NeuroRN
ICU nurse/Moderator
**DISCLAIMER: 1. This is long. I’m sorry but I fell down the rabbit hole and pulled from my own research and found a few other forums discussing the very same thing. 2. I’m no doctor, I didn’t stay at a holiday inn express, BUT the majority of my career has been spent in cardiac ICU’s from open heart to transplant to cardiac caths. And I’ve seen my fair share of old school body builders after years of AAS albeit at abusive levels.
Bystolic (nebivolol) is a third generation cardio selective blocker.
Meaning, it only acts on beta-1 receptor sites (found primarily in the heart and some in the kidneys) and leaves the beta-2 receptors in the lungs alone (important info for those who suffer/have suffered from asthma) and blocking beta-2 receptors is what most often leads to the unwanted erectile dysfunction as well as other negative metabolic impacts Though it would appear that in the case of carvedilol, insulin sensitivity is not negatively impacted. In fact, a recent study found carvedilol and nebivolol to have almost identical effects on blood pressure and metabolic markers:
Results:
Blood pressure and heart rate were significantly and similarly reduced in the carvedilol and nebivolol groups after treatment compared to those before treatment (both P < .001). Serum glucose (P < .001), insulin (P < .01), HOMA-IR (P < .01), HDL (P < .001), LDL (P < .001), total cholesterol (P < .001), and apolipoprotein B (P < .05) levels decreased in a similar manner in the carvedilol and nebivolol groups after treatment compared to those before treatment. Serum triglyceride and apolipoprotein AI levels did not change after treatment with both drugs.
Conclusion:
New generation beta-blockers, carvedilol and nebivolol, efficiently and similarly decrease blood pressure. They have similar favorable effects on glucose, insulin, IR, and the lipid profile.
https://journals.sagepub.com/doi/full/10.1177/1074248416644987
Carvidolol is not selective and will most likely cause some issues with the man downstairs.
My focus here is on preventative health and wellness. If you are already suffering from severe hypertension and or heart failure their may be better drugs out there suited to your needs. However, nebivolol + telmisartan is currently one of the most prescribed combos for those suffering from essential hypertension.
How does AAS negatively impact our cardiovascular health?
While acute administration of testosterone seems to decrease vascular tone, the long-term net effect of androgens appears to be vasoconstriction via upregulation of thromboxane A2 expression, norepinephrine synthesis, angiotensin II expression, and endothelin-1 action. Furthermore, androgens cause cardiac hypertrophy, promote atherosclerosis, vascular remodelling and stimulate renal prohypertensive processes involving the renin-angiotensin-aldosterone system. Androgens seem to promote oxidative stress in the kidney and may also play a role in the differentiation of brain areas involved in blood pressure regulation.
pubmed.ncbi.nlm.nih.gov
We have 4 channels through which AAS exert negative effects on the cardiovascular system, causing damage to blood vessels, heart, and kidneys. Let’s look at each in turn:
1) thromboxane A2
2)norepinephrine
Luckily, the ‘fix’ for this is fairly easy as well. An Angiotensin receptor blocker such as Telmisartan should be able to bring Angiotensin activity back to normal. Of course, ARBs/ACEs are also beneficial in hypertensive people who do not use AAS. It’s just that for AAS users with or without pathological hypertension it is even more crucial.
Hello, my old friend Telmisartan
4) endothelin-1
Cardiac Hypertrophy. We know the Left ventricle is enlarged in most all those who lift weights, however we see even more increased size in those that use AAS.
The heart is capable of growing and shrinking in size in response to the amount of stress it is faced with. Doctors distinguished between 2 types of cardiac hypertrophy: 1) Physiological growth in response to normal stressors such as exercise, pregnancy, and increased muscle mass. 2) Pathological growth due to stressors such as neurohumoral* activation, hypertension, and myocardial injury
www.ncbi.nlm.nih.gov
As shown in the right panel of the figure below, a physiological adaptation to exercise (and pregnancy) consists of proportional growth in the different constituents of the heart. Specifically, the growth of the ventricle (the chamber containing blood before being pumped out) is similar to the growth in the left-ventricular wall (the muscle that pumps the blood out of the chamber).
Some more info on athlete’s heart: Note that the condition mostly is present in people who do a lot of aerobic exercise (endurance sports), and only to a lesser degree in (natural) weightlifters and bodybuilders.
