255-Latest therapeutics in CVD, APOE’s role in Alzheimer’s disease, familial hypercholesterolemia

[@PeterAttiaMD]

In this episode, we discuss: 00:04:30 - Familial hypercholesterolemia (FH): a genetic condition 00:09:45 - Differentiating between phenotype and genotype when it comes to FH 00:15:30 - The pathophysiology related to mutations of FH 00:22:00 - Clinical presentations, physical manifestations, and diagnosis of FH 00:30:15 - Criteria used to make a formal diagnosis of FH 00:34:15 - Why a small fraction of people with FH do not develop premature ASCVD 00:39:45 - Treatment and prevention for those with FH 00:52:45 - Addressing the assertion by some that elevated LDL is not casual in cardiovascular disease 00:55:45 - The history of CETP inhibitors and the role of the CETP protein 01:09:00 - The thrifty gene hypothesis and why genes underlying FH may have been preserved 01:13:00 - The compelling potential of the latest CETP inhibitor (obicetrapib) 01:27:45 - Promising results from phase 3 trials exploring obicetrapib 01:41:30 - Why the APOE4 allele increases the risk of Alzheimer’s disease, and the connection to blood lipids 01:51:45 - The role of APOE in cardiovascular disease 01:57:00 - Takeaways and looking ahead

[@roddunne]

Gotta compliment your interviewing skills Peter - Sharp, concise questions which pull out broader explanations, and never talking over the guest (bugs me when others repeatedly do it :) ). Fascinating subject & story. The Dutch are blazing a trail on this.

[@6789uiop]

As always, gratitude for Dr Attia.

[@thinking-ape6483]

This is why we need complex gene editing asap, so people like me (APEO4 single carrier) don't need to live with this BS and we can stop leaving these things to the genetic lottery.

[@HEARTANDSOULOFMINE]

Exactly!

[@DessicatedCadaver]

Agreed 100%.

[@plants_and_wellness1574]

I wonder how many people believe they have FH but really don’t, it’s their diet. My LDL was 194 when I was drinking raw milk, homemade butter on veggies, and grass fed beef 4-5 times a week. I ate no processed food at all. Smoothie with raw milk for breakfast, huge salad for lunch, and beef or chicken with veggies for dinner. Found out I had super high Lp(a) (380 nmol/L) to go along with high LDL (194) and particle count (over 1800) so I cut out all animal products and now my LDL is down to 112. My particle count was over 1800 (should be (

[@JWB671]

I was at total cholesterol of 315 and LDL of 238…. In 3 months I am down to 110 total and 69 LDL… went from eggs and beef daily to Pritikin diet and it worked. Was told I had FH btw.

[@plants_and_wellness1574]

@@JWB671 69 LDL?! That is awesome! Can you share what a day of eating looks like for you?!

[@everydayhomelife8697]

Just found out my LPa is 318nmol.

[@plants_and_wellness1574]

@@everydayhomelife8697 I’m sorry, it sucks, but I don’t think it’s the end all be all. I think there are things we can do to mitigate our risk but we who have high Lp(a) do have to work harder than those who don’t 😥

[@JWB671]

@@plants_and_wellness1574 170g can of wild caught salmon, 90g chicken breast, 420g sweet potato, 120g steel cut oats, 120g brown rice, 80g quinoa, 100g avocado, 5g macadamia nuts pieces, 250g carrots, 220g cauliflower rice, 250g zucchini, 120g mushrooms, 220g black beans, 240g royal gala apple…. Everything that needs it is cooked and then cut into small chunks and put into a huge bowl and mixed together. Then I weigh it out into 4 meals for the next day. 45 min before each meal I take it out of fridge but I don’t heat it up. The 60g of apple is eaten after each meal…. I like to eat very small amounts of each food at each meal instead of different foods in larger amounts at each meal especially animal protein foods… “The dose is the poison” can be applied to foods in my opinion.

