For the past eight years, I have been preaching the heresy you are about to read, extracted from the latest Science magazine. It is with considerable self-satisfaction that I summarize for you where medical opinion, media attention and even drug company trials are now taking us on the subject of cholesterol, statins and cardiovascular disease causation.
We have all been thoroughly indoctrinated over the years that the role of cholesterol in heart disease is firmly established. Few physicians practicing today doubt this mantra - "for every 2% of cholesterol lowering you gain a year of life expectancy." This was fed to me in the late fifties based upon the Framingham data and it proved to be the fuel that has allowed the statin industry to become what it is today, a multi-billion dollar industry in firm control of our lives.
How could it have missed, I murmur now as I look back on this gigantic beanstalk that rooted only four decades ago, now towering ominously over our heads. The drug companies benefited, the food industry benefited and the doctors benefited. You can use the word cholesterol to frighten small children for cholesterol fixation has now replaced the evil giant looking down on us. Some would liken me to Jack with my tiny hatchet, slowly climbing the beanstalk, seeking out the giant. But Jack has picked up some friends along his strenuous journey.
A well-known cardiologist now admits that cholesterol causation is like religion to some but the story is turning out to be far more complex than everyone had supposed. After years of research, much about this so-called truth about cholesterol causation is poorly understood and does not withstand the close scrutiny of research. An internist asks why it is that people with low cholesterol still have heart attacks. Others specialists ask why it is that statins work even when cholesterol levels remain unchanged?
Other specialists closely involved with the Enhance study, which compared Vytorin with Zocor, still wonder why the excess cholesterol lowering resulting from Vytorin use with its added Zetia did not translate into plaque protection? A group of other specialists that had their hearts set on an HDL lowering drug now doubt the relevance of HDL. Their new drug did nothing more than cost millions only to result in greatly increased heart attacks rates rather than decreased. We thought we understood cholesterol's role in cardiovascular disease and now we realize that Ancel Key's Bible of cholesterol causation was false.
Now, a cardiologist and drug company confidant in Boston says it is time to look beyond cholesterol when considering how to stop atherosclerosis. It is time to look at inflammation. It has been known for years that our CRP (C-reactive protein) test is a marker for inflammation and this cardiologist has observed this relationship with his heart patients. As an intern in 1955 I used to order this test at Walter Reed Army Medical Center. So this has been around a while.
If you have elevated inflammation in your body, your CRP test is apt to be elevated so it is nonspecific but on the other hand it is a sensitive test of inflammation. On the basis of this a drug company has begun testing the benefit of its statin on a low cholesterol high CRP group of patients. On the basis of preliminary results the company announced in March of 2008 that it was halting the trial early because of "unequivocal evidence of benefit."
This is where we are today with statin manufacturers now looking at inflammation, knowing full well that the anti-inflammatory effect of statins is what has been providing the observed benefit of statins these past few years. Cholesterol reduction, the reason for the development of the statin class of drugs in the first place is irrelevant. Statins work entirely by a previously unknown anti-inflammatory effect not disclosed until a paper by Ora Shovman in 2001. It has taken this long for the Bible of Ancel Keys to be edited and the cardiovascular disease treatment section redirected to inflammation. It might have been done in 2001 but there were far too many fingers in the pie to effect an immediate change.
The plague of statin side effects from mevalonate blockade now should slow as doctors realize they can get results with much smaller doses of statins; doses sufficient for inflammation reduction yet too low to significantly block the cellular mevalonate pathway. As soon as word of this gets out my work is done and down comes the beanstalk.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor