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Nov 9, 2023Liked by Richard Sprague

Labs performing tests typically provide you with reference ranges for their tests. Labcorp and Quest for example have the same test method and reference ranges for vitamin D, but use different test methods with slightly different reference ranges for testosterone. I'm guessing SiPhox still needs to establish the reference ranges for whatever it is they are doing.

Like blood sugar and blood pressure, cholesterol (and related markers) changes throughout the day, so it would be useful to both know your "fasting" levels as well as having more continuous data.

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Total cholesterol is an ambiguous test to begin with, as the highest total mortality rate for both men and women is seen below 160 mg/dl. I think it's crazy to flag 200 as high as many labs do, as that is actually where you want to be. We should really be focusing on HDL-C and triglycerides, and both should be taken fasting.

I use fasting triglycerides divided by fasting HDL as a rough estimate of LDL particle size. That ratio ideally should be below 2.0. Lower ratios indicate larger diameter LDL, which is thought to be more benign. I know people with ratios below 1.0, even below 0.5, which indicates to me a relatively low risk of ischemic stroke or heart attack. However, such a person could still have high BP and be at considerable risk for other serious health conditions, such as kidney disease or the type of stroke associated with bursting blood vessels.

An example of a poor ratio would be fasting triglycerides of 250 and fasting HDL of 50, a ratio of 5.0. I would be concerned about the condition of the coronary arteries of such a person and would suspect possible atherosclerotic lesions, with considerably increased cardiovascular risk.

I've had very consistent results with the provider I use and have no particular reason to doubt my lab results, but there is no doubt variability among labs.

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Interesting, and I don't necessarily doubt anything you say. It's very hard to know whether any of those numbers are actionable, especially for a specific person.

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Large diameter vs small diameter LDL is a model, but it's one I tend to buy into, and there is evidence to support the simple triglycerides/HDL calculation correlating with the actual LDL-P test, which measures the number of particles of LDL in your blood and provides insight into particle size. In this model, small diameter LDL is believed to be more atherogenic. However, I have books written by highly intelligent authors with more insight than I may have who do not necessarily agree with this concept.

I use the metabolic syndrome criteria to evaluate my own health, as my understanding is that the inclusion of each of the five was more driven by data than belief. HDL and triglycerides form two of the five criteria. The others are BP, waist circumference, and fasting glucose. All of the five also show evidence as having insulin resistance as a component root cause.

I do not currently meet any of the five criteria but have been over the line on two this year, BP and fasting glucose. While three out of five is required to actually meet the criteria of having metabolic syndrome, I consider poor performance on any of them individually to be a cause for concern. Hence, I began an exercise program this year and made some slight changes to my diet. My numbers dropped, but I am still at the top of the normal range on fasting glucose, likely due the effects of my hormone therapy. That is the best I'm able to do at present.

There is considerable experimental and anecdotal evidence that low total cholesterol is a risk factor for cardiovascular disease, and that individuals in this group have a higher total mortality risk. This is due to low HDL, which correlates with increased total mortality rate. Tim Russert would be an anecdotal example, as his total cholesterol at the time of his fatal heart attack, from my various readings, was approximately 105, with an HDL of approximately 37. The metabolic syndrome criteria for HDL are less than 40 for men and less than 50 for women, with at least 60 being considered desirable.

The combination of low HDL and high LDL is likely a bad one. In that case, the LDL is also much more likely to be small diameter. My belief is that high LDL can be a risk factor for premature death, but it demands additional analysis on particle size to get a handle on what is actually going on.

As I indicated at the beginning, however, this is only a model.

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