From Risk for the Healthy
Remember the last time you scraped your knee? As it healed, it grew red and warm, sometimes leaking pus. That was inflammation at work. Whenever there's an injury to any part of your body, the flow of blood increases as white blood cells rush to the area like rescue workers responding to a train wreck. Ironically, this very process can also damage tissue.What does inflammation have to do with heart disease? As it turns out, plenty. When the lining of the artery is damaged -- say, when LDL particles burrow into the artery wall -- white blood cells flock to the site, resulting in inflammation. Thus, more LDL equals more inflammation. Inflammation not only further damages the artery walls, leaving them stiffer and more prone to plaque buildup, but it also makes any plaque that's already there more fragile and more likely to burst. Other factors that damage the artery wall and trigger inflammation include smoking, high blood pressure, and even germs.
How do you know if your arteries are inflamed? By testing your level of C-reactive protein (CRP), which is produced in the liver whenever inflammation occurs. If your arteries are under attack, your CRP level rises. An estimated 25 million to 35 million healthy middle-aged Americans with normal cholesterol have CRP levels that put them at higher risk of heart attack and stroke.
In a landmark study on CRP and heart disease, researchers at Boston's Brigham and Women's Hospital measured CRP levels in 1,086 apparently healthy men. They followed the men over the next eight years, tracking heart attacks, strokes, and blood clots. The result: The risk of a first heart attack rose fivefold when both cholesterol and CRP were high.
Researchers involved in the Harvard Women's Health Study reported similar results, noting that women with the highest levels of CRP had a sevenfold increase in risk of heart attack or stroke. Even if they didn't smoke, had normal cholesterol levels, and had no family history of heart disease, the women with high CRP were still more likely to have a heart attack or stroke. And a study published in late 2002 found that women with high CRP were twice as likely to die from a heart attack or stroke as those with high cholesterol.
It's important to note that these studies involved healthy people. For those with a known cause of inflammation -- such as rheumatoid arthritis or an active infection -- CRP may not be a reliable indication of heart disease risk.
CRP may function as a marker of inflammation in the blood vessels, but it also can play a direct role in damaging the arteries by interfering with an enzyme involved in nitric oxide production. As you learned earlier, less nitric oxide means artery walls that attract more plaque-forming gunk. CRP also seems to be a marker for metabolic syndrome, another risk factor.
Another marker of inflammation is a molecule called interleukin-18 (IL-18). A four-year German study on patients with coronary heart disease found that those with high levels of this molecule were three times as likely to die from heart disease as those with low levels. Earlier studies had linked high levels of IL-18 to quicker buildup of plaque and more unstable plaque. The results are still preliminary, researchers warn, and the test for IL-18 is too complex for the typical doctor's office.
Still, given the evidence on CRP and IL-18, doctors now suspect that inflammation plays such a powerful role in heart disease that it trumps even high cholesterol as a risk factor -- although you can't treat one and ignore the other, because they are linked. LDL increases inflammation, and inflammation generates free radicals, which oxidize the LDL particles and accelerate the formation of plaque. Many of the same factors that increase inflammation -- such as obesity, diabetes, and metabolic syndrome -- also increase cholesterol.
Prevention by the Numbers
C-reactive protein (CRP) testing is becoming increasingly common as doctors are finding that people with elevated CRP -- even if their LDL is below 150 -- may benefit from lifestyle changes and statin drugs. If you have high levels of CRP and high cholesterol, your risk of heart attack and stroke is nine times that of someone with normal levels of both.The risks of heart attack and stroke begin to rise with a CRP level as low as 0.55 milligram to 0.99 milligram per liter. Above 2.5 milligrams your risk is twofold or even fourfold. Ask for the high-sensitivity CRP test (hs-CRP) at your next checkup. It costs about $20 and is widely available. The standard CRP test, used for diagnosing conditions such as arthritis and inflammatory bowel disease, simply isn't sensitive enough.
Despite CRP's value in predicting heart disease risk, it will never be used by itself, doctors say, because it may be elevated in people with other forms of inflammation (such as arthritis) whose coronary heart disease risk is normal.
Quick Tips
The good news is that CRP levels seem to predict a heart attack six or eight years in the future. That's plenty of time to modify your lifestyle (and, if necessary, take medication).
- Quit smoking. Smoking inflames the arteries and is associated with higher levels of CRP.
- Take fish-oil supplements, which help reduce inflammation throughout the body. Studies have found that those who take fish-oil supplements are less likely to die from a heart attack than those who don't. In a 1998 study on CRP, researcher Paul M. Ridker, M.D., found that men with the highest levels of CRP reaped the greatest benefits from taking asprin.
- Take a daily aspirin if you are at increased risk for heart disease.
- Lose weight. Dr. Ridker's study also found that the more overweight you are, the higher your CRP level.
- Exercise. A study published in August 2002 found that the more active people were, the lower their CRP levels.