HDL and cardiovascular risk - not for the feint of science

[CooSee]

Hey folks,

So most of us know that AAS can lower HDL, and we've been told low HDL is bad, especially if it's in a worse ratio than 1:5 to LDL. What no one I've found talks about, including any of the smart youtubers these days including the doctors who talk about AAS, is this question: If low endogenous T is pretty well associated with higher cardiovascular disease (CVD), then isn't it confusing and a bit contradictory that exogenous AAS would increase risk of CVD? In other words, the exogenous AAS is giving us higher androgens, so shouldn't that reduce CVD risk because it puts our body in the opposite state of what is known to have a high correlation with CVD? Well, I've thought a lot about this topic, so I've wondered, what if the presence of high androgens in the body actually was instead of "forcing" HDL down, was actually "allowing it to go down" due to the fact that the HDL particles were becoming more effective somehow due to the presence of high androgens. As a TRT guy for 10 years, and occasional blaster of T around 500mg or so, I've seen HDL go as low as 18. But my heart feels excellent in all cases. Whereas when I was a teen / 20's with low T and AAS-free, my heart often felt like shit when I would run or do anything.

I know it's a long and intense write-up, but for those who have time, I wanted to share this link because I finally google'd "Why does testosterone lower HDL?" (we usually just hear people answering the question "does testosterone lower HDL?", and the unequivocal answer is yes. So read the whole thing if you want, but if you want to skip to the part that got me excited and wishing more research would be done, and motivated to ask my Doc to do a particle level test on HDL and LDL, skip to the section "Testosterone and lipids", first paragraph, sentence six. Other good sentences are section "Testosterone and lipids" paragraph two, row 10 and 11, and the really big one that actually supports the theory I outlined above is paragraph three, rows 5-8. They say "Interestingly, in-vitro findings suggest that T could accelerate reverse cholesterol transport [53], and it has been suggested that reductions in HDL-c caused by TRT actually could reflect this accelerated process [54]. This raises the possibility that these reductions in HDL-c do not confer increased CVD risk at all and conceivably could reflect a protective effect."

An update on testosterone, HDL and cardiovascular risk in men

Testosterone prescriptions have risen steadily and sharply in the USA despite a lack of clear understanding of the relationship between androgens and cardiovascular disease. In men with increasing age, testosterone levels decline and cardiovascular disease ...

www.ncbi.nlm.nih.gov

This person is saying that the exogenous T is making our HDL more effective, so we don't need as much / many of them!

What do you all think?

 

[PeterBond]

My two cents. They might suggest it, but there's little proof for it. There are quite some studies which suggest the decrease in HDL cholesterol is the result of increased hepatic lipase activity. It's an enzyme that liberates fatty acids from lipids that are part of lipoproteins, including HDL particles. This decreases the fraction of the larger HDL2 particles and increases the fraction of the smaller HDL3 particles, the latter of which are broken down at a higher rate. Consequently you see a drop in HDL cholesterol.

Importantly, they're refering to in vitro research. There have been 2 prospective trials since then that have evaluated HDL cholesterol efflux capacity and HDL cholesterol levels in men receiving testosterone. Let me just copy/paste here from my book:

The crux here is that there doesn't appear to be a connection between the two.

Moreover, there's a cross-sectional trial in AAS users which showed a decrease in efflux capacity, and a marked decrease in HDL cholesterol. Also not in line with the hypothesis that the decrease in HDL cholesterol is the result of increased efflux capacity: Diminished cholesterol efflux mediated by HDL and coronary artery disease in young male anabolic androgenic steroid users - PubMed

This is not to say that the decrease in HDL cholesterol is bad per se. These levels are difficult to translate to changes in cardiovascular disease risk when they're altered by drugs. Pharmacologically increasing HDL cholesterol doesn't appear to impact cardiovascular disease risk, so the inverse doesn't necessarily need to hold true either. AAS users are likely at an increased risk of cardiovascular disease regardless, as there are of course other factors impacting this risk too.

 

[CooSee]

@PeterBond thank you for sharing that! A lot of this is new for me, e.g. I didn't know what Cholesterol Efflux Capacity (CEC) was until I just read up after seeing you refer to it. I guess other things that we don't yet understand, in addition to the ratio of HDL to LDL, and triglycerides, and vLDL can be factors too. As I look at my 12 lipid tests over the last 8 years, I do see that the the two times I stopped my TRT (once to see if I could get spermatogenesis to occur naturally b4 getting married and the second time for the actual conception - so both were 3+ months), even though my HDL came up to 38 and 41, LDL would went up too, so the ratio remained around 1:2 like it is now, with my lower HDL in the 20's. The thing that confuses me the most at this point is that, as you said, several studies have shown that raising HDL doesn't even itself conclusively reduce CVD.


