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.     

Acute exacerbation of idiopathic pulmonary fibrosis: role of Chlamydophila pneumoniae infection

BACKGROUND AND OBJECTIVES: Patients with idiopathic pulmonary fibrosis (IPF) may experience acute exacerbations of their illness. The actual trigger(s) of such exacerbations is unknown. Chlamydophila pneumoniae infection can cause exacerbation of asthma and COPD. A prospective study was conducted to investigate the possible role of C. pneumoniae infection in triggering acute exacerbations of IPF. METHODS: A prospective observational study over 5 years of consecutive IPF patients who fulfilled the criteria for acute exacerbation. Sputum, blood cultures and acute and convalescent serology for C. pneumoniae IgG and IgA (ELISA) were performed. RESULTS: Previous infection with C. pneumoniae is common. Of the 27 study patients, 15 had a C. pneumoniae IgG index of 1.10-2.99 (positive) and 3 had a C. pneumoniae IgG index of >2.99 (strongly positive) at the time of presentation with an acute exacerbation. In addition, 15 subjects had a C. pneumoniae IgA index of 1.10-2.99 (positive) and 6 subjects had a C. pneumoniae IgA index of >2.99 (strongly positive). However, only two of the 15 subjects (13%) for whom paired sera were tested exhibited a significant rise in antibody response (change in index of 1.90 for C. pneumoniae IgG and 1.54 for IgA, respectively) indicating either acute or reactivated infection with C. pneumoniae. There were 15 deaths (56%) despite supportive care that included high-dose corticosteroid therapy and oxygen supplementation. CONCLUSIONS: Mortality is high with acute exacerbation of IPF. Acute infection with C. pneumoniae is uncommon at the time of presentation with acute exacerbation of IPF.     

Prospective study of Chlamydia pneumoniae IgG seropositivity and risks of future myocardial infarction

BACKGROUND: Chlamydia pneumoniae has been hypothesized to play a role in atherothrombosis. However, prospective data relating exposure to Chlamydia pneumoniae and risks of future myocardial infarction (MI) are sparse. METHODS AND RESULTS: In a prospective cohort of nearly 15 000 healthy men, we measured IgG antibodies directed against Chlamydia pneumoniae in blood samples collected at baseline from 343 study participants who subsequently reported a first MI and from an equal number of age- and smoking-matched control subjects who did not report vascular disease during a 12-year follow-up period. The proportion of study subjects with IgG antibodies directed against Chlamydia increased with age and cigarette consumption. However, prevalence rates of Chlamydia IgG seropositivity were virtually identical at baseline among men who subsequently reported first MI compared with age- and smoking-matched control subjects. Specifically, the relative risks of future MI associated with Chlamydia pneumoniae IgG titers >/=1:16, 1:32, 1:64, 1:128, and 1:256 were 1.1, 1.0, 1.1, 1.0, and 0.8, respectively (all probability values not significant). There was no association in analyses adjusted for other risk factors, evaluating early as compared with late events, or among nonsmokers. Further, there was no association between seropositivity and concentration of C-reactive protein, a marker of inflammation that predicts MI risk in this cohort. CONCLUSIONS: In a large-scale study of socioeconomically homogeneous men that controlled for age, smoking, and other cardiovascular risk factors, we found no evidence of association between Chlamydia pneumoniae IgG seropositivity and risks of future MI.     

Lack of association between seropositivity to Chlamydia pneumoniae and carotid atherosclerosis.

Since the Chlamydia pneumoniae (C. pneumoniae)-specific antibody was shown to be associated with acute myocardial infarction and chronic coronary heart disease, the role of C. pneumoniae in the etiology of cardiovascular disease has been studied by a number of groups. We investigated the association between the C. pneumoniae-specific antibody, measured by microimmunofluorescence, risk factors for cardiovascular disease, and atherosclerosis in a randomly selected urban population. Overall, immunoglobulin-G (IgG) seroprevalence to C. pneumoniae in this sample of 1,034 subjects was 58%, whereas IgA seroprevalence was 32%. There was a decline in seropositivity with age for IgG but not IgA. Men were more likely than women to be IgG (66% vs 51%, chi-square p = 0.001) and IgA seropositive (36% vs 28%, chi-square p = 0.005). Current smokers had higher IgA seropositivity than nonsmokers (43% vs 30%). Those patients with a family history of cerebrovascular disease were more likely to have IgG antibody than those without (75% vs 57%, chi-square p= 0.007). Neither IgG nor IgA seropositivity was associated with the standard risk factors of hypertension, hyperlipidemia, or family history of ischemic heart disease, nor was seropositivity associated with carotid intima medial thickening (IMT) or atherosclerotic plaque as measured by carotid B-mode ultrasound. There was no difference between those participants who were IgG or IgA seropositive and seronegative in measurements of mean IMT, prevalence of abnormal IMT, and percentage with atherosclerotic plaque. In conclusion, although C. pneumoniae was associated with several risk factors for cardiovascular disease in a large cross-sectional population, we found no independent association between seroprevalence to C. pneumoniae and carotid atherosclerosis as measured by carotid IMT.     

