Inflammatory findings
Gerald Thornell was 64 years old, with no family history of heart disease, good cholesterol and blood pressure numbers, and normal weight. He'd never smoked, was an avid runner, and had been taking half an aspirin a day for 10 years. Yet the Marion, Mass., college professor had a heart attack a few days before Thanksgiving. Christopher Cannon, his cardiologist at Brigham and Women's Hospital in Boston, blames inflammation.
Cannon is a coauthor of one of a pair of studies in the latest New England Journal of Medicine that make a case for tracking not only LDL (bad) and HDL (good) cholesterol in known and potential heart patients but also their C-reactive protein. Elevated CRP is a signal of inflammation, which most heart experts now agree is involved in coronary artery disease. Cannon, who first saw Thornell after his heart attack, notes that late in 2003 his CRP was 2.7 milligrams per liter. A safe blood level of CRP is considered to be below 1 mg/L; 3 mg/L and above is deemed risky. Thornell, says Cannon, "was doing all the right things, and he still had elevated CRP--so inflammation may literally have been the cause of his heart attack."
Statin drugs reduce heart attack risk by lowering LDL cholesterol. They also cut CRP. After mining data from two of their previously published clinical trials, Brigham and Women's cardiologist Paul Ridker and Cleveland Clinic cardiologist Steven Nissen, lead authors of the two new studies, concluded that reducing CRP is as important for patients with heart disease as is lowering their LDL.
Ridker's prior trial had tested two statins--a high dose of Lipitor and a moderate dose of Pravachol--on the rate of future heart attacks in patients who had already had one or who had severe chest pain. Lipitor yielded benefits so unexpectedly large that Ridker thought another explanation besides LDL was possible. Using an ultrasound device, Nissen's team had directly revealed that high-dose Lipitor in patients with heart disease stopped or shrank the fatty plaque building up in their coronary arteries; a moderate dose of Pravachol slowed the buildup but did not halt or reverse it. Nissen, too, was seeking a reason besides LDL.
They contend it is CRP. Ridker's new findings show that over a 2 1/2-year period, patients who achieved both low LDL (under 70 milligrams per deciliter) as well as low CRP (below 2 mg/L) did far better than patients who met one goal but not the other. And Nissen's data showed that plaque receded only when both CRP and LDL were slashed.
Get tough. Ridker says doctors should be far more aggressive in prescribing statins for heart attack patients and in dosing based on CRP as well as LDL. "The vast majority of patients on statins are on a very small dose," says Ridker. "Physicians are very conservative." Following his advice, he says, would save tens of thousands of lives. "I used to be a CRP skeptic," says Nissen. "I was wrong."
Not everyone considers the two studies a launching pad for a CRP initiative. David Siscovick, codirector of the cardiovascular health research unit at University of Washington Medical School, calls the conclusions a "small step," coming from after-the-fact analysis of previous work done for other reasons, not from a direct test of CRP as an independent risk factor. Siscovick also notes that both Ridker and Nissen receive funds from statin manufacturers and that Ridker is a coinventor of a laboratory process related to CRP measurement.
But orders for CRP tests are bound to rise, and more patients will hear that their CRP is high. If so, the test should be redone in two weeks and the results averaged. Besides statins, losing a few pounds can reduce CRP. In one study, 25 percent of obese participants had elevated CRP compared with 10 percent for those who were overweight and 5 percent for those of normal weight. Even a little regular exercise can be beneficial. Researchers reported recently that among 3,000 healthy Greek individuals, the CRP of those who engaged in modest regular physical activity averaged about 20 percent below that of those who were sedentary. Strangely, aspirin doesn't seem to reduce CRP. Researchers found that various doses of aspirin over a month had little effect on CRP in a group of 57 people. Drugs aimed specifically at lowering CRP are being tested--among them Actos, a diabetes medication, and Acomplia, an antiobesity drug.
Cannon has put Thornell on a high dose of Lipitor. "To people who know me," Thornell says, "the message was that if I've had a heart attack, they could."
TWIN TARGETS
After 2 1/2 years, heart patients whose LDL cholesterol and CR (C-reactive protein) levels both were driven down had a lower rate of heart attacks and heart-related deaths than did patients with reduced LDL or CRP alone.
[Chart data]
Met neither goal 10 pct.
Met cholesterol goal 7 pct.
Met CRP goal 7 pct.
Met both goals 5 pct.
[Relative to the first bar, the second and third bars should be .7 as long and the fourth bar should be .5 as long.]
Source: Brigham and Women's Hospital
Graphic by USN&WR
This story appears in the January 17, 2005 print edition of U.S. News & World Report.