Protein's Link to Heart Disease Is a Mystery

By GINA KOLATA

Published: January 11, 2005

When Richard Newton read in a magazine last year that high levels of a protein called CRP were as powerful as high cholesterol in predicting heart disease risk, he went to his doctor to be tested.

Mr. Newton, a 60-year-old retired electrician in Lynnfield, Mass., assumed that his level of CRP (the letters stand for C-reactive protein) would be low, just like his cholesterol level. His overall health was good. He did not take any prescription drugs and had normal blood pressure. And although he smoked, he was not overweight and he exercised every day, playing tennis or spending an hour on an elliptical cross-trainer.

But to Mr. Newton's astonishment, the simple blood test done by his doctor showed that his CRP level was 3.1, higher than normal, meaning that he ran twice as much risk of having a heart attack or dying from heart disease as people whose levels were lower than 1 milligram per liter of blood.

He asked for the test to be repeated, "just to make sure," he said.

In August, he had another CRP test. Once again, the level was 3.1.

"I don't know how you get it down," Mr. Newton said. "I don't know what it means. Are your arteries swollen up or does it make your arteries swell up?" In the meantime, he worries.

Mr. Newton's quandary is becoming more common as scientists become increasingly convinced that CRP and heart disease are linked but do not know exactly what the relationship is. Until recently, it was the doctors who made the decisions about whether and whom to test for CRP. Most patients had never heard of the protein. That has been changing with increasing publicity; after widespread news reports on two studies published in The New England Journal of Medicine last week, some doctors say they are being flooded with requests from people who want a CRP test, now.

Many insurers pay for the test, whose list price at one national testing laboratory, Quest Diagnostics, is $55, according to Gary Samuels, a company spokesman. "Plans that haven't covered it are re-evaluating it in light of the new studies," he said.

Scientists have known for some time that CRP levels can predict the risk of heart attack as powerfully as better-known risk factors like high blood pressure and high cholesterol. The higher the CRP level, the greater the risk. But they still did not know whether reducing the level would reduce the risk.

The new studies addressed that by analyzing what happened when heart patients took statins, the drugs that lower cholesterol. Statins, it turns out, also lower CRP levels, but that effect is independent of their effect on cholesterol. That allowed the investigators to ask: Is lowering CRP independently protecting patients from heart attacks and the worsening of atherosclerosis?

The answer, the researchers found, appeared to be yes. But the studies involved patients with severe heart disease, not healthy people or people at risk for heart disease. Studies are now under way in healthy people, but, in the meantime, cardiologists are divided about whether it is helpful to measure CRP in most patients and what to do when the level is high.

Some cardiologists - including Mr. Newton's, Dr. Christopher Cannon of Brigham and Women's Hospital in Boston - say nearly all patients can benefit from knowing their CRP. If it is high, he said, that can motivate patients to take measures to reduce their risk of heart disease. (Dr. Cannon, an author of one of the new reports on CRP, receives honorariums and research financing from a variety of companies making drugs for heart disease, and he serves on advisory boards for 10 companies.)

The levels of the protein, which is made in the liver and in cells lining blood vessels, rise with things that make heart disease more likely, like smoking, obesity, high cholesterol and diabetes. They fall when patients stop smoking, lose weight and get their cholesterol and diabetes under control.

But the exact role of CRP remains subject to debate. Infectious-disease specialists note that the protein is part of the body's way of fending off microbes. When an infection begins, CRP latches onto microbial invaders, marking them for destruction by white blood cells.