Chlamydia pneumoniae IgG and IgA antibody titers and prognosis in patients with coronary heart disease: results from the CLARICOR trial

Hilden, Jørgen; Lind, Inga; Kolmos, Hans Jørn; Als‐Nielsen, Bodil; Damgaard, Morten; Hansen, Jørgen Fischer; Hansen, Stig; Helø, Olav H.; Hildebrandt, Per; Jensen, Gorm; Kastrup, Jens; Kjøller, Erik; Nielsen, Henrik; Petersen, Lone; Jespersen, Christian M.; Gluud, Christian

doi:10.1016/j.diagmicrobio.2009.11.011

Cited by 7 publications

(7 citation statements)

References 34 publications

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“…The CLARICOR trial is an investigator‐initiated, randomized, placebo‐controlled, blinded, multicenter, superiority trial that involved 4372 Danish patients with stable coronary heart disease who were randomly assigned by a central algorithm in a 1:1 ratio to clarithromycin versus placebo. The trial was inspired by the hypothesis that coronary vulnerability could be attributable to bacterial colonization of the arterial walls . The CLARICOR trial complies with the Declaration of Helsinki and has been approved by the local ethics committees and regulatory authorities (Regional Ethics Committee KF 01‐076/99 and HB 2009/015; the Danish Data Protection Agency 1999‐1200‐174 and 2012‐41‐0757; and the Danish Medicines Agency 2612–975).…”

Section: Methodsmentioning

confidence: 99%

“…The trial was inspired by the hypothesis that coronary vulnerability could be attributable to bacterial colonization of the arterial walls. [12][13][14][15] The CLARICOR trial complies with the Declaration of Helsinki and has been approved by the local ethics committees and regulatory authorities (Regional Ethics Committee KF 01-076/ 99 and HB 2009/015; the Danish Data Protection Agency 1999-1200-174 and 2012-41-0757; and the Danish Medicines Agency 2612-975). All residents of Copenhagen, Denmark, with a hospital diagnosis of myocardial infarction or angina pectoris (International Statistical Classification of Diseases [ICD] codes I20.9-I21.9) between 1993 and 1999, were identified and, if alive, invited by mail in late 1999 to participate in the trial.…”

Section: Methods Trial Design and Participantsmentioning

confidence: 99%

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10‐Year Associations Between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients With Stable Coronary Heart Disease: A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy

Carlsson

Ruge

Kjøller

et al. 2018

JAHA

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BackgroundWe aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)‐α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.Methods and ResultsCLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all‐cause mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C‐reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05–1.22; P=0.001 for TNFR1; hazard ratio, 1.16; 95% confidence interval, 1.08–1.24; P<0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).ConclusionsIncreased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.

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Section: Methodsmentioning

confidence: 99%

Section: Methods Trial Design and Participantsmentioning

confidence: 99%

10‐Year Associations Between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients With Stable Coronary Heart Disease: A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy

Carlsson

Ruge

Kjøller

et al. 2018

JAHA

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“…It has been suggested that the initially identified serologic markers, such as elevations in IgG, may be more reflective of atherosclerotic processes other than persistent C pneumoniae infection, such as smoking and inflammation. 70 In recent meta-analyses, elevated titers of IgG or IgA to C pneumoniae have been associated with increased stroke risk and increased inflammatory markers. 71,72 …”

Section: Chlamydophila Pneumoniaementioning

confidence: 99%

“…73 The CLARICOR trial, which demonstrated an unexpected increase in long-term mortality after short-term treatment with clarithromycin in patients with stable coronary heart disease, further contributed to doubt in the association. 70 The failure of antibiotic therapies to influence cardiovascular outcomes may reflect a lack of an association but could also result from the limited efficacy of antibiotics to penetrate atherosclerotic plaques or eradicate infection. Alternatively, the initiation of atherosclerosis may depend on transient C pneumoniae infection rather than chronic infection.…”

Section: Chlamydophila Pneumoniaementioning

confidence: 99%

Atypical Pneumonia

Sharma

Losier

Tolbert

et al. 2017

Clinics in Chest Medicine

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SUMMARY CAP due to Legionella, Chlamydophyla, or Mycoplasma continues to be a diagnostic challenge due to the nonspecific clinical and radiographic presentations. The vague clinical presentations of atypical CAP contribute to its underdiagnosis and under-reporting. Advancements in diagnostic techniques bring hope to rapid and accurate diagnosis of atypical CAP. Macrolides and respiratory fluoroquinolones are currently the antibiotics of choice, but this may change in the near future as more antibiotics resistance patterns emerge for atypical CAP. Several controversies still exist in atypical CAP, underscoring the need for continued investigation of preventing atypical CAP and determine its association with chronic lung diseases.

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“…Reinfection is common, and persistence of the agent in the host after the primary infection is a potential risk factor for chronic infection. The associations between C. pneumoniae and atherosclerosis and coronary heart disease have attracted the attention of many investigators [4,5]. The bacterium appears to be associated with hyperlipidemia and might, therefore, represent a further risk factor for cardiovascular disease in human immunodeficiency virus (HIV)-positive patients [6].…”

Section: Introductionmentioning

confidence: 99%

Preparation and evaluation of monoclonal antibodies against chlamydial protease-like activity factor to detect Chlamydia pneumoniae antigen in early pediatric pneumonia

Zheng

Ding

Chen

et al. 2015

Eur J Clin Microbiol Infect Dis

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Chlamydia pneumoniae causes diseases in humans, including community-acquired pneumonia, bronchitis, and sinusitis. It is also associated with atherosclerosis, coronary heart disease, and hyperlipidemia. In this study, we investigated novel materials with which to develop a sensitive and specific method to identify early C. pneumoniae infection, to allow more effective clinical treatment and prevention. We prepared novel monoclonal antibodies (mAbs) against a recombinant protein equivalent to the immunodominant region of chlamydial protease-like activity factor (CPAF) from C. pneumoniae. The mAbs specifically reacted with the endogenous CPAF antigen of the C. pneumoniae type strain in immunoblotting and indirect immunofluorescence (IIF) assays, but did not react with C. trachomatis type strains or genital secretions from patients with acute C. trachomatis infection. The mAb with the highest titer was used to develop a new IIF assay and enzyme-linked immunosorbent assay (ELISA) to detect the C. pneumoniae antigen in clinical specimens from child patients suspected of pneumonia. The sensitivity, specificity, and concordance rate of the mAb-based IIF and ELISA tests were compared with those of polymerase chain reaction (PCR). Our results show that these mAbs have excellent specificity and may be used to develop new screening tools for the diagnosis of early pediatric pneumonia.

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Chlamydia pneumoniae IgG and IgA antibody titers and prognosis in patients with coronary heart disease: results from the CLARICOR trial

Cited by 7 publications

References 34 publications

10‐Year Associations Between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients With Stable Coronary Heart Disease: A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy

10‐Year Associations Between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients With Stable Coronary Heart Disease: A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy

Atypical Pneumonia

Preparation and evaluation of monoclonal antibodies against chlamydial protease-like activity factor to detect Chlamydia pneumoniae antigen in early pediatric pneumonia

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