心血管健康

[adssx]

I’m not an expert. My understanding, primarily based on what I read from others here, is:

• ApoB and Lp(a) are the best lipid metrics.
• Nevertheless, insulin resistance, blood pressure, and other things are as important for atherosclerosis prevention.
• Still, everything else being equal, for ApoB and Lp(a), “the lower, the better” in terms of CVD prevention (as low as 10–20 mg/dL for ApoB?).
• For neuroprotection, the target lipid level for optimal AD risk reduction remains unknown, and for PD, high ApoB seems protective.
• For other conditions (such as cancer), lower lipid levels are neutral or slightly beneficial.
• So, given the higher prevalence of CVD at the population level, I think “the lower, the better.”
• At the individual level, someone with low Lp(a) (< 20 nmol/L?) but a high risk of AD or PD might prefer a less intensive approach (ApoB ~ 70 mg/dL?) until we have more data (I assume it’s a matter of just a few years). That’s my approach so far.
• The therapy used to reach the above targets is as important as the targets themselves. For instance, people with diabetes (or at high risk of) might prefer non-statin lipid-lowering therapies.
• Also, as there are no good treatments to significantly lower Lp(a) to date (but obicetrapib is coming!), Lp(a) is for now mostly a risk factor rather than a target.

[DrFraser]

Hi @RapAdmin

Oh the auto-injectors … very simple to defeat.

So my patients in California (Ca is very hard to get compounded meds into … elsewhere I just use compounded) who are on Mounjaro who are paying cash for it - they often need ~2.5-3.75 mg/week. The autoinjector pens are all 0.5 mL, they all cost the same. So they come as 2.5/5/7.5/10/12.5/15 mg. So a pen with 6 times the amount of drug (15 mg vs 2.5 mg) costs the same.

So … I Rx them the 15 mg pen. Then I teach them to eject this into a 1 mL syringe (you can buy on Amazon), obviously with the needle of the auto injector carefully put into the opening of the syringe, and the plunger fully pulled out to allow the 0.5 mL to go into the 1 mL syringe.

You eject the pen into the syringe, then, for example, if you had 0.5 mL ejected, and needed 5 doses from it – then carefully pull up 0.1 mL (10 units) into each insulin syringe … problem solved!

Make sure to maintain sterility with this. It isn’t that hard once you do it a couple of times. I’ve seen folks not have the needle in the syringe (so wear magnifying glasses to make sure), and also not have the plunger pulled out, so eject it into the syringe without having adequate space for the liquid to go into. Each time this occurs, I believe cursing has ensued … so pay attention - not hard to do … but don’t mess it up.

[desertshores]

@adssx

there are no good treatments to significantly lower Lp(a) to date

Not much you can do about it. Diet and lifestyle have little influence on Lp(a). Drugs that lower other lipids like statins do not affect Lp(a). High Lp(a) increases your CVD risk and reduces your healthspan.
You must make up for this, since there is really nothing you can do about it, by having a healthy lifestyle, exercise, etc. to keep your other risk factors low.

“Lp(a) levels are controlled almost entirely (>90%) by variation in the LPA gene, which encodes apolipoprotein(a). The LPA gene accounts for >90% of variance in Lp(a) levels between individuals. The only effective way to lower Lp(a) is interfering with LPA gene expression.”

[LukeMV]

Great summary here. I have to agree based on my own research. I had no idea high lipids and ApoB were protective of Parkinsons though. That’s a weird one. I take 1.25mg selegeline daily which is supposed to be protective of PD though, and also I’m not at an age where PD happens so maybe not a concern.

Lipids, Apolipoproteins, and the Risk of Parkinson Disease

A Prospective Cohort Study and a Mendelian Randomization Analysis

https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.119.314929

[RapAdmin]

New story in New Scientist magazine:

Those with the unusual gene variant have several traits that protect against heart disease, one of the most common causes of death, which may explain why their life expectancy exceeds that of the general population.

A signalling molecule called insulin-like growth factor-1 (IGF-1) has long been suspected to play a role in longevity. Multiple animals, such as worms and mice, have been found to live longer if their levels of this compound are lowered artificially, such as through genetic modification. Centenarians also have slightly lower levels of IGF-1, on average.

