Using statins with APOE 3/4 genetics

[Seekingforanswers]

I have a 3/4 APOE genetic makeup. My liver enzymes run high normal and I have high total cholesterol and LDL as well as high HDL. I also have high LPa. My cardiologist has wanted me to take statins for years which I have refused. I do have some plaque in my carotids. I am 70 years old and I’m starting to soften to the idea but I’ve read that statins shouldn’t be taken if you have a APOE4 marker. Does anyone know if this is true or could share some current research they have found. Is there a statin of choice for those with the APOE4 marker? Thank you for any information you can offer.

[Alexia C]

I have a 3/4 APOE genetic makeup. My liver enzymes run high normal and I have high total cholesterol and LDL as well as high HDL. I also have high LPa. My cardiologist has wanted me to take statins for years which I have refused. I do have some plaque in my carotids. I am 70 years old and I’m starting to soften to the idea but I’ve read that statins shouldn’t be taken if you have a APOE4 marker. Does anyone know if this is true or could share some current research they have found. Is there a statin of choice for those with the APOE4 marker? Thank you for any information you can offer.

Hi Seekingforanswers,

Welcome to our forum! I am so glad you found us and I am sure our community will help you with answers or guidance to your inquiry.

As a welcome intern, I would like to point out some links/resources that might be helpful as you explore the site further.

First, if you would like to learn more about ApoE4, the Primer is a detailed and informative resource written by a practicing M.D. with ApoE4/4. It includes information about the biochemistry of the ApoE4 gene and offers a variety of research-based prevention strategies.

The How-To Guide shows how to quote members (use the " icon in the upper right of any post) so they get an email notification of your post. It also shows how to use the Search function for topics, and how to subscribe to topics of interest.

Here is a link pulled from our Wiki that you might find useful: Cholesterol, Lipids and Treatments, Including Statins

If you are interested in learning more about other members check out Our Stories. You might find members with experiences like yours that can help to steer you in the right direction.

Again, I am so glad you joined our forum and hope you find the support you need. I look forward to hearing from you in the future. Reach out anytime and continue to ask questions!

Warmly,

Alexia C

[NF52]

I have a 3/4 APOE genetic makeup. My liver enzymes run high normal and I have high total cholesterol and LDL as well as high HDL. I also have high LPa. My cardiologist has wanted me to take statins for years which I have refused. I do have some plaque in my carotids. I am 70 years old and I’m starting to soften to the idea but I’ve read that statins shouldn’t be taken if you have a APOE4 marker. Does anyone know if this is true or could share some current research they have found. Is there a statin of choice for those with the APOE4 marker? Thank you for any information you can offer.

Hi "Seeking",

I am also 70 years old (1952 was a great year for the baby boom!) and am ApoE 4/4 with previous high total cholesterol, high triglycerides, high LDL, moderately high LDL particles, and sky high Lp(a). As you probably know, Lp(a) is mostly inherited and seems unlikely to come down with a statin.

I went on atorvastatin in 2015, about a year after learning my ApoE 4/4 status, since my dad's death at age 67, from cardiac arrest after prior silent heart attack, aortic stenosis and severe coronary artery disease with quadruple bypass, preceded my mom's age of cognitive decline by 15 years. Right now my LDL is 59 (lowest ever), my HDL is 61 (highest ever) and my trigylcerides are 50 (lowest ever). My liver enzymes have only recently nudged a tiny bit into the high normal area, which my PCP is watching. My blood pressure and resting heart rate seem better than in the past--although the credit for that may go to my husband and grandkids!

Aortic stenosis is reported as a specific risk of high Lp(a). So I had a coronary artery calcium scan (CAC) at age 67, with a prescription by my PCP and payment of about $150 by me. Glad to get a score of zero and a "cardiac age 39". Have no idea how I lucked out since I did not have a perfect diet in mid-life--or now. On my mom's side there were strokes, TIA's and high blood pressure, so I had a carotid scan in 2021, and like you I have some carotid plaque. My PCP said those scans are not predictive of strokes in people with high LDL but without a history of coronary artery disease or prior ischemic event, if I'm remembering the gist. I also had an abdominal aortic and peripheral artery scan (all good),
FWIW, I also score fine on cognitive tests, having been in a clinical trial with extensive testing, so statins do not seem to have affected my cognition.

One suggestion might be to arm yourself with some knowledge of your current baseline, if you can afford to do that. This is a very personal decision and you have to feel comfortable with the risk/benefit assessment based on your family history and your sense of why your cardiologist recommends this.

