Cardiovascular Health 2026

[RobTuck]

Thank you for sharing this information. A few thoughts in no particular order.

Vitacost makes a nice supplement mix containing vitamin C, Lysine, Proline, and EECG.

If one limits the evidentiary base to research on humans (which is a good ide in general and more so here because the mouse study is so contrived), my read on the Lp(a), vitamin C, Lysine relationship is that that it is theoretically plausible but lacking in human empirical evidence.

A 2025 review that compiled seven human studies reported that vitamin C supplementation did not significantly change plasma Lp(a) across doses ranging from 500 to 4500 mg/day, in both CAD and healthy cohorts.

The Linus Pauling Institute also summarizes multiple controlled trials (e.g., 1-2 g/day for ~1 month; 4.5 g/day for 12 weeks; 1 g/day for 8 months) that found no significant effect on Lp(a), contrasting with one small uncontrolled study reporting a decrease.

The frequently cited vitamin C/Lysine connection by Dalessandri (Atherosclerosis, 2002) is a letter/comment, with no abstract on PubMed, limiting accessibility of design, controls, and outcomes.

At your age, which is close to mine, I would be concerned that the daily consumption of two grams of vitamin C would be placing undue strain on my kidneys. Most mammals produce vitamin C PRN in response to stress. Maintaining a level that might be eight or more times higher than required to saturate tissues could be doing more harm than good to aging kidneys.

If my Lp(a) level was elevated, I would – in addition to following all of the established data for reducing ASCVD, such as aggressively lowering Apo(b) – immediately initiate therapy with a GLP1 agonist with the idea in mind of switching over to one of the three Lp(a) targeting drugs currently in clinical trials when it becomes available (2027, I believe if all goes well). My understanding is that these new drugs will reduce Lp(a) by 50% or more with no negative side effects and possibly at a relatively low cost. In the interim, you might expect to see a 25-30 percent reduction in Lp(a) from GLP1 agonists and also have to initiate extraordinary measures to preserve muscle mass.

[Deborah_Hall]

I didn’t know that a GLP1 agonist would reduce Lp(a). But I do know that Repatha will reduce it. It lowered mine from 40 to 27. It was a hard sell to get a script for Repatha. I showed my cardiologist my Prometheus report, which shows a 9p21 mutation that raises risk of cardiovascular disease by (in my case) 1.9x.

[RobTuck]

My bad Deborah. I meant to say PCSK9. GLP1i is a minor contribution. I wasn’t paying attention for a moment.

[Davin8r]

@RobTuck

is that these new drugs will reduce Lp(a) by 50% or more

80% to 95+%

[RobTuck]

Yes. I was taking a conservative view but a couple of the phase II trials were astounding. However, it looks like the higher figures are significantly is modulated by the base level and also perhaps by genetic makeup. The SDs I saw were pretty high.

[relaxedmeatball]

A new Peter Attia newsletter reminds us all that atherosclerosis is not the only cause of heart attacks, though of course it is the most common. However, ~5% can arise from other causes, in people who have no measurable atherosclerosis.

There are also very notable differences between men and women.

Full article here:
The absence of atherosclerosis is not an excuse to ignore heart attack symptoms—especially for women.pdf (678.3 KB)

AI summary, with key points highlighted by me:

While atherosclerosis is the most common cause, a meaningful fraction of heart attacks—especially under age 65—occur through other mechanisms like artery tears (SCAD), spasms, or oxygen supply–demand mismatch.

Women under 65 have a different risk profile than men. In this group, fewer than half are atherothrombotic, and about 1 in 10 are due to spontaneous coronary artery dissection, which is over 5× more common in women than men.

Low cholesterol does not equal zero heart-attack risk. Good lipid numbers, normal blood pressure, and overall metabolic health greatly reduce risk—but they do not eliminate it

Women have very different symptoms to men. Women are more likely to experience shortness of breath, nausea, fatigue, lightheadedness, or back/abdominal discomfort rather than classic chest, shoulder and jaw pain

Bottom line: Good biomarkers/scans should never be a reason to dismiss sudden, persistent cardiac symptoms—especially for younger women, who are disproportionately affected by non-traditional heart attack mechanisms.

Very useful information IMO. And especially useful for younger women who can have non-ASCVD heart attacks with “atypical” symptoms, and not go to hospital because they don’t suspect MI.

[RapAdmin]

The New Science of Preventing Heart Attacks | What’s Your Problem?

[adssx]

Already discussed there: Heart Attacks WIthout Plaque, Women More Affected

[RapAdmin]

Functional Health’s approach to helping people understand risk/reward:

[RapAdmin]

Oral PCSK9 Inhibitor Enlicitide Cuts LDL Cholesterol

It’s still experimental but the pill helps rid the body of cholesterol in a way that today can be done only with injected medicines. If approved by the Food and Drug Administration, the pill, named enlicitide, could offer an easier-to-use option for millions of people.

Statins block some of the liver’s production of cholesterol and are the cornerstone of treatment. But even taking the highest doses, many people need additional help lowering their LDL, or “bad,” cholesterol enough to meet medical guidelines.

In a major study, more than 2,900 high-risk patients were randomly assigned to add a daily enlicitide pill or a dummy drug to their standard treatment. The enlicitide users saw their LDL cholesterol drop by as much as 60% over six months, researchers reported in the New England Journal of Medicine.

Experimental cholesterol-lowering pill may offer new option for millions

Oral PCSK9 Inhibitor Enlicitide Matches Injectables in Lowering LDL...

[A_User]

https://totalhealthoptimization.com/2025/09/27/cardiovascular-disease-is-a-solved-problem/

Lifestyle factors actually have a powerful causal effect – specifically isocaloric replacement of SFA with PUFA is powerful. Reducing dietary cholesterol can have an effect. Adding PUFA anecdotally in an isocaloric fashion to a low fat diet can reduce lipids as well. Nuts, nuts, and more nuts!?

