Pat25
#989
That would be great. Perhaps ApoB values could be included also?
And what about age as a factor?
adssx
#990
We can only do polls with one parameter on this platform.
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Pat25
#991
Well, imo the LDL-poll could be a great start to get an impression of the approach other members follow.
I think the medical consensus is that the more you push ApoB/LDL down and the longer you do so (i.e. start at an earlier age) the better the health outcome. Statins of course are not tolerated by all, and for some there are consequential side effects (like glucose control), but they have the longest track record. PCSK9i dont’t have as long one, but on the other hand they are based on the same mechanism that allows some natural populations with gene variants equivalent in effect to PCSK9i a long atherosclerosis and CVD free life. Bempedoic acid is newish. But back to statins - the other aspect of statins is that while they do have side effects, they also have pleiotropic positive effects on cancer and a slew of health conditions, possibly by lowering inflammation. So if you can tolerate statins you might want to take them regardless of your lipid numbers, as studies seem to show benefits for even normal-lipids folks, and the lower the better.
3 Likes
adssx
#993
Statins are great but, as a reminder, they’re not risk free either: Statins aggravate insulin resistance through reduced blood glucagon-like peptide-1 levels in a microbiota-dependent manner. In people with Parkinson’s they also aggravate motor symptoms.
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True enough. However, the net effect seems to still be a positive from a health/lifespan point of view. Same as rapa - side effects, but net positive. And that’s the temptation of polypharmacy - trying to counteract the side effects, some times with success: ITP results tell us combining glucose impact meds with rapa is a further boon. But naturally, polypharmacy drastically increases the risk of unwanted negative interactions.
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Many cardiovascular patients will take around 15 prescription drugs in order to stabilize their condition. I think many people are unjustly afraid of polypharmacy.
I’d say it’s best to take some prescription drugs to prevent cardiovascular problems instead of taking more after you have a cardiovascular problem.
2 Likes
mccoy
#996
I’ve been searching and pondering further but in my ideal optimization, which aims to provide the best results at the best risk profile, taking mini doses of ezetimibe+statin, pill geometry is the governing factor.
I could only find circular-section pills in Rosumibe 5/10 (10/10 is oval) and Crestor 5 mg.
So the strategy I previously hinted at remains so far the only possible, barring further research.
-Day one: 1/4 pill of rosumibe 5/10; Provides Ezetimibe= 2.5 mg, Rosuvastatin 1.25 mg
-Day two: 1/4 pill of Rosuvastatin, provides 1.25 mg
-Day three: 1/4 pill of rosumibe 5/10; Provides Ezetimibe= 2.5 mg, Rosuvastatin 1.25 mg
-Day four: 1/4 pill of Rosuvastatin, provides 1.25 mg
-…same as above
According to literature, the above combo should provide a mean decrease of about 40-50% LDL.
By the way, presently I take no pharmaceutical drugs and my non-HDL cholesterol (the best ApoB proxy) is 122 mg/dL, a viable level (130 is the threshold indicated by Tom DAysprings in lack of other risk factors) but surely not optimal.
What I want to avoid is an increase in fasting blood glucose and that’s the main reason for statin minidosage.
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adssx
#997
Efficacy and safety of low levels of low-density lipoprotein cholesterol: trans-ancestry linear and non-linear Mendelian randomization analyses 2023
Reposting this interesting study showing no lower threshold for LDL in terms of CAD risk reduction but a risk for dementia and stroke below 70 mg/dL. Does anyone have access to the whole article? I’d like to see the curve for stroke and dementia, is it flat above 70?
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Both low and high levels of HDL-C were associated with elevated dementia risk. The association between LDL-C and dementia risk was modest.
https://www.neurology.org/doi/10.1212/WNL.0000000000207876
adssx
#999
That’s an association study. I cited a Mendelian randomization hinting at a causal link between low LDL and dementia.
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adssx
#1001
The one I posted is more recent and looks more serious given that Frontiers is not a great journal.
I think dementia is a tough nut to crack. There is a definite link for high LDL to dementia. Low LDL being linked to dementia seems a bit off.
I would assume that very low LDL levels mean one of two things: 1. The patient is diseased. Or 2. The patient is lowering their LDL in response to earlier detected high levels.
I think it’s very rare for individuals like us to proactively lower LDL without prior high LDL which may have started the dementia ball rolling.
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adssx
#1003
I agree. We know that above 116 mg/dL the risk of dementia is increased (see the recent Lancet paper: Dementia Prevention - 2024 report of the Lancet standing Commission - #5 by adssx ).
Below 116 mg/dL it’s unclear. Dementia also covers several conditions: Alzheimer’s, Parkinson’s dementia, LBD, vascular dementia, etc. The optimal lipid levels might be different for each of these conditions. High LDL might also be a reaction of the body to protect the brain from a dementia process that has started 
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adssx
#1004
For AD we have this recent good quality paper. As noted by the authors:
In addition, we found that circulating APOB (but not LDL) increases risk for AD. This finding for APOB in relation to AD conflicts with that by Williams et al. (2020), who sought to identify genetic support for the repurposing of mipomersen (an antisense oligonucleotide inhibitor of APOB34) for AD prevention. Like us, Williams and colleagues used IGAP GWA study data for the AD outcome source in their two-sample MR. Their study differed from ours in the construction of their genetic instrument, though. Whereas our instruments for APOB contained more SNPs, which were clumped to prevent LD, they used a principal-components-based MR method. We attempted a partial replication of our MR of APOB on AD using a substantially larger GWA study containing more than triple of the number of AD cases. Although our partial replication succeeded in the sense that the results revealed that higher levels of APOB increased risk for AD, the effect estimate attenuated towards the null. Future MR studies of AD, ideally with a larger number of clinically defined cases (and not including IGAP cases) are needed to confirm whether the relationship between APOB and AD is causal.
The distinction between LDL and ApoB might explain some conflicting findings?
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I have tried this and it is not nearly as effective as when the statin is added.
It may be good enough if you already have low LDL levels and you just want to lower it a little bit more.
2 Likes
How do you lower ApoB preferrentially, without affecting LDL quite as much? So if the ApoB is the problem, and you want to smash that down without also crushing LDL below the safety zone?
adssx
#1007
I don’t think you can lower ApoB only. I only mentioned that as a source of complexity.
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That would imply a goldilocks solution, where you want to lower ApoB up to a point, but not further, and it’s basically a tradeoff. Who knows, maybe one day there will be more narrowly focused and less blunt interventions.
I think an example of this is the Lp(a) story - a very nasty particle, which actually goes up with statin use - but we are in a tradeoff situation where statins are still a net positive despite the bad impact on Lp(a) (and diabetes etc.!). However, now there are several drugs in development that zero in on Lp(a) specifically - as someone who has very high Lp(a), I can’t wait.
So what I’m saying is that perhaps there are more narrowly tailored intervention that can affect the other constituents of ApoB, without affecting LDL quite as much.
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