A Different View of the Crestor - JUPITER Study Data

"This was definitely a pretty stunning result," said Dr. Steven E. Nissen, chairman of cardiovascular medicine at the Cleveland Clinic.  "I, for one, will be checking CRP in more patients. If it's elevated, we will be treating them." So went this story in the New York Times on 18 November 2008 as reported by Tara Parker-Pope, referring to results from the JUPITER study.

But there is definitely another way of looking at this. The Vytorin® - Enhance study - scandal broke only a few months ago and I said then that no study better proved the irrelevancy of cholesterol as a marker for cardiovascular risk. In that study the drug company compared the effectiveness of plain, generic, inexpensive Zocor® with the more expensive Vytorin®, consisting of the combination of Zocor® with Zetia®.

Zetia® had already made millions, if not billions, by convincing the medical community that the addition of Zetia® to gain an extra measure of cholesterol reduction was worth the extra cost. So enter gladiator Zetia® into the arena with the result that although Vytorin® resulted in much greater cholesterol reduction, the benefit in plaque status was no better than with Zocor® alone.
There is only one way to interpret the data. Reduction in cholesterol is irrelevant to plaque maintenance. The anti-inflammatory effect of the plain statin is where the cardiovascular benefit lay. This was heresy. Cardiologists and internists were stumbling over each other trying to explain this away. But no further explanation was necessary. After four decades of brainwashing us about the evils of cholesterol, they had done a magnificent job of shooting themselves in the foot with this trial. The last thing they wanted the public to know was that the billions of dollars recently spent on cholesterol reduction was unnecessary. Cholesterol was not the enemy, inflammation was. My grandmother was right all along with her eggs and butter. 

I could hardly believe it when a few weeks later I first heard about the preliminary results from the JUPITER trial. They had chosen patients with normal levels of cholesterol but with elevated levels of C-reactive protein (CRP) to study the effect of Crestor®. Predictably those with elevated levels of CRP got the best response to the statin. The test, which can cost $20 to $50, measures inflammation. There is now little doubt that people with high CRP are at higher risk for heart attack, regardless of cholesterol levels.

A reasonable interpretation of the data tells me that cholesterol is not the CV risk marker we once thought. C-reactive protein comes very close to being the best available marker for CV risk. Those at risk based on elevated CRP levels should be treated with an appropriate dose of statin or other anti-inflammatory agent.
Physicians have been blindly dosing statins at cholesterol reducing doses when all the time it appears the dose should be based on inflammatory response. Why use 80 mg of a statin for example with its established potential for glial cell inhibition and mevalonate blockade when much lower anti-inflammatory doses are all that is needed. Naturally the statin lobby would prefer to treat both cholesterol and CRP elevations. In so doing they are denying the tens of thousands of statin disabled victims as well as the underlying biochemistry in their priority to maximize profits.
The issue here is side effects. We had to wait until 2002 for Frank Pfrieger to announce to the world the special importance to the human brain of cholesterol. The thousands of cases of amnesia, confusion, forgetfulness, disorientation and dementia associated with statin use are because of the effect of statins to inhibit glial cell cholesterol synthesis. The higher the statin dose, the greater the glial cell inhibition.

Shortly after this reality ( which incidentally, the drug companies failed to warn us about ) we learned that in their capacity as reductase inhibitors these statins blocked the vital mevalonate pathway in each of our cells, the pathway that synthesizes not only cholesterol but also CoQ10, dolichols, selenoproteins, Rho and normal phosphorylation. To block the mevalonate pathway sufficiently to inhibit cholesterol synthesis means that inevitably you are reducing bioavailability of these other vital biochemicals as well.

It was Shovman who told us in 2002 about the powerful anti-inflammatory effect of statins and Hilgendorph, who suggested in 2003 such effect was obtained at doses far lower than those required for cholesterol reduction. The pursuit of cholesterol reduction has been misguided from the very beginning. It is perhaps our most essential biochemical, intimately involved in every aspect of our lives. The JUPITER data has served to guide treatment along its proper path.

Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor

Books From Amazon

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Cholesterol is Not the Culprit
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