Data Interpretation

I want to call to the attention of everyone reading my research into atherothrombotic disease (ATD) that a major change in achieving cholesterol goals occurred in about the year 2000. This change was a change in the methodology by which High-density Lipoprotein (HDL) cholesterol was measured. Prior to the year 2000 (a bit earlier in some areas and a bit later in others), HDL-cholesterol was measured by the precipitation method; thereafter it was measured by the enzymatic method. The precipitation method was the gold standard of HDL-cholesterol measurement at the time, but it is a bit complex and the manufacturers of the auto-analyzers (the machines that measure the various cholesterol fractions) decided to try a simpler, easier method. They gave no one I know of any advance warning of this change.
The problem is that the two different methods do NOT give the same result. My hospital lab used the Lexapro 20 and the HDL-cholesterol result obtained using the enzymatic methodology is on the order of 10 mg/dl (0.25 mmoles/L) higher than the result obtained by the precipitation methodology. This results in a “free” boost in HDL-cholesterol level simply by changing measurement technology. In most cases, this “free” boost in HDL-cholesterol is on the order of 25%. But that’s not all. In order to save money, we do not measure low-density lipoprotein (LDL) cholesterol, but rather calculate it on the basis of the Friedewald formula: LDL-cholesterol= total cholesterol minus HDL-cholesterol and minus very-low-density lipoprotein (VLDL) cholesterol (approximated by triglycerides [TG] divided by 5). Technical stuff, but that’s the way it is done in the real world. In most cases, VLDL-cholesterol can be ignored as it does not contribute much, if any, cholesterol to the ATD plaque.
With this in mind, one can readily see that at any level of total cholesterol and TG, if HDL-cholesterol rises by 10 mg/dl, then LDL-cholesterol must fall by 10 mg/dl. Thus one’s test results can look great on paper, but have devastating results at the level of the artery wall. This is not a trivial point. Most of the studies upon which we base our cholesterol goals were done prior to the year 2000 and the goals of treatment suggested were based on the precipitation method. If anyone tries to use those goals on lab values performed today, the earlier goals will need to be adjusted to reflect the newer technology.
As a case in point, I published (with his permission) a case of a 55 year old man whom I was treating for job related stress and depression. He had no obvious ATD risk factors: no smoking, high blood pressure, diabetes, or obesity, and no family history of cholesterol problems or ATD. In any event, he was in Toledo, Ohio, when he had a heart attack. The hospital there was knowledgeable enough to perform a cholesterol profile. (The actual values are given in my Published Letters section under the HDL Measurement Technology title.) The cholesterol profile used the enzymatic method of HDL-cholesterol measurement and the resultant cholesterol profile was somewhat abnormal but not enough to have caused a heart attack at age 55 years. However, when converted back to the equivalent results that would have been obtained using the precipitation method, the cholesterol profile was much worse, and indeed would have predicted an ATD event between the ages of 50-59 years, which of course is when he had his event.
In light of this, if your lab uses the enzymatic method of HDL-cholesterol measurement, then the goals that I have described in this website (which are based on the precipitation method of HDL-cholesterol measurement) must be modified. The threshold line (CRF,SBP) co-ordinates on my graph must be lowered to (0.62,100) and (0.40,140). If one looks only at LDL-cholesterol and CRF in my latest exhibition on the prediction of the population at risk of ATD, then the LDL-cholesterol goal will be less than or equal to 89 mg/dl and the CRF goal will be less than or equal to 0.49. Maximum plaque stabilization/regression will occur at LDL-cholesterol level of 70 mg/dl. (Of course if your lab uses the precipitation method of HDL-cholesterol measurement, all this is of no consequence to you.)
I regret any confusion, but the manufacturers of the auto-analyzers failed to take into account the fact that their switch to the enzymatic methodology, while simpler, was not in accord with the published research about ATD prediction and prevention. Purchasing department of various labs and hospitals likewise took no notice of the change or even that different auto-analyzers use different chemicals in their machines and hence that HDL-cholesterol level may vary from manufacturer to manufacturer. Indeed they may not have even been aware of the enormity of the consequences–for ATD prediction/prevention—of their auto-analyzer choice, a decision probably made on the cost of the machine.
I write this commentary because the “good” results on the lab sheet may not translate to good results at the level of the artery wall, as the case I cited illustrates. Predictions must be made on the basis of research and not on so-called normal ranges. As the late Bill Connor, MD, said many decades ago: one treats, not to achieve some arbitrary level, but rather to prevent disease—in this case, ATD. He was right then and is still right today.

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