2) Pathological growth
Let’s say the pathological growth is caused by someone being overweight, bloated and hypertensive. In order to deal with the higher blood pressure and blood volume, the heart’s muscle, i.e. the ventricular wall, thickens, whereas the ventricle itself (the chamber) does not change in size or even shrinks. this condition is referred to as concentric hypertrophy, and depicted in the middle panel of the figure above. Initially, this growth response is compensatory in nature, i.e. it serves to maintain the heart’s function in the face of a new stressor.
As mentioned above, individual’s who do resistance exercise (i.e. bodybuilders) have a somewhat different pattern of cardiac hypertrophy than endurance athletes. In fact, the adaptations in bodybuilder’s hearts is more similar to the concentric hypertrophy (which is usually considered pathological):
The thing is, though, that 99% of patients who have concentric hypertrophy are not weightlifters, but are rather people with systemic blood pressure and/or past cardiac events. of course the medical profession is gonna focus on these people in their research and definitions. In any case, a non-athlete with concentric hypertrophy is a completely different case. First, the thickening of the ventricular wall can be much more severe in these patients, and given their typically unhealthy lifestyle and nutrition, the body cannot keep up with the required growth of the myocardium. One aspect of that is insufficient blood flow:
AAS and cardiac hypertrophy
There are 3 possible reasons for the observation that concentric hypertrophy is physiological in weightlifters but develops into decompensated (pathological) hypertrophy in most hypertensive patients.
A)
i) AAS increase hypertension through various channels (see first post), leading to concentric hypertrophy
ii) The increased lean body mass from AAS use increases blood volume, leading to mostly eccentric hypertrophy
iii) increased training volume and frequency mean more frequent blood pressure spikes and thus contribute to concentric hypertrophy
B)
Via its upregulation of Angiotensin II, AAS increase the likelihood of fibrotic changes to the myocardium, especially in the presence of hypertrophy.
C)
AAS have a direct impact on myocyes and promote their growth. Thus, for a given stressor, AAS could increase the myocyte growth rate compared to a natural individual.
Similarly, the effects of AAS on Angiotensin II and thereby fibrosis are something than can me ameliorated.
The direct growth stimulation of cardiomyocytes via the androgen receptor is, however, not something that we can do much about. It is reasonable to assume that for a given level of stressors, the anabolic action of AAS on myocytes will produce a greater growth response compared to natural athletes. So on average, the left (and to some extent right) ventricular wall of an AAS user will be larger than that of a natural athlete, even if blood pressure is controlled for.
Whether this increased size of the myocardium in AAS users is a problem is hard to say. If vascularization is sufficient, then in principle the increased size of the myocardium should not impair its functioning, especially since we control blood pressure so that the stressors only consists of higher blood volume and intermittent blood pressure spikes, which tend not to produce pathological adaptations.
However, we cannot expect that the blood supply will keep up with the myocyte growth, especially if the growth is sped up due to AAS.
How does a beta-blocker help
Simple. The slower heart rate allows for more filling time of the ventricles, resulting in less force and frequency needed to pump the blood out to the rest of the body.
Why Nebivolol and not another cardioselective beta blocker like atenolol?
As it turns out, Nebivolol has powerful vasodilating effects which among other things contributes to its ability to lower blood pressure. Thus, for a given level of blood pressure reduction, Nebivolol will require less beta blockage in the heart, thereby maintaining exercise capacity:
Patients treated with beta-blocking agents often complain of fatigue during exercise. Exercise capacity is decreased under this condition. Nebivolol is a new beta 1-adrenoceptor antagonist with a particular hemodynamic profile, which might be due to an ancillary property. Five milligrams once daily seems the optimal dose for antihypertensive treatment. In a double-blind, placebo-controlled crossover study, the effects of nebivolol on maximal and endurance exercise capacity are compared with those of atenolol in healthy volunteers. The hemodynamic and metabolic effects during exercise are also studied. Nebivolol 5 mg once daily and atenolol 100 mg once daily decrease blood pressure at rest similarly. At these dosages nebivolol shows a smaller decrease in heart rate than atenolol. During exercise, the rise in systolic blood pressure and heart rate is less depressed with nebivolol than with atenolol. In contrast to atenolol, nebivolol does not decrease maximal and endurance exercise capacity, and does not increase perceived exertion significantly Changes in hemodynamics influence maximal exercise capacity. Since nebivolol has less effect on exercise hemodynamics than atenolol, this might explain why maximal work capacity is not changed during nebivolol. During endurance exercise metabolic effects are thought to be more important. Under nebivolol glycerol and NEFA production is less depressed during exercise and might explain the preserved endurance capacity. These data suggest less beta blockade during nebivolol than during atenolol at the dosages used in this study. In conclusion, at a dose known to be antihypertensive, nebivolol does not alter exercise capacity significantly in healthy volunteers.
