You Want to Test My Blood for What?

A blood test for a compound called CRP helps predict heart disease. But medical researchers don't agree on its prognostic value, and basic scientists are still debating whether it causes or merely accompanies heart trouble.

At your yearly checkup, your doctor might have given you a new blood test--that for C-reactive protein (CRP). Like high cholesterol, CRP seems to go hand in hand with heart disease: The more you have, the more likely you are to experience angina, a heart attack, or a stroke sometime within the next 10 years. Those over 70 might, however, be better off skipping the test and saving their $10.

But CRP's place in the medical armory is not assured. Although proponents hope that CRP screening will identify people at risk who might otherwise be overlooked, others insist that it won't add to the information gleaned from monitoring accepted risk factors. In addition, detractors doubt that lowering CRP quantities will reduce the risk of heart attack. As the debate rattles on, researchers are conducting large studies that should settle some aspects of the controversy within the next 5 to 10 years.

Although CRP testing for cardiovascular illness arose about 5 years ago, the connection between heart disease and CRP goes back decades. In the late 1920s, researchers discovered that CRP blood concentrations shoot up during inflammation, when the body is fighting off an infection. But in the 1960s, scientists found that CRP concentrations spike after heart attacks, too. Then about 10 years ago, two studies showed that people with cardiovascular illness who had elevated amounts of CRP were more likely to suffer heart attacks or die than were those whose CRP concentrations were normal. More recently, a 2004 study of 6500 Icelanders revealed that individuals with the largest concentrations of CRP have about a 50% greater chance of heart trouble than those at the lowest end of the CRP spectrum. That increase in susceptibility is comparable to the enhanced risk for heart disease in people who smoke or have high blood pressure.

Not counting CRP, screening for factors known to contribute to heart disease, such as smoking, high blood pressure, and high cholesterol, pinpoints up to 80% of people at risk. By plugging these factors and other health stats into an equation, physicians can estimate the likelihood that an individual will have a heart attack or stroke within the next 10 years. Physicians medicate the individuals at highest risk--those whose likelihood exceeds 20%--and congratulate those at lowest risk--those who score below 10%. But they're not sure how to handle people whose numbers fall in between, says lipid researcher Alan Tall of Columbia University Medical Center in New York City.

Enter CRP. Cardiologist Paul Ridker of Brigham and Women's Hospital in Boston, Massachusetts, says that clinicians could use CRP to guide their decisions on who needs treatment--and to identify some of the 20% of susceptible individuals the risk equation misses. Experts at the Centers for Disease Control and Prevention in Atlanta, Georgia, and the American Heart Association agree: They recommend that physicians screen people with a middling risk of heart disease for CRP.

Ridker also says that CRP is a risk factor in its own right. In 2002, he showed that people with low LDL cholesterol but high CRP concentrations are slightly more likely to have cardiac problems than are people with high LDL cholesterol and low CRP concentrations. This observation suggests that CRP can sometimes be a better predictor of heart disease than LDL cholesterol is.

However, immunologist Mark Pepys of the Royal Free and University College Medical School in London, U.K., says that fretting over CRP concentrations won't help physicians treat illness until scientists can determine whether CRP plays a biological role in cardiovascular disease. High LDL cholesterol, for example, contributes to plaques that build up in and harden blood vessel walls. When these plaques burst, a heart attack ensues. Reducing cholesterol concentrations with diet or drugs such as statins helpkeep blood vessel walls supple.

How CRP relates to heart disease is not clear. Because it is present in people who have sickly blood vessels, some researchers thought that the protein might contribute to atherosclerosis. But Pepys has pumped mice full of CRP and found no indication that the protein hardens the arteries or causes plaques to break. He has found, however, that in rats induced to have a heart attack, CRP exacerbates the damage by fueling an inflammatory response that destroys more cardiac muscle cells. For this reason, Pepys has patented CRP as a drug target to lessen the destruction that occurs during a heart attack. Such drugs won't prevent a heart attack, he says, but should lessen the severity of the trauma and perhaps decrease the chance of heart failure in the future.

At the same time, other researchers continue to search for evidence that decreasing CRP quantities might actually reduce the chance of having a heart attack. Cardiologist Steven Nissen of the Cleveland Clinic Foundation in Ohio showed that lowering LDL cholesterol amounts with statin drugs--which reduce the risk of heart attack--also cuts CRP quantities. But no one knows whether slashing CRP concentrations by itself will do the same. Drugs that diminish CRP amounts specifically are currently in development, says Ridker, who holds a patent on screening for CRP as a heart-disease risk factor.

Even if reducing CRP quantities does not directly stave off heart attacks, Ridker sees value in testing: An elevated CRP concentration could warn patients with no other risk factors--and perhaps persuade them to make changes that promote healthy hearts. He would tell a person with low cholesterol but high CRP concentrations, "Your risk is higher than your physician thinks it is," says Ridker. "Would you be more motivated to go to the gym, lose 5 pounds, work out every day, eat a healthier diet? That's the entire question in risk prediction."

Although CRP testing is controversial, the over-70 group might be able to turn a deaf ear to the cacophony. Epidemiologist Stephen Kritchevsky of Wake Forest University School of Medicine in Winston-Salem, North Carolina, measured CRP amounts in 3000 people between the ages of 70 and 79 and found that its concentrations couldn't predict heart disease. He suspects that elderly people wind up with so many disorders that provoke inflammation--arthritis, diabetes, kidney trouble, even periodontal disease--that elevated CRP quantities aren't specific to heart disease. With all that noise, he says, "the signal gets lost."

For the under-70 set, however, it seems likely that some doctors will administer the $10 test, particularly to patients whose other risk factors place them squarely in the middle ground. So, if you want to avoid an extra needle prick, perhaps you should follow Ridker's prescription--cut down on the cheeseburgers and head to the gym.

Mary Beckman is a writer in southeast Idaho who reacts badly to any siphoning off of her blood.