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Although JUPITER (Justification for the Use of Statins in the Prevention: an Intervention Trial Evaluating Rosuvastatin) was designed to study inflammation, its findings also underscore the risk of high cholesterol. The study's statin group clearly benefited from reducing CRP, but they had also simultaneously lowered their LDL levels to nearly 50% below the government-prescribed target of 100 mg/dL. Experts say the JUPITER results may prompt serious rethinking of the current guidelines an issue that health officials have already been debating in recent years. "I would not be surprised if, given these results, we determined that normal LDL should be lower than currently defined," says Dr. Elizabeth Nabel, director of the National Heart, Lung and Blood Institute. Updated cholesterol guidelines are expected in 2009.
That will likely be just one of many changes in the thinking behind heart-disease prevention. JUPITER's results shore up the contention that one heart attack is not the same as the next. Cardiologists think that cholesterol and inflammation conspire to cause heart attacks but that each person's genes and lifestyle influence how those factors interact. Excess cholesterol causes fatty deposits to build up within heart artery walls; those plaques trigger immune and inflammatory reactions in the body that tend to increase the instability and rupture of the plaques, which causes heart attacks. How aggressive the inflammatory response is depends on a person's genes, diet, stress levels and even exposure to chronic infections such as gum disease. So, the more active the inflammatory response, the greater the chance of ruptured plaques and heart attack. In people with elevated CRP, that means the danger lies not so much in the number of plaques (measured by cholesterol) but in how likely they are to burst (measured by CRP).
The new study suggests that screening all patients for CRP (a $10 test) as well as for cholesterol and blood pressure would not be unwise, or perhaps the test should be used for patients with indeterminate heart-disease risk, who may derive benefit from taking a statin. Longer-term trials are still needed, however, to show whether the benefits of statins outweigh their potential side effects the drugs are relatively benign, but they are known in rare cases to cause debilitating side effects such as muscle weakness (which forced Bayer to pull its version off the market in 2001). There was no increase in side effects among JUPITER's study group, but because the trial was terminated early, researchers don't know whether they would have seen more adverse effects later on. It's also not clear whether all statins can provide equal benefit, says Dr. Roger Blumenthal, director of preventive cardiology at Johns Hopkins Hospital.
Despite the questions that remain, cardiologists say the findings of JUPITER put another screening tool in the doctor's arsenal.
"Primary-care physicians now have to add to their battery of tests which include colonoscopy, PSA and breast exams something for the asymptomatic older person for the prevention of heart disease that now has greater benefit than anything we have ever had in the past," says Weaver of the ACC.