全文：

Rare mutation that causes short stature may shed light on ageing

[LukeMV]

I know we’ve had a very constructive back and forth on IGF1 before and I’m still of the opinion that a low IGF1 isn’t desirable.

When I see these extreme low IGF1 levels being linked to longevity, I also think of how low thyroid and castrated men with no testosterone also are somehow linked to longevity, despite the fact all these low hormone levels increase risk of diseases and all cause mortality (weird paradox?). Could it be increased lifespan but worse healthspan?

I know quality of life is significantly reduced without adequate levels of IGF1, thyroid, and testosterone.

HGH has been shown to improve collagen synthesis and increase wound/burn healing, possibly through increased IGF1

Growth hormone stimulates the collagen synthesis in human tendon and skeletal...

Here is a good review of IGF1, suggesting 120-160 is the optimal level (not too low and not too high). I can’t help but wonder why bodybuilders who use high doses of HGH rarely get cancer if IGF1 is cancer promoting. One theory could be the fact they lift weights all the time, which is extremely cancer protective. I do know
That bodybuilders get cardiovascular disease instead.

Association between IGF‐1 levels ranges and all‐cause mortality: A meta‐analysis - PMC).

[Neo]

Can’t see your link for some reason, can you please repost

[Neo]

Thx for the review, will take a look.

(My intuition is different than yours here)

[LukeMV]

They should be working

[Neo]

@LukeMV

[fang-et-al-2019-lipids-apolipoproteins-and-the-risk-of-parkinson-disease.pdf](file:///C:/Users/LVare/Downloads/fang-et-al-2019-lipids-apolipoproteins-and-the-risk-of-parkinson-disease.pdf)

Above is the think that is not working - it’s pointing to your hard disk or something

Not talking about your second message that had multiple links, the message that I had replied to with only one link is the one with the issue

[RapAdmin]

I fixed it - here it is:

https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.119.314929

[Mantheunknown]

Great idea. Thank you Dr. Fraser. I am diabetic. I just switched from Ozympic to Mounjaro this week (stopped my 4 mg/once a week Rapamycin to avoid issues during the transition). Since I am used to working with the syringes (HGH!) it should be very doable. Thanks once again! Cheers

[LukeMV]

Sorry the link made me download it to view it, so it didn’t translate here properly, but @RapAdmin took care of it

[LukeMV]

I just stumbled upon this 2022 study saying too low LDL (and also too high LDL) is associated with higher mortality. I lean on thinking it isn’t biased if they’re also saying too high LDL is bad.

Seeing how my recent LDL was 32, I am going to drop Ezetimibe and just remain on 5mg Rosuvastatin.

https://www.ahajournals.org/doi/full/10.1161/JAHA.121.023690#:~:text=However%2C%20recent%20observational%20studies%20indicated,mortality%20and%20other%20adverse%20outcomes.

[DrFraser]

Pretty much all of the autoinjector pen medications end up being a fixed cost, regardless of dose. So on Mounjaro - I find a lot of patients do well on weight loss in the 3.75 mg/week range (always start no higher than 2.5 mg/week for first 4 weeks is the manufacturer’s recommendation) … so getting 4 doses out of a 15 mg pen is markedly more cost effective, if self paying. But you have to have the skills to do this safely and with sterility.

[Virilius]

@LukeMV

I just stumbled upon this 2022 study saying too low LDL (and also too high LDL) is associated with higher mortality. I lean on thinking it isn’t biased if they’re also saying too high LDL is bad.

It’s an observational study which does not take cofounding factors such as cancer, infections or other health issues into account. When adjusted for those, lower LDL-C (or rather apoB) is always better. That’s why I’m using both 10mg of rosuvastatin and ezetimibe which I tolerate relatively well.

[LukeMV]

I tolerate 5mg rosu and 10mg eze well too. What is your ApoB or LDL?

[Virilius]

My LDL-C is in the low 60s. Don’t know about my apoB as I couldn’t find any inexpensive tests for it.

[LukeMV]

You’re absolutely right. I forgot they probably didn’t account for the fact people in disease states have low LDL which probably accounts for this result. I’ll stick with my 32 LDL and remain on Ezetimibe.

[LaraPo]

Why would you remain on rosuvastatin if your LDL is 32?