Impact of intimal pathogen burden in acute coronary syndromes--correlation with inflammation, thrombosis, and autoimmunity.

BACKGROUND: Increasing evidence supports a link between serological evidence of pathogen burden (PB) and the risk for future cardiovascular events. Our study evaluates the intimal presence of 4 pathogens in atheroma, clinically associated with acute coronary syndromes (ACS) and stable angina (SA), and the effect on the expression of intimal C-reactive protein (CRP), tissue factor (TF) and human heat-shock protein 60 (hHSP60). METHODS: Coronary atherectomy specimens retrieved from 60 primary lesions of patients with ACS (n=35) or SA (n=25) were assessed immunohistochemically for the presence of Chlamydia pneumoniae (Cpn), Helicobacter pylori (HP), Cytomegalovirus (CMV) and Epstein­Barr Virus (EBV) and for the expression of CRP, TF, and hHSP60. RESULTS: Analysis revealed eight lesions without, 22 lesions with one, 19 lesions with two, seven lesions with three, and four lesions with four pathogens. Cpn was present in 73%, HP in 31%, CMV in 16%, and EBV in 40%. Mean value of PB in ACS-lesions was significantly increased. Expressions of CRP, TF, and hHSP60 were significantly higher in ACS lesions. The number of infectious pathogens correlated significant with the expressions of CRP, TF, and hHSP60. CONCLUSIONS: Our data demonstrate the impact of PB in plaque instability and suggest local proinflammatory, prothrombotic, and proimmunogenic effects.

Presence of Chlamydophila pneumoniae DNA but not mRNA in stenotic aortic heart valves.

BACKGROUND: The pathogenesis of aortic valve stenosis may involve inflammation and we have previously demonstrated Chlamydophila pneumoniae (C. pneumoniae) DNA in stenotic aortic heart valves. Dissemination of these bacteria is probably mediated by alveolar macrophages. Bacterial DNA alone does not indicate whether the bacteria are viable and replicating. This study aimed to investigate the presence of C. pneumoniae mRNA, a marker of replicating bacteria, and C. pneumoniae DNA in stenotic aortic valves and the prevalence of C. pneumoniae in peripheral blood mononuclear cells (PBMC). METHODS: DNA was extracted from heart valves and PBMC and mRNA from heart valves from 76 patients undergoing aortic valve replacement surgery. C. pneumoniae DNA and mRNA were measured by real-time PCR targeting the ompA gene. RESULTS: C. pneumoniae DNA was demonstrated in 22% of heart valves and in 5% of PBMC. C. pneumoniae mRNA was not detected in any valve. Patients positive for C. pneumoniae in the valve underwent coronary artery by-pass grafting more often (p=0.01) and suffered from angina pectoris (p=0.02) and arterial hypertension (p=0.03) more often than patients negative for C. pneumoniae in the valve. CONCLUSIONS: These findings support a role for C. pneumoniae in the pathogenesis of aortic valve stenosis and indicate that the bacteria disseminate from the respiratory tract long before the patients were in need of surgery and that the valve infection thereafter entered into a persistent and non-replicative state. Moreover, patients positive for C. pneumoniae in the valve more often needed by-pass grafting because of more advanced coronary disease.

Chlamydophila pneumonia: Specific mRNA in aorta ascendens in patients undergoing coronary artery by-pass grafting.

The objective of this prospective study was to investigate if Chlamydophila pneumoniae (Cp)-specific DNA and mRNA are present in tissue samples from the wall of aorta ascendens in patients undergoing by-pass surgery for coronary artery disease (CAD) that includes stable angina pectoris (SAP, 25 patients) and acute coronary syndrome (ACS, 19 patients). Viable Cp was detected in 8/44 (18%) patients using reversed transcriptase PCR (RT-PCR) against bacterial mRNA with detection of cDNA using real-time PCR against the MOMP gene. Cp DNA was detected by nested PCR in 22/44 (50%) patients and by real-time PCR in 13/44 (30%) patients. In total, 24/44 (55%) patients were positive for Cp nucleic acid in any PCR. Antibodies to Cp were detected in 13/24 (54%) Cp PCR-positive and in 15/20 (75%) Cp PCR-negative patients. Nested PCR was run on throat swabs from all patients. No significant differences were noted between SAP and ACS patients regarding PCR results or serology. It has been suggested that Cp may be a 'silent passenger' picked up by the atherosclerotic plaque. Our findings of viable and metabolically active bacteria in aortic tissue add further support to the hypothesis that Cp may have an active role in the pathogenesis of atherosclerosis.

