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      Chlamydia pneumoniae and Atherosclerosis: No Way-Out or Long Way?

      Kidney and Blood Pressure Research

      S. Karger AG

      Antibodies, Antibiotic trials, Renal failure, Hemodialysis, Vaccine, Confounders

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          Recently, Chlamydia pneumoniae is the microorganism frequently implicated in the infection-based inflammatory atherogenous hypothesis. Although in vitro experimental data and initial sero-epidemiologic, pathology-based studies and antibiotic trials supported this interesting hypothesis, later data are conflicting. Some confounding factors are the causes of uncertainty; lacking of standard methods for C. pneumoniae detection, co-existence of other atherosclerotic risk factors and anti-inflammatory effects of antibiotics used in clinical trials seem to be the principal ones. Standardization of methodology used, antibiotic trials with a different orientation-design and a vaccine preparation that eventually will be tested in clinical trials with a long follow-up, should provide a definite answer regarding the probability C. pneumoniae to be a main, a secondary or an irrelevant factor to atherosclerosis. Studies linking C. pneumoniae to inflammation and accelerated atherosclerosis in renal failure patients are accumulated but limitations are similar to the above mentioned.

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          Most cited references 62

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          Chronic infections and coronary heart disease: is there a link?

          A large number of studies have reported on associations of human coronary heart disease (CHD) and certain persistent bacterial and viral infections. We review the epidemiological and clinical evidence on CHD and Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus (CMV), as well as possible mechanisms. The association between CHD and H pylori may be accounted for by residual confounding from risk factors. Although the association between C pneumoniae and CHD is stronger, the sequence of infection and disease is uncertain. As regards CMV, a limited number of patients with classic atherosclerotic coronary artery disease have been studied. Further studies are needed to resolve these uncertainties.
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            Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure.

            Cardiovascular mortality is excessive in young adults with end-stage renal disease (ESRD). The factors contributing to ESRD-related vascular disease are incompletely understood. Young adults with childhood-onset chronic renal failure (CRF) are uniquely suited for risk factor assessment because of their long-term exposure at an age when vascular pathology in the general population is still minimal. We used novel noninvasive technologies to screen for coronary and carotid artery disease in 39 patients with ESRD aged 19 to 39 years with childhood-onset CRF presently treated by dialysis or renal transplantation. Coronary artery calcification burden was assessed by CT scan with ECG gating and the intima-media thickness (IMT) of the carotid arteries by high-resolution ultrasound. Coronary artery calcifications were present in 92% of patients; calcium scores exceeded the 95th age- and sex-specific percentiles >10-fold on average. Carotid IMT was significantly increased compared with matched control subjects. Both coronary calcium scores and IMT were associated with cumulative dialysis and ESRD time and the cumulative serum calcium-phosphate product. Coronary calcium scores were strongly correlated with C-reactive protein and Chlamydia pneumoniae seropositivity, time-averaged mean serum parathyroid hormone, and plasma homocysteine. C-reactive protein and parathyroid hormone independently predicted coronary calcium accumulation. Smoking, obesity, and HbA1c were correlated with IMT in the control subjects but not in the patients. Young adults with childhood-onset CRF have a high prevalence of arteriopathy associated with indicators of microinflammation, hyperparathyroidism, calcium-phosphate overload, and hyperhomocysteinemia but not traditional atherogenic risk factors. These risk factors persist even after successful renal transplantation.
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              Standardizing Chlamydia pneumoniae assays: recommendations from the Centers for Disease Control and Prevention (USA) and the Laboratory Centre for Disease Control (Canada).

              Chlamydia pneumoniae has been associated with atherosclerosis and several other chronic diseases, but reports from different laboratories are highly variable and "gold standards" are lacking, which has led to calls for more standardized approaches to diagnostic testing. Using leading researchers in the field, we reviewed the available approaches to serological testing, culture, DNA amplification, and tissue diagnostics to make specific recommendations. With regard to serological testing, only use of microimmunofluorescence is recommended, standardized definitions for "acute infection" and "past exposure" are proposed, and the use of single immunoglobulin (Ig) G titers for determining acute infection and IgA for determining chronic infection are discouraged. Confirmation of a positive culture result requires propagation of the isolate or confirmation by use of polymerase chain reaction (PCR). Four of 18 PCR assays described in published reports met the proposed validation criteria. More consistent use of control antibodies and tissues and improvement in skill at identifying staining artifacts are necessary to avoid false-positive results of immunohistochemical staining. These standards should be applied in future investigations and periodically modified as indicated.

                Author and article information

                Kidney Blood Press Res
                Kidney and Blood Pressure Research
                S. Karger AG
                April 2004
                12 August 2004
                : 27
                : 3
                : 134-142
                Renal Unit, Alexandra General Hospital, Athens, Greece
                78146 Kidney Blood Press Res 2004;27:134–142
                © 2004 S. Karger AG, Basel

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                Page count
                Tables: 2, References: 93, Pages: 9
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