#22

Eh, now that is reaching. Diabetes is a huge risk factor for ASCVD but the clinically accepted marker for it is high blood sugar or, more specifically, high HbA1c.

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#23

This is what’s important, and the difference between large, fluffy LDL particles which aren’t a problem because they don’t cross the endothelium into the intima of the arterial wall.

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#24

Every apoB particle size increases risk, sdLDL-p just slightly more so than lfLDL-p and lp(A) is obviously the worst.
LDL Cholesterol: Heart Disease Risk? Does size matter? [Study 171 - 180 Analysis] (youtube.com)

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#25

I just watched the whole hour&20min Physionic video and did not find it convincing. One of his worst that I’ve seen (but it was a year ago). He spends almost the whole video showing how much worse small, dense LDL particles are, and then right at the end says - “but I think large LDL particles still matter”…WTF!!! The video was also pretty simplistic relative to the detail that I’ve been presenting. OK, maybe it’s wrong to say “large, fluffy LDL particles aren’t a problem” but I can and will post numerous studies that show particle size does matter (for both LDL and HDL) and that small, dense LDL particles are vastly more important in starting plaque.

Because the predominance of small, dense LDL has been accepted as a bona fide cardiovascular risk factor,1 this result suggests that we should not estimate the risk of CAD from the LDL-C level alone.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929871/

Small dense low-density lipoprotein particles (sdLDLs) are associated with an increased risk of cardiovascular disease and events. They are a better indicator of CVD risk than LDL-cholesterol. The smaller, denser LDL particles are more prone to oxidation and other modifications that make them more atherogenic. Elevated sdLDLs are also associated with elevated triglycerides, metabolic syndrome, diabetes, and arthritis. A healthy diet and a variety of nutrition supplements can help lower sdLDLs. A low level of sdLDLs is considered healthy

https://www.optimaldx.com/research-blog/lipoprotein-biomarkers-small-dense-ldl-particles

Small, dense low-density lipoprotein cholesterol (sdLDL-c), a type of smaller LDL-c, is considered an emerging risk factor for T2DM and CVD. SdLDL-c levels have been found the association with elevated triglyceride (TG) levels and low HDL-c concentrations, constitutes the ‘proatherogenic lipoprotein phenotype’, a common feature of T2DM and MetS [15,16,17]. The potential mechanism maybe partly because of the lower affinity for the LDL receptor and its multiple atherogenic modifications in blood [18]. And subjects with higher sdLDL-c levels have been shown to be associated with an increased risk factor for cardiovascular disease both in cross-sectional and prospective observational studies.

https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-019-0334-y

The science has clearly established that particle size matters.This is just a start, I can post many more.

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#26

This study just says that sdLDL-p tracks better with ASCVD than LDL-C but it doesn’t say that it tracks better than just raw apoB count.

The number of apoB particles that enter the arterial wall is determined primarily by the number of apoB particles within the arterial lumen. However, once within the arterial wall, smaller cholesterol-depleted apoB particles have a greater tendency to be trapped than larger cholesterol-enriched apoB particles because they bind more avidly to the glycosaminoglycans within the subintimal space of the arterial wall. Thus, a cholesterol-enriched particle would deposit more cholesterol than a cholesterol-depleted apoB particle whereas more, smaller apoB particles that enter the arterial wall will be trapped than larger apoB particles. The net result is, with the exceptions of the abnormal chylomicron remnants in type III hyperlipoproteinemia and lipoprotein (a), all apoB particles are equally atherogenic.

Apolipoprotein B Particles and Cardiovascular Disease: A Narrative Review - PubMed (nih.gov)

In summary, more sdLDL-p get stuck than the lfLDL-p but they deliver the same amount of cholesterol overall.

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#27

Yes, good article (I read the full text version). This section addresses the complxities of what I’m looking at.

In addition, variations in glycosaminoglycan structure and perhaps other elements of the arterial wall might influence the avidity of binding of apoB and therefore increase fractional trapping of apoB particles. 64 Thus, the hypothesis that glycation of apoB particles promotes binding of apoB particles deserves further attention. 65 Finally, there is likely significant interindividual variation in the intensity of the innate and acquired immune responses, ie B and T cell responses, to apoB particles trapped within the arterial wall and therefore significant variation in in the inflammatory-mediated destruction of the arterial wall. 68

Accordingly, variance in the sequence of events after an apoB particle enters the arterial wall will account for much of the individual variance of risk at the same apoB. Nevertheless, everything first depends on the entry of an apoB particle into the arterial wall, and this depends, most of all, on the concentration of apoB particles in the arterial lumen.

Statins lower LDL-C more than non-HDL-C more than apoB 35 because larger cholesterol-rich LDL apoB particles interact more avidly with the LDL receptor than smaller cholesterol-depleted ones. 36 Therefore, their concentration will decrease more than the concentration of smaller cholesterol-depleted apoB particles.

