心血管健康

[RapAdmin]

So, the argument this longevity researcher is making is that now that the Cardiovascular disease problem is “solved” (via early use of statins and other lipid lowering therapies - if used early enough) we should be focusing on cancer…

Source: x.com

[Virilius]

There is plenty you can do about skin and prostate cancer already, but as for the rest, I’m not sure what can be done other than immune therapies. Even mice eventually succumb to cancer despite given multiple treatments at once.

[AnUser]

@adssx

(@AnUser is that correct?)

I don’t know, I think all statins most likely improve all-cause mortality, and so do I think for all of the other lipid lowering treatments unless they’re banned drugs. Atorvastatin is preferred over rousvastatin according to the data IMO because of the diabetes risk difference. It’s also studied in the largest clinical trial ever done in older adults to see if it can reduce dementia risk.

So probably doesn’t matter that much. People who are APOE4 carriers or those with Alzheimer’s family history should probably consider measuring serum desmosterol levels to not crush synthesis too much. If they can’t do that lower dose statins and/or other treatments might be a good idea.

Also, to be honest, a small decrease in LDL from the mean has a massive effect if it’s lifelong, look at the PCSK9 loss-of-function studies.

[John_Hemming]

I think the chances are that you are right in that statins direct acetyl-CoA away from cholesterol. I am not so sure mechanistically about bempedoic acid, but I am not worried about that.

[adssx]

I created a new thread on cancer to keep this one focused on CVD: Prevent and cure cancer

[DeStrider]

Even though cardiovascular problems have been ‘cured’, there are still so many that suffer needlessly from heart attacks and strokes.

[AnUser]

Pooling results across studies using inverse-variance weighted fixed-effects, PCSK9 LOF variants were associated with 35 mg/dL (95% confidence interval [CI]: 32, 39) lower LDL-C in AAs and 13 mg/dL (95% CI: 11, 16) lower LDL-C in whites. PCSK9 LOF variants were associated with a pooled OR for CHD of 0.51 (95% CI: 0.28, 0.92) in AAs and 0.82 (95% CI: 0.63, 1.06) in whites.

PCSK9 Loss-of-Function Variants, Low-Density Lipoprotein Cholesterol, and...

Here’s the type of result I was talking about earlier, unless I misunderstand this, it’s just 35 mg/dl decrease from the mean (~100 mg/dl → 70 mg/dl?), that’s -30% LDL reduction lifelong for 50% lower incidence of cardiovascular heart disease. Not 100% prevention. So starting later in life probably requires a much greater decrease in LDL?

[adssx]

For AAs, we have -35 mg/dL => -49% CHD risk and for -13 => -18%. In both cases the ratio is 1.4. So if the relationship is linear, then if you want -99% it means you need to lower by 71 mg/dL? But what matters if probably more the absolute LDL level rather than the reduction?

[AnUser]

@adssx

So if the relationship is linear, then if you want -99% it means you need to lower by 71 mg/dL? But what matters if probably more the absolute LDL level rather than the reduction?

That’s interesting because just based on this study result and if it’s linear it the mean goes from 100 mg/dl → 30 mg/dl LDL, which is the LDL that many commonly have said is where atherosclerosis doesn’t really develop. I agree it’s the absolute LDL level. We also have short term data from clinical trials around to that level. But below 50 mg/dl LDL is probably very good too. Hard to get that low.

[adssx]

FYI, not a research paper but interesting to see where the mainstream consensus is heading: “But how far below 70 mg/dL should you go? Clinical trials have shown and European guidelines recommend that people with cardiovascular disease at the highest risk should aim for LDL levels below 55 mg/dL. Dr. Cannon notes that the U.S. guidelines have not been updated since 2018, and believes they will eventually follow Europe’s lead and make 55 mg/dL the new target for high-risk individuals.” ( How low should LDL cholesterol go? - Harvard Health )

The American guidelines won’t be updated before 2026, though… ( https://www.acc.org/guidelines/guidelines-and-clinical-documents-in-progress )

Next year Europeans (ESC) will publish the “Focused update of the 2019 dyslipidaemia guidelines” but I don’t think it’ll move the needle much.

@AnUser

But below 50 mg/dl LDL is probably very good too. Hard to get that low.

Why hard? Rosuvastatin + ezetimibe + BA would easily get most people there? And future drugs will make it even easier?