[@melissaann5272]

Thank you! I have FH, confirmed by genetic testing. I’ve had high LDL since my first blood test at age 10. My father at age 60, died while exercising, not an ounce overweight, not a smoker but had no idea he had FH. I’m now 50 and believe me it’s hard to find even cardiologists that are knowledgeable. This podcast was wonderfully informative and insightful

[@LynnFishmanMeditation]

thIs is the issue- finding a local cardiologist who is on top of this information and willing to use it

[@Edwards87]

My grandfather had FH, died early, so did multiple of his siblings. My mom inherited it, has been on lipid lowering meds since her early thirties, low fat diet, always low cholesterol. Angiography came up with calcified arteries, she is on bloodthinners now. I got negative genetic test as a kid, ate low fat anyway, was super scrawny into early adulthood due eating a high carb diet. In my 20s went paleo, gained 12 kg of muscle mass up to now (37). Ldl-c was always mildly elevated in 20s, now on last test it got even higher. Maybe it was also because I have been bulking a lot. The energy surplus thing in combination with these potential ice age genetics may be something awry. Gonna check my apo b and redo the genetic test and do carotid check just in case. Also going to do a cut for summer and stick to high protein and fish/fowl with mufas for a bit. This field has been a huge mess for decades and there is still no clear consensus. 😢

[@dominik13579]

That's great that you know it since age 10. I found out the hard way at age 38...

[@everydayhomelife8697]

I just found out my LPa is 318nmol. Im 35, female. Heart catheterization found 15-20% blockage in 2020 RCA and LAD(all soft plaque). Cholesterol panel is perfect except LDL a little high at 112. CRP is great. Particle count good(pattern A). Not overweight, don't smoke, active, low blood pressure, not diabetic. Im at such a loss.. hoping I'm able to see my babies grow up. Considered FH in my case though I know my ldl isnt extremely high. Also hoping the new drug that seems to be working at lowering lpa will work for me. Great listening though, trying to learn all i can.

[@plants_and_wellness1574]

Your story sounds so similar to mine. I’m 39 and have been health obsessed since I was 29. Found out last year I had high Lp(a), 380 nmol/L and high LDL and high particles, and on and on. Going plant based, fish weekly, has greatly reduced and put back into normal ranges almost all of my cardio bio markers. I have never had heart problems and have never seen a cardiologist. I order my own lab test online, I don’t see a doctor. I had my mom check hers, I paid for it and her Lp(a) was 166. She will be 70 in October and has never had any heart problems but everyone in my family has died really young from heart disease, her mom had three strokes and died in a nursing home at 70, her dad died at 63, all 5 siblings are dead, the only thing she does differently is she doesn’t eat red meat 🤷🏼‍♀️ and so now neither do I. Just fish. I’m trying to mitigate my risk the best I can by lowering my LDL as best I can and eating as healthy as I can. I hope it’s enough.

[@tanvir6356]

The PCSK9 inhibitors (Repatha and Praluent) can lower Lp(a) by roughly 25-30%. Also for an apparently unknown mechanism, daily low dose aspirin seems to be particularly effective at preventing heart attacks for high Lp(a) patients

[@everydayhomelife8697]

@@tanvir6356 thank you for this info!

[@joannepizel2728]

I didn't understand the details BUT this was still so fascinating and exciting. Super guest 😊

[@ThomasHUsher]

This was an eye-opener. The facts related about the little children with FH who would die as early as 25 without a massive effort to bring down their cholesterol has totally convinced me!

[@les0nick]

Great podcast! Gives a feeling of the science edge and can see how new pages in the book called "Medicine" get written... Thanks both for sharing the knowledge!

[@sgill4833]

People should be allowed to try phase 3. Im nearing 50 with double e4s and 200 LDL.

