Nov. 6, 2000 -- Having an infectious disease may put some people at increased risk for hardening of the arteries, heart disease, and death, suggest researchers in two studies published in the Nov. 7 issue of Circulation: Journal of the American Heart Association.
In the first study, researchers from the University of Washington in Seattle found that among a group of people aged 65 and older, those who had evidence in the bloodstream of antibodies to the herpes simplex virus type 1 -- indicating that they had been exposed to the virus at some time in their lives -- were twice as likely to have had a heart attack or die from heart disease, compared to those who had never been exposed.
In the second study, scientists at the University of California at Davis found evidence that Chlamydia pneumoniae bacteria, which cause lung infections and a type of pneumoniae, may piggyback onto immune system cells, traveling through the bloodstream to the arteries near the heart where they can set up shop and possibly start the process that leads to hardening of the arteries and heart attack.
Taken together, the studies add to the mounting body of evidence that infectious diseases and inflammation are major contributors to atherosclerosis, or hardening of the arteries, and to heart disease. Until recently, however, efforts to understand what causes atherosclerosis had tended to focus on the usual suspects: high cholesterol, cigarette smoking, diabetes, high blood pressure, genetic factors, elevated blood levels of the protein homocysteine, or a combination of all or some of these factors.
But as the late Russel Ross, PhD, professor of pathology at the University of Washington School of Medicine, noted in an interview with WebMD in 1999, there is an impressive body of evidence that strongly suggests that atherosclerosis begins with damage to the cells that line blood vessels supplying the heart. The vessels then begin to narrow as the cells attempt to repair themselves, causing inflammation, and that in turn attracts and traps cholesterol and immune system cells the way a bathroom drain traps and becomes choked with hair.
"Certainly the interest and all the work that's been going on in inflammation raises the interest in infections as well," David S. Siskovick, professor of medicine and epidemiology at the University of Washington, tells WebMD. "Whether our observation or other observations related to infection account for the inflammation associations or vice versa is unknown, but it does potentially fit."
In their study, Siskovick and colleagues looked at data on antibody levels in the blood of more than 600 participants aged 65 years or older. The study group included 213 people who had died from a heart attack. The remaining participants in the study were included for comparison purposes. The researchers looked for antibodies to the herpes simplex virus type 1, Chlamydia pneumoniae, and another common infectious agent, cytomegalovirus.
They found that among these older subjects, people who had evidence in the blood of antibodies to the herpes virus were twice as likely as others to have had a heart attack and to have died from heart disease. In contrast, exposure to cytomegalovirus apparently did not increase a person's risk for heart attack, and only those with very high blood levels of antibodies to Chlamydia pneumoniae were at increased risk for heart problems, although the reasons why are unclear.
One expert, though, cautions that antibody levels may not be the most reliable means for determining associations between infection and heart disease. "Antibody [levels] are not very specific in telling who has just been exposed, who is currently infected, or who was chronically infected," says Ignatius W, Fong, MD, professor of medicine at the University of Toronto and head of the division of infectious diseases at St. Michael's Hospital, also in Toronto.
"What you get is a mishmash of patients you look at who may have a combination of previous exposure but are not persistently infected, some who are persistently or chronically infected -- which we think are the ones that will have it in the circulating blood cells and are more at risk for having atherosclerosis -- and the antibody [tests] cannot differentiate them; you can get an overlap and conflicting data from various studies," Fong says.
Siskovick acknowledges that measuring antibody levels essentially gives a snapshot only of prior infections, when "what we're really interested in is chronic infection, reinfection, reactivation of infection, and so on." But because they did not have any way to accurately gauge infections by other means, they designed their study to ask whether previous infection as reflected by the presence of antibodies was related to the risk of heart attack and death from a heart attack in older adults. The signs, Siskovick and colleagues contend, indicate that the answer to that question is probably yes.
In the second study, Ravi Kaul, PhD, associate professor of pediatric infectious disease at the University of California at Davis, looked for evidence of bacterial DNA in cells rather than antibodies in the bloodstream as a sign that a person previously had been infected. They looked for the DNA fingerprints of Chlamydia pneumoniae in immune system cells in 28 patients with coronary artery disease and 19 healthy blood donors.
They found that the bacterial DNA was incorporated into a specific type of immune system cells in 13 of the heart patients and five of the healthy controls. The finding suggests that Chlamydia pneumoniae, which primarily infects lung cells, slips into circulation by piggybacking onto certain immune cells.