Assay of specific anti-Chlamydia pneumoniae antibodies by ELISA method. 3. Setting of serological criteria]

"HITAZYME C. pneumoniae" (or "HITAZYME CPN", for short) is a diagnostic reagent that has been recently developed by adopting an ELISA method for detection of anti-Chlamydia pneumoniae (C. pneumoniae) antibodies. When this reagent is used under a current diagnostic standard that has been set as a provisional standard, however, high antibody positive rates are often produced for both IgG and IgA even using the specimens of healthy persons. So, it is difficult to distinguish C. pneumoniae-infected patients from healthy persons. Therefore, this time, we tried to establish a new diagnostic standard by setting up of special cut-off values for a single serum and rise rates of antibody titers for paired sera to improve the accuracy for diagnosis of C. pneumoniae infection. For a single serum testing, we set a special cut-off value at ID 3.00 for both IgG and IgA, so that most healthy persons fall within the range of the "negative" zone. This value was based on the calculation of "Mean+2SD" using measurement results (or IDs) of healthy persons. When this cut-off value was applied, the rate of > or = ID 3.00 for either IgG or IgA was 7.6% for healthy persons, and 64.9% for infected patients. (The rate reached 76.4% when the highest IDs of multiple specimens taken from each patient for this test were used in calculation) As a diagnostic standard for a single serum, therefore, it was defined that: "If ID is 3.00 or greater for IgG and/or IgA, it is highly likely that the case has an acute or a present infection." Using paired sera, we could confirm almost a linear relationship between the results by HITAZYME CPN and those by micro-IF method. Under micro-If method, if the antibody titer increases four times or greater using paired sera, acute infection is diagnosed. As it was found that the four-fold increase in antibody titer corresponds to the increase of 1.35 in ID for IgG and 1.00 for IgA, we defined a diagnostic standard for paired sera as follows: "If ID increases by 1.35 or greater for IgG, and/or if ID increases by 1.00 or greater for IgA, the case may be diagnosed as acute infection."     

Chlamydia pneumoniae seropositivity and systemic and renovascular atherosclerotic disease

BACKGROUND: Patients with hypertension may be vulnerable to vascular Chlamydia pneumoniae and/or cytomegalovirus (CMV) infection because of increased expression of adhesion molecules. OBJECTIVE: To determine whether C pneumoniae or CMV is associated with the presence of atherosclerotic lesions in hypertensive patients. METHODS: Ninety-six angiographic studies on 100 consecutive patients with of clinical signs or symptoms suggestive of renovascular hypertension were reviewed for the presence or absence of atherosclerotic lesions at the level of the renal arteries as well and abdominal aorta. Also, the presence of a hemodynamically notable renal artery stenosis and antibodies to C pneumoniae (IgG and IgA) and CMV (IgG and IgM) was determined, and all classic risk factors were recorded. RESULTS: Atherosclerotic lesions were documented in 67 patients (70%), and in 49 patients (51%) such lesions were present at the level of the renal artery. In the univariate analysis, significant associations between IgG (odds ratio, 3.8; 95% confidence interval, 1.2-11.7; P =.02) as well as IgA (odds ratio, 2.6; 95% confidence interval, 1.1-6.7; P =.03) antibodies to C pneumoniae and the presence of atherosclerosis were found for both the aorta and the renal arteries. Seroprevalence (IgG) to C pneumoniae in the 23 patients with a hemodynamically notable renal artery stenosis was 100% and differed (P =.01) from those without a notable renal artery stenosis (78%). In the multivariate analysis, IgG seropositivity to C pneumoniae was significantly associated with atherosclerosis (odds ratio, 6.0; 95% confidence interval, 1.33-27.5; P =.02), and age. There was no association between CMV seropositivity and atherosclerosis. CONCLUSION: The presence of antibodies to C pneumoniae was significantly associated with atherosclerosis and renovascular disease in hypertensive patients in whom a renal artery stenosis was strongly suspected.     