So questions I have then (if you cover this in your book, maybe that's enough to motivate me to buy it):
1. Is the HDL particle function test going to give me any incrementally valuable information?
2. Given we don't have clear conclusions and we (me) want to continue using T, is the wise course of action to just do my first coronary calcium score and LVH tests now (at 36 y.o.) and let that be a guide for what kind of deleterious effects exo. T is having (if any) ?

 

[PeterBond]

1. Not that I know of. I discuss this only briefly in my book. There's some evidence indicating that measuring the HDL2 fraction has a stronger predictive power of cardiovascular disease risk than the HDL3 fraction or total HDL cholesterol: High-density lipoprotein subfractions--what the clinicians need to know - PubMed However, there's insufficient evidence to let this guide treatment. (Nor is there for total HDL cholesterol due to lack of an effect on cardiovascular disease risk of pharmacologically increasing it.)
2. Coronary calcium scores are almost always 0 or practically 0 in otherwise healthy individuals under the age of 40. Even in overweight folks who hardly exercise the score is commonly 0. They're largely useless in this context and I'm unsure if they hold predictive power beyond the usual markers that are used for risk assessment below that age. Below the age of 40 the risk of cardiovascular disease is so low that it's very very difficult to get statistically significant results from trials with this.

I'd simply follow the regular guidelines with regard to LDL cholesterol treatment, hypertension treatment and an annual echo of the heart to monitor changes in structure and function.

 

[OmL]

I like the dumbed down version for myself;

LDL takes cholesterol into the arteries. HDL takes cholesterol out of the arteries.
If Cholesterol stays there it hardens.

 

[Youngrobert1]

Good stuff @PeterBond

 

[CooSee]

1. Not that I know of. I discuss this only briefly in my book. There's some evidence indicating that measuring the HDL2 fraction has a stronger predictive power of cardiovascular disease risk than the HDL3 fraction or total HDL cholesterol: High-density lipoprotein subfractions--what the clinicians need to know - PubMed However, there's insufficient evidence to let this guide treatment. (Nor is there for total HDL cholesterol due to lack of an effect on cardiovascular disease risk of pharmacologically increasing it.)
2. Coronary calcium scores are almost always 0 or practically 0 in otherwise healthy individuals under the age of 40. Even in overweight folks who hardly exercise the score is commonly 0. They're largely useless in this context and I'm unsure if they hold predictive power beyond the usual markers that are used for risk assessment below that age. Below the age of 40 the risk of cardiovascular disease is so low that it's very very difficult to get statistically significant results from trials with this.

I'd simply follow the regular guidelines with regard to LDL cholesterol treatment, hypertension treatment and an annual echo of the heart to monitor changes in structure and function.

Awesome, this all makes sense. I'll probably do the HDL particle test just since it's cheap with Labcorp in the US. I'm surprised but glad to know that a calcium score would be basically useless at my age. Thankfully my BP even on 500mg T, 300D and 400Mast earlier this summer was regularly still around 125/75 - I imagine because of a really clean diet and careful with salt.
So your thought is that an echocardiogram might be the best test for folks in my age range? (aside from other bio markers like kidney, liver, lipids etc.) Is there a section in your book discussing how best to monitor various bodily functions over time while using - even if sparingly - AAS? BTW, I really enjoyed the write up on kidney functioning. I'm glad I don't pee out 26g of protein a day! (or any for that matter) as confirmed by my yearly urinalysis.

 

[PeterBond]

Yes, an annual echocardiogram would be recommendation for any chronic AAS user.

I don't have a section dedicated to that specifically, but in every section on a side effect I discuss treatment options (if any) and a recommendation to monitor (if useful). In the case of structural and functional cardiac changes here's my final words on it:

 

[Type-IIx]

Yes, an annual echocardiogram would be recommendation for any chronic AAS user.

I don't have a section dedicated to that specifically, but in every section on a side effect I discuss treatment options (if any) and a recommendation to monitor (if useful). In the case of structural and functional cardiac changes here's my final words on it:
View attachment 151708

Aside from reading that in your book and hearing from reasonably intelligent people that VLDL and apolipoprotein B are what you should definitely be concerned with, I don't know much else about this topic.

 

[CooSee]

Yes, an annual echocardiogram would be recommendation for any chronic AAS user.

I don't have a section dedicated to that specifically, but in every section on a side effect I discuss treatment options (if any) and a recommendation to monitor (if useful). In the case of structural and functional cardiac changes here's my final words on it:
View attachment 151708

Great to know. I’ve always wondered, if we can say that basically all AAS users lift really heavy weight and subject our hearts to high pressure moments over and over - is it the AAS, or the the act of lifting heavy ass weight and that physical, momentary spike in blood pressure that happens on the hard part of completing a lift that actually causes the LVH. In other words, have studies ever looked at long term extreme weight lifters who don’t use AAS to see if their ventricles hypertrophy too? (Does anyone lift really heavy weight for a long time and not eventually use AAS?). Or similarly, what if someone took lots of AAS and didn’t lift heavy weight - would the LVH happen?

