Archive 2008 2009 2010 2011

Your Cholesterol Is Low—Do you Still Need a Statin?

Good news, bad news: At your doctor’s visit, your routine blood test shows that your total cholesterol is in the desirable range (hooray), as is your LDL, or "bad," cholesterol (double hooray). Yet your doctor recommends that you take a statin drug, or at least strongly consider it. You’re over 60 and overweight, but that was true at your last checkup, too, and you’ve never had heart disease. What’s changed, the doctor says, is that your blood test found elevated C-reactive protein, or CRP.

In coming months this scenario will be playing out in more and more doctors’ offices. That’s because the FDA recently approved expanded use of one particular statin drug, rosuvastatin (Crestor), to include an estimated 6.5 million Americans who have desirable levels of LDL cholesterol but high CRP. To fall into this category, you must also be 50 or older if you’re a man, 60 or older if you’re a woman, and have at least one other risk factor, such as high blood pressure, smoking, or a family history of premature heart disease.

But not everyone is willing to jump on the CRP-testing bandwagon.

By JUPITER!

CRP, a protein in the blood, is a marker for inflammation in the body. Such inflammation, especially in the walls of coronary arteries, is now known to play a role in cardiovascular disease. Studies have found that people with elevated CRP are at increased risk for heart attacks and strokes. About half of all people who have a heart attack have high CRP; in people without heart disease, in contrast, high CRP is uncommon. Besides lowering LDL, statins have anti-inflammatory effects, as seen in reductions in CRP. However, it’s still not clear whether CRP directly contributes to heart disease or is just a marker for increased risk.

What has moved CRP to the top of the list of "emerging risk factors" for heart disease was a study called JUPITER, which made headlines when it appeared in the New England Journal of Medicine two years ago. (JUPITER stands for Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin.) It included 17,800 people with desirable levels of LDL cholesterol (below 130) and no heart disease but high CRP. Even though these people wouldn’t qualify for statin therapy according to official treatment guidelines, half were given rosuvastatin, and half a placebo. Rosuvastatin is the newest and most potent statin, and its maker, AstraZeneca, funded the study.

The study was supposed to last four years but was halted after two years because the benefits of the drug were so impressive. LDL was cut in half (to just 55, on average) and CRP by 37%. Treatment resulted in about 50% fewer heart attacks and strokes, plus 20% fewer deaths. Those were the best numbers ever seen in a statin study. There were very few side effects, other than a small increase in the risk of developing diabetes.

Half of all heart attacks and strokes occur in seemingly healthy people who have desirable cholesterol levels. Based on their results, the JUPITER researchers claimed that CRP testing can identify millions of these people who may benefit from statins. In February the FDA agreed, allowing AstraZeneca to mention this potential benefit in its information for doctors and patients and in its ads. In April the European Union followed suit. Last year the Canadian Cardiovascular Society started recommending CRP testing in people at "intermediate" coronary risk and noted that, on the basis of the JUPITER results, those with elevated CRP should consider taking statins.

Why not test everyone?

We still think it’s too soon to recommend routine CRP testing for all healthy people. JUPITER left many unanswered questions:

• Was it the dramatic drop in LDL or in CRP, or both, that was responsible for the benefits? Further analysis of the JUPITER data last year suggested that lowering CRP was beneficial independent of—and in addition to—reducing LDL. But it’s not clear how much additional benefit it provides.

• Would other statins have similar effects? Most likely, but it will take additional studies to find out. Rosuvastatin is available only under the brand name Crestor. Some other statins are now available as generics and are thus much cheaper, but drug makers are unlikely to fund research on them.

• Is it safe to cut LDL to such super-low levels? So far it seems the lower, the better, but there are no long-term data.

• Do the cardiovascular benefits of treating people at relatively low risk outweigh the small increased risk of diabetes and muscle pain from statins? In JUPITER, about 29 people had to be treated for five years to prevent one heart attack, stroke, or death.

• When is CRP too high? Most authorities have used a level above 3 mg/L to define high risk; JUPITER found that levels below 2 mg/L were associated with reduced risk. In any case, it has not been established that lowering CRP should be a goal of treatment.

• Are CRP tests accurate? Lots of things can elevate CRP, such as a cold or certain inflammatory diseases, and the test can be tricky to interpret.

What to do now

Talk to your doctor about your risk factors for heart disease and stroke to determine if you’re a good candidate for CRP testing.

• If you’re at high cardiovascular risk because of undesirable cholesterol levels and/or multiple risk factors, you don’t need a CRP test to tell you to take aggressive action—that is, make lifestyle changes and, if those don’t help enough, begin drug treatment. Unfortunately, regardless of their CRP levels, millions of Americans who clearly should be on statins or other treatment are not—whether it’s because they haven’t been screened, don’t want to take the drugs, or can’t afford them.

• If you’re at intermediate risk, and thus you and your doctor are on the fence about your starting drug therapy, you should consider CRP testing. A high result can tip the balance toward statins. Even if elevated CRP doesn’t cause heart disease, it still indicates increased risk.

• If you’re at low risk, there’s no evidence you would benefit from a CRP test. That includes men under 50, women under 60, and older people with no cardiac risk factors (besides age).

Keep in mind: As with undesirable cholesterol levels, life-style changes are your first line of defense for elevated CRP. These include losing weight if you’re overweight, quitting smoking, and controlling blood pressure. Regardless of your CRP level, these steps are crucial for cardiovascular health.

UC Berkeley Wellness Letter, July 2010