Neo
#2882
Since cardiovascular disease - and heart disease stroke alone - are the by far biggest killers and drivers of awful disability - in the western world, I think one has to see normal Apo B as one of one’s largest risks (even if healthy, exerciser, etc).
Not until you have optimal Apo B should you be satisfied if health and longevity optimization is your goal.
Especially in the context that there are powerful meds with side effects profiles that are good.
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I dont know what this is.
I not researched this. Most recently i have been working on getting my rhr and bp dpwn following a metabolic boost. I now am back to a hr just over 50, but with a higher stroke volume. I am curious about these figures, but they dont seem a priority.
I do weekly tests so can compare labs. I have no reason to doubt randox, but they do a broader test.
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Neo
#2886
I the last test in the bloodwork summary that you shared:
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adssx
#2887
Long-term safety profile of statins does not look 100% good to me unfortunately… Rilmenidine vs Telmisartan or other BP meds for Longevity - #29 by adssx
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Neither RCTs nor MR studies have shown any negative effect of statins on dementia rates.
I may still get an occasional full cholesterol test. But, in light of more recent studies.
ApoB is a better indicator of future cardiovascular outcomes.
This has been debated before in this and other threads. I was on the fence on this but I have changed my mind so that I like ApoB better than an ordinary lipid panel test.
Because I like to keep my supplement stack as low as possible, I would also like to keep my blood tests as few as possible while still maintaining the health information to make decisions in my diet etc. So, for the most part, I will just get my ApoB tested and not a cholesterol panel.
“The risk of myocardial infarction was best predicted by APOB levels, independent of LDL-C or triglycerides”
These studies may have already been posted, but I just got around to reading them.
This a large cohort study The primary study outcome was incident myocardial infarction (MI).
“Of the 389 529 individuals in the primary prevention group, 224 097 (58%) were female, and the median (IQR) age was 56.0 (49.5-62.5) years. Of the 40 430 patients with established atherosclerosis”
(“Patients with established atherosclerosis” would include just about everybody over the age of 30 because it starts quite early in life)
https://sci-hub.se/10.1016/j.cca.2020.05.001
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adssx
#2890
No but several longitudinal + MR studies showed that there seems to be a causal relationship between high cholesterol and lower risk of PD: Lipids, Apolipoproteins, and the Risk of Parkinson Disease - PubMed
And RCT of statins in PD failed.
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adssx
#2891
And actually there are MR showing detrimental effects: Mendelian Randomization Study of PCSK9 and HMG-CoA Reductase Inhibition and Cognitive Function
In contrast, we observed adverse neurocognitive effects related to HMGCR inhibition, which may well be outweighed by the cardiovascular benefits of statin use, but nonetheless may warrant pharmacovigilance.
There seems to be a tradeoff between CVD, AD, and PD 
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It doesn’t say dementia but cognitive impairment. But yes if you’re worried about PD, I would definitely take precautions. Despite that, lowering apoB is still a must.
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Neo
#2893
The data you showed points to potentially a trade-off with the statins (though I think that randomized trials have suggested otherwise so the MR effect on cognition impact might be impacted by having HMGCR inhibition during fetal development or early childhood stages of life when the brain needs extra cholesterol - which is not when you’d now drug that pathway via a statin as an adult).
In any case, you have other options than statins. As one example, the paper you quoted form above has a sentence before what you quoted in it’s abstract that says:
Using data from a combined sample of ∼740,000 participants, we observed a neutral cognitive profile related to genetic PCSK9 inhibition, with no significant effects on cognitive performance, memory performance, or cortical surface area.
AnUser
#2894
The effect is too small, it doesn’t matter. It’s not clinically significant.
Relatedly, the finding that HMGCR inhibition was associated with slowed reaction time translated to an increase of 0.067 milliseconds per 1 SD decrease (38.7 mg/dL) in LDL-C. For comparison, previous work evaluating choice reaction time tasks among healthy adults aged 18-65 years found an increase in reaction time latency of 2.8 milliseconds per year, suggesting a small impact of HMGCR inhibition.62 Therefore, we emphasize that any potential adverse effects of HMGCR inhibition on neurocognition found in this study likely do not outweigh the cardiovascular benefits of statin use.