Trapping of apoB lipoprotein particles within the arterial wall is the fundamental step that initiates and drives the atherosclerotic process from beginning to end, from the first appearance of fatty streaks to the ultimate development of the complex lesions that are vulnerable to the acute transformations, such as plaque rupture and endothelial erosion, that are the immediate precursors of clinical events. 1 The concentration of apoB particles within the arterial lumen is the primary determinant of the number of apoB particles that will be trapped within the arterial wall. But the proportion of apoB particles that are trapped within the arterial wall versus the proportion that pass harmlessly through is also influenced by the size of the apoB particles and by the structure of the glycosaminoglycans within the subintimal space of the arterial wall. Trapping of apoB particles deposits atherogenic cholesterol within the arterial wall.

I’m still not convinced of their conclusion that " all apoB particles are equally atherogenic."

Here’s an opposing view.

Several studies have reported that small dense low-density lipoprotein (sdLDL) levels increase the risk of ASCVD.[22–24] Ikezaki et al demonstrated that sdLDL is the most atherogenic lipoprotein parameter compared to other lipoprotein parameters, including low-density lipoprotein triglycerides, triglyceride-rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, direct LDL-C, Lp (a), large buoyant LDL-C, and VLDL-C.[24] The increased atherogenesis of sdLDL is associated with the specific biochemical properties of these particles. The small size makes penetration into the arterial wall easier, and smaller LDL particles have a decreased receptor-mediated uptake. Therefore, the half-life of sdLDL is longer than that of the large LDL particles. A longer circulation time increases the possibility of atherogenic modification of sdLDL in the blood.[25] The LDL-C/Apo B ratio has been identified as a marker of small dense low-density lipoprotein (sdLDL). Hirano et al found that an LDL-C/Apo B ratio of 1.2 corresponds to an LDL diameter of 25.5 nm, has been proposed as a cutoff value between sdLDL and large buoyant LDL.[26] A low LDL-C/Apo B ratio has been associated with increased ASCVD risk.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9829249/

#28

There are no trials showing that independent reduction of sdLDL-p reduces events or acm yet and statins work well despite apparently working better on larger LDL-p. SGLT2i do cause a reduction in sdLDL-p while slightly increasing lfLDL-p and yet SGLT2i cause a reduction in events and acm, though SGLT2i have various effects on the kidneys, blood pressure and on cancer inhibition so it’s not clear which one of those is causing that effect.
From all this info I would say that even if LMHR genotypes do exist, they would still be well-advised to get on medication.

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#29

Just my opinions here. What if what if all this recent research into (my views) splitting of hairs re ApoB vs this vs that. Little mention of each scenario’s state of inflammation (CRP, Homocyctine etc) vs out come.

What if this is all just systems and not root cause?

What if the root cause was a new item that crept into our food chain that predisposes the body to these ends; heart / vacular issues, cancer etc.

What if seed oils, canola, excess linoleic acid in our diet weakening the cell membrane increasing insulin resistance…

An over view: https://www.youtube.com/watch?v=7kGnfXXIKZM

Prior to excess linoleic, 100yrs ago, subtracting out the death from disease, war, accident, death was not from heart or cancer…

Good luck to all, curt

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#30

Even people thousends of years ago had heart disease.
Ötzi the Iceman Was a Heart Attack Waiting to Happen | Live Science

It is not the result of the sneed oils and carbs.

#31

Lots of info here on inflammation relative to the intima and endothelium of the arterial wall because that is at the root of the initiation of plaque. I watched the Dr. Knobbe youtube and the problems with processed/ultra-processed food and mitochondrial disfunction are now widely accepted. The evils of omega 6? I’ll watch for more info. And when he said the amount of carbs or saturated fat in the diet don’t matter…I don’t think that will pass the science test. But, insulin resistance absolutely is important and a root cause of many problems.

What the LMHR study is doing, and even lipidologists consider this sound, is regular (I think at least yearly) imaging for plaque. At zero plaque even a cardiologist would say that medication for lipids is unnecessary (optional with high ApoB). Plaque is slow forming, it doesn’t become a problem in less than a year. The studies I’ve been posting indicate that if you’ve gone at least 5-10 years with high ApoB and zero plaque that you may not need lipid-lowering medication - but definitely should keep vigilantly testing for plaque as you age. I would love to solve the plaque problem without medications. Here’s an article on what may be a minor factor (who knows) but worth noting.

Can I Lower My Cholesterol Without Taking a Statin?

Here’s what the evidence suggests can work.

https://www.nytimes.com/2024/09/04/well/eat/lower-cholesterol-statin.html

Just as an aside…When I was young, I used to look at old people and was astounded by all the medications they had to take. I came to associate pharmaceuticals with being way too old, so I have a natural resistance to becoming a walking pharmacy.

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#32

Are the techniques for detecting plaque buildup accurate enough?

I would love to solve the plaque problem without medications.

If we all had the right genetics we wouldn’t need to take any medications at all and still live to be 120+. But it’s important to understand that if your ancestors didn’t happen to live that long, you most likely won’t either. Do you have ANY ancestor or relative who ever had a stroke or heart attack? If so, you know your susceptible to plaque buildup and require medication.

