Quite sure. Read the linked source (more recent, better team and better journal): Cardiovascular Health - #310 by adssx
I can also confirm from N1 from my father. His hsCRP score fell by about 66%. His ApoB fell by about 40-50%. BA + EZ is a winner for both ApoB and CRP.
That study does not explain to me how aging “… persists as an independent contributor when all other known factors are controlled”, how they came to that conclusion in the introduction, there is no citation. It looks like mechanistic speculation and it does not prove it with genetic data, human outcome data, or an experimental study. Without such a study we don’t know how much aging contributes to ASCVD either. Based on current evidence that the majority of young people have detectable atherosclerosis, and the compounding effects of suboptimal lipids, there is little room for the aging hypothesis of atherosclerotic cardiovascular disease. SGLT2i improves heart failure though.
It’s a paper from 2012. Although highly cited, I would prefer more recent sources.
This is a later one with a free full text @AnUser My view is that lipids and aging (senescence) are both part of atherosclerosis. I think it probably links to the usual acetyl-CoA channel.
If we look at the citation for this quote:
Aging is an independent risk factor for the increased morbidity and mortality of atherosclerosis (North & Sinclair, 2012)
It is just remarking on the fact that older people have higher rates of cardiovascular disease:
The most important determinant of cardiovascular health is a person’s age. By 2030, approximately 20% of the population will be aged 65 or older. In this age group, cardiovascular diseases (CVD) will result in 40% of all deaths and rank as the leading cause. Furthermore, the cost to treat cardiovascular disease will triple in that time.1,2
This does not prove that it is aging itself and not time that is causing most of the disease. Because the majority of young people have atherosclerosis detected, even if everyone magically was 20 years old biologically their entire life, the leading cause of death would still be atherosclerosis because it were already building up in youth and thus would continue even if they were in a youthful state throughout life.
What’s the source of this?
It’s citing this study:
The most recent paper I posted has in the abstract:
Recently, emerging evidence has demonstrated that senescence of various types of cells, such as endothelial cells (ECs), vascular smooth muscle cells (VSMCs), macrophages, endothelial progenitor cells (EPCs), and adipose-derived mesenchymal stem cells (AMSCs) contributes to atherosclerosis.
Senescence of cells is an aging thing. I am entirely happy to accept that lipids are a partial cause to this, but a body with a propensity to senescence (which I think is partially interleukin-10) is also a partial cause.
I just don’t know the magnitude of the problem. The current data suggests it is not large, else why is everyone developing atherosclerosis in youth?
Senescence is stochastic and occurs in people of all ages, moreso in the older, but also to lesser extents in younger people.
This is interesting, from another study cited:
A restudy of the problem by one group of investigators in 100 consecutive men did not demonstrate a linear increase in the incidence with age but did show that the process increased rapidly in the 30- to 49-year age period, reaching a maximum in the 50- to 59-year age group and thereafter remaining at a fairly constant level.
This aligns well with the findings from the Framingham Study I mentioned a while ago, indicating that LDL-C levels (and likely other risk factors) are most significant in individuals under the age of 50, but become less important later in life.
Is stress a significant trigger for senescence as well? I’ve noticed that stress is rarely discussed as an independent risk factor in ASCVD, let alone thoroughly explored for its causality. Could senescence be the link between stress and ASCVD?
It depends upon what you mean by stress.
There are AIUI different causes of senescence. One I particularly focus on is when a stem cell fails to differentiate into the correct state. I see this as caused by a problem with the energy levels of the cell during that phase of the cell cycle. This is measured by the cytosolic acetyl-CoA levels.
Lots of things can affect that. Mitochondrial damage can be part of it as can IL-10 levels.
Psychological stress and its physiological effects, particularly heightened inflammation levels, are factors to consider. It’s worth noting that psychological stress can lead to increased inflammation, and senescence is known to be heavily involved in inflammatory processes. This connection suggests a potential link between stress and the development of ASCVD.
Psychological stress can increase cortisol which is likely to increase glucose levels. That can lead to more ROS more mitochondrial heteroplasmy and hence inefficient mitochondria (part of the cause of senescence).
Most people who have a PCSK9 loss of function resulting in very low apoB or LDL are protected from ASCVD, I think the only person in one such study who got the disease was someone who had obesity and were smoking with a high Lp(a). Aging of course has little effect if lipids are low. I would never bet on anything else in exclusion of this, only as an adjunct therapy.
I accept that if lipids are low that is protective. The question for someone like me whose lipids are OK is whether to try to drive them lower or to focus on resolving the key aging pathways (acetyl-CoA, mitochondria).
I looked at the paper in your post. The authors themselves of the paper you point to are not interpreting it the that way
… rather their own synthesis is that PCSK9i (and CETP meds are basically neutral on CRP
… and they also say that that is line with their understanding from the rest of the literature:
And they don’t even discuss PSCK9i (non-effect) in their entire conclusion:
So for me it seems like the current conclusion from their and other literature is that it is neutral.
The jury might still be out, but saying that those drugs increase CRP in a black and white/strong confidence way does not seem at all warranted or correct at this point.
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BTW: if one looks at inflammation broader than CRP, the picture that emerged further asks the question if PSCK9 is driving many types of inflammation up and hence inhibition/PCSK9i drive synchronous broader inflammation markers down down.*.
Hopefully more studies will help us understand this better in the coming years.
For the 20% of population with high Lp(a) (including to some extent me) PCSK9i might be even more anti inflammatory.
The nice thing with personalized medicine is that measuring a range of inflammation markers is relatively easy so any individual trying a specific Apo E lowering medicine can track and evaluate the impact on their inflammation levels to a relatively good degreee.
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*See eg
Section PCSK9 and Inflammation
and
Tables 1 and Table 2
in
Effects of PCSK9 Targeting: Alleviating Oxidation, Inflammation, and Atherosclerosis
https://www.ahajournals.org/jaha/doi/10.1161/JAHA.121.023328