Statins when you’re homozygous APOE4

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Nords
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Statins when you’re homozygous APOE4

Post by Nords »

Long post alert: 900 words.

I've read through the last couple years of statins posts, and it's probably better to start a new thread with these questions. I write to make sense of my life, and sharing it here helps me write. This time it’s age-related humblewhining about Dr. Attia’s “Outlive” chapter on heart disease with APOE4. Maybe my thoughts will help others think through their choices-- or show me the flaws in my logic.

Last month my annual metabolic & lipid profile tests were mostly in normal ranges, yet the statin word has reared its ugly head due to my age and elevated LDL.

Working from the AHA’s risk flowchart for atherosclerotic cardiovascular disease, my family doctor calls the cholesterol part “mixed hyperlipidemia”:
- Total cholesterol 257
- LDL 170
- Non-HDL cholesterol 181
- 63 years old
.
AHA ASCVD risk flowchart Cholesterol Primary Prevention.jpg
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(This comes from page 11 of the AHA’s 2018 guidelines on cholesterol.)


Here’s my history over the last three decades:
.
Screenshot cholesterol history.JPG
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I’d rather continue pursuing diet & lifestyle changes before experimenting with statins.

In the last year I’ve lost 10 pounds of fat. I’m back down to my high-school weight (now with surfing muscles) and a 34” waist. I’m on a sustainable trend and in the next year I could lose another 10 pounds. My remaining knee cartilage is happier about my weight trend but apparently my cholesterol doesn’t care.

The family doc suggested a different set of tests, and I said: “You must be tired of your patients quoting Peter Attia at you.” He replied “Actually, you’re the first one to mention him to me.”
Those additional results are:
- Lp(a) 107 nmol/L, which is considered moderate leaning toward high, and
- ApoB 106 mg/dL, also moderate leaning toward high.
He wrote: “Both your LP(a) and apolipoprotein B places you in the moderate risk category for major adverse cardiac events including heart attack and stroke. You would benefit from statins.”

Lp(a) might be more genetic than environmental, so it’ll probably stay around this level for the rest of my life.
ApoB can be lowered by lifestyle (diet & exercise) and, of course, statins.

Although my overall numbers are not horrible, the trend is a concern. My ASCVD flowchart risk is rising into the borderline range (5%-7.5%). Plugging my numbers into the ASCVD Risk Estimator tool gives 9.2%, edging into intermediate.

While I’m at least 90% likely to avoid a major heart attack in the next decade, it’s certainly possible that I’d encounter angioplasty & stents. And in the next 30 years... well, that gets uglier. I have no family history of heart disease because 1) they didn’t live that long or 2) they succumbed to dementia first.

Appealing to my internal locus of control, my family doc also wrote:
“We can consider obtaining a coronary CT scan for further risk stratification if you wish.”
I’ll make the appointment. (Apparently a CT angiogram is better with its contrast IV injection.)

Other lifestyle parameters:
- I’m surfing 2-3 times per week and chasing my preschooler granddaughter almost daily (including on a trampoline). There’s also breaking sweat on my daily chores of cleaning, home repairs, or yardwork.
- Between my osteoarthritis and repeatedly injuring my hip flexors, I feel maxed out on my exercise levels. The issue is not “move more and sit less”, but rather how much stretching & rolling it takes to avoid repetitive injuries.
- If I added any other exercise to this list, it’d be a treadmill walk of 30 minutes at about 3 MPH. My spouse and I walk all the time when we’re on travel, but I rarely walk at home unless the surf is awful.
- I’d assess my diet as healthy-ish. I don’t use tobacco and I stopped drinking alcohol 13 years ago. I’ve tracked numbers with MyFitnessPal since 2016. We’ve cut out the sugar & simple carbs. I eat fish & chicken nearly every day, and rarely red meat.
- My indulgences are one frozen meal per day (Lean Cuisine, Atkins, Healthy Choice) and a couple dozen high-cacao chocolate chips. I could cut back the saturated fat in my daily serving of Greek yogurt and cottage cheese. I feel mildly guilty about a cup of pad thai for 3-4 lunches per week. I won’t apologize for buying Costco’s BBQ ribs and rotisserie chicken every six weeks.
- I take supplements: a multivitamin, CoQ10, astaxanthin, vitamin E, glucosamine/chondroiton, turmeric, and fish oil.

