Cardiovascular Health 2026

[qBx123Yk]

Over 30 years, this ARR is likely to more than triple. This ARR is only for the most complex procedures, and we know that with age the likelihood of needing more complex procedures climbs. Having that reduced is great.

This study only looked at preventing the most complex surgeries. Over 30 years, early vs. delayed treatment also drastically impacts MACE.

This stuff is very much like compound interest. 1% of interest over 30 years on your principal starts looking pretty impressive.

[DeStrider]

If only I had found this website earlier and started statins and lipid lowering in my late 30s or early 40s.

[Bicep]

Back then you would have been stuck with primitive statins and muscle pain. Need a time machine too.

[desertshores]

@RapAdmin

you can’t argue that lower cholesterol is not better

I find that I can put my cholesterol numbers anywhere that I want to. Unfortunately, I can’t do the same with my fasting cholesterol.

Right now I use pitavastatin, bempedoic acid, and ezetimibe. Using one, two, or all three a
I can adjust it to any level I want to. I am generally in the lower the better camp, but lately I’ve been reading some articles suggesting that for someone my age, lower the better might not be the best. So, the debate continues, and I am still researching the best level for someone my age. For most people, I think that the standard statins plus bempedoic acid, and ezetimibe will set LDL levels quite low.

[Kelman]

@desertshores

I find that I can put my cholesterol numbers anywhere that I want to

Out of curiosity why the big jump into red in summer of 2024? Did you stop everything cold turkey for a while?

[desertshores]

@Kelman

Did you stop everything cold turkey

“Yes, I did.” I got my weight down which of course brought my BMI down to 22. So I thought I would see how my cholesterol levels would be without all the cholesterol meds.

[RapAdmin]

Its the area under the curve (AUC) that matters, when it comes to APO-B (and LDL-C, usually) as they track closely for most people…

Source: Pablo Corral MD on X: "👉Lifetime LDL-C Exposure: The Forgotten Determinant of Atherosclerotic Risk 📍LDL-C is not just a number—it’s cumulative exposure over time. 📍Think beyond LDL-C levels. Think plaque-years. 📍The earlier you lower LDL-C, the greater the lifetime benefit. 📍Starting treatment at https://t.co/MMTOXjwbak" / X

[DeStrider]

I have thought about this quite a lot. I wish I had known this before age 47 when I actively started lowering lipids. I hope that my children can start in their early 30s. I do think 20s may be a bit too much.

[Satchel]

https://medicalxpress.com/news/2026-07-uncover-muscle-pain-widely-cholesterol.html
Just clarifies statin muscle pain is immune driven. -and that blocking the muscle pain effects does not affect the statin benefits as they are completely seperate pathways.
I am currently having great success with 3mg Naltrexone daily and 1mg Rapamycin weekly and can now tolerate lipid lowering medication with no muscle pain. I wish I had found this out 10yrs ago. I am retesting all the LLM against this protocol, and will let you know.

[DeStrider]

That may be true for some of the effects of statins, but I was on Rapamycin and statins and the muscle effects persisted. Switching to Pitavastatin was the only statine that did not cause these muscle issues.

[Davin8r]

@DeStrider

was on Rapamycin and statins and the muscle effects persisted

It’s possible that weekly rapa isn’t enough to inhibit the NLRP3 inflammasome and that the low dose naltrexone is doing the heavy lifting. This is pretty exciting if it turns out to be a viable option for those of us who can’t even tolerate pitavastatin.

[RapAdmin]

I researched this issue (whether naltrexone and rapamycin suppress the NLRP3 inflammation) and this is what Claude Fable 5 says:

Does Naltrexone Impact NLRP3?

• Indirectly plausible, NOT directly demonstrated for LDN in humans. Evidence Level D, with an important negative finding. The logic is: TLR4 provides “signal 1” (priming) for NLRP3 inflammasome assembly, so a TLR4 antagonist should reduce NLRP3 priming and downstream IL-1β/IL-18. This is inference, not measurement. Critically, the human immune-cell study found that while naltrexone suppressed TNF-α and IL-6, it did NOT directly inhibit LPS-induced IL-1β — the canonical NLRP3 output. Naltrexone inhibits IL-6 and TNFα (but not IL-1β), Front Immunol (2017); (+)-naltrexone/(+)-naloxone equipotent TLR4 inhibitors, did not inhibit IL-1β, Br J Pharmacol (2016). Live searches returned no dedicated study showing LDN reduces NLRP3/caspase-1 expression in an animal model, and none in humans. Verdict: “naltrexone lowers NLRP3” is an extrapolation from TLR4 biology, and the one relevant human dataset argues against a direct effect on the NLRP3 endpoint (IL-1β). Tell it like it is: unproven, and partially contradicted.