#33

I would say yes, cardiologists rely on them. CCTA probably the best, CIMT make sure to get a skilled and experienced operator, and CAC - although it misses soft plaque is statistically considered a good test.

I don’t think that’s true. My ancestors knew nothing about the science…or optimizing diet, exercise, sleep and mental health. We’re far more advanced and knowledgeable over even 20 years ago. I monitor my sleep, heart rate, optimize my exercise and correct problems that show show up in my blood biomarkers with diet (even without pharmaceuticals). I feel sure that I will outlive my ancestors - even if I didn’t take a statin.

Here’s a good primer on LDL particles and the value of their size. Advanced my knowledge. However, it contradicts something that I had picked up from the Physionic video you posted above - that said that ApoB particles have a positive charge and are attracted to negative charges in the intima - this article says small dense ApoBs are negatively charged.

There are distinct and constant differences in the electrical charge of LDL subfractions at neutral pH of 7.4 arising as a result of either dissimilarities in the relative proportions of charged phospholipids or of sialytion of associated proteins [11, 20]. Negative charge increases with increasing density of LDL particles. Small LDL particles have significantly lower neutral carbohydrate and sialic acid content [20, 21]. LDL particles with lower sialic acid content have greater affinity for proteoglycans in the arterial wall and could be preferentially involved in the development of atherosclerosis.

The filtration rate of LDL particles into subendothelium is inversely proportional to particle size, thus small LDL particles are transported more effectively from the circulation to the subendothelial space of artery wall than are large LDL particles.

Small, dense LDL particles have greater affinity for intimal proteoglycans than do other LDL particles [48]. This may be related to their lower sialic acid content and to different exposures of the apoB region that influences interactions with proteoglycans. Binding to intimal proteoglycans leads to extracellular lipid accumulation which is an important component of atherogenesis.

LDL particle size is related to endothelial vasodilator dysfunction in patients with CAD, independent of other lipoprotein variables [50]. Small, dense LDL particles stimulate thromboxane (TX) A2 synthesis in vitro, more than large LDL particles [51]. Since TXA2 stimulates platelet aggregation and is a potent vasoconstrictor this could contribute to the progression of CAD. Production of 8-epi-PGF2α as a result of non-enzymatic oxidation of arachidonic acid in small, dense LDL particles could also promote vasoconstriction and platelet aggregation.

In view of the strong relationship between elevated plasma triglycerides and the small dense LDL phenotype, triglyceride lowering therapies could be expected to have a greater impact on LDL size and density than predominantly cholesterol lowering therapies.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014286/

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#34

I don’t think that’s true. My ancestors knew nothing about the science…or optimizing diet, exercise, sleep and mental health.

Some forms of veganism, exercise etc were already practiced a hundred years ago.

The filtration rate of LDL particles into subendothelium is inversely proportional to particle size, thus small LDL particles are transported more effectively from the circulation to the subendothelial space of artery wall than are large LDL particles.

Okay, but this is in line with the previous review that while smaller LDL particles get stuck easier, the larger ones getting stuck results in more cholesterol desposits so the net result is the same overall, making all LDL particles equally artherogenic.

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#35

There’s a reason why CVD and stroke are the leading killers of all mankind and have been for quite some time. The question is are you going to do something about it or just hope you get lucky. I’m going to reduce my ApoB as much as possible and try to avoid the normal man’s fate.

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#36

Hey, I did something about it based on what I knew at the time. I started atorvastatin 10mg and ezetimibe 5mg about 6 months ago and my ApoB dropped from 87 to 63. But then I decided to take a closer look and really understand exactly what was happening. That’s the whole point of being here on Rapanews for me. Not just to hear people say “do this” and then doing it, but actually learning and studying exactly how the body works, so I can knowledgeably experiment. I want to take the fewest pharmaceuticals to get the most healthy results (not like you! :wink:). All the major aging problems, particularly CVD, dementia, cancer and some primary root causes like blood sugar and inflammation are important and if I can find ways to improve them without pharmaceuticals, I will. Most people seem to just want to sit back in the easy chair and pop pills.

I’m still not convinced of this but I continue to investigate. I’ll let you know…

#37

If you really want to do this, why don’t you track everything you consume and do a pearson correlation between average daily intake and blood biomarkers like Lustgarten? (Biomarker on one axis, one average daily intake of a food or supplement on the other).

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#38

Lustgarten is doing great work and I am following him. I just hope he’s getting loads of “joie de vivre”. He always seems too serious. He needs to find, like I have, a good community to make fun of :wink: (I hate emoticons). Loads of laughs and a barrel of monkeys might get you to 120.
@ConquerAging I hope you’re listening.

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#39

Most people seem to just want to sit back in the easy chair and pop pills.

Cause it works. Anything that reduces acm in clinical trials or extends lifespan in mice in the ITP has a good chance of actually extending the individuals healthspan and lifespan.

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#40

Yeah ideas are cool and all, but I have a preference for things that work. Especially things that just works.

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#41

like plastic surgery?
Life isn’t like cooking in an easy bake oven.
Or the meta-universe.