Cardiovascular Disease
BMC Infect Dis. 2007 May 30;7(1):48 [Epub ahead of print]
Higher incidence of persistent chronic infection of Chlamydia pneumoniae among coronary artery disease patients in India is a cause of concern.
* Jha HC,
* Vardhan H,
* Gupta R,
* Varma R,
* Prasad J,
* Mittal A.
I am very excited to present the following article that summarizes Dr. Stratton's recent observations on Chlamydia pneumoniae infection. Putting it together has contributed greatly to my own understanding of Cpn as well as to my appreciation of Dr. Stratton's generosity with his time, and his great depth of knowledge of this area. Thanks to him for his contribution. Jim K Recent observations by Dr Recent observations by Dr. Charles Stratton on Chlamydia Pneumoniae (Cpn) Infection
I don't believe we have this linked to our Research Pages (Marie?). This is a brilliant dissertation from the Finnish group, some of the world's experts on Cpn as some of the faculty in Helsinki were part of the original group who discovered the very existence of Cpn.This dissertation demonstrates a number of important findings:
Go to the link and you can download the whole thing in pdf form. Experimental Chlamydia pneumoniae infection model: effects of repeated inoculations and treatment
Lääketieteellinen tiedekunta, Oulun yliopisto
Summary of our Cpn Treatment Poll:The poll was out for two weeks, and represents a snapshot of protocol users at this point in time. We had slightly different numbers participating in each section of the poll, perhaps some questions did not have exclusive answers for those voters. Obviously, 25-28 people is not enough to draw scientifically valid results from, but I intend to speculate on some suggestive patterns in the data. Gender: Female: 61% (17 votes) Male: 39% (11 votes) Total votes: 28 This ratio is commonly reported in CFS/FM, MS and other "autoimmune" diseases, so is not surprising. We would expect that if more people with Cardiac diseases were searching out Cpn treatment, with a higher male to female ratio, this might change. Age: 20-29 years = 7% (2 votes) 30-39 years = 14% (4 votes) 40-49 = 32% (9 votes) 50-59 years = 39% (11 votes) 60-69 years = 7% (2 votes) Total votes: 28 Our largest group is between ages 40 to 59. I suspect that this age does not reflect the period when people are morel likely to be infected, but rather a range where long term persistent infections are have accumulated enough damage to force us to seek out "desperate measures" such as the multi-antibiotic protocol recorded here. Primary diagnosis: Over half the total in the poll have a diagnosis of MS. The second largest group are those with a diagnosis of CFS/FMS. This likely influences the treatment response reported later which suggest that improvements are noticed most after 5 or more pulses. CFS/FM = 28% (8 votes) MS = 55% (16 votes) Asthma = 3% (1 vote) Cardiac disease = 3% (1 vote) OTHER = 10% (3 votes) Total votes: 29 Serology Positive blood test for Cpn 48% (12 votes) Negative blood test for Cpn 16% (4 votes) Not been tested for Cpn 36% (9 votes) Total votes: 25 Well over half either have negative or no serology for Cpn, suggesting that they are engaging in a completely empirical (based on symptoms or theoretical connection between disease and Cpn) protocol. Antibiotics I take AT LEAST TWO of: doxycycline/azithromycin/roxithromycin/rifamcin/minocycline/INH-: 73% (19 votes) Single antibiotic only: 20% (5 votes) I take only INH: 8% (2 votes) Total votes: 26 This poll speaks for itself. 