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
