心血管健康

[Neo]

Not saying you should, have you historically tried very small almost micro doses of a statin(s)? The dosages in @adssx example show a remarkable bang for the buck even low dose.

(Similarly you could eg do just one fifth of PCSK9i dosage which while not free would be substantially different than the high full dosages).

[RapAdmin]

@Neo

one fifth of PCSK9i dosage

How exactly would you do this? It comes in a pre-packaged syringe, doesn’t it? You’re saying do partial injections over a period of a few months? Interesting idea.

[Neo]

I think someone mentioned that they did it a while back here on the forum, but can’t remember who.

[RapAdmin]

I have to wonder if this is a good idea… its basically “reusing” the needle, which seems like a very bad idea. Perhaps some of the medical professionals here can comment on this idea… spreading out a Repatha injection over a few months for those who want to lower their cholesterol a bit more, but not suffer the full monthly cost of Repatha’s full dose.

@DrFraser @Dr.Bart Any thoughts on how this could be done in a safe manner?

[Neo]

No I don’t think that person reused the needle, I think (s)he extracted the solution and did smaller injections (assumably with different needles)

… is there a way to search the forum with google or something and not the built in search function that only seems to understand extract words and not synonyms and same meaning with different words?

[RapAdmin]

I just searched on Repatha and found it here: Statin usage and Desmosterol - #35 by ben_nichols

You are right. Put it into new sterile vials, and then use one at a time. I guess that would likely work fine. Its a great idea, it seems. @ben_nichols how has this worked out for you. What type of needles do you use for this?

[Neo]

@RapAdmin

guess that would likely work fine

One would still have to learn how to do the injection (unless one can find injectors that can be loaded that can substitute the way Repatha “pens” work).

[Neo]

Hi @ben_nichols - could you share more on your experience of this?

[DeStrider]

Ancient Alleles Shed Light on Atherosclerosis Risk

ABOVE:The study of ancient DNA isolated from mummies helps researchers understand the evolution of genetic risk factors for cardiovascular disease.©ISTOCK, MIK38

Ancient humans had clogged arteries thousands of years before smoking, cinnamon buns, caramel macchiatos, and couch potatoes were in style.1,2 Take for instance Ötzi the Iceman, who died over 5000 years ago at around age 45 with an arrowhead lodged in his shoulder.3 CT scans of his mummified body showed that he had atherosclerotic plaques, which precede cardiovascular disease, in his arteries.4 Had he not been killed, perhaps Ötzi would have eventually died of a heart attack or stroke. But what were the chances?

Ancient Alleles Shed Light on Atherosclerosis Risk

[adssx]

@DeStrider

Thanks, but I am statin intolerant.

Which statin have you tried before? At which dose?

Statin intolerance is highly dependent on the type of statin and the dose used:

Statin Intolerance: the Clinician’s Perspective 2015:

In patients with statin intolerance , very low doses of statins administered via an altered dosing regimen should be attempted and, if tolerated, should be gradually increased to achieve the highest tolerable doses. With this cautious approach, the majority of patients are able to tolerate at least some degree of statin therapy.

Statin Intolerance 2015:

The intolerance can be either partial (ie, only some statins at some doses) or complete (ie, all statins at any dose).
Before considering the use of a second-line alternative drug, patients should try statin rechallenge, alternative regimens, doses, or types of statins. In most cases, rechallenge with a statin after a brief period of drug discontinuation (“drug holiday”) can be successful. In a study of 11 124 patients in whom statins were discontinued at least temporarily because of clinical events or symptoms believed to have been caused by statin use, 92% of those who were rechallenged were still taking a statin 12 months after the statin-related event.

NLA scientific statement on statin intolerance: a new definition and key considerations for ASCVD risk reduction in the statin intolerant patient 2022

To classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest approved daily dosage.
To identify a tolerable statin regimen it is recommended that clinicians consider using several different strategies (e.g., different statin, dose, and/or dosing frequency).
An acceptable statin treatment regimen can be identified for most patients with statin intolerance which may require a different dose, statin, or dosing schedule.

For instance, I know someone intolerant to atorvastatin who uses rosuvastatin without any problem. See also:

My guess is that rosuvastatin 2.5 mg and atorvastatin 5 mg are identical to placebo in terms of tolerance at the population level, of course this might differ at the level of the individual. Pitavastatin seems also very interesting (check papers about it).

(By the way, I don’t say you should use a statin, I’m just commenting on their tolerability.)

[DeStrider]

I was intolerant to Rosuvastatin 5 mg. I couldn’t handle it even on an EOD schedule.

Bempedoic Acid and Ezetemibe work for me. I guess I could try a low dose of atorvastatin.

[adssx]

If you were even intolerant to rosuvastatin 5 mg EOD, then you might have “complete” intolerance. Atorvastatin seems to have a higher rate of intolerance, so it might not be worth trying, but you never know.

[DeStrider]

Yes. Bempedoic Acid and Ezetemibe are a real lifesaver for me. I would have had to take my chances with relatively high cholesterol without them! Thank goodness for modern medicine.

And Indian suppliers.

[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