Regressing atherosclerosis

[Eddy Edson]

I have peripheral artery disease/intermittent claudication, which I hate - walking has always been a major pleasure for me & it gives me the $%#$#% that I can't do it so well anymore.

Since giving up the fags & settling into a replacement addiction to vaping it's a ton better & I'm averaging 9km+ per day. Which is good, but I want more!

To that end, I've been digging into atherosclerosis regression, and it does seem like there's some support for the idea that getting LDL very low and increasing HDL can in fact give results. Eg, the ASTEROID trial from 2006, https://jamanetwork.com/journals/jama/fullarticle/202629 and discussion in this, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262135/ Etc etc.

My simple take-away from ASTEROID and the discussion is this: get LDL below 1.6 and HDL above about 1.3, and there may well be some regression. In ASTEROID the intervention was Rosuvastatin 40mg, and the discussion suggests that increasing HDL with niacin might have good effects, in this context.

I'm on Rosuvastation 10mg and my LDL is 1.6. There's a bunch of evidence that in terms of general CV outcomes, there's no lower bound for a good LDL level - the lower it is, the lower the risk.

Putting this together, I'm going to talk with my doc about increasing my Rosuvastatin to (say) 20mg. I can't see that it would have any downside, given that I don't seem to be one of the tiny number of people who experience statin side-effects, and any further reduction of LDL would be all to the good, even without regression. (Looking at the guidelines, I would have thought 20mg was a more appropriate regime for me, anyway.)

My HDL has edged up to 1.0 from 0.8 at diagnosis & it may be that it will continue to improve, now that I'm not smoking, but I guess it might be worth thinking about niacin if that improvement stalls out. There do seem to be some nasty side effects, though.

Anyway, a strategy to try.

 

[mikeyB]

Think of it as a five year plan after quitting the fags. Takes that long for the body to generally recover.

 

[Eddy Edson]

Think of it as a five year plan after quitting the fags. Takes that long for the body to generally recover.

That would put me well into Trump's 2nd term, by which time I expect God might have decided to chuck the whole thing in the bin, out of disgust.

 

[Madeline]

Do you measure your cholesterol differently? My HDL is 1.8, and considered very low.

 

[Eddy Edson]

Do you measure your cholesterol differently? My HDL is 1.8, and considered very low.

Hmmm ... sure you don't mean LDL? I think HDL = 1.8 would normally be seen as pretty much ideal.

 

[Madeline]

Possibly, I’m not sure. I was just told it was exceptional and well done, not that I have any control over it, it’s been so low in the past that they’ve insisted on retesting.

 

[Sharron1]

That would put me well into Trump's 2nd term, by which time I expect God might have decided to chuck the whole thing in the bin, out of disgust.

I don' t get any of the science and numbers stuff. But a 2nd term of Trump and no doubt Mrs May will still be attempting to get Brexit plan through, u might want to consider your plan of action for the sake of your health😱

 

[Eddy Edson]

Possibly, I’m not sure. I was just told it was exceptional and well done, not that I have any control over it, it’s been so low in the past that they’ve insisted on retesting.

I think LDL = 1.8 would usually be seen as triffic. It's the level which "high risk" people like me are supposed to target. Generally, the lower the better. I'd be well over 2 without the statin.

HDL goes the other way, higher the better, except there's increasing research to the effect that too much above 1.8-ish isn't great.

 

[everydayupsanddowns]

Good luck in reducing your atherosclerosis Eddy. Hope you find a way that works for you.

Do you have a source for ‘no lower limit’ of LDL cholesterol?

There seem to be fairly agreed levels at which lack of LDL becomes problematic (though I’m not sure whether statins would get you down to that level - especially since we don’t measure LDL in this country, we calculate it with a formula.

Found this among other searches:

Dangers of Low LDL
While it would be fair to assume that a low LDL is a good thing, there are rare circumstances in which chronically low levels may increase your risk of certain diseases.

LDL is what's called a carrier protein, whose role it is to deliver chemicals to every cell in the body. It is also a critical component of cell membranes, serves as a brain antioxidant, and is used by the body to create the hormones estrogen, progesterone, and testosterone.

Chronically low LDL levels may impair brain and hormonal activity and increase the risk of hypobetalipoproteinemia, a condition linked to depression, cirrhosis, preterm birth, hemorrhagic stroke, and certain types of cancers.

These conditions can affect both sexes but tend to impact women with an LDL below 50 mg/dL (1.3 mmol/L). Men, by contrast, are more likely to be affected when their LDL dips below 40 mg/dL (1.0 mmol/L).

While there remains strong debate as to the associations, given the disparate nature of the conditions, it may be reasonable to assume that the depletion of LDL may increase the oxidative stress on the brain, impacting both brain function and vascular integrity.

https://www.verywellhealth.com/can-total-cholesterol-levels-be-too-low-697599

 

[Eddy Edson]

Good luck in reducing your atherosclerosis Eddy. Hope you find a way that works for you.

