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.

MCMV infection increases early T-lymphocyte influx in atherosclerotic lesions in apoE knockout mice.

BACKGROUND: Multiple epidemiological studies have suggested that cytomegalovirus (CMV) infection is associated with atherosclerotic disease. However, conclusive proof that the virus is directly related to the progression of the disease is still lacking. OBJECTIVES: The goal of this study was to investigate whether MCMV is able to exacerbate the atherosclerotic process in atherosclerosis-susceptible mice. STUDY DESIGN: apoE knockout mice kept on a chow diet were sacrificed at both 2 and 20 weeks post infection (p.i.). C57Bl/6J mice fed an atherogenic diet were sacrificed at 2 weeks p.i. Lesion area, lesion composition (endothelial cells and smooth muscle cells) and inflammatory influx (T-lymphocytes and macrophages) in lesions were determined. The former one was determined by means of a microscope coupled to a computer-assisted morphometry system. The latter ones were scored after immunohistochemical staining. RESULTS: In the chronic phase of the infection mean lesion size was significantly increased after MCMV infection in the apoE knockout mice. This increase could to a large extent be attributed to a significant increase in type V lesion area after MCMV infection. Also, a significant increase in T-lymphocyte influx was observed in the acute phase of the infection in lesions from apoE knockout mice after MCMV infection while this effect was absent in C57Bl/6J mice. After MCMV infection no increase was observed in macrophage, smooth muscle cell and endothelial cell number in lesions from both mice strains. CONCLUSIONS: MCMV infection may exacerbate the atherosclerotic process in apoE knockout mice by means of an acute lymphocytic inflammatory response. In contrast to the MCMV induced effect in apoE knockout mice, MCMV infection did not increase the influx of T-lymphocytes in atherosclerotic lesions of C57Bl/6J mice.

Differences in virus prevalence and load in the hearts of patients with idiopathic dilated cardiomyopathy with and without immune-mediated inflammatory diseases.

Infections with cardiotrophic viruses and immune-mediated responses against the heart have been suggested to play a dominant role in the pathogenesis of idiopathic dilated cardiomyopathy (DCM). Furthermore, immune-mediated inflammatory diseases (IMIDs) may result in DCM. It has not previously been assessed whether DCM patients with and without an IMID have different prevalences and quantities of cardiotrophic viruses in the heart. Therefore, we compared the profiles of cardiotrophic viruses in heart tissue of DCM patients with and without an IMID. Serum and myocardial tissue samples were obtained from 159 consecutive patients with DCM and 20 controls. Patients were subdivided into three groups, the first two based on the presence (n = 34) or absence (n = 125) of an IMID and the third being a control group. The parvovirus B19 virus genome was detected in equal quantities in the non-IMID DCM patients (100/125) and the control group (15/20) but in lower quantities in the IMID patients (21/34, P = 0.02). Both the non-IMID and IMID DCM patients demonstrated increased myocardial inflammation compared to controls: 12.5 ± 1.8 and 14.0 ± 3.2 CD45-positive inflammatory cells, respectively, versus 5.1 ± 0.7 for the controls (P < 0.05 for both). Importantly, significantly higher parvovirus B19 copy numbers could be amplified in non-IMID than in IMID patients (561 ± 97 versus 191 ± 92 copies/µg DNA, P < 0.001) and control subjects (103 ± 47 copies/µg DNA, P < 0.001). The present study shows decreased parvovirus B19 prevalence and copy numbers in hearts of DCM patients with an IMID compared to those without an IMID. These findings may suggest that DCM patients with an IMID have a different pathophysiologic mechanism from that which is present in the virus-induced form of DCM.

Intravenous immunoglobulin therapy for patients with idiopathic cardiomyopathy and endomyocardial biopsy-proven high PVB19 viral load.

BACKGROUND: Parvovirus B19 (PVB19) persistence in the heart has been associated with progressive cardiac dysfunction and evolution to dilated cardiomyopathy. In the present study, we investigated whether immunomodulation with intravenous immunoglobulin (IVIg) in addition to conventional heart failure therapy is safe and achieves virus reduction. Such therapy might improve cardiac function in patients with chronic dilated cardiomyopathy (DCM) and a significant PVB19 viral load in the heart. METHODS: PVB19 viral load was studied in 25 post-mortem cardiac samples of patients with a normal heart. Then, 17 consecutive patients (mean age 53 +/-3 years) with DCM and symptomatic heart failure for >1 year with a PVB19 viral load in endomyocardial biopsies of >250 copies/microg DNA were treated with a high dose of IVIg (2 g/kg). RESULTS: The post-mortem cardiac samples revealed a PVB19 presence in 80% with a mean load of 131 +/-40 copies/microg DNA. In the treated patients, IVIg resulted in a significant decrease of PVB19 viral load from 1,420 +/-216 to 619 +/-200 copies/microg DNA (P=0.004) and significantly improved the ejection fraction from 33 +/-3% 6 months before treatment and 34 +/-3% at baseline to 41 +/-3% 6 months (P=0.001) after IVIg therapy. The New York Heart Association classification significantly improved from 2.5 +/-0.1 at baseline to 2.1 +/-0.1 at follow-up (P=0.004). No therapy-related complications were noted. CONCLUSIONS: The present pilot study demonstrates that IVIg significantly reduces viral load and improves cardiac function in patients with DCM related to increased PVB19 viral load in the heart.