#42

Deadly wrong!

Mendelian randomization studies prove massive effects because of time of lowering LDL, of course during periods of CAC 0.

POSITIVE CAC IS ADVANCED CARDIOVASCULAR DISEASE.

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#43

regarding LDL, is it true that it uniformly increases vascular risk?
• Notes 09:03 Thu Jan 4

今Q 64%0

Article Text

• bmjopen.bmj.com — Private

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Cardiovascular medicine

Research

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Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a

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systematic review

Uffe Ravnskov’, David M Diamond 2

, Rokura Hama 3, Tomohito Hamazaki 4, Björn

Hammarskjöld 5, Niamh Hynes 6

, Malcolm Kendrick 7, Peter H Langsjoen 8, Aseem

Malhotra°

, Luca Mascitelli 10

, Kilmer S McCully 11

, Yoichi Ogushi 12

, Harumi Okuyama 13, Paul

J Rosch 14

, Tore Schersten 15

, Sherif Sultan 6, Ralf Sundberg 16

Correspondence to Dr Uffe Ravnskov; ravnskov@tele2.se

Abstract

Objective It is well known that total cholesterol becomes less of a risk factor or not at all for all-cause and cardiovascular (CV) mortality with increasing age, but as little is known as to whether low-density lipoprotein cholesterol (LDL-C), one component of total cholesterol, is associated with mortality in the elderly, we decided to investigate this issue.

Setting, participants and outcome measures We sought PubMed for cohort studies, where LDL-C had been investigated as a risk factor for all-cause and/or CV mortality in individuals ≥60 years from the general population.

Results We identified 19 cohort studies including 30 cohorts with a total of 68 094 elderly people, where all-cause mortality was recorded in 28 cohorts and CV mortality in 9 cohorts. Inverse association between all-cause mortality and LDL-C was seen in 16 cohorts (in 14 with statistical significance) representing 92% of the number of participants, where this association was recorded. In the rest, no association was found.

In two cohorts, CV mortality was highest in the lowest LDL-C quartile and with statistical significance; in seven cohorts, no association was found.

Conclusions High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: CC BY-NC 4.0 Deed | Attribution-NonCommercial 4.0 International | Creative Commons

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#44

You have still not answered my questions I posted in another thread.

Feel free to answer so we’ve built some goal posts.

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#45

I don’t think we can say:

Mendelian randomisation studies have their own inherent limitations. And “prove” is a strong word.

Could you link to the paper showing the effects of low ldl during CAC=0 periods?

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#46

The trouble with these cohort studies is that several diseases lead to reduced ldl-c. That may skew the association quite dramatically.

Each study type has its own limitations of course. RCTs tend to be underpowered for All cause mortality and insufficiently long term. They all also tend to focus on those with preexisting CVD.

And the Mendelian randomisation studies are inherently limited as to causation because there may be correlations with other genetic factors that we’re unaware of.

But while it may not be “proven”, i do think there’s strong evidence to target apo B. The big question is how low to target.

https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(21)00120-3/fulltext

3 Likes
#47

In my opinion, lowering LDL-C to the point of seeing some reduction in plaque in sufficient to prevent cardiovascular disease. Usually that occurs at levels between 60-70mg/dL though cofounding factors such as obesity, diabetes and high blood pressure may make it necessary to target even lower levels below 50mg/dL.

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#48

DrFraser, Did these trials use the same dose of Atorvastatin and Rosuvastatin or was the Rosuvastatin dosed at half that of the Atorvastatin? I ask this because you noted Rosuvastatin being twice as effective as Atorvastatin?

On a different note what are your thoughts on simply using Ezetimibe instead of a statin when LDL-C is not excessively high, but Apoliprotein B is above 90? I know Ezetimibe has a weaker effect, but would it’s side effect profile be better? You may have already answered this, but if so I didn’t see it?

Thanks.

