Should women with normal cholesterol be taking a statin?

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A major study suggests that statins also quell inflammation. Now what?

With February come thoughts of the heart, and this year you may be wondering if you should be doing more for yours. For instance, what about taking a statin, one of those medications best known for their ability to lower LDL (bad) cholesterol? Most of us with healthy LDL levels assumed we didn't need a statin to reduce our risk for cardiovascular disease. In November 2008, that assumption may have been proved wrong when a large international study — the JUPITER trial — found that the statin drug rosuvastatin (Crestor) slashed the rate of heart attacks and strokes in people with normal LDL cholesterol who had elevated levels of C-reactive protein (CRP), a marker of inflammation. There is increasing evidence that low-grade inflammation raises cardiovascular risk.

Many experts responded by recommending the prescription of statins for people whose LDL cholesterol levels would otherwise place them at low risk. Some have also urged wider use of a high-sensitivity blood test for low-grade inflammation — the hsCRP test — to identify people who might benefit. Others say those changes are not worth the cost, because people with low LDL have a very low risk of heart attack and stroke even when their blood tests show signs of inflammation. Some also think that the study, which lasted two years, was too brief to assure the safety and effectiveness of this unconventional use of statins.

The debate will continue, and there will undoubtedly be changes in the official guidelines for the assessment of cardiovascular risk and the preventive use of statins. But for now, here are some things to consider before seeking the hsCRP blood test or requesting a statin prescription.

The findings

The JUPITER (Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin) study involved 17,802 apparently healthy people, 40% of them women, from 26 countries. The men were ages 50 and over and the women, ages 60 and over — the ages when cardiovascular risk begins to rise. Participants had no history of heart attacks or strokes, and their LDL cholesterol levels were under 130 milligrams per deciliter (mg/dL). In fact, the average was 108 mg/dL, a level considered excellent for people with no cardiovascular risk factors. On the other hand, the participants had high CRP levels, ranging from 2 to 7 milligrams per liter (the level considered normal is less than 1 milligram per liter).

Subjects were randomly assigned to take either 20 mg of Crestor or a placebo pill daily and monitored for cardiovascular events — heart attacks, strokes, bypass surgery or angioplasty, hospitalization for unstable angina, and death from a cardiovascular cause.

JUPITER was designed to last for four years, but it was halted just short of two years, because the statin takers were doing so much better than those taking the placebo. They were 54% less likely to have a stroke, 48% less likely to have a heart attack, and 44% less likely to have any serious cardiovascular event, including cardiovascular death. Among the statin users, LDL levels dropped by an average of 50%, and CRP levels by an average of 37%. These levels were unchanged among the placebo takers. Side effects, such as muscle pain and problems with liver or kidney function, were the same in the two groups, although there may have been an increase in diabetes among those taking Crestor.

Results of the study were published in The New England Journal of Medicine (online Nov. 9, 2008, and in print Nov. 20, 2008). The study was funded by Astra Zeneca, the maker of Crestor, and patent rights to the hsCRP test are owned by the lead investigator, Dr. Paul M. Ridker, and Harvard-affiliated Brigham and Women's Hospital in Boston.

Broadening JUPITER's scope

Many experts are suggesting a go-slow approach to the use of statins by middle-aged adults with normal cholesterol and no history of diabetes or cardiovascular disease. Although Crestor reduced the risk of cardiovascular events to a statistically significant degree, the numbers involved were small. Among 17,802 participants, only 393 cardiovascular events occurred: 142 in the Crestor group (a 1.6% rate) and 251 in the placebo group (a 2.8% rate). If these results are confirmed, about 95 people would need to be treated for two years to prevent a single cardiovascular event. Public health experts have to consider such numbers because they must weigh the absolute benefits against the costs and risks. Crestor, which is not available in a generic form, costs about $1,200 a year, more than generic statins such as lovastatin and pravastatin.

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