Once the doctor and I get the calcium score we can have a more informed conversation about statins. My biggest questions are:
- What more can I do with diet?
- Is there significance to a low ratio of TGL/HDL?
- Side effects of statins, especially muscle pain. I feel that I already have enough muscle pain in my body, but there seem to be enough varieties of statins to hopefully avoid this issue.
- I’m not sure how my two copies of APOE4 would interact with statins. Statins might help avoid vascular dementia, but it’s hard to tell about Alzheimer’s from the current literature.
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Re: Statins when you’re homozygous APOE4

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Nords wrote: Thu Mar 21, 2024 2:27 pm Once the doctor and I get the calcium score we can have a more informed conversation about statins. My biggest questions are:
- What more can I do with diet?
Avoid processed foods, minimize saturated fat. Gundry likes perilla seed oil (and he likes Dr. Adorable brand on Amazon). He mentions a specific fatty acid he likes in it, but you'd need to search on him and perilla to get the details. When I do really minimize sat fat, I get the best lipid results. However Gundry looks at CVD as an autoimmune disease. The PULs test is one he uses and one of the tests in it is IL 16. When my wife & I started fermenting yogurt from A2 dairy (we consumed no other dairy) and we were doing this for a specific bacteria, her IL 16 went up 10x and mine doubled. When we quit, our IL 16 went back to baseline. Just mentioning this for example.
- Is there significance to a low ratio of TGL/HDL?
A TGL/HDL ratio <=1 in mg/dL units is a marker of good metabolic function.
- Side effects of statins, especially muscle pain. I feel that I already have enough muscle pain in my body, but there seem to be enough varieties of statins to hopefully avoid his issue.
- I’m not sure how my two copies of APOE4 would interact with statins. Statins might help avoid vascular dementia, but it’s hard to tell about Alzheimer’s from the current literature.
Though I preordered Outlive, I've yet to read it. I do recall podcasts with Attia and also a webinar with Dr. Kellyann Niotis (who works with Attia) mentioning specifically not recommending statins for E4's. Again don't have the references handy, you'd need to search for them.
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Re: Statins when you’re homozygous APOE4

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Thanks, @Tincup, I think I'm on the right track with the food recommendations.

It's interesting looking up the APOE and statins keywords in Outlive. Attia specifically mentions a bunch of lifestyle standards for APOE4s (exercise, diet) and never mentions statins. He specifically mentions a bunch of statin benefits on apoB and cardiovascular heart disease, but never mentions Alzheimer's or APOE4.

Going down the research Internet rabbit hole, there's no clear association between Alzheimer's and statins in either direction. One could conclude that there's enough findings on both sides to show that statins will keep APOE4s from dying of heart attacks until they die from dementia.

I'd feel really stupid for taking statins for a few years (even a low dose of a mild hydrophilic like rosuvastatin) only to learn much later that it happens to accelerate dementia in APOE4s.

I'll get the CT scan for a calcium score, and I'll have the APOE4 discussion with my family doctor. I've never raised that issue with him (it hasn't been relevant), and that new info might evoke a different set of recommendations from him.
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Re: Statins when you’re homozygous APOE4

Post by JD2020 »

Nords wrote: Sat Mar 23, 2024 6:25 pm Going down the research Internet rabbit hole, there's no clear association between Alzheimer's and statins in either direction. One could conclude that there's enough findings on both sides to show that statins will keep APOE4s from dying of heart attacks until they die from dementia.
Maybe the answer depends upon the specific chemistry of each individual. I read Lipitor, Thief of Memory long ago. It was written by Dr. Duane Graveline, former astronaut, aerospace medical research scientist, flight surgeon, and family doctor, so written by someone with excellent credentials. Nevertheless, his reaction to the drug is obviously much different from most and must be balanced with the reality of a person's individual risk for heart disease.
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Re: Statins when you’re homozygous APOE4

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JD2020 wrote: Sun Mar 24, 2024 10:53 am Maybe the answer depends upon the specific chemistry of each individual. I read Lipitor, Thief of Memory long ago.
Also with a half-dozen different types of statins (and a couple newer options for lowering apoB) I think the studies are going to need another decade or two before there's a clear trend.
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Re: Statins when you’re homozygous APOE4

Post by NewRon »

I think I recall that the lipidologist Thomas Dayspring recommends a desmosterol test before putting Apo E4's on statins. He seems to be the current favourite of Attia for lipids.

