Monday, January 10, 2005
Reducing the levels of a certain protein secreted by the body may be as powerful a tool in slowing heart disease and preventing heart attacks and cardiac-related death as lowering cholesterol, two teams of researchers are reporting today.
One of those researchers is Paul Ridker, the media's favorite cardiologist, holder of a patent for the CRP test, and the most vocal advocate of CRP as cardiac risk factor:
"What we now have is hard clinical evidence that reducing CRP is at least as important as lowering cholesterol," said Dr. Paul Ridker of Brigham and Women's Hospital in Boston, the lead author of one of the studies.
Dr. Ridker's study does show improvement in relative risk, even when he controls for other conditions such as diabetes and hypertension and age which can also increase the risk of heart disease. He does not, however, give us the absolute risk or the raw data for those categories. That should make us supsicious that perhaps the absolute risk isn't so impressive.
Others, with less bias, also urge caution:
But other heart disease researchers cautioned that more work was needed to prove that CRP directly causes heart disease. And most agreed that because the new studies involved only people with severe heart disease, it remained unknown whether healthy people would benefit from reducing their CRP levels.
...Others, though, said CRP could instead be a marker for something else being fought by statin drugs to reduce heart disease risk.
"These are very important papers," said Dr. James I. Cleeman, coordinator of the National Cholesterol Education Program at the National Heart, Lung and Blood Institute. "They are provocative. But we need to recognize that the relationship between CRP and heart disease is a developing story. This adds to the evidence, but I'm not sure it settles the issue."
The burning question is, is CRP a cause of heart disease or a symptom? Chest pain, for example, is a symptom. Eliminating chest pain would eliminate a good number of heart attacks and reduce heart disease. However, not all chest pain is caused by heart disease. The second study, from the Cleveland Clinic, attempts to determine CRP's role:
Dr. Nissen's study, sponsored by Pfizer, examined plaque in the coronary arteries of 502 patients with heart disease, comparing intense statin therapy against moderate and using the same doses of the same drugs as in Dr. Ridker's research.
Intense therapy resulted in lower cholesterol levels and slower growth of plaque, Dr. Nissen reported. But he also suspected that something else was going on, because some patients seemed to be doing much better than others with the same cholesterol levels.
Upon further analysis, Dr. Nissen found that levels of CRP dropped independently of cholesterol and that these reductions were independently associated with a slowing of disease progression. In patients who achieved low levels of both CRP and cholesterol, he found, plaque in the coronary arteries actually regressed.
"I'm looking right at the plaque, and when your CRP level is reduced, you are stopping the disease," Dr. Nissen said. "We are saying that CRP is a direct participant in atherosclerosis."
When he says he's "looking right at the plaque," he means that he's using an
ultrasound probe that's threaded into the artery. It uses sound waves to estimate the diameter of the blood vessel and the size of the plaque. How reliable is the estimate? Hard to say. It's still a rather experimental procedure, not one that's been widely adopted by hospitals or by doctors of varying skills.
A similar technique, however, is widely used to measure the degree of plaque build-up and stenosis in much larger arteries, although it doesn't require the use of an intravascular probe since the arteries in question are so much closer to the surface of the body. That technique is the carotid artery doppler. And, while it's a useful screening test, as an accurate measure of the amount of plaque and stenosis, it leaves a lot to be desired. I have had patients who made absolutely no changes in their smoking or medical regimen but whose carotid artery dopplers vary by as much as 20% from year to year. They may start out with a reading that indicates they have 50% stenosis, for example, but a follow-up ultrasound in another year shows it to be only 30%. The interpretation varies so much from reader to reader, and the technique varies from test to test that it's really only useful as a screening tool, not as an absolute measure of disease. (For that we use the much more invasive angiography which involves the injection of dye into the arteries.)
Granted, the intravascular coronary ultrasound has the advantage of having its probe inside the vessel, but caution is still needed when it comes to interpreting the significance of C-reactive protein as a cause of coronary artery disease, much less a screening test for it.
posted by Sydney on 1/10/2005 08:50:00 AM 0 comments