Friday, May 8, 2009

Cholesterol and Heart Disease (1)

There have been many, many articles published, both in refereed medical journals and in newspapers, as well as reports from medical conferences about the correlation/statistical link between elevated cholesterol and heart disease, and about who would benefit from having his/her cholesterol lowered.

All commentators agree that elevated cholesterol is a "risk factor" for heart disease, in that, all else being equal, the higher the cholesterol, the greater the risk for plaque build-up in the coronary arteries. The real question, of course, is whether or not lowering the cholesterol lowers the risk for heart disease and/or heart attacks. The answer ab initio is far from obvious. No one would expect to lower an elevator in an office building by pulling down on the indicator arrow.

An excellent demonstration of the disconnect between risk indicators and risk improvement has been shown between high blood pressure, heart attacks, and strokes. Many studies have shown that untreated high blood pressure is a risk factor (i.e. is positively correlated with) both heart attacks and strokes, but, as far as I know, every study on the benefits of lowering elevated blood pressure only shows a reduction in the risk for strokes, and NOT a reduction in the risk of heart attacks. We may believe that we also help prevent heart attacks by lowering blood pressure, but there is no scientific data to support this belief. A doctor should only act on facts demonstrated by scientific research, or, to be fair to the patient, specify when he/she is acting on his own beliefs.

We also have to discriminate between primary prevention and secondary prevention. The greatest risk factor for having a heart attack is having had one already. Preventing a second heart attack would be called "secondary prevention", and since this group is at such high risk
it is easy to show the benefits or non-benefits of intervention. Showing the benefits of primary prevention is much more difficult, since the event rate is lower.

There has been a lot of argument in journals about various methods to obtain primary prevention, or reduction in primary risk. As a general rule, if scientists have to argue about the proper interpretation of data, then the data is probably useless. (Just try to follow any of the arguments of the use of meta-analyses.) Also, many studies confuse statistical significance (chance of interpretation being false less than 5%) with clinical significance (saves a significant number of lives in an absolute sense). For instance, if I could reduce your chance of being killed by a lightning bolt by 50% (relative benefit), but this meant a risk reduction from 1:1,000,000 to 1:2,000,000, you probably wouldn't be interested.

This initial blog is just setting up the framework for an in-depth discussion of cholesterol-lowering and heart disease prevention. Two caveats:(1) no one knows why lowering cholesterol with the use of Zetia or Vytorin showed no additional benefit, (2) the medical patients with the lowest total cholesterol levels, approx. 100, are patients with ulcerative colitis, who also have one of the highest rates of colon cancer.

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