pubmed.ncbi.nlm.nih.gov
Takeaway:
Bystolic blocks beta-1, lowers heart rate increasing ventricle filling time, lessens the effects of norepinephrine synthesis of the heart, and lowers BP by increasing nitric oxide content cause vasodilation.
Nitric oxide increases our pumps and vascularity. As well as our erectile strength. (Anabolic doc swears by this effect, I don’t agree with him on a lot of things but this makes a lot of sense to me.
Now as far as what other benefit does this bring us? @Aude_Aliquid_Dignu
If you are someone with a low resting heart rate, but hypertensive I’d say start with an ARB preferably telmisartan. It has more overall lifestyle and health benefits on its own.
If you are someone with a high resting heart rate, with or without hypertension Bystolic may be for you. We see improved lipid profile, increase insulin sensitivity, and defense against cardiac Hypertrophy.
If telmisartan isn’t cutting it for you with BP control, low dose telmisartan and Bystolic is a go to in BP control and the combo seems to block the gambit of negative health consequences we see from AAS use.
Minor points:
Bystolic (nebivolol) is a third generation cardio selective blocker.
Meaning, it only acts on beta-1 receptor sites (found primarily in the heart and some in the kidneys) and leaves the beta-2 receptors in the lungs alone (important info for those who suffer/have suffered from asthma) and blocking beta-2 receptors is what most often leads to the unwanted erectile dysfunction as well as other negative metabolic impacts Though it would appear that in the case of carvedilol, insulin sensitivity is not negatively impacted. In fact, a recent study found carvedilol and nebivolol to have almost identical effects on blood pressure and metabolic markers:
Results:
Blood pressure and heart rate were significantly and similarly reduced in the carvedilol and nebivolol groups after treatment compared to those before treatment (both P < .001). Serum glucose (P < .001), insulin (P < .01), HOMA-IR (P < .01), HDL (P < .001), LDL (P < .001), total cholesterol (P < .001), and apolipoprotein B (P < .05) levels decreased in a similar manner in the carvedilol and nebivolol groups after treatment compared to those before treatment. Serum triglyceride and apolipoprotein AI levels did not change after treatment with both drugs.
Conclusion:
New generation beta-blockers, carvedilol and nebivolol, efficiently and similarly decrease blood pressure. They have similar favorable effects on glucose, insulin, IR, and the lipid profile.
https://journals.sagepub.com/doi/full/10.1177/1074248416644987
Carvidolol is not selective and will most likely cause some issues with the man downstairs.
My focus here is on preventative health and wellness. If you are already suffering from severe hypertension and or heart failure their may be better drugs out there suited to your needs. However, nebivolol + telmisartan is currently one of the most prescribed combos for those suffering from essential hypertension.
How does AAS negatively impact our cardiovascular health?
While acute administration of testosterone seems to decrease vascular tone, the long-term net effect of androgens appears to be vasoconstriction via upregulation of thromboxane A2 expression, norepinephrine synthesis, angiotensin II expression, and endothelin-1 action. Furthermore, androgens cause cardiac hypertrophy, promote atherosclerosis, vascular remodelling and stimulate renal prohypertensive processes involving the renin-angiotensin-aldosterone system. Androgens seem to promote oxidative stress in the kidney and may also play a role in the differentiation of brain areas involved in blood pressure regulation.