#49

In general, atorvastatin is 50% as potent mg per mg as rosuvastatin, although 40 mg rosuvastatin will get slightly better results than 80 mg of atorvastatin (max dose of both agents).
I guess I’m going to go into a long answer on this one.
Philosophically, everyday one lives not maximizing evidence based approaches for longevity, you are aging faster. I have traditionally, only prescribed and recommended things that have solid evidence. So rapamycin is a complete outlier on the spectrum of things I now will advise, only when a patient wants this … as I suspect it will slow aging to a ratio of <1.0 and with little risk, done correctly. I just cannot definitively prove it today, and by the time I can, I’ll be dead.
So vascular death/disability = #1 cause of death (including in Cardiologists). My Dad is a Cardiologist and top researcher for over 40 years on lifestyle and longevity.
I’m a bit surprised to see such divergent opinions on the board on this topic. It is simple, but the conspiracy theories started when Pfizer was making 15 billion a year off of Lipitor and everyone decided doctors were doing bad things to make money. Surprisingly, no one is making money off of Lipitor anymore as it is generic and the doctors continue acting the same way.
The problem is, we are interested in an N=1 … what happens to us, or in my case my patient is critical.
Currently, I’ll see someone who has seen their doctor a month ago, told their lipids are good, no need for treatment, with an LDL of 150 mg/dL, then they see me in the ER with a stroke or heart attack, and now suddenly our goal is <70 mg/dL for their LDL. How stupid is this? The harm has been done.
Regardless of how we get it there, APOB in the <80 category for most people, those with risks maybe less then 70, and for those with an Lp(a)>30 would go for 50’s on APOB.
Whatever it takes to achieve this is smart. Statins, unless one has some specific reason for not taking them should be part of the treatment as they may have other independent factors of anti-inflammatory action over just improving APOB. Certainly one can add other agents - I favor low to moderate doses of multiple agents over pushing one too high in dosing, as side effects often follow doing this. So adding ezetimibe is sensible in many cases.
This ties in to blood pressure control - 110-115/70-75 mmHg is optimal - beyond this worsening outcomes.
I see people being reassured by CAC scores — totally the wrong approach, there is also micro vascular damage — so having your low CAC or following it won’t be that interesting when you have cognitive decline or stroke
Bottom line is primary care is all too often watching people with suboptimal lipids and blood pressure - causative of the number one cause of death and disability and not optimizing.
I’d say optimize those first - we have strong evidence, then do things to optimize risk for malignancy and cognitive decline … then start looking at all the fancy stuff like rapamycin … but optimize the others first.
The only role I see for a CAC is a one off test to convince a patient reluctant to manage their lipids, who I know will have vascular disease to take my recommendations seriously. Apart from that, most Cardiologists see no role or utility … I agree with them.

So there is my long answer, which is a general answer, not at all to give any specific medical guidance or care to any individual, but to contextualize my thoughts on this.

Would love comments!

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#50

@DrFraser Excellent and insightful post. :slight_smile: It’s comments like this that make my day.

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#51

It’s a given that large periods will be at CAC 0 at lifelong LDL reduction. If you think in causal processes, and not require everything to be explicitly said in studies, that will make future things more clear. Peter Attia is good at this.

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#52

DrFraser, Well, it is a long answer and I appreciate your feedback. I’m not sure where the answers to my specific questions lie within your response, but I’ll re-read it and search for them. Thanks.

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#53

Very good. More and more I understand aging to be a progressive deterioration of the infrastructure (bones, immune / repair system, etc). Once a problem has emerged the damage is bad and hard / impossible to reverse. “Science” doesn’t known everything but it is all we have. And science is the body of work not a study or two.

Everyone has to make their bets. I have decided to save my energy by not trying to convince people to do things. I just say what I do and why.

If I was younger, more of this stuff would be academic. But for me now, I am out of time to take action. I have been misled by well meaning people and by self interested people over the years. That is my fault. I needed to take more responsibility.

My doctor helps me when I get sick but is of no help on these topics. The medical industry is evolving slower than I am aging. I have to take responsibility for myself.

I’m glad to have this forum to learn from wise people who are ahead of me on this adventure.

Thanks.

7 Likes
#54

That’s probably the right approach for long-term happiness, as it’s almost like trying to convince an alcoholic to stop drinking when talking about many of these interventions.

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#55

Hi Jay,

Generally trials will have Rosuvastatin at 0.5 x mg dose of Atorvastatin.

Ezetimibe is an excellent choice but I’d say add it to statin if needed, I wouldn’t select it as first item, unless have a contraindication / adverse effect of statin.

LDL-C is interesting, but ultimately APOB is the measure - you need to go by that. I order a single lipid profile on patients, for giggles and laughs … as people want to see what these numbers are - and I guess I do like to see the triglycerides in regard to other risks, but APOB is the measure for vascular risk on the lipid side.

There is a glycemic risk and BP risk on vasculature in addition as the ones I focus on.

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#56

I’m not sure it is a given that what you say is “proven”. I think you’re making an assumption. That’s fine, and my guess would be that the assumption is correct. But i think you need to be careful about bandying about words like “proven” about when you’re actually making an assumption.
“that will make future things more clear”

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#57

Apologies if you’ve linked these elsewhere. But i’d love to see the rosuvastatin=) type 2 diabetes paper(s).

#58

DrFraser, Excellent! Thanks.

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#60

I don’t want to take a side in this argument, but unusually I take weekly blood tests with a number of labs.

This includes LDL-C always and sometimes ApoB. I don’t fast for my tests, but LDL-C bounces around the UK SI threshold of 3 mmol/L. Hence I am not inclined to fuss.

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#61

Great point. If society can’t even ban something we know is 100% bad for you like smoking, how can we count on society to look out for our health?

Hell, they’re even promoting smoking now with the legalization of marijuana. Society (as a whole) cares more about taking your money than helping you. You must educate and help yourself.

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#62

He did a podcast recently with Rhonda Patrick where he names them and gets into some detail.

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