Chlamydia pneumoniae seropositivity and early carotid atherosclerosis in a suburban Japanese population

To evaluate the association between Chlamydia pneumoniae (C. pneumoniae) infection and carotid atherosclerosis (CA), we investigated CA assessed by carotid B-mode ultrasound and known or suspected atherosclerotic risk factors including C. pneumoniae IgG and IgA antibodies in 2410 residents (mean age 54.5+/-13.6 years, 697 men) of a suburban Japanese town. CA was found in 30.1% of men and in 14.0% of women, IgG in 59.4% and in 51.4%, and IgA in 36.9% and in 32.4%, respectively. In univariate analysis, most conventional atherosclerotic risk factors and IgA antibody were significantly associated with CA in both sexes, but not IgG. In multivariate logistic regression analysis, independent risk factors for CA were confirmed with age and triglycerides (TG) in men and age, systolic blood pressure, pack-years of smoking, and low-density lipoprotein cholesterol (LDL-C) in women, but not IgG and IgA in either sex. These results do not support C. pneumoniae infection as an important risk factor for CA in this Japanese population.     

An association between an antibody against Chlamydia pneumoniae and common carotid atherosclerosis

OBJECTIVE: Chlamydia pneumoniae (C. pneumoniae) is an important pathogen for infections of the respiratory tract, and there are recently also a number of reports suggesting its relation with atherosclerosis. This study was performed to clarify the relation between C. pneumoniae infection and sclerotic lesions of the common carotid arteries. METHODS AND PATIENTS: We evaluated sclerotic lesions of common carotid arteries by ultrasonography in 147 in-patients (mean age, 70 years; 95% confidence interval, 68-72) in the internal medicine ward, and studied the relation of the known risk factors for atherosclerosis including C. pneumoniae infection. An ultrasonograph and 7.5 MHz linear type B-mode probe were used by a specialist to evaluate sclerotic lesions of common carotid arteries. C. pneumoniae infection was determined by measuring anti-C. pneumoniae IgG specific antibody level (IgG index) using enzyme-linked immunosorbent assay (ELISA) method with serum of fasting blood, which had been preserved at -70 degrees C. RESULTS: IgG index (p=0.0263), from multiple regression analysis using various risk factors as explanatory variables, was a significant independent contributing factor (R2=0.3465, p<0.0001) along with known risk factors such as male (p=0.0289), age (p=0.0007), Brinkman index (p=0.0067), hypertension (p=0.0443) and T-Chol (p=0.0220). CONCLUSION: This study confirmed that the observations of an association between antibody against C. pneumoniae and common carotid atherosclerosis in Western nations is also present in Japan. Our results suggests that C. pneumoniae infection is also an important risk factor for common carotid atherosclerosis.     

Lack of association between Chlamydia pneumoniae seropositivity and aortic atherosclerotic plaques: a population-based transesophageal echocardiographic study

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 >or=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 (>or=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 >or=4 mm thick (p = 0.99), plaques >or=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.     

The relation between Chlamydia pneumoniae and atherosclerosis.

Dilatation of the brachial artery occurs after flow is increased, and an attenuation in this response is seen in subjects with cardiovascular risk factors, and in those with established coronary artery disease. The mechanisms linking ischaemia, flow changes, and brachial artery dilatation are unclear, and it is not known how these are affected by arterial disease. For the present it might be more appropriate to refer to flow associated rather than flow mediated dilatation, to describe the phenomenon in the brachial artery. Despite these caveats, the non-invasive measurement of brachial artery following ischaemic dilatation represents a significant advance, and its suitability as a surrogate marker for coronary artery dysfunction appears promising. The technique has potential as a tool for screening those at high risk of vascular disease, and as a surrogate endpoint in intervention studies. Further research should clarify the mechanisms involved, and lead to greater insights into the nature of endothelial dysfunction and cardiovascular disease.     