Do you have a source for ‘no lower limit’ of LDL cholesterol?

There seem to be fairly agreed levels at which lack of LDL becomes problematic (though I’m not sure whether statins would get you down to that level - especially since we don’t measure LDL in this country, we calculate it with a formula.

Found this among other searches:

Dangers of Low LDL
While it would be fair to assume that a low LDL is a good thing, there are rare circumstances in which chronically low levels may increase your risk of certain diseases.

LDL is what's called a carrier protein, whose role it is to deliver chemicals to every cell in the body. It is also a critical component of cell membranes, serves as a brain antioxidant, and is used by the body to create the hormones estrogen, progesterone, and testosterone.

Chronically low LDL levels may impair brain and hormonal activity and increase the risk of hypobetalipoproteinemia, a condition linked to depression, cirrhosis, preterm birth, hemorrhagic stroke, and certain types of cancers.

These conditions can affect both sexes but tend to impact women with an LDL below 50 mg/dL (1.3 mmol/L). Men, by contrast, are more likely to be affected when their LDL dips below 40 mg/dL (1.0 mmol/L).

While there remains strong debate as to the associations, given the disparate nature of the conditions, it may be reasonable to assume that the depletion of LDL may increase the oxidative stress on the brain, impacting both brain function and vascular integrity.

https://www.verywellhealth.com/can-total-cholesterol-levels-be-too-low-697599

https://jamanetwork.com/journals/jamacardiology/article-abstract/2695047

Question Is the clinical benefit of low-density lipoprotein cholesterol (LDL-C) lowering preserved in patient populations starting with LDL-C levels averaging 1.8 mmol/L (70 mg/dL) or less, and is LDL-C lowering safe in such patients?

Findings In this meta-analysis, for statins and nonstatins, the risk of major vascular events was significantly reduced by 21% for each 1-mmol/L (38.7-mg/dL) reduction in LDL-C, which was virtually the same magnitude as seen in the overall Cholesterol Treatment Trialists Collaboration analysis in which the starting LDL-C was nearly twice as high. No adverse safety signal was detected for LDL-C lowering.

Meaning Further lowering of LDL-C beyond the lowest current targets is associated with further reduced cardiovascular risk with no offsetting safety risks.

-------------------------------------------------

This piece is a good summary of the latest state of play with regards to cholesterol & statins overall: https://sciencebasedmedicine.org/the-cholesterol-controversy/

Also, an increasing amount of evidence suggests that we should be pushing cholesterol levels even lower than we currently are. The concern that your cholesterol can be too low has been with us since the CPPT trial, including the concern that lowering your cholesterol could affect brain function. The data though suggests that lowering cholesterol below current targets of 1.8 mmol/L or 70 mg/dl provides a benefit with no trade-off in risk.

 

[Madeline]

Hmm, interesting. Two prem births and late loss, chronic depression for decades, and my liver is not a happy bunny despite never drinking in my life

 

[mikeyB]

It’s screamingly obvious that there must be a lower safe level of LDL. It’s part of the way the body works in just about every mammal. Keep lowering the level, you get into unintended consequences. So you may be able to live for years without heart problems, but that won’t be appreciable if you are a drooling idiot with a squishy brain and liver failure.

 

[Madeline]

that won’t be appreciable if you are a drooling idiot with a squishy brain and liver failure.

You know, I do like you Mike, you make me laugh, but you have got to stop spying on me 😱

 

[Eddy Edson]

It’s screamingly obvious that there must be a lower safe level of LDL. It’s part of the way the body works in just about every mammal. Keep lowering the level, you get into unintended consequences. So you may be able to live for years without heart problems, but that won’t be appreciable if you are a drooling idiot with a squishy brain and liver failure.

Anyway, there doesn't seem to be any real evidence to date of excess harms from driving LDL well below 1.0, even down to rabbit-like levels, and presumably if there were strong a priori reasons for anticipating significant harms the recent trials in the area wouldn't have made it through their ethics committees. (Cue Big Pharma blah blah blah, I suppose.)

https://www.sciencedaily.com/releases/2017/08/170828093749.htm
https://www.tctmd.com/news/ultra-low-ldl-levels-fourier-suggests-efficacy-evolocumab

The group also analyzed patients who achieved ultra-low LDL cholesterol levels. In FOURIER, 5% of patients achieved an LDL level of less than 15 mg/dL and 2% of patients achieved an LDL of less than 10 mg/dL. For the 504 patients who achieved the lowest levels, the mean LDL cholesterol concentration was 7 mg/dL. To put those results in perspective, Giugliano said that rabbits have an LDL cholesterol level of approximately 8 mg/dL when fed a low-cholesterol diet.

Among patients who achieved these ultra-low levels, the risk of cardiovascular events was significantly lower when compared with patients who had the highest LDL levels. The findings show that “LDL can be safely reduced to unprecedented low levels with a combination of a statin and a PCSK9 inhibitor,” said Giugliano.

