心血管健康

[adssx]

Does this suggest that CVD is a disease of ageing and that maybe it’s not about ApoB levels per se but early intervention to slow down the ageing and restore some functions (reverse cholesterol transport?)?

[John_Hemming]

I don’t think there is any doubt that CVD is a disease of aging, but it also appears to be exacerbated by high levels of ApoB.

[DeStrider]

I believe that CVD has two important variables that affect it - ApoB and inflammation. Both increase as you age. Both are also alleviated by Bempedoic Acid and Ezetemibe. Rapamycin also reduces inflammation.

Of course this is just a simplified version as there are many other factors involved but I believe these two are the biggest for CVD.

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@DeStrider

Both are also alleviated by Bempedoic Acid and Ezetemibe.

Inflammation as measured by which marker(s)? And how does bempedoic acid/ezetimibe compare to statins on this?

[DeStrider]

Inflammation as measured by hsCRP. The literature says BA reduces hsCRP by 20%. For my father, it was reduced by 66%.

[adssx]

Ok thanks. Statins also reduce hsCRP by a lot: Effect of lipid-lowering therapies on C-reactive protein levels: a comprehensive meta-analysis of randomized controlled trials | Cardiovascular Research | Oxford Academic

CETPi and PCSK9i increase it though. And yet reduce MACE. Why? (poke @Neo)

[AnUser]

LDL-c causes heart disease via apoB, independent of any pleiotropic effect of a medication like statins.

The Low-Density Lipoprotein Cholesterol Hypothesis: An Update

[Joseph_Lavelle]

Yes, I understand it’s particle count and time (age). No doubt other variables are in play but high apoB times many years is enough to kill a person most of the time.

[Neo]

Could be as simple as massive lowering of Apo B dominates any (smaller) hs-CRP increase?

How big is the CRP increase with those? (My hs-CRP on now full dose repatha is still below the lowest threshold of the test so I don’t know if mine has changed).

[AnUser]

@Neo

Could be as simple as massive lowering of Apo B dominates any (smaller) hs-CRP increase?

I think that is the case. Statins increase Lp(a), as well, but still have a worthwhile effect (probably primarily) due to the decrease in apoB, and hs-CRP and other pleiotropic effects contribute some.

[L_H]

This is interesting. Psk9 inhibiting genes have lots of pleiotropic benefits

“Investigations in animals and humans suggest that the impact of PCSK9 inhibition is not limited to reduction in LDL-C but also affects other aspects of lipoprotein metabolism, inflammation, thrombosis, and immune function.”

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.116.023687

[AnUser]

@John_Hemming

I don’t think there is any doubt that CVD is a disease of aging,

If that is the case then few young people should have atherosclerosis, same source as above:

“We know that atherosclerosis begins early in life. In fact, a study from the 1990s looked at 111 casualties of the Korean War who died from non-cardiac trauma. 78.3% of these relatively healthy individuals with a mean age of 26 years showed coronary atherosclerosis. Over one-fifth had greater than 50% narrowing and just as many had left main or significant two and three-vessel involvement suggesting that ASCVD begins much earlier in life than usually presumed [58].”

I don’t think atherosclerosis has much to do with aging, it is proven it has everything to do with time and exposure to sub-optimal levels of apoB.

How do you know whether something is an age or time based disease?

Suboptimal levels of apoB have large effects with time. That’s all you need to know, practically.

[scta123]

@AnUser

Suboptimal levels of apoB have large effects with time. That’s all you need to know, practically.

How do you explain that some people with familial hypercholesterolemia die or have advanced disease in their thirties and some with same level of lipids have no sign of ASCVD into the old age?

[Virilius]

Some people are genetically more resistant to plaque formation than others. That’s the same reason why some obese cake-munchers never go on to develop diabetes.

[scta123]

@Virilius

Some people are genetically more resistant to plaque formation than others.

This prompts me to ask how these genetic differences work. What does this mean mechanistically? Would you care to explain? Did you intend for this statement to have no real significance, or does it hold some meaning?

[AnUser]

First, can you post some statistics how many with familial hypercholestrolemia who are untreated, have no sign of ASCVD into old age?

[scta123]

There isn’t any statistical evidence only anecdotal cases of individuals with FH only becoming aware of their condition when their children are diagnosed with advanced ASCVD. Typically, people become aware of their ASCVD when they start experiencing symptoms or are diagnosed with the condition. It’s crucial to explore alternative explanations and approaches when traditional hypotheses reach limitations. Certainly, when the LDL-C hypothesis reaches a dead end, alternative explanations become elusive.

[AnUser]

@scta123

There isn’t any statistical evidence

So how do I know whether what you said is true? How do you know?

@scta123

How do you explain that some people with familial hypercholesterolemia die or have advanced disease in their thirties and some with same level of lipids have no sign of ASCVD into the old age?

[scta123]

@AnUser

So how do I know whether what you said is true? How do you know?

From anecdotal reports by people familiar with the field. One was suggested by you, John Kastelein.

[AnUser]

Do you have a link to the timestamp where he says what you say?