It’s relatively small and can be mitigated in other ways.
Neo
#2895
@adssx this is perhaps the 10th time you have taken a holistic concept and picked out a more narrow subset, criticized that subset but not evaluated the larger holistic concept.
In this case, I never mentioned the word “statin”. (And while I support them in many cases, I have personally never taken a statin in my life). My comment was about that (a) cardiovascular is a massive risk for virtually anyone (except genetic mutants in PSCK9) and
(b) Not until you have optimal Apo B should you be satisfied if health and longevity optimization is your goal.
and
(c) Especially in the context that there are powerful meds with side effects profiles that are good.
As @AnUser argued you many not have to worry about the statin effect, but let’s assume for sake of argument that you should worry about that, what do you think about the rest of statement (c)? Just as examples, you could do really low statin (most of the cardiovalular protection comes as very low dose and then is more incremental dose response from their) alone or combined with Eze of Bemp Acid. Or you could do those without any statin at all or you could use one that don’t cross the blood brain barrier as the others do. Or you could do PCSK9i - or any other low dose combo of the many powerful options without statins at all.
and importantly, what do you think about part (a) and (b) of my post that you replied to?
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AnUser
#2896
If someone wants to live 200 years they must have optimal apoB.
If someone just wants to live to 50-80 yrs old and avoid PD, that’s different.
Even if the very small increase risk of PD is realized, all else equal, lower apoB might allow one to live longer for curative treatment. It’s an important consideration, but it just means the risk have to be mitigated in other ways for me, as there is no way to leave apoB off the table, or even worse, try to increase it.
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Neo
#2897
I agree and would even say that threshold probably starts kicking in already if one wants to live to 70 or 80
just think about how many life ending or crushing strokes or heart attacks still occur in 60-70 year olds
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Neo
#2898
I approach this a bit differently
I want to keep my supplements stack as low as possible to avoid unintended interactions and because there is a small contamination risks with each agent that is added
On the data size I want as much possible, subject only to when the economic costs is do high.
In general more data can decrease risks in decision making while more supplements can increase risks
Since cholesterol markers are generally on the cheaper side, it’s an area where the small cost to also see that is happening beyond Apo B is often worth it for me.
But of course costs do matter and there are a lot of other tests that I have triage and not do all off at each blood draw
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I know i have the test, but it is part of a package and i dont know what it means.
The package costs GBP 255 for two tests. It is IMO really good value.
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L_H
#2900
But it does beg the question, what is optimal apoB? And does that optimal range vary if inflammation, bp, oxidation and other factors are optimal.
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adssx
#2901
I apologize; I didn’t frame my comment correctly. I did not mean to criticize anything. That said, please chill out and assume good faith and best intentions. We’re all here to help each other reach our goal(s). These goals might be different. And not everything is rational; we may have our own fears, justified or not. Or at least, I have. So I should have been clearer in my previous reply that because I have a family history + genetic risk of neuro-psychiatric conditions (MDD, AD, PD, etc.), I put more weight on this risk than on others such as CVD. Maybe unreasonably so. Still, @AnUser summed it nicely, “If someone wants to live 200 years they must have optimal apoB.” and “If someone just wants to live to 50-80 yrs old and avoid PD, that’s different.” I feel like I prefer to die at 80 from a heart attack than live 100yo with AD or PD starting at age 60 and seeing myself decline every single day, incontinent and demented. Again, it might be illogical, but that’s how I feel now. I didn’t care that much before when my ApoB was at 68 mg/dL, but in my latest test, it surprisingly jumped to 97, and now I wonder what to do (First, redo the test… 
) There are more and more MR and longitudinal studies published so I’m convinced that this question will be solved in the next 24 months. Researchers might find that non-statin lipid-lowering agents have a better long-term safety profile for people at risk of PD (or other NDDs). Or they might actually dismiss all the previous fears around statins and prove that the effects were not causal. Time will tell. For now, for me, the jury is still out. For the general population, I agree with your statements (a), (b), and (c).
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