For years I have been saying that cholesterol is irrelevant to cardiovascular disease. At first my "hopeless bias" was based primarily on my awareness that in some 50% of new heart attacks, cholesterol values were well within the accepted norm for the times.
And this observation has persisted over the years. The hypothesis for cholesterol causality did not fit. Additionally cholesterol seemed so important to body function i.e. membrane function, ATP and anti-oxidation. A biochemical this important having such a lethal dark side made no sense.
Naturally I have been looking for evidence to support my radical thoughts. This new Framingham data (Association of Circulating Cholesteryl Ester Transfer Protein Activity With Incidence of Cardiovascular Disease in the Community, Ramachandran S and others. Circulation. 30 November, 2009) is unusually convincing.
The Framingham study was started just after my internship in 1955 and has proven to be of tremendous help to public health and preventive medicine. Initiating a longitudinal study of all the factors associated with cardiovascular disease was the original intent of this program but while I was getting my MPH ( Master in Public Heath ) at Johns Hopkins in 1958, cholesterol's role suddenly changed from associated to causative with not even one piece of
In retrospect, I feel the win/win promotional efforts of the drug companies played a primary role in this general acceptance of cholesterol causation. As most of you must recall, the drug companies would win, the food industry and health care industry would win and the patient was promised extra years of useful life from abruptly painting cholesterol as the bad guy.
Doctors were delighted when the drug companies gave us our truly big gun - statins. More recently we learned that statins worked not only by cholesterol reduction but also by anti-inflammation and CRP began to point to cardiovascular disease risk much better than cholesterol levels.
Now enter cholesteryl ester transfer protein activity (CETP), long been known to correlate with lipid levels. The lower the CETP the higher the HDL and the higher the HDL, the lower the CV risk, presumably. However, an initial clinical trial last year with Torcetrapib, a CETP inhibitor, resulted in a catastrophe of CV disease and had to be stopped prematurely. Something clearly was wrong with the underlying concepts.
Now this concept has been evaluated using the old, reliable Framingham study. The plasma CETP values of 320 study participants were followed as these people went on about their life and, in some cases, death, from coronary heart disease, cerebrovascular disease, peripheral vascular disease, or heart failure.
The results were that a robust inverse relationship existed between CETP and CV disease risk. The lower your CETP ( and the higher the HDL ) the greater the incidence of these problems.
The authors state that these observations, if confirmed, challenge the concept that CETP inhibition may lower CVD risk. What they could just as correctly have said is that the entire concept of cholesterol causation has been challenged. The only reasonable explanation for these extraordinary findings is that cholesterol is irrelevant to the atherosclerotic process.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor