Is Your Heart on Fire?
Not long ago, most doctors thought of heart attacks as primarily a plumbing problem. Over the years, fatty deposits would slowly build up on the insides of major coronary arteries until they grew so big that they cut off the supply of blood to a vital part of the heart. A complex molecule called LDL, the so-called bad cholesterol, provided the raw material for these deposits. Clearly anyone with high LDL levels was at greater risk of developing heart disease.
There's just one problem with that explanation: sometimes it's dead wrong. Indeed, half of all heart attacks occur in people with normal cholesterol levels. Not only that, as imaging techniques improved, doctors found, much to their surprise, that the most dangerous plaques weren't necessarily all that large. Something that hadn't yet been identified was causing those deposits to burst, triggering massive clots that cut off the coronary blood supply. In the 1990s, Ridker became convinced that some sort of inflammatory reaction was responsible for the bursting plaques, and he set about trying to prove it.
To test his hunch, Ridker needed a simple blood test that could serve as a marker for chronic inflammation. He settled on Creactive protein (CRP), a molecule produced by the liver in response to an inflammatory signal. During an acute illness, like a severe bacterial infection, levels of CRP quickly shoot from less than 10 mg/L to 1,000 mg/L or more. But Ridker was more interested in the low levels of CRP — less than 10 mg/L — that he found in otherwise healthy people and that indicated only a slightly elevated inflammation level. Indeed, the difference between normal and elevated is so small that it must be measured by a specially designed assay called a high-sensitivity CRP test.
By 1997, Ridker and his colleagues at Brigham and Women's had shown that healthy middle-aged men with the highest CRP levels were three times as likely to suffer a heart attack in the next six years as were those with the lowest CRP levels. Eventually, inflammation experts determined that having a CRP reading of 3.0 mg/L or higher can triple your risk of heart disease. The danger seems even greater in women than in men. By contrast, folks with extremely low levels of CRP, less than 0.5 mg/L, rarely have heart attacks.
Physicians still don't know for sure how inflammation might cause a plaque to burst. But they have a theory. As the level of LDL cholesterol increases in the blood, they speculate, some of it seeps into the lining of the coronary arteries and gets stuck there. Macrophages, alerted to the presence of something that doesn't belong, come in and try to clean out the cholesterol. If, for whatever reason, the cytokine signals begin ramping up the inflammatory process instead of notching it down, the plaque becomes unstable. "This is not about replacing cholesterol as a risk factor," Ridker says. "Cholesterol deposits, high blood pressure, smoking — all contribute to the development of underlying plaques. What inflammation seems to contribute is the propensity of those plaques to rupture and cause a heart attack. If there is only inflammation but no underlying heart disease, then there is no problem."
At this point, cardiologists are still not ready to recommend that the general population be screened for inflammation levels. But there's a growing consensus that CRP should be measured in those with a moderately elevated risk of developing cardiovascular disease. At the very least, a high CRP level might tip the balance in favor of more aggressive therapy with treatments — such as aspirin and statins — that are already known to work.