Chlamydia pneumoniae infection is not involved in carotid artery stenosis

Recent studies have suggested the existence of a close relationship between Chlamydia pneumoniae infection and atherosclerosis. However, it has been speculated that C. pneumoniae infection is not associated with early atherosclerosis but with advanced atherosclerosis. In the present study, we test this hypothesis. In 524 consecutive patients who underwent cerebral angiography were recruited for the study. From the films obtained during angiography, percent stenosis of neck internal carotid artery was calculated according to the method of the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Serum C. pneumoniae IgG and IgA antibodies were measured by a commercial ELISA enzyme immunoassay kit. Cerebrovascular risk factors such as age, gender, hypertension, diabetes mellitus, hyperlipidemis and smoking were assessed by interview. Old age above 60 years and diabetes mellitus were found to be independent risk factors for carotid artery stenosis in this study after adjustment for cerebrovascular risk factors. When we defined carotid artery stenosis as the presence of greater than 30% stenosis of one artery, there was no association after adjustment for other risk factors between C. pneumoniae IgG and IgA seropositivity and the presence of carotid artery stenosis for any cut-off value of seropositivity. When we defined carotid artery stenosis as the presence of greater than 70%, there was also no association between C. pneumoniae IgG and IgA seropositivity and the presence of carotid artery stenosis for any cut-off value of seropositivity. These results suggest that C. pneumoniae infection is not associated with carotid artery atherosclerosis.     

Possible role of chronic infection with Chlamydia pneumoniae in Japanese patients with acute myocardial infarction

Chlamydia pneumoniae, a common human respiratory pathogen, has been implicated in the pathogenesis of coronary heart diseases (CHD) in several seroepidemiological studies. The present case-control study investigated the relation between serologic evidence of C. pneumoniae infection and CHD in a Japanese population. Two groups of cases were enrolled: 26 patients with acute myocardial infarction (AMI) and 46 patients with effort angina pectoris (e-AP). Their data were compared with 58 age-matched healthy controls and also compared with 53 patients with vasospastic angina (VSA) as pathological control subjects. Anti-C. pneumoniae specific IgA and IgG antibody titers were measured by enzyme-linked immunosorbent assay (ELISA). The mean indices of IgG-type antibody in AMI and e-AP were not significantly different from those in either the normal controls or VSA group. On the other hand, the mean indices of IgA-type antibody in AMI were significantly higher than in the normal controls (1.39+/-0.83 in AMI vs 0.84+/-0.58 in controls, p<0.001) and VSA (1.39+/-0.83 in AMI vs 1.05+/-0.61 in VSA, p<0.05) group. However, the differences in the IgA titers in the e-AP group compared with the normal controls did not reach a significant level. The odds ratio associated with the seropositivity of IgA for AMI against the normal controls was 3.89 (95% confidence interval (CI): 1.16-13.10) and that against VSA was 6.90 (95% CI: 1.73-27.52) after adjustment for risk factors for CHD and/or age, sex and smoking status. In 6 patients the elevated IgA titers were sustained even at 3 months after the episode of AMI. These results suggest that seropositivity for IgA-type antibody against C. pneumoniae may be a significant risk factor for the development of AMI. The possible mechanisms include chronic inflammation in the coronary artery due to persistent C. pneumoniae infection.     