73% are already on the dual antibiotics, a small number appear to be early in treatment, confirmed by findings below that 40% have not yet done a pulse of bacteriacidal, and have only added one agent. As INH is used as a single agent with the flagyl pulses in some versions of the Cpn protocol and, together with NAC for the EB phase I have reported it separately. Bacteriacidal Agent Used- I take metronidazole (Flagyl) for bacteriacidal pulses 81% (13 votes) I take tinidazole (Tinactin) for bacteriacidal pulses 19% (3 votes) Total votes: 16 Pulses of bacteriacidal I've done NO pulses yet of metronidazole/tinidazole 40% (10 votes) I've done some partial pulses of metronidazole/tinidazole 4% (1 vote) I have had LESS than 5 full pulses (at least 5 days each) of metronidazole/tinidazole 24% (6 votes) I have had MORE than 5 full pulses (at least 5 days each) of metronidazole/tinidazole 32% (8 votes) Total votes: 25 Over half in this small pole have done at least a full pulse of bacteriacidal agent, with only 8 people reporting 5 full pulses or more. This shows that we are still, as a group, in earlier phases of treatment. As the results below suggest, more significant improvement starts to accrue beyond 5 pulses of the bacteriacidal. Response to treatment- 1. On 1 0r 2 antibiotics ONLY My primary condition is the SAME or WORSE 13% (3 votes) 2. On 1 0r 2 antibiotics ONLY My primary condition is SOMEWHAT improved 13% (3 votes) 3. On 1 0r 2 antibiotics ONLY My primary condition is SIGNIFICANTLY improved 13% (3 votes) 4. Less than 5 full pulses: My primary condition is the SAME or WORSE 13% (3 votes) 5. Less than 5 full pulses: My primary condition SOMEWHAT improved 9% (2 votes) 6. Less than 5 full pulses: My primary condition SIGNIFICANTLY improved 4% (1 vote) 7. MORE than 5 full pulses: My primary condition is the SAME or WORSE 0% (0 votes) 8. MORE than 5 full pulses: My primary condition SOMEWHAT improved 13% (3 votes) 9. MORE than 5 full pulses: My primary condition SIGNIFICANTLY improved 22% (5 votes) Total votes: 23 These results are more obvious when grouped. If we collect together everyone in early phase of treatment (#1-6) and we see that 26% are the SAME or WORSE 28% are SOMEWHAT IMPROVED 17% are SIGNIFICANTLY IMPROVED Actually, to have 35% already reporting any improvement in their condition this early in the protocol is striking to me. I expected less noticeable improvement at this stage, especially given the numbers being treated for otherwise "intractable" diagnoses such as MS and CFS/FM. But it is when users of the protocol get to 5 pulses (#7-9) or more, in this small sample, that the number in SIGNIFICANTLY IMPROVED seems to begin to creep upwards. Perhaps when we get a better sample of longer term users we will be able to sort out the "magic number" of pulses where more significant improvements take place. From reports in blogs and forums on this site, somewhere around 7-9 pulses seems to be a period where people are feeling much better and more significant changes in their primary diagnosis are occurring.
J Infect Dis. 2006 Jan 1;193(1):136-45. Epub 2005 Nov 29. Links
Chlamydia pneumoniae Alters Mildly Oxidized Low-Density Lipoprotein-Induced Cell Death in Human Endothelial Cells, Leading to Necrosis Rather Than Apoptosis.
Nazzal D, Cantero AV, Therville N, Segui B, Negre-Salvayre A, Thomsen M, Benoist H.
INSERM U466, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil and Universite Paul Sabatier, Toulouse, France.