I'm in the same situation as you, lipids-wise and waiting to see a cardiologist.
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Re: Statins when you’re homozygous APOE4

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NewRon wrote: Mon Mar 25, 2024 4:12 pm I think I recall that the lipidologist Thomas Dayspring recommends a desmosterol test before putting Apo E4's on statins.
Here is Dayspring's X post on the topic.
Low desmosterol, a biomarker related to cholesterol synthesis & low levels predict AD. When using statins at any dose in patients with AD risk (apoE4, family history) I reduce statin dose when absolute concentrations of desmosterol hits or is < 20th %tile cut point. This is not a common occurrence but bears watching. If needed lower apoB by adding other Rx - No other lipid lowering Rx inhibits brain cholesterol synthesis. This is outside of the box thinking
Identification of a new plasma biomarker of Alzheimer's disease using metabolomics technology
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Re: Statins when you’re homozygous APOE4

Post by Nords »

Tincup wrote: Tue Mar 26, 2024 5:18 am
Here is Dayspring's X post on the topic.
Thanks, Tincup.
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Re: Statins when you’re homozygous APOE4

Post by Tincup »

Nords wrote: Tue Mar 26, 2024 9:04 am
Here is a niacin case study on Lp(a)

Also, Gundry has me take Amla for my mildly elevated Lp(a) . It mildly reduces Lp(a) and keeps my serum results in the good zone. From a transcript of me talking to him about this:

Me: Okay. Okay, the thing that's maybe not tooth related is the, which is always there,
is the LP(a). Is there anything I ought to be doing more for that?
1:00:18 Dr G: Yeah. So LP(a), there's a small paper, that gave 20 people amla, Indian Gooseberry
Me: Okay. Okay, the thing that's maybe not tooth related is the, which is always there,
is the LP(a). Is there anything I ought to be doing more for that?
1:00:18 Dr G: Yeah. So LP(a), there's a small paper, that gave 20 people amla, Indian Gooseberry
Me: Yup.
Dr G: And they gave them 500 milligrams twice a day. And it brought their LP(a)s down by 20%. And I've done it on a number of people and quite frankly gotten mixed results. Some people had a pretty nice affect, other people it didn’t change a thing. But I think (overtalk)
Me: How long do you expect to see that it would take? 1:01:00 Dr G: Oh, immediately. So (overtalk)
Me: (overtalk) ...test and see what happens.
1:01:08 Dr G: Yeah, why don't you do it. Yeah, a 20% result would you know would put you in the
normal range.
Me: Right: Okay.

I've been taking 2 tsp of this powder/day. The bag says 1 scoop - 1 gram. I've never searched for the scoop in the powder, nor have I weighed 1 tsp. However my Lp(a) remains in the normal range. I think some years before Gundry also talked to me about taking plain Niacin for it. I've not gone back to my notes to see what he suggested. I'm pretty sure it is in one of the linked transcripts in this post.
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Re: Statins when you’re homozygous APOE4

Post by mike »

Stanford put a stent in me a year ago and after my trouble with muscle breakdown on any kind of statin, they referred me to someone that works on hard to treat cholesterol. They started me off by seeing a geneticist who discussed my maybe needing genetic testing to see if there might be a combination of genes contributing, but none triggering alarm on their own. When I saw the doctor later, he was thinking that I didn't need genetic testing, because he thought my 4/4 status explained it completely... (!?). He asked me about my diet, and I told him he wouldn't like it, my being keto and fairly high fat. I said I needed it to keep my blood sugar in better control. It didn't seem to bother him. He just said they would need to treat it with drugs... Modern drugs. Who woulda thunk!?
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