Association of seropositivity for antibody to Chlamydia-specific lipopolysaccharide and coronary artery disease in Japanese men

Recent studies suggest an association between Chlamydia pneumoniae infection and coronary artery disease (CAD). To examine this relationship in Japanese men, serum IgA and IgG antibodies to Chlamydia-specific lipopolysaccharide were measured by enzyme-linked immunosorbent assay in 507 patients with CAD and 200 age-matched controls. CAD patients were divided into (1) 269 patients with myocardial infarction (MI) and (2) 238 patients with chronic coronary heart disease (CCHD). Compared with the control group, the CAD group did not differ in the prevalences of both antibodies (IgA: 23.7 vs 18.0%, p=0.10; IgG: 52.7 vs 51.0%, p=0.6). The index of IgG antibody was not significantly different between CAD and control groups (median 1.19 vs 1.18, p=0.3), whereas the index of IgA antibody was significantly higher in CAD than control group (median 0.60 vs 0.46, p<0.0001). Compared with the control group, the MI group had a significantly higher prevalence of IgA antibody (28.6 vs 18.0%, p=0.007); however, there was no difference in the prevalence of IgG antibody (58.0 vs 51.0%, p=0.13). The CCHD group did not differ in the prevalences of both antibodies (IgA: 18.1 vs 18.0%, p=0.9; IgG: 45.6 vs 51.0%, p=0.2). After the adjustment for coronary risk factors, odds ratios (ORs) of seropositive antibodies for CAD were 1.59 [95% confidence interval (CI): 0.88-2.87, p=0.12] for IgA seropositivity and 0.92 (95%CI: 0.58-1.47, p=0.7) for IgG seropositivity in all cases. In the MI and control groups, ORs of seropositive antibodies for MI were 2.67 (95%CI: 1.32-5.38, p=0.007) for IgA seropositivity, and 1.36 (95%CI: 0.79-2.36, p=0.2) for IgG seropositivity. This study discovered that IgA antibody to Chlamydia was significantly associated with CAD, especially with MI, in Japanese Men and the findings suggest that chronic infection of Chlamydia may be linked to the pathogenesis of MI.     

Chlamydophila pneumoniae infection status is dependent on the subtypes of asthma and allergy.

This study was undertaken to investigate the association of Chlamydophila pneumoniae infection (CPI) with asthma and allergy. One hundred forty-one patients with asthma aged 3-21 years, 125 healthy controls aged 3-21 years, and 62 allergic but nonasthmatic patients aged 4-20 years participated in this study. C. pneumoniae-specific antibodies were measured by ELISA. There were no significant differences in the percentage of patients positive for C. pneumoniae-specific antibodies between the three groups. Significantly more allergic asthmatic patients were positive for C. pneumoniae-specific IgA and IgA + IgG than nonallergic asthmatic patients, and this difference remained significant after adjustment for age and gender: adjusted odds ratio (OR) = 5.9 (1.7-26.2) and p = 0.01 for IgA, and OR = 5.2 (1.6-25.8) and p = 0.02 for IgA + IgG. The prevalence of the C. pneumoniae-specific IgA and the IgA + IgG positivity also was significantly lower in the nonallergic asthmatic group than in the allergic and control groups (p < 0.005). No food/drug-allergic patient was positive for C. pneumoniae-specific IgA, whereas 41.6% of the inhalative-allergic patients were positive for this antibody (p = 0.002). In our population CPI does not associate directly with asthma and allergy, but chronic or recurrent infection is associated with allergic asthma and inhalative allergy as opposed to nonallergic asthma and noninhalative allergy.     

Correlation of hyperhomocysteinaemia and Chlamydia pneumoniae IgG seropositivity with coronary artery disease in a general population

BACKGROUND: Both Chlamydia pneumoniae infection and hyperhomocysteinaemia have been assumed to increase the atherosclerotic risk independently of each other and independently of the classic risk factors. The correlation between hyperhomocysteinaemia, C. pneumoniae infection and coronary artery disease (CAD) have not been investigated in the general population. METHODS: In an ancillary study to the Persian Gulf Healthy Heart Study, a cohort study of men and women aged >or=25 years, a random sample of 1699 (48.9% males, 51.1% females) subjects were evaluated. Total homocysteine, high sensitivity C-reactive protein (CRP) and IgG antibodies to C. pneumoniae were determined by ELISA. Minnesota coding criteria of a 12-lead resting electrocardiogram was used for evaluation of CAD. RESULTS: A total of 12.4% of the subjects had electrocardiogram-defined (Minnesota-coding criteria) coronary artery disease. Hyperhomocysteinaemia (>14 micromol/l) and IgG seropositivity were found in 50.8% and 37.7%, respectively. Neither of hyperhomocysteinaemia nor C. pneumoniae IgG seropositivity showed a significant association with CAD after adjusting of sex and age. Concurrent elevated CRP level (>8.2mg/l) and C. pneumoniae seropositivity (chronic C. pneumoniae infection) had a significant association with CAD [OR=1.73, CI (1.09-2.75); p=0.01] after adjusting for age, sex, systolic and diastolic blood pressures, BMI, and serum levels of LDL-cholesterol, fasting blood sugar and triglyceride as covariates in a logistic regression model. This odds ratio increased to 2.11, CI (1.18-4.12; p=0.02) when concurrent hyperhomocysteinaemia and chronic C. pneumoniae infection, as a single covariate entity; was adjusted for multiple risk factors in another logistic regression model. CONCLUSION: Concurrent hyperhomocysteinaemia and chronic C. pneumoniae infection, as a single entity, was independently associated with coronary artery disease in the general population. This synergism may have important implications for risk-stratification and intervention trials.     

