Saturday, March 26, 2011

What is the Friedewald Measure of LDL??

BLUF:  You care about how your lipids are measured because Friedewald calculations over-estimate LDL in folks on a low carb diet.  Doctors mired in the statin muck will often want to put you on drugs based on a high LDL number.  What follows is a brief, relatively speaking, description of why you might want to resist that recommendation (a slightly different take is here).

In short, Friedewald is a method to estimate LDL concentrations which is cheaper than direct measurement.  However, like all LDL measures, it is a poor predictor of future risk because there are so many variations of LDL.  Lipoproteins might be thought of as 'cholesterol boats'.  They are formed from cholesterol, which has the unique characteristic of being insoluble in water.  The dangerous kinds of LDL are termed 'small and dense', and consist of the lipoprotein 'boat' which is empty of content (the more fat/triglyceride, the less dense the lipoprotein).  Small, dense LDL results from consumption of a high carb diet, in which the liver is constantly converting blood sugar into triglycerides, and constructing new lipoprotein 'boats' (VLDLs or very low density lipoprotein - very low because they are stuffed with fat!) in which to send the tryglycerides out into the body.  Once the triglycerides have been dropped off at their destination, the remaining lipoprotein 'boat', no longer stuffed with fat, is a small, dense LDL.  These are thought to be easily oxidized (in effect, they rust easily like bare iron), and seem to be particularly significant in the genesis of arterial disease - possibly as a cause, but more likely as a correlate for the underlying highly inflammatory disease state that results in arterial damage, and produces (based on genetic variation) either heart attack, stroke, or, in severe diabetes, amputation.

Based on the above description, it makes sense that small, dense LDL correlate very closely to triglycerides, which correlates very closely with carbohydrate intake (except in folks with uncommon genetics).  SUMMARY:  high carb intake results in the atherogenic profile - high triglycerides, a large quantity of small, dense LDL, a below average quantity of HDL, and generally also high blood pressure and obesity. 

Now, the Friedewald details:
Then in 1972, Friedewald and coworkers, they came up with a simple way of calculating LDL. You measure total cholesterol in plasma, you measure HDL cholesterol in plasma, and then you can subtract VLDL cholesterol, and VLDL cholesterol is estimated as your triglycerides number divided by five; if in milligram per deciliter, and the triglyceride divided by 2.2, if all values are in millimoles per liter, and then you get a calculated LDL cholesterol. So that's the standard practice today.
http://www.aacc.org/events/podcast/documents/052709mora.pdf

Summary of the rest of the transcription:  either direct measurement of LDL or estimation via Friedewald formula results in an LDL number equally predictive of risk unless triglycerides are very high.  However, triglycerides were a much stronger predictor of future risk:
Dr. Børge Nordestgaard: We studied 7,600 healthy women and 6,400 healthy men who had triglycerides measured nonfasting back in 1976–78. So this was a single measurement. Then we followed them from 28–31 years. During that period, 3,500 developed a myocardial infarction, 1,500 had an ischemic stroke, and 7,800 died, approximately half or even more than half.  What did we find then? We very clearly found that the higher the nonfasting triglycerides, the higher the content of remnant cholesterol plasma, and at the same time, the higher the risk of all these three endpoints: myocardial infarction, strokes, and early death.  To give an example of the results, if we compare those with triglycerides above 5 millimoles per liter, which is 440 milligram per deciliter, versus those with less than 1 millimoles per liter in triglycerides, which is equal to less than 98 milligram per deciliter, then for women, these women with the high triglycerides had 17-fold risk of myocardial infarction, fourfold risk of stroke, and fourfold risk of early death, which is an extraordinarily high number. The corresponding values in men were fivefold, threefold, and twofold.

I played around with an online calculator, here, inputting my numbers over a period of years, and it closely recalculated my Friedewald estimates, and provided a different estimate using the "Iranian" formula - and as predicted the differences were significant when my triglycerides were at or below 65 or so.  In my latest fasting lipid profile, my F-LDL was 131, but the I-LDL was 112, a 14% difference; and who wouldn't like to lower their LDL without even having to take statins?!?  I'm joking of course, because I know I don't have the dangerous size of LDL.  Sadly, the statistical "trickery" that lowered LDL is just about as relevant to my longevity as statins are, but that wouldn't stop some doctors from trying to 'treat' my LDL number.

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