Limited association of Chlamydia pneumoniae detection with coronary atherosclerosis

The association of Chlamydia pneumoniae (C. pneumoniae) detection with atherosclerosis has been controversial because of recent conflicting results. In order to assess how and to what extent C. pneumoniae detection contributes to atherosclerosis, the association between immunohistochemical detection of C. pneumoniae antigen, intimal lesions, and the intimal thickening ratio was examined in 1674 left anterior descending coronary arterial segments from 100 autopsied Japanese patients being free from coronary heart disease. These specimens contained full spectrum of atherosclerotic lesions as defined by the American Heart Association classification. The intimal thickening ratio increased in C. pneumoniae-positive sections comparing to that in C. pneumoniae-negative sections only in the group with normal intima and diffuse intimal thickening, but there was no such association in the other advanced intimal lesion groups. Furthermore, in 50 C. pneumoniae-positive cases out of 100 investigated, the frequency and extent of immunoreactivity did not associate with progression of intimal lesions or the intimal thickening ratio, and the mean score of C. pneumoniae detection did not correlate with the mean intimal thickening ratio in individual cases. These results suggest only a limited association between C. pneumoniae detection and coronary atherosclerosis development and that C. pneumoniae does not influence promotion of atherosclerotic lesions. The role of C. pneumoniae on atherogenesis may be limited only at the beginning stage of atherosclerosis development.     

Chlamydia pneumoniae and atherosclerosis

Chlamydia pneumoniae is the third species of the genus Chlamydia and has been known to cause respiratory tract infections. Since the association between the seropositivity of C. pneumoniae and ischemic heart diseases was reported in 1988, the association between C. pneumoniae and atherosclerosis has been noteworthy. Positive findings of the association between C. pneumoniae and atherosclerosis have been reported as the result of seroepidemiological surveys, histological studies to detect C. pneumoniae in human atherosclerotic tissues, and animal infection models. These data supported that C. pneumoniae infection occurs in human vascular walls and may accelerate the foam cell formation of macrophage and smooth muscle cells, and may play a causative role in atherosclerosis. Several large-scale studies of the antimicrobial prevention of secondary cardiac events are in progress. The genome projects for C. pneumoniae have recently been reported. A number of issues remain unclear, however, and further intensive research is necessary.     

Chlamydia pneumoniae and atherosclerosis

Chlamydia pneumoniae (C. pneumoniae) is a common respiratory pathogen. Many reports have documented the presence of C. pneumoniae in atheromatous coronary arteries, aorta, carotid arteries, and peripheral arteries using a variety of techniques. There is clear experimental evidence that C. pneumoniae can infect macrophages, endothelial cells, smooth muscle cells, and induce the formation of foam cells. Evidence from basic research and epidemiologic studies suggest that C. pneumoniae can induce macrophage foam cell formation by dysregulating native LDL uptake or metabolism (or both). Relatively small, secondary prevention studies, have suggested that antibiotic therapy might reduce monocyte activation and C. pneumoniae antibody titers, reduce inflammatory markers and possibly reduce adverse cardiovascular events. It is possible that C. pneumoniae enhances atherogenesis by causing inflammation and eliciting immune responses and may be one of the factors contributing to this multifactorial disease process.     

Chlamydia pneumoniae and atherosclerosis

Chlamydia pneumoniae is a human respiratory pathogen that causes acute respiratory disease. Multiple studies have associated C. pneumoniae with cardiovascular disease including seroepidemiologic studies, direct detection of the organism within the lesion, and isolation of the organism from atheromatous tissue. The most critical question to be answered by researchers in the field is whether C. pneumoniae plays a role in atherogenesis. This review summarizes in vitro studies, results in animal models of C. pneumoniae infection and atherogenesis, and human intervention studies that provide some support of a mechanistic role.     