Here's a few articles: The second author on this 2017 article on the benefit of statins is Dr. Roberta Diaz Brinton,, Director of the Center for Innovation in Brain Science at the University of Arizona.
Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease Dr. Brinton's research has focused on the risk women face for Alzheimer's and in particular women with ApoE 4 and she won a $37 million grant from the NIH for a current Phase 2 clinical trial (not of a statin): Can the Alzheimer’s Brain Regenerate and Recover?

The opposing view is represented in the 2019 abstract of a longitudinal study following women ages 47-75 with one first-degree relative (parent, sibling etc.) with probable AD:DIFFERENTIAL EFFECTS OF STATINS ON COGNITION IN WOMEN AT RISK FOR ALZHEIMER’S DISEASE

Here's what they found:

Statistically significant interactions were found between statin use and APOE4 status in RAVLT [Rey Auditory Verbal Learning Test] total learning and immediate memory. Statin use in women APOE4 non-carriers was associated with better verbal learning and immediate memory performances whereas statin use in women APOE4 carriers was associated with worse performances on these same tasks. Conclusions. Findings suggest that sex and APOE4 status may be important factors in consideration of statin use.

It's not clear from the abstract whether ApoE4 women without statins ALSO did worse than ApoE 3 women, which might indicate an earlier impact on immediate memory in ApoE 4 carriers, with or without statins.

Good luck with this decision--and let's enjoy our 70's!

Nancy

[Seekingforanswers]

Dear Nancy,
Thanks so much for your detailed response. I wish I could find a cardiologist who could think outside of the box and consider my liver, APOE4 status, and lipid profile. It seems overwhelming to put all of the pieces together without a medical background. Thanks again.

[grommet]

One suggestion might be to arm yourself with some knowledge of your current baseline, if you can afford to do that. This is a very personal decision and you have to feel comfortable with the risk/benefit assessment based on your family history and your sense of why your cardiologist recommends this.

Thanks Nancy for such a great write up. Have you experienced any side effects on your statin?

My wife and I are both 4/4 but are super healthy otherwise so we don’t really have experience with this. She’s also pretty high in Lp(a) (150 mmol/L) so we’re talking with her PCP about getting her on a low dose statin. Her PCP is not really educated on the nuances of lipidology outside of the normal tests but is very open to learning thank goodness.

[NF52]

Thanks Nancy for such a great write up. Have you experienced any side effects on your statin?

My wife and I are both 4/4 but are super healthy otherwise so we don’t really have experience with this. She’s also pretty high in Lp(a) (150 mmol/L) so we’re talking with her PCP about getting her on a low dose statin. Her PCP is not really educated on the nuances of lipidology outside of the normal tests but is very open to learning thank goodness.

Hi grommet,

I haven't experienced any side effects from atorvastatin, and recently took a CoQ10 test for the first time since I had been told by friends that I definitely needed to supplement with that on a statin. The results showed my levels were solidly mid-range. So no need to add another supplement, I assume.

In August 2021 I increased from 10 to 20 mg on the atorvastatin and also felt no side effects. A year later, in addition to the results I posted above, my LDL-P and small LDL-P have both dropped by a third and are less than the 50%ile. And let your wife know that my Lp(a) is 190 as of 2021, so I have her beat But my latest ECG was described as "couldn't be more perfect" by my doctor, and my resting pulse is in the 60's. I'm can't claim to lead a perfect life, so have to give some credit to my ancestors for passing down some good resilience along with the ApoE4!

[BrianR]

... but I’ve read that statins shouldn’t be taken if you have a APOE4 marker.

For what it's worth, Peter Attia uses blood plasma levels of desmosterol as an indicator of whether statins might be adversely affecting brain lipid levels in his patients:

From a clinical perspective, low desmosterol levels in patients with cognitive symptoms may serve as an indication that cholesterol synthesis is over-suppressed and the statin dose should be decreased (or stopped altogether in favor of a different drug class). We don’t like to see absolute concentrations of desmosterol below 0.8 mg/L in our patients. We also treat patients with one or two copies of the APOE e4 alleles or a family history of dementia with kid gloves and make sure they have a desmosterol level greater than 1.0 mg/L. While we don’t know for sure whether low desmosterol from statin use increases the risk of dementia, a personalized approach may be necessary

from https://peterattiamd.com/does-low-cholesterol-cause-cognitive-impairment-part-ii/