Speaking with the media, Giugliano said they also analyzed the safety of treatment. Overall, serious adverse events (SAEs) occurred in 6,106 patients, with less than 4% of all patients having an event that led to drug discontinuation. They saw no differences in SAEs based on achieved LDL cholesterol levels. Specifically, there appeared to be no risk of new-onset diabetes, cataracts, neurocognitive events, malignancy, or hemorrhagic stroke, among others.

“[Event rates] were really extremely similar across the five groups of achieved LDL,” said Giugliano.

 

[everydayupsanddowns]

I think what would worry me is the whole ‘LDL is an essential component of every cell in the body’ thing.

I’ve read lots of stuff about inflammation in relation to atherosclerosis which would be the basis of my approach I think, rather than trying to drive down LDL to ultra-low levels. This may be because I have an acquaintance on another forum with very high total chol, but who has been scanned and found to have no atherosclerosis (of course... one person... plural of anecdote is not anecdata etc etc)

Good luck with your quest, and I hope it gives you the results you are after.

 

[Eddy Edson]

I think what would worry me is the whole ‘LDL is an essential component of every cell in the body’ thing.

I’ve read lots of stuff about inflammation in relation to atherosclerosis which would be the basis of my approach I think, rather than trying to drive down LDL to ultra-low levels. This may be because I have an acquaintance on another forum with very high total chol, but who has been scanned and found to have no atherosclerosis (of course... one person... plural of anecdote is not anecdata etc etc)

Good luck with your quest, and I hope it gives you the results you are after.

Thankee! Nothing is certain, obviously, but just from my digging, every recent study I've found fails to find any harms from ultra-low LDL. Eg: https://www.ncbi.nlm.nih.gov/pubmed/28295777

Even at extremely low LDL-C levels, critical capacities of steroid hormone and bile acid production are preserved, and the presence of a cholesterol blood-brain barrier protects cells in the central nervous system. Apparent relationships sometimes reported between less pronounced low LDL-C levels and disease states such as cancer, depression, infectious disease and others can generally be explained as secondary phenomena. Drug-related side effects including an increased propensity for development of type 2 diabetes occur during statin treatment, whilst further evaluation of more potent LDL-lowering treatments such as PCSK9 inhibitors is needed. Experience from the recently reported and ongoing large event-driven trials are of great interest, and further evaluation including careful analysis of cognitive functions will be important.

I don't know enough about inflammation, but I would note that some of the atherosclerosis regression studies point to a combination of LDL lowering and HDL increase, the latter partly based on anti-inflammatory properties.

And statins of course have strong anti-inflammatory properties and again the studies point to these as being perhaps more important in reducing adverse events, compared to the atherosclerosis regression effects of strong LDL reduction. So it all seems to converge on upping statin dosage as something worth trying, for me.

 

[AndBreathe]

@Eddy Edson - have you watched any of the Professor Sikaris presentations on YouTube a thread all?

I found him and his presentations t be incredibly informative, and whilst he is clearly highly educated in the field, his explanations are clear and I found them easy to understand.

He has a few relevant presentations on YouTube, on when to worry about lipids, partical sized and also some on CVD.

I'm not making any comment on the paper you cite, except to say that 2006 is getting on a bit now and lipids seem much better understood these days.

Good luck with it all. Undoubtedly, you have already done the most important hing of ll form your cardiovascular health and stopped smoking.

I have never smoked, but I understand it can be an incredibly hard thing to give up, so well done from me.

 

[Eddy Edson]

have never smoked, but I understand it can be an incredibly hard thing to give up, so well done from me.

Thanks, but I really can't claim any credit, much as I'd like to. I've simply replaced cig addiction with vaping addiction. It's a zillion times better for me, I'm sure, but the real test of resolve will be cutting out nicotine completely ...

 

[Northerner]

Thanks, but I really can't claim any credit, much as I'd like to. I've simply replaced cig addiction with vaping addiction. It's a zillion times better for me, I'm sure, but the real test of resolve will be cutting out nicotine completely ...

When I stopped smoking there was no such thing as vaping. I had smoked for 20 years and wanted to stop, and saw a documentary on the TV about a guy called Allen Carr. This was on a Friday evening - I bought his book the following day and read it over the weekend. I last had a cigarette 24 years ago, on that Sunday! The difficulty wasn't so much giving up the nicotine, which takes about a month to break, but the habit and process of smoking - something to do with my hands etc. So, vaping wouldn't have really helped me, except by removing a lot of the toxins from my habit - I would still be controlled by nicotine, which is what I really needed to break, and I'd still be spending money and remain dependent on access to a 'cigarette'

 

[Eddy Edson]

So, vaping wouldn't have really helped me, except by removing a lot of the toxins from my habit - I would still be controlled by nicotine, which is what I really needed to break, and I'd still be spending money and remain dependent on access to a 'cigarette'

Yup. But the money saved by vaping is a really big factor too, hugely more than it would have been 20 yrs ago (here, at any rate).