 

[PeterBond]

Great to know. I’ve always wondered, if we can say that basically all AAS users lift really heavy weight and subject our hearts to high pressure moments over and over - is it the AAS, or the the act of lifting heavy ass weight and that physical, momentary spike in blood pressure that happens on the hard part of completing a lift that actually causes the LVH. In other words, have studies ever looked at long term extreme weight lifters who don’t use AAS to see if their ventricles hypertrophy too? (Does anyone lift really heavy weight for a long time and not eventually use AAS?). Or similarly, what if someone took lots of AAS and didn’t lift heavy weight - would the LVH happen?

There are several indications to assume it really is the AAS causing it. While it is true that athletes, and especially those that engage in strength sports, have thicker left ventricular walls, the studies show some marked differences.

One is that there's commonly a disproportionate increase in the septal thickness vs. the LV posterior wall thickness. This is something that's not seen (or definitely not to the same extent) in AAS-free athletes, and it's an observation that's usually seen in certain diseases. (A confounder with these trials is that I'm doubtful that all the athletes in the AAS-free groups are indeed 100% AAS free. This skews results a bit.)

Another reason is that there have been various cross-sectional studies which compared AAS users to non-AAS users which also engaged in strength sports with similar intensity. The only difference often being a few kilograms of body mass and some less strength. Those small differences wouldn't account for the relatively large differences in thickness that is seen.

Yet another reason is that functional parameters are also affected. Parameters indicative of diastolic function often show a decrease, as well as systolic function (most evidently: a reduction in ejection fraction). This is something that absolutely does not happen in non-AAS using athletes.

But perhaps most importantly: these changes occur rather rapid when using AAS. A recent prospective trial, called the HAARLEM trial (unpublished results), demonstrated marked changes in cardiac structure and function over the time course of a single AAS cycle. And, consequently, most trials show these changes to be (at least partially) reversible within months after cessation.

 

[PeterBond]

There's an article pending for Meso in which I cover the effects of anabolic steroids on cardiac structure and function. I suspect @Millard will publish it somewhere this month. It also includes (as for now unpublished) results from the HAARLEM trial.

 

[OmL]

Thanks for looking out for us, Bond, Peter Bond.

 

[CooSee]

There's an article pending for Meso in which I cover the effects of anabolic steroids on cardiac structure and function. I suspect @Millard will publish it somewhere this month. It also includes (as for now unpublished) results from the HAARLEM trial.

Awesome !

 

[CooSee]

There are several indications to assume it really is the AAS causing it. While it is true that athletes, and especially those that engage in strength sports, have thicker left ventricular walls, the studies show some marked differences.

One is that there's commonly a disproportionate increase in the septal thickness vs. the LV posterior wall thickness. This is something that's not seen (or definitely not to the same extent) in AAS-free athletes, and it's an observation that's usually seen in certain diseases. (A confounder with these trials is that I'm doubtful that all the athletes in the AAS-free groups are indeed 100% AAS free. This skews results a bit.)

Another reason is that there have been various cross-sectional studies which compared AAS users to non-AAS users which also engaged in strength sports with similar intensity. The only difference often being a few kilograms of body mass and some less strength. Those small differences wouldn't account for the relatively large differences in thickness that is seen.

Yet another reason is that functional parameters are also affected. Parameters indicative of diastolic function often show a decrease, as well as systolic function (most evidently: a reduction in ejection fraction). This is something that absolutely does not happen in non-AAS using athletes.

But perhaps most importantly: these changes occur rather rapid when using AAS. A recent prospective trial, called the HAARLEM trial (unpublished results), demonstrated marked changes in cardiac structure and function over the time course of a single AAS cycle. And, consequently, most trials show these changes to be (at least partially) reversible within months after cessation.

This is really making me think. I have to say, I still think that in point number one, it could still be the increased level of intensity that coincides with AAS users (the psychographic of people willing to use AAS is the same psychographic of folks who are going to mentally push themselves far more intensely - thats just my opinion though) that causes the septic thickness deltas.

for point two, they would have also had to look at the amount of weight these folks are moving / maxing to solve for whether the AAS users simply may have been maxing much heavier therefore impacting the heart more. AAS users could have been lifting 10% more weight and had 10% thicker walls, no?

for point three, again thinking of non AAS users using less weight and less intensity, that could be the explanation there.

for four, have we looked at whether it happens quickly with non AAS users lifting similar weights? It could be that it happens quickly whether AAS is present or not, if weight movement levels are the same.

just trying to play devil’s advocate on those few since they strike me as a little suggestive but not a lot without answering some more questions.