Does Rapamycin Impact NLRP3?

• Yes — rapamycin suppresses NLRP3 in pre-clinical models via mTOR inhibition and autophagy. Evidence Level D (robust pre-clinical, no human NLRP3-endpoint RCTs). This link is mechanistically much better established than for naltrexone. mTOR inhibition (a) enhances autophagic clearance of pro-IL-1β and damaged mitochondria/mtROS, (b) permits STAT1-mediated transcriptional repression of NLRP3, and (c) breaks an NLRP3–p38 MAPK–NF-κB positive-feedback loop (p62/autophagy-dependent). Rapamycin regulates macrophage activation by inhibiting NLRP3–p38 MAPK–NFκB, Oncotarget (2017); mTOR modulates NLRP3 activation via nuclear translocation and STAT1 inhibition (2025); Rapamycin improves neuroprotection via NLRP3 inhibition after TBI, Brain Res (2019). TRANSLATIONAL GAP: All in macrophages/rodents. mTOR inhibition is context-dependent and can be pro- or anti-inflammatory depending on cell type and dose; no human RCT demonstrates rapamycin lowering NLRP3-driven disease via this pathway. Do not translate directly to human dosing advice.

[cl-user]

@RapAdmin

this is what Claude Fable 5 says

Are you sure It’s Fable 5? It still has restriction on biology questions and switches automatically to Opus 4.8.

Switched to Opus 4.8
Fable’s safeguards flagged this message. The safeguards are intentionally broad right now and may flag safe and routine coding, cybersecurity, or biology work.

[Satchel]

I have panclass myalgia from all LLT-especially statins (including pitavastatin) and Repatha BA. I uploaded my genome reports into Opus 4.8, and Claude suggested LDN for my mLoy affected macrophages and Rapa for the cytokine release. I can only report that I can tolerate Repatha now and based on my LDL numbers next month I will decide wether to layer in BA. I am not brave enough to throw statins at this thereapy yet.

[RapAdmin]

@cl-user

Are you sure It’s Fable 5

Ah - you are correct. I missed that little note that they auto-switched it back to Opus.

[DeStrider]

Oral PCSK9I approved by FDA.

FDA approves 1st-of-its-kind pill to reduce cholesterol

[DavidCary]

Interesting.

No goodrx price yet. List is mentioned at $300/month.

Has to be taken first thing in the am with no food for 30m. Black coffee, tea, water ok.

Only approved in US for now.

[Beth]

I wonder how long until it’s available in India?

In the meantime, for those interested, repatha is now available on goodrx for aprox $250 per month.

I personally much prefer a shot every 14 days that I don’t have to think about, but obviously the pills will be life changing for many.

[qBx123Yk]

With an Amgen card and insurance, it’s 50 for 3 months now. I’m told that most insurance plans these days don’t require prior authorization to get it now. You can go here to find out coveragfe information: Coverage Information | Repatha® (evolocumab) HCP

[qBx123Yk]

I’ve always had the impression that PCSk9i were the future LDL-c lowering medication (set to replace statins), but when I looked at data comparing them to statins for ACM and MACE, I was surprised to find that based on the available data, statins beat them.

Here are 2 studies comparing them:
Niu, Q. (2025). Which is the optimal choice in lipid-lowering therapy for reducing major cardiovascular events? A network meta-analysis. Frontiers in Pharmacology. Read the study on PubMed Central

Riesen, W. F. (2025). Lipid-lowering Medications - Statins Versus PCSK9 Inhibitors. Journal of Clinical Cardiology and Cardiovascular Interventions. Read the publication on ResearchGate

Results for MACE

• Statin Monotherapy: Highly effective. Statins possess pleiotropic effects such as reducing vascular inflammation and stabilizing arterial plaques to prevent them from rupturing.
• PCSK9 Inhibitor Monotherapy: While effective, some large-scale network meta-analyses suggest that PCSK9 inhibitor monotherapy does not consistently outperform statins alone. A comprehensive NMA published in Frontiers in Pharmacology reviewed 29 randomized trials totaling over 68,000 patients and found that the clinical benefits of statin monotherapy were not inferior to PCSK9 inhibitor monotherapy .

Results for ACM

• Statins: Have a multi-decade, robust track record of significantly reducing both cardiovascular mortality and all-cause mortality (with a relative risk reduction of roughly 9% to 10% compared to placebo).
• PCSK9 Inhibitors: Despite dramatically lowering LDL-C and reducing non-fatal heart attacks and strokes, major dedicated cardiovascular outcome trials (like FOURIER for evolocumab and ODYSSEY OUTCOMES for alirocumab) failed to show a statistically significant reduction in all-cause mortality. Meta-analyses confirm that adding a PCSK9 inhibitor to background statins yields no additional ACM benefit over statins alone.