[Rupture of the atherosclerotic plaque: is Chlamydia pneumoniae a possible agent?]. / Studio osservazionale la chlamydia pneumoniae è correlabile con la rottura della placca aterosclerotica?

BACKGROUND: The natural history of atherosclerosis has not clearly been elucidated yet. Some works reported that flogosis plays a role in plaque instability. Why does this inflammatory process start? We investigated the correlation between Chlamydia pneumoniae acute infection and plaque rupture. METHODS: We compared blood concentrations of IgM anti-Chlamydia pneumoniae in patients affected by acute myocardial infarction (AMI) and in patients affected by stable angina. RESULTS: Our results showed a minimal statistical difference, with a more positive value in patients with AMI. Subsequently, the group affected by AMI was divided into two subgroups with and without plaque rupture: the subgroup with plaque rupture showed a higher blood concentration of Chlamydia antibodies. This subgroup was also divided into two other subgroups according to blood white cell concentration: the subgroup with normal concentration of white blood cells showed the highest value of Chlamydia antibodies. CONCLUSIONS: Chlamydia pneumoniae could play an important role in atherosclerotic plaque instability

Stent implantation, but not pathogen burden, is associated with plasma C-reactive protein and interleukin-6 levels after percutaneous coronary intervention in patients with stable angina pectoris.

BACKGROUND: The systemic inflammatory response to percutaneous coronary intervention (PCI) is associated with recurrent cardiac events; however, the pathophysiology of this inflammatory response is not well understood. The present study was performed to investigate the role of pathogen burden of infection in determining the magnitude of C-reactive protein (CRP) and interleukin 6 (IL-6) response to PCI. METHODS: One hundred patients with stable angina pectoris undergoing elective PCI at a single center were recruited. Antibodies against cytomegalovirus, Chlamydia pneumoniae , Epstein-Barr virus, Helicobacter pylori , and herpes simplex virus types 1 and 2 were determined before PCI. Plasma CRP and IL-6 levels were measured before and 6, 24, 48, 72 hours after PCI and data presented as area under the curve. RESULTS: Plasma CRP and IL-6 concentrations increased significantly after PCI. Neither antibodies against single nor multiple pathogens were associated with the CRP or IL-6 response to PCI. No correlations were found between the inflammatory markers and troponin T levels after PCI. With the exception for CRP and body mass index (R = 0.20, P < .05), neither risk factors for coronary heart disease nor medication but stent implantation was associated with increased plasma CRP (76 vs 61 mg/L, P < .005) and IL-6 (74 vs 64 pg/mL, P < .005) levels after PCI. CONCLUSION: Stent implantation, but not pathogen burden, is associated with the plasma CRP and IL-6 response to PCI.

Seroprevalence of IgG antibodies to Chlamydia pneumoniae and Helicobacter pylori among coronary heart disease patients and normal individuals in South Indian population.

In recent years, the role of infectious agents in the aetiology of atherosclerotic disease has come to the forefront. In the present study, seroprevalence (IgG) of chlamydia pneumoniae and helicobacter pylori in patients with atherosclerotic coronary heart disease was compared to normal healthy adults. Out of a total of 117 patients 101 had unstable angina (UA) and 16 had chronic stable angina (CSA). C. pneumoniae seropositivity was found in 66% of patients with UA and 94% of CSA patients. The corresponding figures for H. pylori were 58% and 56% respectively. In comparison, 81% of healthy adults were seropositive for C. pneumoniae and 53% for H.pylori. No significant association was found between CHD and the infectious agents. However, this study has revealed a high infection by C. pneumoniae as well as H.pylori in this part of India.

Serologic markers of persistent Chlamydia pneumonia infection and long-term prognosis after successful coronary stenting.