Chlamydia pneumoniae and atherosclerosis

OBJECTIVE: To review the literature for evidence that chronic infection with Chlamydia pneumoniae is associated with atherosclerosis and acute coronary syndromes. DATA SOURCES: MEDLINE and Institute of Science and Information bibliographic databases were searched at the end of September 1998. Indexing terms used were chlamydi*, heart, coronary, and atherosclerosis. Serological and pathological studies published as papers in any language since 1988 or abstracts since 1997 were selected. DATA EXTRACTION: It was assumed that chronic C pneumoniae infection is characterised by the presence of both specific IgG and IgA, and serological studies were examined for associations that fulfilled these criteria. Pathological studies were also reviewed for evidence that the presence of C pneumoniae in diseased vessels is associated with the severity and extent of atherosclerosis. DATA SYNTHESIS: The majority of serological studies have shown an association between C pneumoniae and atherosclerosis. However, the number of cases in studies that have reported a positive association when using strict criteria for chronic infection is similar to the number of cases in studies which found no association. Nevertheless, the organism is widely found in atherosclerotic vessels, although it may not be at all diseased sites and is not confined to the most severe lesions. Rabbit models and preliminary antibiotic trials suggest that the organism might exacerbate atherosclerosis. CONCLUSION: More evidence is required before C pneumoniae can be accepted as playing a role in atherosclerosis. Although use of antibiotics in routine practice is not justified, large scale trials in progress will help to elucidate the role of C pneumoniae.     

Chlamydia pneumoniae and atherosclerosis

There is widespread consensus that atherosclerosis is an inflammatory disease. Between possible pathogenetic mechanisms, infective hypothesis has received increasing attention. Researches have recently focused their attention on the role of Chlamydia pneumoniae, a gram-negative intracellular organism, as infection by this bacterium has been demonstrated frequently associated with atherosclerosis. This review attempts to analyze and critically evaluate available data of the literature about the association between Chlamydia pneumoniae and atherosclerosis in order to provide updated elements of judgement concerning a possible future revolutionary scenario: the consideration of atherosclerosis as an infective disease, susceptible to prevention and treatment by means of antimicrobial therapy. More than twenty sero-epidemiological studies have found a two-fold or greater risk of cardiovascular events in subjects with serological evidence of Chlamydia pneumoniae infection. The organism has been identified in over 50% of atherosclerotic plaques examined by various histopathological techniques, while it has been only rarely found in normal artery tissues; moreover, viable Chlamydia pneumoniae has recently been isolated from coronary and carotid atherosclerotic plaques. Several experimental studies have shown that the biological properties of Chlamydia pneumoniae can explain its potential role in initiating and/or modulating plaque formation. The most relevant issue, i.e. the possibility of preventing or slowing progression of the disease with antimicrobial treatment, is still unsolved: only data from experimental studies on animals and four small intervention trials on humans are available, and their encouraging results require confirmation in larger prospective studies. In conclusion, while the association between Chlamydia pneumoniae and atherosclerosis seems to be established, it is still uncertain whether or not the organism plays a causal role in atherosclerosis and its complications. It is hoped that the results of wide scale clinical intervention trials with antibiotics for the secondary prevention of atherosclerotic diseases now in progress will clarify this problem.     

Lack of association between serum gamma-glutamyltransferase and carotid atherosclerosis: The Namwon study

Objectives: There is little evidence for an association between gamma-glutamyltransferase (GGT) and carotid atherosclerosis, an independent predictor of cardiovascular disease. We examined the association between serum GGT and carotid atherosclerotic parameters, including carotid intima-media thickness (IMT) and plaques, in a large general population. Methods: The study population consisted of community-dwelling adults who participated in the baseline survey of the Namwon Study. A total of 9120 subjects aged 45–74 years were included in the analyses. High-resolution B-mode ultrasound was used to measure carotid IMT and to evaluate the presence of carotid plaques. A mean carotid IMT of ≥1.0 mm was classified as ‘high carotid IMT’. Results: Serum GGT levels were classified into quartiles. In a fully adjusted model, we found no linear trend between GGT quartile and mean carotid IMT (P for trend = 0.167). Compared with the first quartile (the reference category), the odds ratios (ORs) and 95% confidence intervals (CIs) for high carotid IMT were 0.89 (0.68–1.16), 1.10 (0.84–1.43), and 0.97 (0.71–1.33) for the second, third, and fourth quartiles (P for trend = 0.754), respectively. The ORs (95% CIs) for carotid plaques were 0.89 (0.77–1.02), 0.95 (0.82–1.10), and 0.94 (0.79–1.11) for the second, third, and fourth quartiles, respectively, in the fully adjusted model (P for trend = 0.644). Conclusions: No significant association of GGT concentration with carotid IMT or plaques was found in this large cross-sectional study. Further longitudinal studies are needed to confirm our findings.     

