Statins Cut Risk of Heart Disease in Half, Landmark Study Finds

In a landmark study, nearly 18,000 apparently healthy men and women with normal cholesterol levels were able to reduce, by 50 percent, their risk of heart attacks, strokes and cardiovascular deaths by taking a statin drug traditionally used only to lower high cholesterol. Experts say the findings could dramatically change the basic guidelines for the prevention of heart disease and immediately alter standard care.

The study, led by researchers at Harvard University’s Brigham and Women’s Hospital in Boston, looked at men over age 50 and women over age 60 who had healthy cholesterol levels and no history of heart disease, but who did have elevated levels of high-sensitivity C-reactive protein (hs-CRP), as measured by a simple blood test. The hs-CRP molecule is produced by the liver in response to inflammation. Researchers say this study, dubbed “Jupiter,” demonstrates that an elevated hs-CRP level is a major risk factor for cardiovascular disease—and that statins can dramatically reduce that risk.

“Our results are relevant for patient care and the prevention of heart attack and stroke,” says lead researcher Paul Ridker, M.D., director of the Center for Cardiovascular Disease Prevention at Brigham Hospital.

The Jupiter results, presented Nov. 9 at the 2008 Scientific Sessions of the American Heart Association in New Orleans, will be published in the New England Journal of Medicine later this month.

Ridker says doctors can no longer assume that monitoring a patient’s cholesterol levels is enough: “We have confirmed that patients with increased hs-CRP are at high risk even if cholesterol levels are low, and we now have evidence that a simple and safe therapy cuts that risk and saves lives.”

“For older people,” he adds, “it’s important to note that the benefits come quickly, in months, not years.”

“The bottom line here is simple—if your hs-CRP is high, you should be on statin therapy regardless of your cholesterol level,” says James Willerson, M.D., director of the Texas Heart Institute in Houston and one of the authors of the study. “This is an approach we can start using tomorrow.”

Coronary heart disease is the number one cause of death in the United States. Stroke is the number three cause of death and a leading cause of serious disability, according to the American Heart Association.

For years, growing evidence has suggested that inflammation plays a key role in developing heart disease, and hs-CRP is one of the most widely studied markers of inflammation. But whether measuring hs-CRP helps predict risk for cardiovascular disease independent of traditional risk factors such as age, cholesterol levels, blood pressure, diabetes and smoking has been hotly debated.

The director of the National Heart, Lung and Blood Institute, Elizabeth G. Nabel, M.D., said in a statement that the Jupiter results are likely to move scientists to include high hs-CRP levels as another risk factor for heart disease, and will be studied by an expert panel the institute has engaged to review and update cardiovascular risk factors and treatment guidelines.

Jupiter, Nabel said, “demonstrates for the first time that a strategy of treatment decisions based on hs-CRP levels in otherwise healthy individuals significantly improves outcomes.”

While conceding the study is a blockbuster, some experts question putting relatively healthy adults on a long-term, expensive drug therapy that can have side effects ranging from an increased risk of diabetes to liver problems.

“Long-term safety is clearly important in considering committing low-risk subjects without clinical disease to 20 years or more of drug treatment,” Mark A. Hlatky, M.D., a professor of health research at Stanford University, writes in an editorial in the upcoming issue of the New England Journal of Medicine. Until further research is done, he recommends keeping the current standard for hs-CRP monitoring, which is to test for the protein only in people with other traditional risk factors that place them in an intermediate risk category for heart disease.

Clearly, the study has touched off a heated debate about whether hs-CRP testing should be expanded to include a broader range of healthy adults.

Men and women in the study had healthy levels of cholesterol: Their “bad” cholesterol, or LDL, was just above 100 and their average “good” cholesterol, or HDL, was nearly 50. Their elevated hs-CRP levels had to be at least 2, but the median was 4. The subjects taking statins were on a daily dose of 20 mg of rosuvastatin (Crestor). Researchers say that while rosuvastatin is the most potent statin, past research has shown that all statins lower cholesterol and hs-CRP.

Although the study, conducted in 26 countries, was designed to continue for four years, the findings were so dramatic, it was halted after 1.9 years by an independent safety monitoring board. Compared with the people taking a placebo, those on the statin saw a 54 percent reduction in heart attack, a 48 percent reduction in stroke and a 46 percent reduction in the need for angioplasty or bypass surgery, researchers report. There also was a 20 percent decrease in mortality compared with the participants who were given a placebo.

AstraZeneca, the maker of Crestor, funded the study, but the researchers say the company had no access to unblinded trial data and played no role in analysis or interpretation.

They also say the results were significantly better than the results doctors expect when they prescribe statins for patients with high cholesterol, underscoring the importance of elevated hs-CRP as a major risk factor for heart disease.

Although Jupiter demonstrated a significant reduction in heart attacks and strokes, “it was not designed to answer the question of whether the impact on risk was due to a reduction in inflammation (marked by hs-CRP)” or a reduction in cholesterol, Timothy Gardner, M.D., president of the American Heart Association, said in a statement.

One study author predicts its data will transform the model for preventive care. “This is a win-win for patients and for health care providers,” says Antonio Gotto, M.D., dean of the Weill Cornell Medical College in New York.

Gotto maintains that the results are “so clear and so powerful” that men and women should routinely have their blood hs-CRP tested along with their cholesterol. Even people already taking a statin for cholesterol should be tested to “see if their hs-CRP level is elevated,” Gotto says. “Just because your statin is managing your cholesterol doesn’t mean it is adequately lowering your hs-CRP.”

Ridker cautions doctors and patients not to confuse the blood test for hs-CRP with the blood test for CRP, since “they are two very different measurements.”

Barbara Basler is a senior editor at the AARP Bulletin.