DALLAS, May 13 – Chronic infections, autoimmune conditions and inflammation work together to increase the risk of heart disease, according to the first study to examine a possible relationship between the three conditions and the development of heart attacks. It's reported in today's rapid access issue of Circulation: Journal of the American Heart Association.
Earlier studies indicated an association between elevated levels of antibodies against the pneumonia-causing pathogen Chlamydia pneumoniae (C pneumoniae) and atherosclerosis. In this study, researchers found that elevated levels of those antibodies by themselves did not significantly raise the risk of heart attack or other coronary events, says lead author Tiina Huittinen-Sävykoski, M.Sc., a Ph.D. candidate at the National Public Health Institute in Oulu, Finland.
Other factors seem to be needed to cause heart disease.
Researchers analyzed data from 4,081 men in the Helsinki Heart Study, a large study of middle-aged Finnish men with high blood cholesterol. Researchers tested blood samples from 241 men who had fatal or non-fatal heart attacks and from 241 men (controls) without heart attack. Researchers were looking for the presence of three factors: C pneumoniae antibodies, human heat-shock protein 60 (hHsp60) antibodies and C-reactive protein (CRP).
The presence of hHsp60 antibodies indicates an autoimmune response. It's thought to be critical in autoimmune disease and it has been suggested that autoimmune response may lead to the development of atherosclerosis. CRP is an indication of low-grade inflammation. "Ours is the first study to look for possible synergistic effects of these three factors, and those effects appear to be strong," Huittinen-Sävykoski says.
After adjusting for age and smoking status, the researchers found that during more than eight years of follow up, men with persistently elevated levels of antibodies to C pneumoniae or hHsp60 had about twice the risk of having a fatal or non-fatal heart attack than those with low levels of C pneumoniae and hHsp60 antibodies.
However, the risk of heart attack associated with C pneumoniae and hHsp60 antibodies was much higher when CRP level was also elevated. Men with persistently elevated CRP and C pneumoniae antibody levels had more than four times higher risk for coronary events than men with normal CRP and C pneumoniae antibody levels, Huittinen-Sävykoski says. The risk was similar for those with elevated CRP and hHsp60 antibody levels. The risk was highest when all three factors were elevated.
"One of our interesting findings was that all three conditions were found in 17 patients but in only one member of the control group," she says.
In addition, inflammation (elevated CRP levels) was only weakly associated with coronary risk if the C pneumoniae or hHsp60 antibody levels were low.
"Almost everybody gets infected with C pneumoniae at least once during their lifetime and reinfections are also common," Huittinen-Sävykoski says. "But it does not always promote heart disease."
"If ongoing clinical trials find that antibiotics can prevent heart attacks, it will become very important to be able to identify people with active chronic infections for treatment," she says. "This study suggests that a combination of persistently elevated levels of C pneumoniae and hHsp60 antibodies and CRP would be a useful marker."
Atherosclerosis, the process that narrows the blood vessels and can lead to heart attack and stroke, is now considered an inflammatory process. Inflammatory cells and other indications of the body's response to injury are present in fatty plaque clogging arteries. Several studies have also found C pneumoniae present in the plaque.
Living creatures produce heat-shock proteins to protect themselves from damage from chemical and other environmental factors, including microbial infections. Bacteria also produce the proteins, she says.
"C pneumoniae causes stress to the cells in which it resides and the cellular defense against the bacterium causes stress to the Chlamydia, which leads to expression of both human and bacterial heat-shock proteins," Huittinen-Sävykoski explains.
Because heat-shock proteins are similar in many species, some scientists have theorized that in the course of the body's efforts to eliminate the bacteria, it might mistakenly attack its own heat-shock proteins in addition to the bacteria, thus producing antibodies to both the chlamydial Hsp60 and to its own hHsp60, she says.
The association only held when the infection or autoimmune processes were persistent – appearing in two blood samples taken at different times – rather than transient, she notes.
"It seems that chronic infection, autoimmunity and inflammation may have combined in causing a part of coronary events in this study population," Huittinen-Sävykoski says.
Co-authors are Maija Leinonen, Ph.D.; Leena Tenkanen, Ph.D.; Hanna Virkkunen, M.Sc.; Matti Mänttäri, M.D., FESC; Timo Palosuo, M.D., Ph.D.; Vesa Manninen, M.D., Ph.D.; and Pekka Saikku, M.D.; Ph.D.
The above post is reprinted from materials provided by American Heart Association. Note: Materials may be edited for content and length.
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