By now, virtually everyone who owns a television knows how heart attacks happen, or thinks they do: an excess of cholesterol, especially the kind called LDL (low-density lipoprotein) leaves deposits of plaque on artery walls, narrowing the passage for bloodflow until a clot comes along to block it entirely. This concept led to the development of cholesterol-lowering statins, such as Mevacor (lovastatin), Zocor (simvastatin), Pravachol (pravastatin), Lipitor, Lescol and Crestor. Increasingly, however, researchers are focusing on another culprit that also plays a key role: inflammation, which can make artery plaques rupture, very often the trigger that turns artherosclerosis into a heart attack.
Now a large international study (the JUPITER trial) lends support to that idea and also shows that the same statins that control cholesterol also act to reduce inflammation. (Strictly speaking, the trial only tested one such drug, Crestor, whose manufacturer, AstraZeneca, paid for the study.) JUPITER included nearly 18,000 seemingly healthy volunteers in prime heart-attack age—men age 50 and over, women age 60 and older. While their LDL cholesterol levels were healthy, the volunteers all had above-normal levels of C-reactive protein, or CRP, a sign of inflammation. (Normal CRP is below 1 milligram per liter; the volunteers all showed levels above 2.) Half of the volunteers took a daily 20mg tablet of Crestor; the rest took a placebo. LDL cholesterol levels dropped by roughly half and the CRP levels dropped by about a third in the statin group. In the placebo group, LDL and CRP levels didn't budge.
Even more impressive, there were about 50 percent fewer heart attacks and strokes in the statin group than in the placebo group. Unlike many earlier trials using statins, JUPITER included a large number of women, Hispanics, and blacks. Each of these groups benefited from statin therapy as much as white men.
JUPITER has changed my thinking about the high-sensitivity CRP test and about when to prescribe statins. Like many cardiologists across the country, I am now recommending the test more often. (The hospital in which I work receives patent revenue from the test, but I do not.) The CRP test is not for everyone, though. If someone already has been diagnosed with heart disease, the test adds little or no useful information, because the implications for treatment aren't clear yet. The same is true for those at very low risk—people younger than the volunteers in the JUPITER study, without other risk factors for heart disease.
The test is most useful for people in the middle of the risk curve. A high CRP level is a factor that may weigh on the side of starting statin therapy; a low reading may be taken by some as an indication it's not needed. How do you know where you stand? Risk tools such as the Framingham score and Your Disease Risk estimate your chances of having a heart attack in the next 10 years. (For links to these tools, go to health.harvard.edu/newsweek.) There are other considerations. Statins are expensive—a year's supply of Crestor or one of its competitors can cost more than $1,500. And although millions of people take them safely, they can cause pain in some people, and in rare cases muscle damage and, possibly, memory loss. To put the numbers from the JUPITER study into perspective, during the two-year trial, 1.5 percent of the participants who were taking the placebo had a heart attack or stroke, compared with 0.7 percent of those taking Crestor. That means 25 people would have to take a statin for five years to prevent one cardiovascular event. As treatments go, that's not bad, but it doesn't mean we should be putting statins in the water supply.
There are other ways you can fight inflammation than by taking a statin: If you smoke, stop. If you are overweight, shed some pounds. Adopt a Mediterranean-style diet based on fruits, vegetables, whole grains, nuts, and olive oil. Eat more fatty fish. Exercise almost every day. Get enough sleep. Reduce stress.
If you have heart disease or are at high risk for it, taking a statin and adopting healthful lifestyle changes make sense, even if your LDL is in the normal range. If you are a man age 50 or greater, or a woman age 60 or greater, and you are healthy but have a high CRP, the JUPITER results suggest you could benefit from the same strategy.
In 2009, researchers will be testing other ways to detect inflammation besides CRP, and developing genetic tests that may be more accurate predictors of heart-attack risk than the tools now in use. New drugs against inflammation are also in the works. The best approach, though, is something available to everyone today—living well to prevent atherosclerosis from ever taking hold.