Background. Atherosclerosis is characterized by oxidative stress that induces lipid and protein oxidation in the vascular wall. Oxidized low-density lipoproteins (oxLDLs) are present in lesions, and one of their actions is to induce apoptosis or necrosis in vascular cells. A role for Chlamydia pneumoniae in atherosclerosis has been proposed, but the mechanisms involved remain largely unknown.Methods. The in vitro effect of C. pneumoniae infection on apoptosis induced by mildly oxidized LDLs (moxLDLs) in human endothelial cells was studied.Results. Infection inhibited apoptosis, as was demonstrated by a decrease in such apoptotic features as cytochrome c release, caspase activity, 89-kilodalton poly(ADP-ribose) polymerase (PARP) fragment formation, nuclear condensation and fragmentation, and DNA fragmentation. However, the inhibition of apoptosis did not favor cell survival, because infection promoted cell death with necrotic features, as was illustrated by an increase in lactate dehydrogenase release, an enhancement of necrotic cellular morphological characteristics, and generation of low-molecular-mass PARP fragments. The increase in occurrence of necrosis-like cell death was correlated with a strong increase in intracellular reactive oxygen species (ROS) concentration. Vitamin E inhibited ROS production and promoted cell survival, underscoring the involvement of ROS in cell death induced by the combination of C. pneumoniae and moxLDLs.Conclusion. C. pneumoniae infection enhances the inflammatory action of oxLDLs in the vascular wall, leading to cell necrosis rather than apoptosis.
Circulation. 2004 Mar 16;109(10):1230-5. Epub 2004 Mar 1. Related Articles, Links
Heat-shock protein 60-reactive CD4+CD28null T cells in patients with acute coronary syndromes.
Zal B, Kaski JC, Arno G, Akiyu JP, Xu Q, Cole D, Whelan M, Russell N, Madrigal JA, Dodi IA, Baboonian C.
Cardiological Sciences, St George's Hospital Medical School, London, UK.
BACKGROUND: CD4+CD28null T cells are present in increased numbers in the peripheral blood of patients with acute coronary syndrome (ACS) compared with patients with chronic stable angina (CSA). The triggers of activation and expansion of these cells to date remain unclear. METHODS AND RESULTS: Twenty-one patients with ACS and 12 CSA patients with angiographically confirmed coronary artery disease and 9 healthy volunteers were investigated. Peripheral blood leukocytes were stimulated with human cytomegalovirus (HCMV), Chlamydia pneumoniae, human heat-shock protein 60 (hHSP60), or oxidized LDL (ox-LDL). CD4+CD28null cells were separated by flow cytometry and assessed for antigen recognition using upregulation of interferon-gamma and perforin mRNA transcription as criteria for activation. CD4+CD28null cells from 12 of 21 patients with ACS reacted with hHSP60. No response was detected to HCMV, C pneumoniae, or ox-LDL. Incubation of the cells with anti-MHC class II and anti-CD4 antibodies but not anti-class I antibodies blocked antigen presentation, confirming recognition of the hHSP60 to be via the MHC class II pathway. Patients with CSA had low numbers of CD4+CD28null cells. These cells were nonreactive to any of the antigens used. Circulating CD4+CD28null cells were present in 5 of the 9 healthy controls. None reacted with hHSP60. CONCLUSIONS: We have shown that hHSP60 is an antigen recognized by CD4+CD28null T cells of ACS patients. Endothelial cells express hHSP60 either constitutively or under stress conditions. Circulating hHSP60-specific CD4+CD28null cells may, along other inflammatory mechanisms, contribute to vascular damage in these patients.
Vnitr Lek. 2003 Feb;49(2):109-14. Related Articles, Links
Comment in:
Vnitr Lek. 2003 Feb;49(2):91.
[Effect of chronic Chlamydia infection with non-specific inflammation on cardiovascular complications in acute myocardial infarct]
[Article in Slovak]
Jaber AJ, Murin J, Hricak V, Tomasovic B, Kinova S, Kozlikova K, Ghanem W, Radman A.
