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Heart disease and stroke remain the No. 1 and No. 3 causes of death in the United States. Combined, they were responsible for almost one-third of the total number of deaths reported in 2005. Several factors are well known to increase the risk of heart attack and stroke, including tobacco smoke, obesity, diabetes, high blood pressure and high cholesterol. This information has allowed people with these conditions to change their lifestyle or take medications to reduce their risk. However, about half of all heart attacks and strokes occur in people whose cholesterol is normal, raising questions about what other factors might also be involved. Evidence has been building that inflammation may play a critical role by causing plaque inside arteries to rupture, causing blood clots that block blood flow. But the usefulness of this information has remained far from clear—until now.
Findings of a highly anticipated study presented at a meeting of the American Heart Association in New Orleans produced powerful evidence that seemingly healthy people having what are considered safe cholesterol levels and no apparent risk for heart disease could lower their chances of having a heart attack or stroke or dying from any cause by taking a widely prescribed cholesterol medication—Crestor. “The potential public health benefits are huge,” said Dr. Paul M. Ridker of the Brigham and Women's Hospital in Boston, who presented the findings. “It really changes the way we have to think about prevention of heart attack and stroke.”
The study began in 2003 when Dr. Ridker and colleagues started prescribing either a daily 20 milligram dose of Crestor or a placebo to 17,802 middle-aged and elderly men and women in the U.S. and 25 other countries. One-fourth were black or Hispanic and 40 percent were women. Men had to be 50 or older, women, 60 or older. None had a history of heart problems or diabetes. All participants had safe cholesterol levels but had high CRP, a substance in the blood called C-reactive protein that signals inflammation. The study was slated to last for five years, but was stopped in March after an average follow-up of two years when an independent monitoring panel concluded that the benefit was too great to continue withholding the real drug from the participants receiving the placebo.
Compared with the placebo group, those taking Crestor were 54 percent less likely to have a heart attack, 48 percent less likely to have a stroke, 46 percent less likely to need angioplasty or bypass surgery to open a clogged artery, 44 percent less likely to suffer any of those events and 20 percent less likely to die from any cause. For example, there were 136 heart-related problems per year for every 10,000 people taking placebos versus 77 for those taking Crestor. While some of the participants had risk factors for heart disease, such as being overweight or having high blood pressure, the findings held true even for those who had no known risks other than their high CRP levels. “If you’re skinny it worked, if you’re heavy it worked. If you lived here or there, if you smoked, it worked,” Dr. Ridker said. “We were both shocked and elated.”
“These are very, very dramatic findings,” said Elizabeth G. Nabel, director of the National Heart, Lung and Blood Institute. “This really validates inflammation as being an important factor in the development and progression of heart disease, and that treating inflammation, even in the setting of a normal cholesterol level, may be very important for certain individuals.” Nabel noted that two other studies presented at the meeting also support the value of CRP testing.
Leading authorities predict these findings will prompt many doctors to use CRP testing to screen patients for inflammation and begin prescribing either Crestor or a less expensive generic statin to those who get worrisome results. Dr. Ridker said one of his colleagues predicted that over five years, an estimated 250,000 heart attacks, strokes, angioplasties or deaths from heart attacks could be prevented in the United States alone. “We could prevent a lot of heart attacks, stroke, bypass surgeries, angioplasties and save a lot of lives,” Ridker said. “To me that’s a good thing.”
Still, other experts are skeptical, arguing that the actual risk reduction for an individual would be very small. Dr. Mark A. Hlatky, a Stanford University cardiologist who wrote an editorial accompanying the study, said about 120 people would have to take Crestor for two years to prevent a single heart attack, stroke or death. “This would be a huge expansion of the boundaries of drug therapy,” he said. “Everybody likes the idea of prevention. We need to slow down and ask how many people are we going to be treating with drugs for the rest of their lives to prevent heart disease, versus a lot of other things we’re not doing (to improve health).”
Using federal health statistics, Drs. James Stein and Jon Keevil of the University of Wisconsin-Madison project that 7.4 million Americans, more than 4 percent of the adult population, are like the people in the study. They calculate that treating them all with Crestor would cost $9 billion a year and prevent approximately 30,000 heart attacks, strokes or deaths. “That’s pretty costly. This would be a very difficult sell” unless a person also had a family history or other risk factors for heart disease, said Dr. Thomas Pearson of the University of Rochester School of Medicine and Dentistry. Pearson was co-chairman of a joint government-heart association panel that wrote current guidelines for using CRP tests to guide treatment.
“We’re already struggling to provide health services for the 46 million Americans who don’t have health insurance in the United States,” said John Abramson, a clinical instructor at Harvard Medical School. “This is going to drain away a lot of money from the system for little or no benefit. We know that there are lifestyle interventions that are effective.”l