[CronosTempi]

If we are comparing statins, then it seems the real star by far is pitavastatin. More potent than any other (1.7 more than rosuvastatin), lowers LDL more than any other, has a better impact on HDL, and lowers CV events more than any other, while having fewer side effects especially on muscle and diabetes. Also, is NOT affected by grapefruit, and importantly for us juggling many drugs, it has fewer interactions with drugs. In other words, a runaway star of statins.

[AnUser]

I think that one looks good, however what about all-cause mortality? Maybe it doesn’t matter so much that as far as I know it hasn’t detected it. I like that it doesn’t interact with much stuff and that it’s potent.

See comparison on blood glucose livalo vs. atorvastatin which I think many of us considered the gold standard:

https://www.livalorx.com/discovering-livalo/compare-statins/lipitor/

@adssx

Why hard? Rosuvastatin + ezetimibe + BA would easily get most people there? And future drugs will make it even easier?

True that should probably be enough, sometimes it has to be combined with a PCSK9 inhibitor and it depends also diet (saturated fat).

[adssx]

Pitavastatin looks interesting but it’s not studied enough. There’s an ongoing Korean trial comparing it to atorvastatin. Results next year: ClinicalTrials.gov

[CronosTempi]

One interesting aspect of statins, is the issue of combos. As my ApoB/LDL numbers deteriorated despite being on 10mg/day of atorvastatin, I started wondering if combining statins might not be a way. Basically, the effectiveness of statins drops off drastically with increasing doses. Most of the LDL lowering is accomplished with the lowest dose. Increasing the dose, even substantially, gives you only tiny further gains, while raising the risks of side effects.

So, I thought to myself - why not stay on my 10mg/day atorvastatin and just add a low dose rosuvastatin, instead of upping the dose of atorvastatin for meager gains. That way, you are taking a low - and most effective - dose of both. The idea being that they work along different pathways, one is lipophilic, the other hydrophylic.

I tried googling if this is a viable strategy, but found it difficult to gather any info in this regard.

Anyhow, I ran this idea past a cardiologist and he said basically that he had many patients who had the same idea, but in fact that it’s a BAD idea, and combining statins is also very negative for the liver, so this idea is not a good one.

I think this is an example of where we need to be cautious when reasoning ourselves into taking a drug or combo of drugs. We don’t have the clinical experience to navigate such interactions, and googling doesn’t always give you the answers.

Just wanted to throw this in, because I think our crowd of self-experimenters is prone to polypharmacy and therefore we might be more exposed to such hazards. YMMV.

[CronosTempi]

So now my idea is to add bempedoic acid + ezetimibe to my low dose of atorvastatin. Would love a PCSK9i, but alas, can’t afford the cost.

[Pat25]

Has anyone been taking solely bempedoic acid + ezetimibe without taking a statin, and kept track of their LDL/trigs/ApoB levels?
Do we know if just this combination without a statin could also yield good results?

[AnUser]

Yes, it lowers LDL by about the same as a moderate intensity statin.

Study Results With NEXLIZET

So if someone doesn’t want to take statins for whatever reason this is available, and inexpensive if you live in the U.S. and can order from India.

[Pat25]

Fantastic, thanks Anuser.

It would be great if we would have a thread or poll what approach members follow with regard to taking statins and/or (a combination with) bempedoic acid + ezetimibe.

Generally I’m wondering from what age and with what LDL/trig/ApoB numbers most members here would consider taking a statin and/or (a combination with) bempedoic acid + ezetimibe.
Is it indeed a better idea to start taking these from a (relatively) younger age, and pushing these numbers further down, even if they are not yet outside the ‘normal’ range?

[adssx]

We could start a poll “What’s your LDL target?” with options like < 50 mg/dL, < 70, < 100, < 130, “I have no LDL target”.

[DeStrider]

For Bempedoic Acid and Ezetemibe results, see here:

Bempedoic Acid and Ezetemibe Results

I am over the moon! My 78 yo father just got his results from his blood work back. His ApoB went from 120 to 65 and his hsCRP went from 1.2 to 0.57. He hasn’t gotten his LDL, TG, TC and HDL results back, but so far I am ecstatic. This is after 1 month taking the drugs in one pill together. It’s the Indian Generic Brillo EZ from Jagdish Nikose. I’m taking it as well and will report my numbers when I get them. It feels like he bought an insurance policy against heart disease!!