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.     

Antibodies to Chlamydia pneumoniae in blood serum of patients with ischemic heart disease and presence of complicated lesions in coronary arteries

Levels of IgM, IgG and IgA antibodies to Chlamydia pneumoniae were measured in 107 patients (age 33-75 years) with documented coronary atherosclerosis and 39 subjects with intact coronary arteries. Rates of seropositivity to C. pneumoniae were 77.6 and 25.6% in patients and "healthy" subjects, respectively (p<0.05). Seropositive (n=83) compared with seronegative (n=24) patients had higher prevalence of complicated lesions (p<0.05).     

The association of seropositivity to Helicobacter pylori,Chlamydia pneumoniae,and cytomegalovirus with risk of cardiovascular disease: a prospective study

OBJECTIVES: We sought to determine whether seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus (CMV) is an independent predictor of incident cardiovascular disease. BACKGROUND: Recent reports have suggested that infections may contribute to risk of cardiovascular disease. However, prospective studies of these associations in a free-living population are lacking. METHODS: We measured serum H. pylori IgG, C. pneumoniae IgG and IgA, and CMV IgG levels in Framingham Heart Study cohort participants. Blood samples were drawn during the 16th biennial examination cycle (1979 to 1982) from 1,187 participants free of cardiovascular disease (mean age 69 years) and stored at -20 degrees C. A pooled primary end point of myocardial infarction, atherothrombotic stroke, and coronary heart disease deaths was studied in relation to serology. Using a Cox model, hazard ratios (HR) and 95% confidence intervals (CI) were calculated, adjusting for age, gender, and established risk factors. RESULTS: Seropositivity to H. pylori IgG, C. pneumoniae IgG, C. pneumoniae IgA, and CMV IgG was 60%, 45%, 11%, and 69%, respectively. During 10 years of follow-up, incident cardiovascular disease occurred in 199 participants (16.8%). In age- and gender-adjusted models, H. pylori IgG (HR 1.09, 95% CI 0.81 to 1.46), C. pneumoniae IgG (HR 0.91, 95% CI 0.68 to 1.20), C. pneumoniae IgA (HR 0.65, 95% CI 0.39 to 1.07), and CMV IgG (HR 0.84, 95% CI 0.62 to 1.12) were not associated with incident cardiovascular disease. These associations were further attenuated after adjustment for risk factors including body mass index, total and high-density lipoprotein cholesterol, diabetes mellitus, smoking, and hypertension. These estimates did not change for the individual components of cardiovascular disease, and seropositivity to more than one organism did not alter these risk estimates substantially. CONCLUSIONS: In this elderly cohort, chronic H. pylori, C. pneumoniae, and CMV infections, as evidenced by seropositivity, were not associated with increased risk for cardiovascular disease. Additional studies are needed to determine the relations of chronic infections to cardiovascular disease risk in younger persons.     