The evolving relationship between Chlamydia pneumoniae and atherosclerosis

A body of evidence supports an association between Chlamydia pneumoniae and atherosclerosis. Recent prospective, seroepidemiologic studies have refined estimations of relative risk. Advances in diagnostic testing with the polymerase chain reaction have created a potential opportunity to screen for infected individuals. New insights into the pathogenesis of infection with C. pneumoniae have been reported, many of which are relevant to the development of atherosclerotic plaque. Clinical trials have now been initiated and should provide guidance as to the utility of antibiotics in the treatment or prevention of coronary artery disease.     

Chlamydia pneumoniae in atherosclerosis

Chlamydia pneumoniae is currently the infectious agent most often associated with the inflammation found in atherosclerosis. The seroepidemiological association and the actual presence of pathogen in lesions has been confirmed in numerous studies, in which technical difficulties seem to be the only limitation. Besides animal experiments and intervention trials, we need information of possible pathogenic mechanisms. Recently, several studies have suggested mechanisms by which C. pneumoniae infection could participate in the development of atherosclerosis.     

高敏C反应蛋白和肺炎衣原体感染与颈动脉粥样硬化及缺血性脑卒中的相关性研究

目的探讨高敏C反应蛋白水平、肺炎衣原体抗体与颈动脉粥样硬化及缺血性脑卒中TOAST亚型的关系。方法缺血性脑卒中组135例,对照组135例,测定2组的高敏C反应蛋白水平、肺炎衣原体IgG抗体、颈动脉内膜中层厚度及颈动脉粥样硬化程度。结果(1)高敏C反应蛋白水平升高与颈动脉内膜中层厚度及颈动脉粥样硬化程度相关,OR值分别为3.44和6.82;高敏C反应蛋白水平升高与大动脉粥样硬化性脑卒中危险性升高相关,OR值为10.11。(2)肺炎衣原体抗体的阳性率与颈动脉内膜中层厚度及颈动脉粥样硬化程度相关,OR值分别为1.76和4.89。结论高敏C反应蛋白水平和慢性肺炎衣原体感染与颈动脉粥样硬化密切相关,同时高敏C反应蛋白水平升高,可增加发生大动脉粥样硬化性脑卒中的风险。     

Lack of association between prior infection with Chlamydia pneumoniae and acute or chronic coronary artery disease

BACKGROUND: Higher than normal serologic titers and the detection of bacteria within atheroma have suggested an association between Chlamydia pneumoniae (C. pneumoniae) infection and coronary heart disease (CHD), but the relationship has not been well established. HYPOTHESIS: The study was designed to establish a lack of relationship between chronic C. pneumoniae infection and CHD. METHODS: Chlamydia-specific IgG-antibody was assayed using an indirect immunofluorescence test in the serum of 159 patients with severe arterial disease and 203 patients with a heart valve prostheses and no demonstrable CHD. Fatal and nonfatal vascular events and systemic thromboembolism were recorded over a 2-year period. RESULTS: In the arterial group 107 patients (67.3%) and in the valvular group 120/203 (59.1%) were positive for C. pneumoniae antibody. The number of patients with fatal or nonfatal vascular events (double end point) in the arterial and valvular groups was 23 and 2, respectively (p < .0001). Triple end points (fatal plus nonfatal vascular events plus thromboembolism) were also more frequent in the arterial group (p < 0.002). The prevalence of chlamydia antibody positivity was the same in the arterial and valvular groups, and the occurrence of clinical events was also the same for chlamydia-positive (227 patients) as for chlamydia-negative (135 patients). After adjustment for confounding variables, only arterial disease was a predictive factor for double (OR 17.0; 95% CI 3.94-73.3) or triple (OR 3.12; 95% CI 1.56-6.25) end points. CONCLUSION: We find C. pneumoniae chronic infection not to be an independent risk factor for acute or chronic arterial disease.