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The Fires Within #4/8 ( By TIME - Feb. 23. 2004 )

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.

A NEW VIEW OF DIABETES

Before Dr. Frederick Banting and his colleagues at the University of Toronto isolated insulin in the 1920s, doctors tried to treat diabetes with high doses of salicylates, a group of aspirin-like compounds. (They were desperate and also tried morphine and heroin.) Sure enough, the salicylate approach reduced sugar levels, but at a high price: side effects included a constant ringing in the ears, headaches and dizziness. Today's treatments for diabetes are much safer and generally work by replacing insulin, boosting its production or helping the body make more efficient use of the hormone. But researchers over the past few years have been re-examining the salicylate approach for new clues about how diabetes develops.


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