Testosterone and blood pressure regulation - PubMed
The effects of sex steroids on different parts of the renal-vascular system are complex and often contradictory. In sum, net effects of androgen action seem to be vasoconstriction, atherosclerosis and stimulation of the renin-angiotensin-aldosterone system. Therefore, androgens may determine...
pubmed.ncbi.nlm.nih.gov
We have 4 channels through which AAS exert negative effects on the cardiovascular system, causing damage to blood vessels, heart, and kidneys. Let’s look at each in turn:
1) thromboxane A2
So how can we remedy the AAS induced upregulation of Thromboxane A2? Based on the information above, a baby aspirin every day should suffice. There are cardiovascular health benefits of aspirin in non-enhanced people, but it seems that for AAS users it is even more important. if you have known GI BLEEDS or any other clotting cascade disorders I would recommend staying away from aspirin
2)norepinephrine
3) angiotensin II
The second study in particular shows that AAS induced changes in Angiotensin are probably the biggest contributing factor to cardiac hypertrophy and fibrosis. The first study suggests that the mechanism of action is an potentiation of Angiotensin II action in the heart and kidneys.
Luckily, the ‘fix’ for this is fairly easy as well. An Angiotensin receptor blocker such as Telmisartan should be able to bring Angiotensin activity back to normal. Of course, ARBs/ACEs are also beneficial in hypertensive people who do not use AAS. It’s just that for AAS users with or without pathological hypertension it is even more crucial.
Hello, my old friend Telmisartan
4) endothelin-1
what are our other cardiac concerns with weightlifting and AAS?
Cardiac Hypertrophy. We know the Left ventricle is enlarged in most all those who lift weights, however we see even more increased size in those that use AAS.
The heart is capable of growing and shrinking in size in response to the amount of stress it is faced with. Doctors distinguished between 2 types of cardiac hypertrophy: 1) Physiological growth in response to normal stressors such as exercise, pregnancy, and increased muscle mass. 2) Pathological growth due to stressors such as neurohumoral* activation, hypertension, and myocardial injury
- Neurohumoral activation refers to increased activity of the sympathetic nervous system, renin-angiotensin system, vasopressin and atrial natriuretic peptide.
New frontiers in heart hypertrophy during pregnancy - PMC
During Pregnancy, heart develops physiological left ventricular hypertrophy as a result of the natural volume overload. Previously we have characterized the molecular and functional signature of heart hypertrophy during pregnancy. Cardiac ...
www.ncbi.nlm.nih.gov
As shown in the right panel of the figure below, a physiological adaptation to exercise (and pregnancy) consists of proportional growth in the different constituents of the heart. Specifically, the growth of the ventricle (the chamber containing blood before being pumped out) is similar to the growth in the left-ventricular wall (the muscle that pumps the blood out of the chamber).
Some more info on athlete’s heart: Note that the condition mostly is present in people who do a lot of aerobic exercise (endurance sports), and only to a lesser degree in (natural) weightlifters and bodybuilders.
2) Pathological growth
(http://www.nejm.org/doi/full/10.1056/NEJMra072139)
Let’s say the pathological growth is caused by someone being overweight, bloated and hypertensive. In order to deal with the higher blood pressure and blood volume, the heart’s muscle, i.e. the ventricular wall, thickens, whereas the ventricle itself (the chamber) does not change in size or even shrinks. this condition is referred to as concentric hypertrophy, and depicted in the middle panel of the figure above. Initially, this growth response is compensatory in nature, i.e. it serves to maintain the heart’s function in the face of a new stressor.
As mentioned above, individual’s who do resistance exercise (i.e. bodybuilders) have a somewhat different pattern of cardiac hypertrophy than endurance athletes. In fact, the adaptations in bodybuilder’s hearts is more similar to the concentric hypertrophy (which is usually considered pathological):
So even though (natural) bodybuilders develop concentric hypertrophy, where only the wall increases in size while the ventricle stays the same, this has no negative effect on heart function. So what I would conclude from that is that concentric heart hypertrophy need not be considered pathological in and of itself.
The thing is, though, that 99% of patients who have concentric hypertrophy are not weightlifters, but are rather people with systemic blood pressure and/or past cardiac events. of course the medical profession is gonna focus on these people in their research and definitions. In any case, a non-athlete with concentric hypertrophy is a completely different case. First, the thickening of the ventricular wall can be much more severe in these patients, and given their typically unhealthy lifestyle and nutrition, the body cannot keep up with the required growth of the myocardium. One aspect of that is insufficient blood flow:
Such insufficient blood flow can lead to small areas of muscle to die (apoptosis), and/or lead to fibrotic changes in the structure of the muscle, impairing its function. Furthermore, we have learned before that chronic inflammation as well as activity of angiotensin II promote fibrotic changes in the myocardium, and your typical hypertension patient will have high levels of both (and compared to an in-shape weighlifter).