 

[Type-IIx]

This is really making me think. I have to say, I still think that in point number one, it could still be the increased level of intensity that coincides with AAS users (the psychographic of people willing to use AAS is the same psychographic of folks who are going to mentally push themselves far more intensely - thats just my opinion though) that causes the septic thickness deltas.

for point two, they would have also had to look at the amount of weight these folks are moving / maxing to solve for whether the AAS users simply may have been maxing much heavier therefore impacting the heart more. AAS users could have been lifting 10% more weight and had 10% thicker walls, no?

for point three, again thinking of non AAS users using less weight and less intensity, that could be the explanation there.

for four, have we looked at whether it happens quickly with non AAS users lifting similar weights? It could be that it happens quickly whether AAS is present or not, if weight movement levels are the same.

just trying to play devil’s advocate on those few since they strike me as a little suggestive but not a lot without answering some more questions.

Nah. While heavy loading can cause some adaptive changes in cardiac muscle, decades of empirical evidence demonstrates AAS users dropping dead from cardiac events while the naturally stronger non-AAS users live healthy, long lives. Aside from the mountains of empirical evidence, scientists (and Peter Bond would be very knowledgeable on this) understand the mechanisms of androgens (and beta-2 adrenergic agonists, another class used/abused frequently) causing cardiac hypertrophy. Here's an unpopular opinion: usually it's the guys with less talent that abuse AAS, while there are non-AAS users that adapted to heavier loading and are by and large healthy by comparison.

 

[Millard]

There's an article pending for Meso in which I cover the effects of anabolic steroids on cardiac structure and function. I suspect @Millard will publish it somewhere this month.

It's online now:

The Effects of Anabolic Steroids on the Heart's Structure and Function

Perhaps one of the most worrying side effects of prolonged anabolic steroid use are those related to the heart. Indeed, a startling amount of case reports

thinksteroids.com

 

[CooSee]

It's online now:

The Effects of Anabolic Steroids on the Heart's Structure and Function

Perhaps one of the most worrying side effects of prolonged anabolic steroid use are those related to the heart. Indeed, a startling amount of case reports

thinksteroids.com

I just finally got around to reading that write up. Thank you for that. It's the most clear articulation of the association I've seen. I do still think there's a chance the walls get thicker due to the roids making folks stronger. For example, 10% higher weight resistance on average (very realistic strength increase for 900mg), could put more pressure on the heart during lifts, thickening the wall more than the natural bodybuilder who is moving less weight. I'm surprised they let the wall thickness measurers know what group they were measuring. And I wish they would do this again and solve for the amount of weight folks are moving. In this case then yes roids would cause the thickening, but not due to chemical reaction, but indirectly from their causing the user to be stronger.

 

[PeterBond]

The thing is that the changes in cardiac function (e.g. decrease in E/A ratio, ejection fraction, strain rate) are not seen in strength athletes who don't use AAS, but whom are strong regardless. This includes Olympic athletes who compete in wrestling and weight lifting. (And even in them the changes in wall thickness aren't even close to what is seen in AAS users in these studies.)

If an increase in strength would cause these changes, you would see a decrease in cardiac function and increase in wall thickness parallel to increases in strength in natural athletes too. This is not the case. If it actually was the case, this change would be especially pronounced in people who just start lifting, as both their relative and absolute increases in strength are very big over a small scale of time. Definitely a lot bigger than just a single AAS cycle would cause, as seen in the HAARLEM trial for example.

 

[CooSee]

"you would see a decrease in cardiac function and increase in wall thickness parallel to increases in strength in natural athletes too."
>> "Having said that, the left ventricular septal thickness was 13.7, 12.4, and 9.2 mm in the AAS-using bodybuilders, non-AAS-using bodybuilders, and inactive control group, respectively.

It sounds like the HAARLEM data (did they have to use that name acronym god it makes me think of the city and the globe trotters every time) does suggest changes in ejection fraction and E/A ratio.

In the two quotes from you above, I'm trying to understand, does the 2nd one say that the thickness of non-AAS lifters was 12.4 and the inactive control was 9.2? That feels to me like the 33% (big) difference we'd expect to see when one goes from not lifting at all to lifting (9.2 up to 12.4), while the 12.4 to 13.7 feels like the ~10% delta that non AAS to AAS might convey if caused by the increase in weight/resistant loads that AAS users are able to subject their heart to. I could be understanding this totally wrong, but as it sits in my mind right now, this does jive a bit with the possibility that the heart changes are because of the resistance increase, not the presence of the hormone or chemical....?

I see the attention these studies are paying to "does AAS affect the heart?" and making some probably true correlations. Has anyone mused on an answer to "why does AAS affect the heart"?