CRP: Molecule of the Moment

We don't think of molecules as fashions, but in fact medical science has its own version of rising and falling hemlines. And C-reactive protein appears to be the "in" molecule at the moment. Scientists who study atherosclerosis—that's the disease that clogs your arteries with fat and triggers heart attacks and strokes—have recently rediscovered this age-old agent that rises like a fever when the body is fighting off injury or infection. The renewed interest is this: It appears that CRP tends to be higher in people whose arteries are clogging, so it may be a better risk factor than LDL, the so-called bad cholesterol that we've focused on for years.

Perhaps so. The new research is exciting. But it doesn't mean that we should take cholesterol out of our risk calculations. And, before we search for a drugstore measure-it-at-home-kit, it's prudent to put CRP in its biological context. Arteries don't just wear out like old tires. Atherosclerosis is a sneaky, chronic, inflammatory process that slowly ravages arteries. Early on, the artery damage is pretty benign: a yellow streak on a clean white landscape of cells lining an artery. As the disease advances, we see an ugly, ulcerating killer beast, loaded with cholesterol crystals, liquid fat, dead tissue, calcium, nasty-looking white blood cells, scars, and the beginnings of blood clots that in a flash can choke off an artery and strangle blood flow.

Untold story. Getting to that point is a dramatic story, not yet fully written in the annals of medicine. Injury and dysfunction of the cells that line the arteries are central players. These cells send out SOS signals to the rest of the body that they are wounded. The signals activate the immune system to send in forces—specialized white cells and a host of molecules, including CRP—to try to contain and repair the injury and fight off the offender. Many factors can injure the artery wall and incite this response. Bad cholesterol itself can trigger such a response and is a known culprit at least half the time. High blood pressure stresses arteries, as does diabetes. Tobacco is a brutal toxin. Age, genes, and male gender also weigh in. All of these risk factors tend to pile on, each making the other worse.

The good news is that we can do something about this toxic mess. Lowering cholesterol and blood pressure, cutting out tobacco—all these steps prevent the slow burn of the atherosclerotic process. The frustrating news is that 1 in 4 patients with severe atherosclerosis has no known risk factors—no family history, decent blood pressure, and normal lipid readings. It's a stark reminder that some heart disease culprits are still out there, on the loose.

But CRP, for all its promise, can still be a tremendously difficult marker to read. For example, certain medicines can raise CRP, for no known reason. Obese children have higher CRP readings. Women on average have higher levels of CRP than men, even though they are less likely to have atherosclerosis. Any infection can cause CRP to rise. Many have scoffed at the notion of microbes as agents of atherosclerosis. But that is exactly what microbes of syphilis were until penicillin knocked the raging atherosclerosis of late syphilis into oblivion and off the risk-factor radar screen. Microbe hunting is regaining respectability, especially in light of some provocative new studies associating atherosclerosis with microbes like chlamydia and helicobacter, the bacterium that causes stomach ulcers. But CRP also increases with infection or inflammation that does not involve arteries—such as arthritis or bronchitis. We need to know what all this means and when an elevated CRP signals artery disease and when it's a false alarm. Until we do, it's premature to think of using this promising protein to screen healthy individuals as a matter of course.

Caveats aside, CRP is a hot molecule. And it will be even hotter if we find that lowering CRP (with aspirin, for example) reduces heart attacks and strokes. That would suggest that CRP is not just a marker but also another cause of atherosclerosis. At the very least, CRP is emerging as an intriguing monitoring and prediction tool for suspected cardiovascular disease. A colleague of mine, infectious-disease specialist Robert Munford of Dallas, calls elevated CRP the "eyes of the hippopotamus"—the sign of a huge beast lying below the river's surface. We just need to keep in mind that the eyes are not the beast and that looking in a beast's eyes doesn't enable us to tame its terrible behavior.