BACKGROUND: Previous studies have shown an incremental role of inflammation in late prognosis following coronary stenting (CS). In particular, high preprocedural levels of plasma C-reactive protein (CRP) have been related to increased hazard of late ischemic complications. Persistent Chlamydia pneumoniae (Cp) infection, detected by positive IgA anti-Cp titers, may be associated with this inflammatory process and portend a high risk of late adverse prognosis after CS. METHODS: A total of 483 consecutive patients with either stable or unstable coronary syndromes were followed-up for 1 year after successful CS. The composite of cardiac death, myocardial infarction, rehospitalization for rest-unstable angina, and exertional angina, whichever occurred first, was the clinical end point. Additionally, the rate of in-stent restenosis and progression of coronary artery disease during this period were evaluated. Anti-Cp titers and plasma CRP levels were measured before the procedure. RESULTS: Positive immunoglobulin A (IgA), but not positive immunoglobulin G (IgG), titers were significantly associated with high plasma CRP levels in patients with unstable coronary syndromes (P =.005), but not in those with stable angina (P =.7). Moreover, positive IgA titers were significantly related to increased risk of both the composite clinical end point (P =.04) and progression of coronary artery disease (P <.001) in patients with unstable coronary syndromes but not in those with stable angina. Neither positive IgA nor positive IgG titers were associated with the rate of in-stent restenosis. CONCLUSIONS: Persistent Cp infection may drive an inflammatory response in the coronary vasculature and portends an adverse late outcome after CS in patients with unstable coronary syndromes.

Roxithromycin in prevention of acute coronary syndrome associated with Chlamydia pneumoniae infection: a randomized placebo controlled trial.

The role of Chlamydia pneumoniae infection in precipitating acute coronary syndrome (ACS) is unclear. Some studies have indicated that intervention with macrolide antibiotics might reduce coronary events in patients with ACS. A double blind, randomized, placebo-control trial was conducted on 84 ACS patients. Patients were randomized to 30 days of treatment with roxithromycin (150 mg, twice daily) or matching placebo. The follow-up period was 90 days, and the primary clinical end point included cardiovascular death, unplanned revascularization and recurrent angina/MI. Anti-C. pneumoniae IgG positive in 24 of 43 (55.8%) patients in the roxithromycin group and 23 of 41 (56.1%) patients in the placebo group. Anti-C. pneumoniae IgA positive in 20 of 43 (46.5%) patients in the roxithromycin group and 13 of 41 (31.7%) patients in the placebo group. Thirty-three cardiac events occurred (2 cardiovascular deaths, 9 CABG, 12 PTCA and 10 recurrent angina/MI) with 17 events in the roxithromycin group and 16 events in the placebo group. There was no significant difference of cardiac events between the roxithromycin and placebo groups. The present study suggests that antibiotic therapy with roxithromycin is not associated with reduction of cardiac events as reported by other investigators. However, therapeutic interventions may need to be specifically targeted to a group of patients who are confirmed with chronic C. pneumoniae infection.

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.

Seropositivity against Chlamydia pneumoniae in patients with coronary atherosclerosis.

BACKGROUND: Results of therapy in patients with unstable coronary syndromes with antibiotics directed against Chlamydia pneumoniae have been variable, perhaps due to the heterogeneity of patients in these trials. HYPOTHESIS: The aim of the present study was to correlate the severity of coronary artery disease (CAD) with seropositivity against C. pneumoniae prospectively. METHODS: We measured the frequency of seropositivity (IgG levels > or = 1/64 and IgA levels > or = 1/16 against Chlamydia pneumoniae) in 110 patients with CAD and in 49 controls. RESULTS: As expected, traditional CAD risk factors were seen more often in patients with CAD than in controls. Mean values of total cholesterol (184 +/- 52 and 166 +/- 44 mg/dl, respectively) and triglyceride (143 +/- 60 and 112 +/- 63 mg/dl, respectively) in serum were significantly higher in patients with CAD than in controls (both p < 0.04). There were no significant differences between the two groups in serum high-density lipoprotein cholesterol (34 +/- 13 and 32 +/- 14 mg/dl, respectively) and lipoprotein (a) (Lp(a):241 +/- 247 and 223 +/- 263 mg/l, respectively) levels. The rate of IgG seropositivity was 52% (28/54) in patients with stable CAD, 41% (23/56) in patients with unstable CAD, and 35% in controls (p = NS). The rate of IgA seropositivity was 25% (14/54) in patients with stable CAD, 12% (6/49) in patients with unstable angina, and 12% (6/49) in controls (all p = NS). CONCLUSIONS: Only a small percentage of patients with CAD demonstrate seropositivity against Chlamydia pneumoniae. Antibiotic therapy in these selected patients, but not in the remaining patients, may be considered rational. These considerations may underlie the failure to see consistent benefits of antibiotic therapy in patients with CAD.

