][Medline]
- Kato A, Odamaki M, Takita T, et al. Association between interleukin-6 and carotid atherosclerosis in hemodialysis patients. Kidney Int (2002) 61:1143–1152.[CrossRef][Web of Science][Medline]
- Kato A, Takita T, Maruyama Y, Hishida A. Chlamydial infection and progression of carotid atherosclerosis in patients on regular haemodialysis. Nephrol Dial Transplant (2004) 19:2539–2546.
[Abstract/Free Full Text] - Haubitz M, Brunkhorst R. C-reactive protein and chronic Chlamydia pneumoniae infection–long-term predictors for cardiovascular disease and survival in patients on peritoneal dialysis. Nephrol Dial Transplant (2001) 16:809–815.
[Abstract/Free Full Text] - Paniagua R, Frias Y, de Ventura MJ, et al. C-reactive protein and anti-Chlamydia pneumoniae antibodies as risk factors of cardiovascular death in incident patients on peritoneal dialysis. Perit Dial Int (2003) 23:132–137.
[Abstract/Free Full Text] - Bots ML, Evans GW, Riley WA, et al. Carotid intima-media thickness measurements in intervention studies: design options, progression rates, and sample size considerations: a point of view. Stroke (2003) 34:2985–2994.
[Abstract/Free Full Text] - Lemne C, Jogestrand T, de Faire U. Carotid intima-media thickness and plaque in borderline hypertension. Stroke (1995) 26:34–39.
[Abstract/Free Full Text] - Numazaki K, Ikebe T, Chiba S. Detection of serum antibodies against Chlamydia pneumoniae by ELISA. FEMS Immunol Med Microbiol (1996) 14:179–183.[CrossRef][Web of Science][Medline]
- Heinemann M, Susa M, Simnacher U, et al. Growth of Chlamydia pneumoniae induces cytokine production and expression of CD14 in a human monocytic cell line. Infect Immun (1996) 64:4872–4875.[Abstract]
- Kalayoglu MV, Byrne GI. A Chlamydia pneumoniae component that induces macrophage foam cell formation is chlamydial lipopolysaccharide. Infect Immun (1998) 66:5067–5072.
[Abstract/Free Full Text] - Fan P, Dong F, Huang Y, et al. Chlamydia pneumoniae secretion of a protease-like activity factor for degrading host cell transcription factors required for major histocompatibility complex antigen expression. Infect Immun (2002) 70:345–349.
[Abstract/Free Full Text] - Ezzahiri R, Nelissen-Vrancken HJ, Kurvers HA, et al. Chlamydophila pneumoniae (Chlamydia pneumoniae) accelerates the formation of complex atherosclerotic lesions in Apo E3-Leiden mice. Cardiovasc Res (2002) 56:269–276.
[Abstract/Free Full Text] - Nishimura M, Hashimoto T, Kobayashi H, et al. Close association of Chlamydia pneumoniae IgA seropositivity by ELISA with the presence of coronary artery stenosis in haemodialysis patients. Nephrol Dial Transplant (2005) 20:1944–1950.
[Abstract/Free Full Text] - Arcari CM, Gaydos CA, Nieto FJ, et al. Association between Chlamydia pneumoniae and acute myocardial infarction in young men in the United States military: the importance of timing of exposure measurement. Clin Infect Dis (2005) 40:1123–1130.[CrossRef][Web of Science][Medline]
- Kato A, Takita T, Furuhashi M, et al. Association between seroprevalence of anti-chlamydial antibodies and long-term cardiovascular mortality in chronic hemodialysis patients. Atherosclerosis (2006) 188:120–125.[CrossRef][Web of Science][Medline]
- Zoccali C, Mallamaci F, Tripepi G, et al. Chlamydia pneumoniae, overall and cardiovascular mortality in end-stage renal disease (ESRD). Kidney Int (2003) 64:579–584.[CrossRef][Web of Science][Medline]
- Tsirpanlis G. Chlamydia pneumoniae and atherosclerosis: no way-out or long way? What about renal failure patients? Kidney Blood Press Res (2004) 27:134–142.[CrossRef][Web of Science][Medline]
- Stenvinkel P, Heimburger O, Jogestrand T. Elevated interleukin-6 predicts progressive carotid artery atherosclerosis in dialysis patients: association with Chlamydia pneumoniae seropositivity. Am J Kidney Dis (2002) 39:274–282.[Web of Science][Medline]
- Verkooyen RP, Willemse D, Hiep-van Casteren SC, et al. Evaluation of PCR, culture, and serology for diagnosis of Chlamydia pneumoniae respiratory infections. J Clin Microbiol (1998) 36:2301–2307.
[Abstract/Free Full Text]
Accepted in revised form: 7. 9.07
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