[@sherriedaubenmire3364]

Thank you for enlightening podcast. Not asking for medical advice, just sharing frustration. I was dx with FH and hypertriglyceridemia 35 yrs ago without a family history taken or any genetic testing done. No where along the way did any other practioner think to do genetic testing or look at root cause..continuing to prescribe higher dosed statins, statin extenders like zetia, and fenofibrate for hypertriglyceridemia....I subsequently developed type 2 DM. I found a very low carb diet has put me in remission from T2DM. I stopped the statins for a break due to the side effects suffered. I feel so much better without the statins. But my LDL is near 300 now and triglycerides 154. My current pcp refused to order genetic testing, testing for CAC score and is threating to fire me if I continue to refuse statin. I have to see a cardiologist, but looking for a low carb friendly on my insurance plan has been a roadblock. Im now 65. What to do. Looking for a low carb friendly pcp...way time consuming..

[@RoccoStanzione]

This changed my mind on statins and a number of other things. Absolutely wonderful.

[@tbainbridge]

No mention of Acetylcholine esterase inhibitors for Alzheimer's. And anything which increases acetylcholine such as smoking, being protective of Alzheimer's. (Not advocating smoking btw); As for ASCVD cholesterol is only 1 risk factor, by itself it doesn't always cause acute MI. It's a combination of inflammation, shear stress, age, gender, diabetes status, waist circumference and blood pressure. Personally I think low dose aspirin should be started way earlier in many people, and people at risk should be better informed and trained on having some GTN handy.

[@artsiecrafty4164]

I am a double apoe4! I recently learned that nicotine delivery, patch, gum, is being studied for Alzheimer’s. I’ve been on the patch for a few months, and I’m experiencing increased energy, activity and increased cognitive ability. I also have Familial hypersholesteremia. I am on a keto diet for eight years. My triglycerides dropped very low. My LDL is way high. I doubt I am at risk for heart attack. I eat zero sugar, carbs and processed foods.

[@vitennis9109]

I'm looking for research on familial condition with very low lipids. Ex ( LDL 20, HDL 80, triglycerides 30) . No lipid absorption issues.

[@thinking-ape6483]

More depressing news for an APOE4 carrier like me, cannot wait!

[@plants_and_wellness1574]

Are you following Dr Dale Brededen?! If not, please do so 🙏

[@jillmeincke9202]

Agree… was waiting for the good news but it never came, jesus

[@plants_and_wellness1574]

Please please look into Dr Kellyann Niotis, she is a preventative neuroscientist and talks about ways to mitigate risk. Also look into Dr Dale Bredesen, he has a protocol that has reversed people’s early onset dementia. I’ll give you a heads up, both promote the Mediterranean diet. A diet without saturated fat, high in fatty fish, nuts and seeds, fruits, veggie, and legumes. This diet outperforms every diet every time it it studied. Keep your LDL/ApoB low and that will help you a lot.

[@nab626]

Fascinating! I hope this information eventually enlightens those who would benefit the most. But it will be slow! Thank you!

[@Philly1958]

Can you discuss if ldl can be driven too low and the health risks.

[@plants_and_wellness1574]

I think he has. Look for the episode with Dr Thomas Dayspring

[@mtothel657]

Its briefly touched on when they discuss that developing children have an average LDL of 10-20mg/dL during the most intensive period of development in life. That being that case, there is no reason why fully grown adults could not operate just fine at similarly low LDL levels

[@andreac5152]

The fact that a calcium score of zero is rare on middle age people with FH has been disproven Just a few days ago in a series, almost 50% of people with FH had a CAC of 0. They were treated but the LDL years burden was 12000 on average so very high anyway.

[@WereAllThatBored]

Myself, and several others in my family have LDLs near 200. High HDL. Low Trigs. Low VLDL. My mom being 76 has a CAC score of 0. Not a single person on her side of the family have had heart issues.

[@andreac5152]

@@WereAllThatBored I'm not suggesting that cholesterol is not important, on the contrary, I believe it is. I'm only pointing out an incongruity, it's important that people have the right information, without exaggerating or underestimating. I would like to see reliable and comprehensive real world data.