I. interna klinika Lekarskej fakulty UK a FN, Bratislava, Slovenska republika.
It is known that local and systemic inflammatory processes play an important role in the genesis and development of atheroclerotic lesions and in the pathophysiology of acute coronary syndromes. This hypothesis is supported by findings of elevated parameters of the "inflammatory" reaction in the affected blood vessels but also in the blood of atherosclerotic patients. Known risk factors do not explain quite satisfactorily epidemiological cardiovascular phenomena and different manifestations of coronary heart disease. It is very probable that also Chlamydia pneumoniae is a risk factor. This assumption is based on evaluation of seroepidemiological data, examination of atherosclerotic plaques not only in humans but also in animal models with chlamydial infection. Based on retrospective and prospective evaluation of case-records the authors analyzed the incidence of cardiovascular complications in 83 patients with acute myocardial infarction (AIM), incl. 51 patients (31 men and 20 women, mean age 64.4 +/- 3.4 years who had a non-specific inflammation and chlamydial infection, and 32 patients (24 men and 8 women, mean age 64.7 +/- 3.6 years) who had chlamydial infections but no non-specific inflammation (in the blood). These patients were selected from all patients hospitalized during 1998-2001. When diagnosing acute myocardial infarction we applied WHO criteria, and the presence of at least two of three criteria was necessary: a history of prolonged (more than 20 min). stenocardia, electrocardiographic changes typical for ischaemia and/or necrosis and elevation of myocardial enzymes in serum, Non-specific inflammatory activity was present in patients (i.e. positive) if the following laboratory parameters were recorded: C-reactive protein > 5 mg/l assessed by the radial immunodiffusion method; fibrinogen > 4 mg/l assessed by the coagulation method according to Claus; leukocytes > 9.6 x 10(3)/microliter, leukocytes were counted automatically in a Coulter chamber; lymphocytes > 3.4 x 10(3)/microliter. Red cell sedimentation rate > 20 mm/hour. The activity was evaluated as positive when all parameters were elevated. The presence of chronic infection with Chlamydia pneumoniae was assessed qualitatively by antibody positivity (IgG) in serum using the microimmunoflurescent method (using a set from Labsystems Co.). The incidence of associated risk factors (obesity, smoking, diabetes, hyperlipidaemia and hypertension) is higher in the sub-group of patients with Chlamydia infections without inflammation, however, the difference is not statistically significant. The incidence of cardiovascular attacks was higher in the sub-group of patients with chlamydial infection and concurrent inflammation as compared with the sub-group of patients with chlamydial infection without inflammation. In case of re-infarction of the myocardium, a sudden cerebrovascular attack, death and arrhythmia the difference was statistically significant, while in case of cardiac failure and cardiogenic shock the difference was not significant. Patients with acute myocardial infarction with chlamydial infection and a concurrent non-specific inflammation had to be treated more often by combined (i.e. more intense) treatment, thrombolytic treatment, PTCA and surgery (bypass) of the coronary vessels as compared with patients with Chlamydia infections but without inflammation. The authors assume therefore that not only different risk factors but also the effect of non-specific inflammation and Chlamydia infection contribute towards the increased number of cardiovascular postinfarction complications. Therefore a therapeutic approach involving eradication of infection and suppression of the inflammatory reaction should be considered.
N Engl J Med. 2005 Apr 21;352(16):1637-45. Related Articles, Links
Comment in:
N Engl J Med. 2005 Apr 21;352(16):1706-9.
N Engl J Med. 2005 Aug 4;353(5):525-8; author reply 525-8.
N Engl J Med. 2005 Aug 4;353(5):525-8; author reply 525-8.
N Engl J Med. 2005 Aug 4;353(5):525-8; author reply 525-8.
Azithromycin for the secondary prevention of coronary events.
Grayston JT, Kronmal RA, Jackson LA, Parisi AF, Muhlestein JB, Cohen JD, Rogers WJ, Crouse JR, Borrowdale SL, Schron E, Knirsch C; ACES Investigators.
Department of Epidemiology, University of Washington, Seattle 98195, USA.