[Chlamydia pneumoniae in coronary plaques: Increased detection with acute coronary syndrome]. / Chlamydia pneumoniae in koronarem Plaquegewebe: Vermehrter Nachweis bei akutem Koronarsyndrom.

BACKGROUND AND OBJECTIVE: There is seroepidemiologic and experimental evidence for a link between Chlamydia (C.) pneumoniae and arteriosclerosis. However, the clinical importance and the pathogenic pathways implicated remain unclear. In the present study, we sought to evaluate the presence and the location of C. pneumoniae in coronary atheroma, as well as a potential prevalence with unstable versus stable angina. PATIENTS AND METHODS: Retrospectively, coronary plaque material of primary lesions from 51 consecutive patients (44 men, 7 women, mean age 59.6 +/- 9.4 years) was examined for the presence of C. pneumoniae by use of immuno-histochemistry and transmission electron microscopy. The findings associated with clinically acute coronary syndrome according to Braunwald's classification (n = 31) were compared to those with stable angina (n = 20) and regarded for potential relations to characteristic intimal features. RESULTS: Immunoreaction for C. pneumoniae was found in 32 of 51 (63%) coronary plaques. Signals (% prevalence of specific intimal features) were present with necrotic areas (40%), sparse cellularity (40%), neo-vascularization (29%), thrombi (20%), ruptured plaque areas (19%), and fields rich in foam cells and calcifications (13%). Intimal hyperplasia and inflammatory infiltrates showed no signals. As the central finding in this report, C. pneumoniae immunoreaction was more frequently (P < 0.001) found in 26 of 31 (84%) lesions associated with unstable angina or acute myocardial infarction, compared to 6 of 20 (30%) lesions with stable angina (P < 0.001). Intact vessels devoid of arteriosclerotic disease, such as mammarial arteries and saphenous veins, were without C. pneumoniae signals (negative controls). Ultrastructurally, chlamydial elementary bodies were found in foam cells and phagocytosing macrophages, also in fragmented extracellular matrix adjacent to apoptotic and necrotic intimal cells. CONCLUSIONS: Chlamydiae pneumoniae were detected in 32 of 51 (63%) coronary primary lesions of symptomatic patients. Most importantly, there was a highly significant prevalence of lesions associated with acute coronary syndrome. Predilection sites of C. pneumoniae were areas that revealed small healing activity and (or) propensity to plaque rupture. The present in situ findings indicate a pathogenic role of Chlamydiae pneumoniae in human (coronary) plaque rupture.

[Chlamydia pneumoniae infection in patients with myocardial infarct and angina pectoris]. / Chlamydia pneumoniae fertö zöttség myocardialis infarctus és anginapectoris eseteiben.

In a prospective open study we investigated Chlamydia pneumoniae infections in 36 consecutively admitted patients: 26 males, mean age 53.4 yr, range 36-70 yr, 10 females mean age 57.7 yr, range 47-70 yr, suffering myocardial infarction (24 acute, 2 previous) or angina pectoris (10). Antibody serum levels were measured by the immunefluorescent method and they were as follows: negative 5, low 12, medium/high 11, chronic infection 5, recent infection 3. The 3 cases considered as recent infections are described in detail.

[Septic thrombophlebitis of the internal jugular vein and Lemierre syndrome]. / Thrombophlébite septique de la veine jugulaire interne et syndrome de Lemierre.

The authors report a case of Lemierre's syndrome. This uncommon clinical entity is characterized by a septic internal jugular vein thrombosis with secondary metastatic abscesses and Fusobacterium necrophorum septicemia, following an acute oropharyngeal infection. The diagnosis is primarily clinical and it should be suspected when a severe septicaemic illness, with pulmonary symptoms, occurs after an acute pharyngotonsillar infection. This article reviews the clinical picture, microbiology and treatment of this forgotten complication of acute tonsillitis.