[@WereAllThatBored]

@@andreac5152 exactly. Absolute data that includes healthy participants would be a start. Another great option would be state funded research that excludes drug manufacturers money or input on trial guidelines. I’ve worked in research and most will not go through it unless they’re positive their inclusion and exclusion will produce the results they want.

[@andreac5152]

@@WereAllThatBored just saying, there's another incorrect information about LDL levels on little kids. It is true that newborns have an LDL of 30-40 but by the age of 1-2 is already at 100. I've seen this in a new paper just yesterday.

[@WereAllThatBored]

@@andreac5152 I'll just say Im a little shocked at how early folks resort to Statins in minors.

[@carltaphouse]

Great discussion. I'm cautiously optimistic about the impacts that obicetrapib could have on ASCVD.

[@Thenachobear101]

Phenomenal discussion

[@jamesgordon8867]

I wish they would study photobiomodulation for LDL removal 😊

[@RexHavoc]

My research showed that while CETP inhibitors do reduce bad cholesterol and raises good cholesterol drug companies dropped research because there were no long-term cardiovascular benefits. How is it that his inhibitor is any better?

[@ceeweedsl]

Perhaps it's best not to assume that anything which inhibits CETP will behave exactly the same as the CETP inhibitors initially developed and tested. Is it possible that there are different types of CETP inhibitors? It seems that there were some details in the discussion about differences.

[@ladagspa2008]

He said this one lowers LDL much more than the previous cetp inhibitors

[@DebiDalio]

That was fascinating. Give me an LDL lowering drug that doesn't cause side effects and I'll take it in an instant.

[@MattWilsonTravel]

Sounds like Wim Hof became an MD.

[@edwardaligonzalez123]

Thanks for sharing! Great information, 🧠💥💯💪🏽👍🏾 any Genetic Testing company recommendations ??

[@plants_and_wellness1574]

23andme is a great one

[@AZ89231]

54:40 "Genetic mutations in or near LDLR are expected to affect not only LDL receptor function, but also blood coagulability through the coagulation factors IX, X, and protein C, inflammatory tone through tumor necrosis factor (TNF)-α, epidermal growth factor (EGF)-related physiology, and infectivity through complement C9."

[@Ahdbfbfbeh]

How often do you see a “DeNovo” FH mutation or clinic phenotype based on numbers and personal h/o events? I have many patient with concerning numbers but no FH ASCVD….

[@mattp3626]

Oh and it's Christmas Vacation not Planes, trains and automobiles. But i loved the reference 😂

[@thesophiagibson]

Can you do a post on Lipodemia/ Lipedema?

[@bellelacroix5938]

So then what's the diet for people who have an LDL / 100 especially regarding saturated fat, irregardless of FH.

[@bryansmant870]

Super interested in newer treatments. I've tried a few stations and ezetimibe, all of which work, but all drive my CPK over 400.

[@sgill4833]

All drive it or 1 is the culprit? Im debateing to take ezetimibe.

[@jamesgordon8867]

Do they look at insulin resistance?

[@worldreformmedia6593]

why is peter attia too shy to tell us if his heart rate at LT1 and how it compared to his calculation to MAF for HR.

[@mtothel657]

Excellent podcast. I wish the quacks that think an LDL in the 300s is a good thing would listen to this.

[@advertiserfriendlyusername5362]

_[One Of My Mentors, Tom Dayspring, Intensifies]_

[@AZ89231]

1:40:10 why wouldn’t an explanation be improvement of insulin resistance therefore less hyperinsulinemia and like antinatriuresis?

[@ladagspa2008]

This was fantastic.

[@Flaviu111]

If the LMHR risk study will show us that LMHRs have lower risk for CVD than the general population this video will age very badly.

[@wmp3346]

Would like to see Peter interview some non conventional medical people. Conventional medicine primarily treats symptoms and does not treat the root causes.

[@tanvir6356]

You should try listening to more of his podcasts. He never stops talking about exercise and much of his early work was focused on nutrition