Cardiovascular Health – Rapamycin Longevity News

Did you have Lp(a) measured ?

Before my heart attack they were only doing the standard lipid panel, which I don’t think includes apoB.

LDL was 103, 65, 78, 65, 83, 91, 87

I wouldn’t be surprised if you’re Lp(a) positive with those numbers. “Good” by conventional standards, but not sufficient over long time periods, especially with high Lp(a)

Related, where was your blockage that caused the heart attack?

High Lp(a) tends to be associated with aortic valve stenosis:

Per the attached reference:
ApoB considerably underestimates risk in individuals with high Lp(a) levels. The association between apoB and incident CHD is diminished or even lost. These phenomena can be overcome and explained by risk-weighted apoB.
Lipoprotein(a) and risk-weighted apolipoprotein B: a novel metric for atherogenic risk – PMC

Thanks. Clearly with an average LDL of about 80 mg/dL, 99% of doctors would say your LDL is perfect. (And they would be wrong, but that’s the state of our sickcare system…)

Are your LDL and apoB discordant now? Or are they always almost identical?

Another issue our healthcare system may miss is the negative effect of inflammation on what the LDL or the ApoB numbers mean. If inflammation is high, as measured by hsCRP (high sensitivity C Reative Protein), then it may be that levels of OxLDL (oxidized LDL) are relatively high and may be detrimental to health.
Further, the spectrum of LDL particle sizes is also an issue. If particles are larger, they may not have an effect on the vascular wall, but if particles are small and dense they may be more easily absorbed to create soft plaque.
hsCRP is a separate test.
OxLDL is a separate test
particle size can be obtained by nmr by Lipofit

So… what effect does a relatively high LP(a) have on the discordance measurement ?
Looking for “one metric to rule them all” may not be the wisest choice in trying to understand CVDz which is clearly multifactorial.

ApoB and Lp(a) is rate limiting, so if you lower them enough and early enough you can’t get atherosclerosis (stroke, heart attack, vascular dementia…). That’s the point, and why they are the one metric to rule them all… But do the other things as well for other reasons and to target residual risk from already developed soft and calcified plaques. That should be obvious.

Only 20% of people have the genetics to have LP(a)
For this unfortunate 20%, nothing they do (diet, exercise, meditation, drugs) will lower their genetically induced LP(a) levels.
Statins which effectively lower ApoB… have no effect on LP(a)
Perhaps that’s why ApoB and Lp(a) are independent risk factors for CVDz
Fortunately, newer medications such as PCSK9i medications do lower LP(a).

For those who are interested, there is a phase 3 trial enrolling to evaluate whether a siRNA medication (Lepodisiran) can reduce MACE in those with elevated LP(a) > 175nmol.
Run by Eli Lilly, with whom I have no financial interest
A Study to Investigate the Effect of Lepodisiran on the Reduction of Major Adverse Cardiovascular Events in Adults With Elevated Lipoprotein(a) (ACCLAIM-Lp(a))

Pharmaceuticals to reduce LP(a) are very close to being released onto the market. Soon there will be a treatment to help. It’s just going to take a few years until a cheap generic will be available.