Most people have of a clear image of how atherosclerosis, popularly known as hardening of the arteries, causes a heart attack — fatty deposits called plaque build up in a coronary artery until the day the blood flow that sustains the heart is blocked.
If only they were right. In reality, severe coronary artery blockages almost always cause chest pain known as angina and other symptoms as they form. But among those who suffer heart attacks, half of the men and two-thirds of the women report never experiencing a warning symptom. And autopsies of such victims frequently show blood clots jammed into arteries that have been only modestly narrowed.
Standard atherosclerosis therapies include bypass surgery to route blood around blockages, angioplasty and stenting to clear blockages from inside the artery, and drugs like statins that reduce cholesterol levels to slow the formation of plaque. But they have not been enough to prevent 200,000 to 500,000 American deaths annually from what doctors refer to as coronary artery disease.
As a result, many researchers have turned their attention from atherosclerosis in general to the tendency of some patients to develop a form of plaque prone to inflammation and rupture, which can spill a stew of cells into the bloodstream that can incite rapid clotting. Such plaques have been called “vulnerable” plaque.
But little is known about how such plaques form and even less about how long they last or what makes them rupture. “Figuring out who is going to have plaque rupture would be the Holy Grail of cardiology,” said Dr. Deepak L. Bhatt, a leading research cardiologist at the Cleveland Clinic Foundation.
The broadest effort yet to do that will be announced today by a consortium pledging to invest $30 million over four years in an international plaque research program that will be overseen by Dr. Valentin Fuster, a cardiologist at Mount Sinai Medical Center in New York.
The initial sponsors include Humana, a leading manager of health plans; AstraZeneca and Merck, from the drug industry; and BG Medicine, a start-up company in Waltham, Mass., formerly known as Beyond Genomics. Royal Philips Electronics, which makes a variety of diagnostic machines widely used to scan the heart, the arteries that supply it with blood and other parts of the circulatory system, has participated in the planning and is expected to join them.
The centerpiece of the research will be a study of 4,000 to 6,000 Humana patients with at least two known risk factors for heart attacks. As the outcome for the patients becomes clear over the next few years, researchers hope the profiles that emerge from the study will, in hindsight, show patterns pointing directly to the high-risk patients who actually suffered heart attacks. That in turn could help the companies create new therapeutic products.
The payoff could be enormous for health care companies. Coronary stents, which limit the symptoms of atherosclerosis and the damage from heart attacks, but do not reduce the likelihood of future attacks, make up a $6 billion market for device makers and produce some of the biggest profit margins the industry has ever seen.
Drug makers have fared even better with statins, which partially reduce the risk of new attacks and top $20 billion in worldwide sales.
“How we treat the disease is up for grabs,” said Andrew S. Plump, who monitors early-stage research on warning signs and new medicines for cardiovascular disease at Merck’s research center in Rahway, N.J.
The initiative spotlights the growing lineup of research projects and technology investments that reflect competition between drug makers and device companies over who can develop the safest, most effective and cheapest products to combat atherosclerosis.
This summer, doctors financed by Abbott Laboratories finished enrolling 700 patients in a clinical study that is identifying the type and location of plaque in coronary arteries. Researchers are using ultrasound probes and other devices mounted at the end of long catheters. The catheters are inserted into the thigh and pushed carefully up into the coronary arteries, the same procedure used to clear blockages in angioplasty and to implant stents.
There are some doubts, however, that better understanding of vulnerable plaques will do much to improve preventive therapy, particularly that with devices. Atherosclerosis attacks the entire circulatory system, so skeptics predict that visions of stenting to reinforce thin-capped reservoirs of dangerous plaque would lead to a losing game of medical whack-a-mole — fixing one trouble spot, then finding many others.
“Multiple studies show that if you have one ruptured plaque, you have many,” said Dr. Steven E. Nissen, a Cleveland Clinic cardiologist and the current president of the American College of Cardiology.
