November 9, 2008--It is estimated that half of all heart attacks and strokes occur among people without traditional risk factors for cardiovascular disease (such as high cholesterol or diabetes).  However preventative treatment with cholesterol lowering medications, most commonly statins, is usually prescribed only for patients with high cholesterol levels.

This approach to preventing heart disease is now challenged by the compelling results of a large trial presented today at the American Heart Association's Scientific Sessions, and also published in the November 20 issue of the New England Journal of Medicine.

The trial, known by the acronym JUPITER, evaluated nearly 18,000 apparently healthy patients who had normal cholesterol numbers, but elevated levels of high sensitivity CRP (hsCRP), a marker of inflammation.  hsCRP readings below 1 mg/L are considered acceptable.  Elevated hsCRP levels (especially over 3 mg/L) have been shown in previous studies to identify patients who are at a higher risk for developing subsequent cardiovascular events.  It has been unclear, however, whether acting on an increased hsCRP level affects outcome.

At the start of the JUPITER trial, all of the participants had LDL (bad) cholesterol levels of less than 130 mg/dL, and none had diabetes or known heart disease. But they all had hsCRP levels of 2.0 mg/L or higher.

In the study, half of the 18,000 participants received Crestor 20 mg per day, and half received a placebo.   Over the course of the trial, Crestor users lowered their LDL cholesterol by an average of 50% and their hsCRP by 37%.  Half of all Crestor users attained an LDL level below 55 mg/dL, much lower than current treatment guidelines.

Although the trial was originally designed to last 4 years, it was discontinued after 1.9 years because of the stark differences in outcome between the two groups of patients.  The investigators found that the patients taking Crestor experienced half the heart attacks, strokes, or deaths from heart related causes.  They were also half as likely to require angioplasty or bypass surgery compared to participants who were given a placebo. In all, 0.9% of statin users experienced a cardiovascular event during the course of the trial, compared to 1.8% of placebo users. 

"Physicians can no longer assume that patients are at low risk for heart disease simply because they have low cholesterol. We have confirmed that patients with increased hsCRP 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," says Paul Ridker, MD director of the Center for Cardiovascular Disease Prevention at

Brigham and Women's Hospital and lead author of the study.

The implications of these results are striking, and suggest a more mainstream role for the measurement of hsCRP levels and a shift in prevention strategies.  Dr Robert Glynn, the study statistician, estimates that approximately 250,000 heart attacks, strokes, revascularization procedures, or cardiac deaths could be avoided in the US alone if the strategy tested in JUPITER was applied over a five year period.

Many physicians are understandably enthusiastic about the findings.

"The JUPITER trial data are paradigm shifting and a win-win for patients and for health care providers" said Dr. Antonio Gotto, Dean of the Weill-Cornell Medical College in New York. "We should regularly measure hsCRP along with lipids when we determine cardiovascular risk."

"JUPITER should dramatically change prevention guidelines" said Dr. James Willerson, Director of the Texas Heart Institute in Houston. "The bottom line here is simple - if your hsCRP is high, you should be on statin therapy regardless of your cholesterol level. This is an approach we can start using tomorrow".

However, initial enthusiasm about these results needs to be tempered, argues Dr. Mark Hlatky, from Stanford University School of Medicine.   In an editorial accompanying the published study, Hlatky points out the lack of long term safety data for this approach and the cost of therapy (approximately $3.45 per day for Crestor) cannot be overlooked.  He also notes that the trial really addressed the benefits of statin treatment, rather than the benefits of hsCRP testing, leaving the question of whether this test should be used routinely up in the air.

Nevertheless, the JUPITER trial is likely to have an effect on future prevention guidelines and patient management. 

The study was funded by AstraZeneca, the maker of Crestor, who had no access to unblinded trial data and played no role in analysis or interpretation of the study data nor in manuscript preparation. Dr. Ridker is listed as a co-inventor on patents that relate to the use of inflammatory biomarkers (hsCRP).