Comments on: Cardiovascular disease is a solved problem

By: Antoine Dusséaux

Antoine Dusséaux — Sun, 15 Feb 2026 06:50:45 +0000

Associations with Parkinson’s disease are causal as confirmed by Mendelian randomization studies: https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.119.314929

By: Tiago Vasconcelos

Tiago Vasconcelos — Thu, 05 Feb 2026 19:45:31 +0000

When taking statins — particularly potent ones like Rosuvastatin or the commonly used Rosuvastatin + Ezetimibe combo — it is advisable to monitor liver enzyme levels, especially ALT and AST.

In a small percentage of patients, these markers can become elevated.

While pravastatin may be less effective at reducing ApoB or LDL-C at equivalent doses, it can be a reasonable alternative for patients who experience liver enzyme increases on higher-potency regimens, provided lipid goals are still achievable.

By: A. Lincoln

A. Lincoln — Thu, 05 Feb 2026 04:13:36 +0000

This is a thoughtful post that is well-grounded in the evidence. I think the picture is changing with the pending approval of enlicitide. That promises increased LDL lowering with a better side effect profile in a pill format. There’s good evidence from the other PCSK9 treatments that suggests this will be a broadly effective strategy. We probably should be thinking about ASCVD risk in 30-year horizons (not 10) and I think things will shift in that direction as treatments get better.

By: JJ

JJ — Thu, 05 Feb 2026 03:52:45 +0000

It’s interesting that while PCSK9 loss-of-function drops CVD dramatically the effect on life expectancy is more muted. Seems about 1 year.

I’ll take it of course, but would have expected more from a 90% reduction of the biggest killer.

By: Maciek Kolodziejczyk

Maciek Kolodziejczyk — Mon, 06 Oct 2025 03:39:27 +0000

This is an excellent write-up, the best set information on CVD in written form I have encountered so far.

Only one minor-to-moderate quibble. I a not sure the following statement is warranted:
“Additional studies or subgroup analyses have also conclusively ruled out a role of low LDL levels in insulin resistance (…)”

Two most prescribed statins (atorvastatin and rosuvaststin) have consistently been associated with higher HbA1c levels (most often by about 0.1%-0.2%).

see: https://www.ccjm.org/content/90/1/53

From JUPITER trial (rosuvastatin):
“(…) there was a minimal difference in the median glycated hemoglobin value (5.9% and 5.8%, respectively; P=0.001). Nevertheless, physician-reported diabetes was more frequent in the rosuvastatin group (270 reports of diabetes, vs. 216 in the placebo group; P=0.01); these events were not adjudicated by the end-point committee.”

In any case, given that:
1) statins have much stronger lipid-lowering effect than any possible detrimental effect on glucose levels
2) 8x more people die from cardiovascular disease than from diabetes

the positive effects of statins could be about 2 orders of magnitude larger than the negative ones.

By: Peter McCluskey

Peter McCluskey — Tue, 30 Sep 2025 18:35:12 +0000

I agree that doctors ought to focus less on disease and more on improving health in a broader sense.

I’m confused as to how you got to the conclusion that low LDL levels fully solve cardiovascular disease. I have vague intuitions that some additional pathways contribute.

The benefits of getting LDL down to 10 look unclear. Claude says: “The few studies reaching LDL ~30-40 mg/dL (like FOURIER with evolocumab) showed CV benefit but **no reduction in all-cause mortality**”.

Rosuvastatin has enough minor side effects that I don’t want to take more than I need to get my LDL down to about 70. Talking with Claude just now led me to realize that rosuvastatin probably caused my testosterone to drop below 400. Maybe I should partly replace rosuvastatin with ezetimibe.

I’m trying to follow a good deal of Bredesen’s advice, which includes keeping total cholesterol above 150. It doesn’t look like I can get my LDL below about 66 without getting my total cholesterol below 150.

>Circulating levels of lipoproteins are largely genetically determined, with minimal influence from lifestyle factors

How do you reconcile that with the large differences in LDL and cardiovascular disease between cultures?

My saturated fat consumption had large effects on my LDL levels for a decade, until I started using a statin. That’s not too common, but it’s more than a “minimal influence”. (Saturated fat seems to have no effect now that I’m on a statin).