@A_User

Replacing 1% of energy of SFA (saturated fat) with 1% energy from Carbs decrease apoB by 3.6 mg/dl.

Replacing 1% of energy of SFA (saturated fat) with 1% energy from MUFA decrease apoB by 7.8 mg/dl.

Replacing 1% of energy of SFA (saturated fat) with 1% energy from PUFA decrease apoB by 10.2 mg/dl.

But cardiovascular disease includes disease like heart failure, or TTR amyloidosis from aging.

[RapAdmin]

New study from The Lancet on Statins:

Almost all side-effects listed for statins are not caused by the drugs, according to the world’s most comprehensive review of evidence.

Other than the well-known risks around muscle pain and diabetes, only four of 66 other statin side-effects listed on labels – liver test changes, minor liver abnormalities, urine changes and tissue swelling – are supported by evidence. And the risks are very small, according to the systematic review and meta-analysis published in the Lancet.

Assessment of adverse effects attributed to statin therapy in product labels: a meta-analysis of double-blind randomised controlled trials

Findings

19 trials compared statin versus placebo (123 940 participants, median follow-up 4·5 years [IQR 3·1–5·4]). In addition to previously reported effects on muscle outcomes and diabetes, only four of 66 further undesirable outcomes that had been attributed to statins were FDR significant: abnormal liver transaminases (783 participants [0·30% per annum] allocated statin vs 556 [0·22% per annum] allocated placebo, RR 1·41 [95% CI 1·26–1·57]) and other liver function test abnormalities (651 participants [0·25% per annum] allocated statin vs 518 [0·20% per annum] allocated placebo, RR 1·26 [1·12–1·41]; absolute annual excess of 0·13% for combined liver function test abnormality), urinary composition alteration (556 [0·21% per annum] allocated statin vs 472 [0·18% per annum] allocated placebo, RR 1·18 [1·04–1·33]), and oedema (3495 [1·38% per annum] allocated statin vs 3299 [1·31% per annum] allocated placebo, RR 1·07 [1·02–1·12]). Analysis of the four trials of more intensive versus less intensive statin regimens also found significant excesses for abnormal liver transaminases and other liver function test abnormalities (supporting a dose-dependent effect), but no significant excess was found for urinary composition alteration or oedema.

Interpretation

Adverse event data from blinded randomised trials do not support causal relationships between statin therapy and most of the conditions (including cognitive impairment, depression, sleep disturbance, and peripheral neuropathy) listed in product labels as potential undesirable effects. In light of these findings, such labelling and other official sources of health information should be revised so that patients and their doctors can make appropriately informed decisions regarding statin therapy.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01578-8/fulltext

Statin pills much safer than advertised, major review finds

Most statin side-effects not caused by the drugs, study finds

[A_User]

Estimated small, dense LDL-C (E-sdLDL-C) outperforms LDL-C in predicting ASCVD risk and adds value beyond ApoB.

https://x.com/RZubiranS/status/1956043350353551647#m

[relaxedmeatball]

IMO this sort of information is academically interesting but it’s only useful if there would be some sort of different action taken based on the result. So while some additional risk may be “missed” by LDL-C or ApoB alone - what is the action or outcome from testing it? The person is still going to end up on statins, ezetimibe, PCKS9i, BA etc. And those are things that I assume most people would want to do anyway if their total LDL-C is >70mg/dl.

So here the the only “useful” thing (IMO) is that, a bit like Lp(a), it might be a deciding factor in whether to treat a “normal” LDL-C or not, or to be more aggressive. But I’m a fan of being very aggressive on lipid reduction anyway.

[A_User]

70 mg/dl LDL-C might be high if you are discordant with higher apoB or E-sdLDL-C(?)

[Viracocha]

It can change your strategy because statin may be more useful at reducing your small dense LDL while Ezetimibe may not be that useful.
Also, it brings insulin sensitivity in the spotlight and the general population starts talking about it.

[relaxedmeatball]

@A_User

70 mg/dl LDL-C might be high if you are discordant with higher apoB or E-sdLDL-C(?)

Exactly my point, haha. If it’s >70 then you’d be wanting to take medication no matter what.

@Viracocha

It can change your strategy because statin may be more useful at reducing your small dense LDL while Ezetimibe may not be that useful.

Fair point, but I think ezetimibe monotherapy is pretty uncommon, so I would assume anybody taking Ezetimibe would already be on a statin.

(And besides, I reckon most doctors are still just ordering total and LDL-C. We can barely convince GPs and other “normal” doctors to order ApoB or Lp(a), let alone thinking about particle sizes haha!)

[DeStrider]

Most doctors still don’t prescribe Ezetemibe. That’s a head scratcher there. If there is a prescription for a statin, it should always be paired with Ezetemibe IMHO. There’s just no reason not to.

[relaxedmeatball]

Yes, I had to almost bully my mother’s GP into prescribing it for her. He was saying it’s an old drug, not very good etc. I said “humour me”, and lo-and-behold her LDL-C dropped another 30% from 10mg/d just as I said it would.

[Beth]

@relaxedmeatball

And besides, I reckon most doctors are still just ordering total and LDL-C. We can barely convince GPs and other “normal” doctors to order ApoB or Lp(a), let alone thinking about particle sizes haha!)

Don’t even get me started!!! My sister and brother each have a ‘good’ cardiologists. I had to get them get them to test their apob and lp(a) AND to get ezetimibe.

I also just found out that no one has been testing my much older brother’s A1C, vit d, or b12… (many other thing could be added to the list, but those are less common)… AND no A1C test even though his fasting glucose is high… criminal.