Autoimmunity to human heat shock protein 60, Chlamydia pneumoniae infection, and inflammation in predicting coronary risk

Heat shock protein 60 (Hsp60) and Chlamydia pneumoniae infection have both been associated with cardiovascular diseases. Our aim was to study the role of Hsp60 antibodies as coronary risk predictors and their association with C pneumoniae infection and inflammation. This was a prospective, nested, case-control study. The cases consisted of 239 middle-aged Finnish men who developed myocardial infarction or coronary death during the follow-up. Baseline levels of IgA and IgG antibodies to human-specific and C pneumoniae-specific Hsp60 were measured by enzyme immunoassay. Human Hsp60 IgA, but not IgG or C pneumoniae Hsp60, antibodies were a significant risk factor for coronary events (odds ratio 2.0, 95% CI 1.1 to 3.6, when the fourth and first quartiles are compared). When an elevated human Hsp60 IgA antibody level (above the second quartile) was present simultaneously with a high C pneumoniae IgA antibody level (the third quartile) and an elevated C-reactive protein level (the second quartile), compared with all factors at low levels, the risk was 7.0 (95% CI 2.6 to 19.1) without adjustment and 5.0 (95% CI 1.8 to 14.2) when adjustment was made for age and smoking. In conclusion, an elevated human Hsp60 IgA antibody level was a risk factor for coronary events, especially when it was present together with C pneumoniae infection and inflammation.     

Serological markers of Chlamydia pneumoniae infection in men and women and subsequent coronary events; the Scottish Heart Health Study Cohort.

AIMS: To investigate the relationship between serum markers of Chlamydia pneumoniae infection and subsequent coronary events. METHODS and RESULTS: In a nested case-control study, based on the Scottish Heart Health Study cohort, we estimated IgG, IgA and IgM antibodies to C. pneumoniae, and circulating immune complexes containing C. pneumoniae antigen in baseline serum samples from 217 cases experiencing a subsequent coronary event during follow-up (mean 7.5 years) and from their matched controls. In men, the proportion of specimens positive for IgG, IgA and IgM antibodies showed no case-control differences (80% vs 80%, 57% vs 53% and 3% vs 3%, respectively). The odds ratio for a coronary event was 1.00 (95% confidence interval 0.59-1.69) for the presence of IgG antibodies to C. pneumoniae; 1.21 (0.76-1.92) for IgA and 0.75 (0.17-3.35) for IgM. Similar results were seen in women. The proportion of specimens with circulating immune complexes with C. pneumoniae antigen also showed no case-control differences (12% vs 12%, both sexes combined) with an odds ratio of 1.00 (0.57-1.76). CONCLUSION: Prior infection with C. pneumoniae, as estimated by these markers, does not appear to be a risk factor for subsequent coronary heart disease.     

Influence of Chlamydia pneumoniae infection on aortic stiffness in healthy young men

Though Chlamydia pneumoniae infection has been implicated in the pathogenesis of atherosclerosis, its role in early atherogenesis has not been well elucidated. To clarify whether C. pneumoniae infection was related to early atherogenesis, we evaluated the association between serological detection of C. pneumoniae antibodies and aortic stiffness in 102 healthy young male volunteers (mean age 27.1+/-0.4 years). Serum C. pneumoniae IgA and IgG antibodies were measured by the enzyme-linked immunosorbent assay (ELISA). Aortic stiffness was estimated using the brachial-ankle pulse wave velocity (PWV). No significant differences were observed between IgA seropositive and seronegative groups with regard to conventional cardiovascular risk factors. However, the mean PWV value was significantly higher in the IgA seropositive group than the seronegative group. Analyses of subgroups according to C-reactive protein (CRP) level showed that those subjects with IgA seropositivity and a high CRP level (>0.17 mg/l) had the highest PWV values. Multivariate logistic regression analysis revealed that a combination of C. pneumoniae IgA seropositivity and a high CRP level was an independent predictor of high values of PWV. These results suggest that C. pneumoniae infection might contribute to early atherogenesis, which might be associated with chronic inflammation.     

Chlamydia pneumoniae IgA titres and coronary heart disease; prospective study and meta-analysis.

AIMS: To examine associations between Chlamydia pneumoniae IgA titres and incident coronary heart disease, and to compare them with associations previously reported between C. pneumoniae IgG titres and coronary heart disease. METHODS AND RESULTS: We measured serum concentrations of C. pneumoniae IgA antibodies in 502 coronary heart disease cases and in 1005 age- and town-matched controls 'nested' in a community-based prospective study of 5661 British men (mean follow-up in controls, 16 years), and conducted a meta-analysis of published prospective studies to place our findings in context. Two hundred and twenty-one (44%) of the cases were in the top third of C. pneumoniae IgA titres compared with 336 (33%) of the controls, yielding an odds ratio for coronary heart disease of 1.84 (95% confidence interval 1.40-2.43) which was largely unchanged after adjustment. In aggregate, the present study and nine previously reported prospective studies of C. pneumoniae IgA titres involved 2283 cases, yielding a combined odds ratio for coronary heart disease of 1.25 (1.03-1.53), with no significant heterogeneity among the ten studies (chi(2)9=7.8; P>0.1). This combined odds ratio is compatible with that previously reported for C. pneumoniae IgG titres and coronary heart disease (1.15, 0.97-1.36). CONCLUSION: Neither C. pneumoniae IgA titres nor IgG titres are strongly predictive of coronary heart disease in the general population.     

