Probing the Workings of Hearts and Minds
A subtle, unexpected attack on the coronary arteries by the body’s own immune system may be the cause of as many as half of all of heart attacks and cases of coronary artery disease, Harvard scientists report today.
It may also explain why aspirin is so good at preventing heart attacks.
If the study is confirmed, it suggests that pharmaceutical companies should explore development of a whole new class of heart drugs that focus on inflammation, the researchers said. It also suggests that a high risk of heart attack in at least some patients could be detected with a simple blood test as long as eight years in advance of a potential heart attack.
The research suggests that white blood cells, triggered perhaps by a virus or bacterium, can eat away at the walls of the blood vessels to produce an ulcer-like lesion that eventually triggers formation of a life-threatening clot, cardiologists said.
The idea that this inflammation of the arteries can cause heart attacks has been circulating through the cardiology community for at least two years, but the new study, in the New England Journal of Medicine, appears to provide the strongest support for it yet.
The Harvard team, operating out of Brigham and Women’s Hospital in Boston, gauged inflammation in 1,086 volunteer doctors by measuring blood levels of a substance called C-reactive protein.
They found that men with the highest levels of the protein were three times as likely to have a heart attack and twice as likely to have a stroke as men with the lowest levels, independent of other risk factors for heart disease.
They also found that aspirin, which has been widely touted in preventing heart attacks because of its anti-clotting properties, reduced the risk of heart attack by 55% in the men with the highest levels of C-reactive protein, but had little effect in men with the lowest levels.
That suggests that it is the anti-inflammatory properties of aspirin that produce its protective effect, more than its blood-thinning properties.
Researchers have been interested in the role of infectious agents and inflammation in heart disease because the conventional risk factors--smoking, hypertension, high cholesterol levels--explain only about half of all heart attacks. The other half “is a substantial unknown territory,” said Dr. George Sopko of the National Heart, Lung and Blood Institute.
“I think this is a very important paper that highlights for us . . . the potential role of infectious agents in heart disease,” Sopko said. “This is a lead that I consider very exciting.”
The work “supports the concept that inflammation can cause heart disease,” added Dr. Valentin Fuster of the Mt. Sinai Medical Center in New York City.
“But we should be very cautious in extrapolating the data to test for C-reactive protein in large numbers of people,” Fuster added. “It needs more research.”
Some researchers have found traces of viruses or bacteria--particularly herpes viruses, chlamydia and helicobacter (which causes ulcers)--in artery-blocking clots. Those traces have been isolated events that are considered suspicious, but not proof of the role of infectious agents.
More recently, however, many researchers have shown in autopsies and biopsies from heart attack victims that the clots contain unusually high numbers of monocytes, white blood cells crucial to the immune response.
Pathologist Benjamin Victor and cardiologist Dr. Richard Helfant of UC Irvine, among others, have reported that these monocytes secrete enzymes that literally eat away at artery walls, weakening them and triggering clot formation.
The new Harvard study strongly supports the role of inflammation. The vast majority of the physician volunteers in the study, part of the Physicians’ Health Study begun in 1982, were healthy individuals with few of the conventional risk factors for heart attacks or stroke.
Like them, “a large number of people who suffer heart attack and stroke have no readily apparent risk factors,” said Dr. Paul Ridker, who headed the study. This study suggests that inflammation smoldering in blood vessels for a period of years may be the most important risk factor for them, he added.
But the team cautioned that they have not studied women and that they did not attempt to determine what produced the inflammation. While it is possible that it could be the result of an infection, Sopko noted, it could also be caused by environmental toxins, such as tobacco smoke, or other unsuspected agents. Fuster thinks such inflammation may be a response to the accumulation of even small amounts of cholesterol in the walls of blood vessels.
Clearly, added Dr. Charles Hennekens, who heads the Physicians’ Health Study, more research is needed.
