Seeking insight: extremely high HDL (120 mg/dl)

I have always had very high HDL. It has been as high as 125. Slightly lower now after about 8 months on Repatha (also have high Lp(a). We know now that having high HDL (higher than about 80mg/dl) increases risk of atherosclerotic disease. I have family history and a whole complex of polymorphisms that some Ashkenazi Jews have. I believe that my high HDL has a genetic cause and I am worried that I have impaired reverse cholesterol transport. I would like to get the HDL Function test – anyone have that done or can provide any guidance?

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https://peterattiamd.com/danrader/

I recently listened to this Peter Attia podcast with Dan Rader (HDL/lipid expert). It’ s all about HDL. It’s worth listening to. They do discuss high HDL. I don’t remember specific details, but with HDL = 125, you should listen.

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Thank you, I have already listened to it and actually considered going to see Rader in Philadelphia. But, after going through that pod cast several times, all I got out of it is that high HDL might be a genetic issue that results in compromised reverse cholesterol transport. And that you have to know what your particles sizes and function is to know if your high HDL is putting you at risk. So. I want to get the test. I also wrote to Alan Sniderman, who responded that he is getting into research on HDL but has nothing to say about it right now.I have also listened to the Tom Dayspring series on cholesterol, which is very good, but didn’t say anything much about very high HDL. The best information I’ve seen just shows that it is a U shaped curve: both very low HDL and very high HDL confers risk – but for different reasons. And, that very high HDL usually has a genetic cause (just like high Lp(a).) Also, that if you have a lot of the bad size HDL particles, it can increase risk for neurodegenerative disease. Since my mother has AD, that is a concern. I think I have accumulated as much information as I can, but we are in largely uncharted territory when it comes to HDL. I need to get that test,

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I’m very impressed by all of the research you’ve done. I guess that’s what we have to do now as it’s just about impossible to find a GP that knows much- the science changes too fast and they are too busy to do much research…

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FWIW, in Nir Barzilai’s book, Age Later, he reports that one of the characteristics of the very old is very high HDL.

He says that HDL tends to drop with age, so he figures that the high values he measured were higher when they were younger. Also, many of his subjects are Ashkenazi Jews, so I gathered.

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Don’t know if you have seen the study summary below:

Very High High-Density Lipoprotein Cholesterol Levels and Cardiovascular Mortality - PubMed.

Very high HDL-C levels are associated with an increased risk of all-cause death and cardiovascular death among men but not in women in the general population free of coronary artery disease.

That is the summary. Full text available below. Study population was high -

https://www.ajconline.org/article/S0002-9149(21)01187-5/fulltext

But the specific article is paywalled. I got to download other articles of that issue, not about high HDL.

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Hello Deborah,

Being in your 70’s… have you considered having a Coronary Calcium Scan? In February its heart health month and many hospitals run a special on Heart scans… $90 … verses regular price of $350.

My mom’s side passed genetically to me familial hypercholerolaemia. Always had LDL- C above the 130 norm… sometimes 170 last few years.

That said, no heart issues back generations (we are Czechoslovakian).All long-lived… healthy. About 13 years ago my family doctor suggested statins… told her I would change my eating habits. Was easier to not see her again. Truth.

Actually in my research with familial hypercholerolaemia… diet, statins and exercise has little improvement effect.

Did my Coronary Calcium Scan at age 64. score of zero. Heart of a person under 35 years.

Will retake now two years later… only do a 3-D check…CT coronary angiogram look for soft plaque this time. Do this in heart month February if I find a sale.

Thank you all for your responses and the information you shared. At the risk of hijacking this rapamycin form with discussion of blood lipids, I will respond to the points you made and share what (little) I know about high HDL. To be fair, not a whole lot is known, and there are no therapies that I am aware of.

While there are behaviors that can lower or raise HDL, there are no meds. Axtzanthin has been said to have some ability to lower HDL. I take that.

I have read that particle size of HDL matters. Whereas with LDL it is the small dense
(and not the “fluffy bouyant”)particles that are most atherogenic, in the case of HDL it is the reverse: the larger particles are most dangerous. The functionality test would give me some insight into whether my particular HDL is dangerous.

I am particularly concerned as there seems to be a link between high HDL and dementia / AD. My mother is 97 and has advanced AD. Her sister died at 98, and had AD. Their mother died at 103 --and had AD. None had significant CVD and I have no idea what their lipids were. OH-- and we are Ashkenazi Jews, the population that Barzilai has been focusing on because of the high numbers of long lived people, especially women.

Of course, if you live long enough and manage not to have gotten CVD or cancer, you are probably going to get neurocognitive decline, which, from what I have seen up close and personal, is not a good outcome even if you manage to become a centenarian

So, my biggest fear right now is not CVD. It’s cognitive decline.

I have eschewed the statins for a couple of reasons. First, I have high Lp(a) and did not want to take anything that would raise it. Second, while I wanted to get my LDL and APOB down, I wanted to first see if the Repatha by itself would get me to where I wanted to be (and it has). I did not want to get the LDL much lower than that because at very low levels there is a (small?) risk of hemhoraghic stroke. My father died of a hemhoragic stroke at 69. Statins are good drugs – they reduce inflammation and they can be anti-cancer. But every drug, every initiative, involves tradeoffs. Looking at the whole picture I decided to take just the PCSK9i. Not everyone would agree. Tom Dayspring says that if you have any CVD – any evidence of plaque (I had a Calcium Score and it came back at “1” with a note of slight plaque on the LAD) – you need to “make him (the patient) like a kid again with his APOB.” So Tom Dayspring would probably tell me to add on the statin.

I feel pretty sure that my HDL is caused by a mutation of the SRB1 gene – this is a "scavenger"gene that supports reverse cholesterol transport. The HDL particles need to be unburdened of their cholesterol when the return to the liver, and when the scavenger gene is not working sufficiently well, that function is not happening. Anyway, that’s my story, until I can get genetic testing and get the HDL functionality test.

Incidentally, I found all this out by (1) getting my 23&Me data uploaded to Promethease, which highlighted some risks for CVD (2) reading Outlive where I first heard about Lp(a) (3) insisting on getting the blood test for Lp(a) (“we don’t do the test because we don’t have any way to treat it”) and APOB, (4) insisting on getting the CAC, (5)literally begging my cardiologist for the Repatha – and after the CAC was done, he was able to get it approved.

Also, incidentally, the Repatha has raised my blood glucose. Well know “tradeoff” if you’re on a statin, and apparently same for PCSK9i. I’m now on metformin and am fine with that-- for several reasons.

Thanks again and would welcome any other pointers or thoughts about HDL

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All my life I’ve had a particularly high HDL (2.8 mmol here in Europe). So has my mother (she’s 80), so had her father (he lived to be 99 and died of pneumonia)… it’s probably genetic and if I were you, I’d try not to worry.

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This forum seems to love discussing blood lipids. I don’t think you need to worry about boring people. :laughing:

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