High HDL risk factor for AD

[Jafa]

https://jamanetwork.com/journals/jamane ... le/2805006

Oh No! Man the risk factors keep coming. My HDL runs between 82mg/dl and 95mg/dl. I guess giving up my daily half avocado, Evo, oily fish and exercise is not a plan

[marymac]

My HDL is usually over 100. What's the best way to bring it down?! My doctors always praised this number in the past.

[BrianR]

Oh No! Man the risk factors keep coming. My HDL runs between 82mg/dl and 95mg/dl. I guess giving up my daily half avocado, Evo, oily fish and exercise is not a plan

You might want to listen to this podcast to get an excessively better understanding of HDL, to the extent it's understood.

#240 ‒ The confusion around HDL and its link to cardiovascular disease | Dan Rader, M.D.

As far as the HDL measurement provided in a typical lipid panel, Dr. Rader asserts:

"It is now well established that the cholesterol efflux capacity of HDL is a better predictor of ASCVD risk than simply measuring HDL cholesterol"

Unfortunately, they also note that there are not any generally available lab tests to measure HDL cholesterol efflux capacity.

On the positive side for those of us with high HDL, Dr Attia asserts the typical lipid panel measurements for HDL and Triglycerides are useful as a proxy for insulin resistance:

“In non-African American patients, the ratio of triglyceride to HDL cholesterol (when both are in milligrams per deciliter) is reasonably associated with insulin resistance… the higher the ratio, the more insulin resistant they are”

That is, assuming the right demographic, if your HDL value is relatively high and your Triglyceride value is relatively low, then that's probably a good thing.

[Julie G]

That is, assuming the right demographic, if your HDL value is relatively high and your Triglyceride value is relatively low, then that's probably a good thing.

That's my understanding as well. (Fingers crossed!) Another good sign would be accompanying relatively low LDL-C and particle number, suggesting that the HDL efflux capacity is functional.

[Jafa]

Thankyou BrianR. I listened to The Dan Rader interview and learned a little more but of course dosn’t answer some questions. High HDL (at midlife if I remember correctly) poses a high risk for Alzheimers according to the Jamanetwork study. If the brain has its own independent lipid system it’s hard to make sense of this. Thankfully I am doing okay with a low measure of Triglycerides. Thankyou Julie for your input also. I think I have a moderately high LDL 143. We don’t do a particle number in New Zealand . My docs wouldn’t consider a Statin cos of my ‘Fab’ Hdl . Just have to keep the fingers crossed.

[Plumster]

This article agrees with BrianR's entry that high HDL may be about metabolic disorder in those over 75, and dementia risk.

Here's a link to the study in Lancet.

[Julie G]

This article agrees with BrianR's entry that high HDL may be about metabolic disorder in those over 75, and dementia risk.

Thank you for sharing, Plumster. I'm having a hard time understanding the concept of high HDL as a "metabolic disorder" as low HDL is associated with metabolic syndrome. Can anyone help?

[NF52]

This article agrees with BrianR's entry that high HDL may be about metabolic disorder in those over 75, and dementia risk.

Thank you for sharing, Plumster. I'm having a hard time understanding the concept of high HDL as a "metabolic disorder" as low HDL is associated with metabolic syndrome. Can anyone help?

It sounds like scientists don't understand exactly why there is an association either, from this excerpt of the Lancet article's Discussion section:

The explanation as to why high HDL-C might be associated with an increased risk of dementia is unclear. Earlier studies linking HDL-C to cognitive function had suggested that moderately high HDL levels were associated with better cognitive function and that low HDL- C levels were associated with an increased severity of Alzheimer’s disease. However,HDLs are complex particles with various physiological functions likely determined by proteins and other compounds carried in their phospholipid coating. Plasma HDL-C levels do not necessarily reflect functional aspects of lipid transport and at very high levels this may be dysfunctional. The possibility also exists that increased dementia and very high HDL are both consequences of a separate and unrelated pathology...these findings are timely and may suggest that identifying individuals with very high HDL-C could act as a new strategy for the early identification of high-risk individuals. However, further research is needed to determine the pathophysiological explanation for these findings..

Association of plasma high-density lipoprotein cholesterol level with risk of incident dementia: a cohort study of healthy older adults

It might make everyone feel better to see the baseline characteristics of the ASPREE study in "healthy" people who were taking one aspirin a day. I doubt that many have the same lifestyle factors as those with HDL over 80, which suggest some combination of other variables that triggers the risk.

Baseline characteristics in ASPREE study.png

[aphorist]

I think it is an issue related to HDL quality, corresponding to the metabolic environment. Potentially, smaller HDL particles (size) represent HDL particles that can more readily engage in cholesterol exchange (i.e. clean-up oxidized LDL), a total HDL cholesterol value that is sufficient, but not too high with underlying composition of smaller HDL particles composing an HDL cholesterol value might be beneficial.

The small HDL particle hypothesis of Alzheimer's disease (authors incl. Ron Krauss)
https://alz-journals.onlinelibrary.wile ... /alz.12649

Perhaps a very high HDL-C of 70-100 (mg/dl) in the context of larger HDL particles, represents an HDL response that is insufficient for the burden faced by the immune/lipid system.

I think there is conflicting evidence with some papers showing high HDL particle size being protective in cardiovascular disease. But I would suspect more HDL, small particles would be consistent with interventions like Bexarotene which stimulate HDL formation, and protective against disease.

Obviously a low HDL cholesterol of perhaps 30 mg/dl or less would be indicative of the underlying risk of insufficient HDL particles and insufficiency in an HDL response to injury. I would assume a very low particle count, with high particle size leading to ~30 mg/dl in HDL-C would be quite bad.

There is probably a bit more complexity here, because HDL has ~48 different proteins associated with lipid metabolism, proteinase inhibition, acute phase response, and complement regulation.