WEDNESDAY, Nov. 5, 2003 (HealthDayNews) -- A manmade cholesterol that mimics the blood of unusually healthy Italian villagers took only six weeks to reverse atherosclerosis in patients whose arteries had become clogged over a period of decades.
If the success of this therapy continues, it could open a new front in the war against heart disease. In the last decade, the gold standard of preventive medicine has been the use of statin drugs, which lower low-density lipoprotein (LDL, or the "bad" cholesterol). In this case, the patients got an intravenous infusion of synthetic high-density lipoprotein (HDL, or the "good" cholesterol).
"This is an extraordinary and unprecedented finding," Dr. Steven Nissen, a Cleveland Clinic cardiologist who directed the study, said in a statement. "This is the first convincing demonstration that targeting HDL, good cholesterol, can benefit patients with heart disease, the leading cause of death in the United States."
Details of the research appear in the Nov. 5 issue of the Journal of the American Medical Association.
The development of the manmade cholesterol started 30 years ago, when researchers noticed that 40 people living in the village of Limone sul Garda in northern Italy were heart-healthy despite having very low levels of HDL, which should have left them vulnerable to disease. They lived long lives, and their arteries were remarkably clear.
"Normally, we get very, very concerned because they're at high risk," said Dr. E. Murat Tuzcu, a cardiologist and professor of medicine at the Cleveland Clinic who took part in the study. "There was clearly something that was abnormal."
The researchers discovered that these people carried a variant in a blood protein called apolipoprotein A-1, which is a component of HDL. They named it ApoA-I Milano, after the city of Milan, where the original work was done. Researchers at Esperion Therapeutics Inc., a biotech firm in Ann Arbor, Mich., derived a synthetic version of this protein through recombinant DNA technology. The company sponsored the trial.
The study, led by the Cleveland Clinic team, was conducted at 10 centers across the United States. The trial was small, involving only 47 patients, aged 38 to 82, who had a cardiovascular event such as heart attack or angina. Their arteries were measured by highly sensitive ultrasound for clogging.
The patients were assigned to three groups: 11 got a placebo, with the rest getting either a high or low dose of the synthetic cholesterol. The injections were weekly for five weeks.
After six weeks, the team conducted ultrasounds again on the arteries. Tuzcu said those who got the therapy saw their arteries clear by 4 percent. "That may not sound great, but actually it is," he said. "It is the first time in a human being that we can change or regress atherosclerosis in six weeks. Incredible."
"You can take away a couple of years of the accumulation of cholesterol," said Roger Newton, president and chief executive officer of Esperion Therapeutics. The company won the rights to develop this method of reversing heart disease in 1998, and it was the "cornerstone" of its founding, he added.
Tuzcu said he envisions a two-pronged approach to fighting atherosclerosis, using both this drug and statins. "This offers the possibility that there's a whole new weapons system that's been developed," he said.
More, larger studies are needed, Tuzcu cautioned. However, "we are at the beginning of a journey. It is a very exciting time."
Newton also said that combining this with statins would produce a "synergistic" effect, since every 1 percent increase in HDL lowers a person's heart risk by 2 percent to 3 percent.
Dr. Roger Blumenthal, a cardiologist at Johns Hopkins School of Medicine and a spokesman for the American Heart Association, called the new research "very provocative and very exciting work and could potentially be the next main thing to deal with people who get a high amount of cholesterol."
Blumenthal said most of the focus of existing medicines to treat heart disease has been on lowering LDL and triglycerides. But this study shows the benefits of trying to raise HDL levels, which "is another way to go about the problem of high cholesterol."
"This is very innovative work," he adds. "Its impact won't be from infusion, but whether or not we can give the medicine orally, in pill form."
That's not likely to happen anytime soon, Newton said, adding, "it will always be an infusion."
The next step is to expand the trial to 1,500 to 2,000 patients and follow their progress for a year, Newton said. Another possibility is to see how it works in preventing a first cardiovascular event in those at high risk.
"We've done OK, but we can do better," he said.
More information
For more on cholesterol and how to keep it low, visit the American Heart Association or the National Institutes of Health.