BACKGROUND: Epidemiologic, laboratory, animal, and clinical studies suggest that there is an association between Chlamydia pneumoniae infection and atherogenesis. We evaluated the efficacy of one year of azithromycin treatment for the secondary prevention of coronary events. METHODS: In this randomized, prospective trial, we assigned 4012 patients with documented stable coronary artery disease to receive either 600 mg of azithromycin or placebo weekly for one year. The participants were followed for a mean of 3.9 years at 28 clinical centers throughout the United States. RESULTS: The primary end point, a composite of death due to coronary heart disease, nonfatal myocardial infarction, coronary revascularization, or hospitalization for unstable angina, occurred in 446 of the participants who had been randomly assigned to receive azithromycin and 449 of those who had been randomly assigned to receive placebo. There was no significant risk reduction in the azithromycin group as compared with the placebo group with regard to the primary end point (risk reduction, 1 percent [95 percent confidence interval, -13 to 13 percent]). There were also no significant risk reductions with regard to any of the components of the primary end point, death from any cause, or stroke. The results did not differ when the participants were stratified according to sex, age, smoking status, presence or absence of diabetes mellitus, or C. pneumoniae serologic status at baseline. CONCLUSIONS: A one-year course of weekly azithromycin did not alter the risk of cardiac events among patients with stable coronary artery disease. Copyright 2005 Massachusetts Medical Society.
CPn and Cardiovascular Issues -
Z Kardiol. 2003 Jun;92(6):455-65.
Chlamydial and human heat shock protein 60 homologues in acute coronary syndromes. (Auto-)immune reactions as a link between infection and atherosclerosis
[Article in German]
Andrie R, Braun P, Welsch U, Straube E, Hopp HW, Erdmann E, Luderitz B, Bauriedel G.
Medizinische Klinik und Poliklinik II, Universitatsklinikum Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Recent studies provide evidence that infectious agents play a causal role in the pathogenesis of atherosclerosis. In this respect, a chronic persistent Chlamydia pneumoniae infection, indicated by the presence of chlamydial heat shock protein 60 (cHSP 60), is of central interest. Both cHSP60 and endogenous human (h) HSP60 are upregulated under stress conditions in intimal cells and serve as a target for cross-reactive cytotoxic HSP-serum-antibodies. Therefore, the present study evaluates the expressions of both HSP60 homologues in advanced human coronary lesions and a correlation between intimal tissuebound protein and serum antibodies (Ab) to HSP65. Coronary atherectomy specimens retrieved from 114 primary target lesions of patients with acute coronary syndrome (ACS; n=46) or stable angina (SA; n=68) were assessed immunohistochemically for the presence of cHSP60 and hHSP60. Chronic persistency of Chlamydia pneumoniae was additionally examined by transmission electron microscopy. Blood samples from30 patients were tested for anti-Chlamydia pneumoniae-IgG/IgA- and anti-HSP65-Ab titers and for serum CRP levels. Coronary plaques revealed immunoreactive cHSP60 in 47% and hHSP60 in 57% of the lesions colocalized within macrophages/foam cells. Chlamydia in foam cells most often presented ultrastructural patterns that pointed to the persistency of the pathogen. Intact, non-atherosclerotic vessels showed no signals. Mean expressions were 3.1% for cHSP60 and 3.3% for hHSP60. As a central finding, the expression of both HSP homologues was significantly (each p<0.001) higher in ACS lesions compared to SA lesions (cHSP60: 6.2 vs 1.0%, and hHSP60: 7.2 vs 0.7%). Moreover, we found positive correlations between both determinants in ACS and SA lesions (r=0.41, r=0.37; p<0.01). Most interestingly, cHSP60 revealed no relationship with anti-Chlamydia pneumoniae-IgG/IgA titers, whereas expression of cHSP60 as well as that of hHSP60 correlated with anti-HSP65-Ab titers (r=0.50, p<0.01, and r=0.42, p<0.05, respectively).cHSP60 and hHSP60 colocalize within coronary primary atheroma, most prevalent in lesions associated with ACS. For the first time, our data demonstrate a significant correlation between the intimal expression of these HSP60 homologues and serum HSP65 antibodies, thereby suggesting that humoral immune reactions to bacterial and human HSPs may play an important role in coronary atherosclerosis and plaque instability.