Smoking increases the risk of coronary artery disease in Chinese with Chlamydia pneumoniae infection

BACKGROUND: The infection with Chlamydia pneumoniae (Cp) has been claimed to associate with coronary artery disease (CAD). However, the seroepidemiological study of association between Cp infection and CAD still remains a source of controversy. The aim of the present study is to investigate the possible association of Cp infection with CAD in Chinese mainland population and the potential role of Cp infection combined with the traditional risk factors in CAD. METHODS: 1422 hospitalized patients with angiographically demonstrated CAD and 297 controls were recruited and tested for specific Cp IgG with enzyme-linked immunoassay (ELISA). RESULTS: The prevalence of Cp IgG seropositivity in patients with CAD was significantly higher than that in controls (31.1% vs. 24.9%, P=0.035). Unadjusted odds ratios (OR) and 95% confidence intervals (CI) for CAD with the presence of seropositivity of IgG to Cp was 1.4 (1.0-1.8). After full adjustment for possible confounders on multiple logistic regression analysis, only a weak association of Cp infection with CAD was found. The adjusted OR (95% CI) for CAD associated with Cp infection was 1.3 (0.95-1.71, P=0.1). To further delineate the potential role of Cp infection in CAD, we divided subjects into seropositive (n=516) and seronegative (n=1203) groups according to their Cp IgG status. Notably, the adjusted OR (95% CI) for CAD associated with smoking was 4.0 (1.8-8.6) in the seropositive group, 0.9 (0.5-1.4) in the seronegative group, indicating that smoking can significantly increase the risk of CAD in subjects with Cp infection. CONCLUSIONS: Cp infection is not strongly associated with CAD in Chinese mainland population; however, smoking increases the risk of CAD in those with Cp infection.     

Chlamydia pneumoniae infection and its association with coronary heart disease and cardiovascular risk factors in a sample South Asian population.

Recent studies have suggested that a chronic infection with Chlamydia pneumoniae (C. pneumoniae) may be associated with the risk of developing coronary heart disease (CHD). A case control study was conducted to investigate the association between C. pneumoniae infection and coronary heart disease and coronary risk factors in a sample South Asian population. C. pneumoniae specific IgG antibody was measured by microimmunofluorescence. Among controls 56.6% were seropositive (> or =1/32) compared to 58.5% of acute myocardial infarction (AMI) patients (n=41, odds ratio 1.08, CI 0.37--3.12, P=0.93) and 73.3% of stable coronary heart disease (SCHD) patients (n=30, odds ratio 2.1, CI 0.63--7.19, P=0.27). The highest geometric mean titre of control subjects (n=30) was significantly lower (74.7) compared to AMI patients (101.5, P<0.05) and SCHD patients (138.6, P<0.05). Patients who were non-smokers had higher odds ratios for CHD than smokers when seropositive at IgG antibody titres of 1/32, 1/64 and 1/128, suggesting an association between smoking and C. pneumoniae infection. In patients with CHD there was a significant association between diabetes mellitus and seropositivity (P=0.008) in those over 50 years of age. Non-smoking CHD patients with high cholesterol/HDL-C ratio had a higher trend for seropositivity. Other risk factors (smoking, systolic and diastolic blood pressure, waist/hip ratio, triglycerides) showed no association when controlled for age. In the control group, smokers with high cholesterol/HDL-C ratio had a higher trend for seropositivity. These results do not provide strong support for the hypothesis that C. pneumoniae infection is a risk factor for clinical CHD in this South Asian population. Results suggest that C. pneumoniae infection may be linked to CHD through its interaction with some of the known risk factors such as blood lipids, diabetes and smoking.