When such detrimental changes happen to someone with concentric hypertrophy, the ventricular wall’s pumping capacity deteriorates over time, leading to wall thinning. To compensate for the lower pumping power of the heart, the ventricle increases in size, which at first is once a gain beneficial in maintaining cardiac function. This situation can be described at eccentric hypertrophy (See left panel of figure). Eventually, volume becomes too large, and you end up with dilated cardiomyopathy.
AAS and cardiac hypertrophy
There are 3 possible reasons for the observation that concentric hypertrophy is physiological in weightlifters but develops into decompensated (pathological) hypertrophy in most hypertensive patients.
- The difference between the chronic stressor of hypertension and the intermittent stressor of exercise induced blood pressure spikes may be sufficient to explain why the former leads to degenerative changes in the ventricular wall, whereas the latter allows the myocardium to remain functional.
As an analogy, think of doing curls 24/7 without any weight in your hand. It may well be that the muscle damage induced by this is sufficiently low for your body to repair. But if you gradually increase the weights of a dumbell in that hand, then at some point, you are creating too much muscle damage for the body to repair properly. The micro tearing due to constant stretching and contraction will lead to excessive local inflammation and subsequent fibrosis. Even worse, the chronic inflammation may lead muscle cells to die in troves rather than be repaired. A similar situation may occur in the myocardium in response to the chronically elevated pressure due to hypertension. - It may be that the hypertrophy induced by hypertension is not different compared to that from resistance exercise, but the more chronic stimulus leads to more rapid and extensive growth. If the microvasculature were able to keep up with this higher growth, then the growth of the ventricular wall might be perfectly physiological. But as studies have shown, blood flow does typically not keep up with the growth of the myocardium in hypertensive patients, thereby leading to insufficient nutrient and oxygen delivery and subsequent cell death and scarring (fibrosis).
- It may be that the body would be perfectly able to deal with the growth induced by hypertension in the sense of having sufficient nutrient delivery to the muscle cells and a high enough ability to repair the micro damage induced by constant exertion against high pressure. The problem in the typical hypertensive patient would instead be the high levels of pro-fibrotic agents such as angiotensin II, as well as overactive systemic inflammation that attacks the damaged muscle cells in the heart.
- It may be a mix of the potential factors. That is, chronic pressure from hypertension is uniquely damaging even in the otherwise healthy individuals, neovascularization is generally insufficient if the growth of the myocardium is too fast and extensive, and pro-fibrotic and pro-inflammatory factors contribute towards pathological changes in the ventricular walls.
A)
i) AAS increase hypertension through various channels (see first post), leading to concentric hypertrophy
ii) The increased lean body mass from AAS use increases blood volume, leading to mostly eccentric hypertrophy
iii) increased training volume and frequency mean more frequent blood pressure spikes and thus contribute to concentric hypertrophy
B)
Via its upregulation of Angiotensin II, AAS increase the likelihood of fibrotic changes to the myocardium, especially in the presence of hypertrophy.
C)
AAS have a direct impact on myocyes and promote their growth. Thus, for a given stressor, AAS could increase the myocyte growth rate compared to a natural individual.
The indirect effect of AAS on hypertension can be controlled (See the first post), but the impact on blood volume and training intensity are not something that can or should be avoided in bodybuilders. So compared to a natural athlete, AAS users will face additional stressors that cause cardiac hypertrophy (which does not have to be pathological though).
Similarly, the effects of AAS on Angiotensin II and thereby fibrosis are something than can me ameliorated.
The direct growth stimulation of cardiomyocytes via the androgen receptor is, however, not something that we can do much about. It is reasonable to assume that for a given level of stressors, the anabolic action of AAS on myocytes will produce a greater growth response compared to natural athletes. So on average, the left (and to some extent right) ventricular wall of an AAS user will be larger than that of a natural athlete, even if blood pressure is controlled for.
Whether this increased size of the myocardium in AAS users is a problem is hard to say. If vascularization is sufficient, then in principle the increased size of the myocardium should not impair its functioning, especially since we control blood pressure so that the stressors only consists of higher blood volume and intermittent blood pressure spikes, which tend not to produce pathological adaptations.
However, we cannot expect that the blood supply will keep up with the myocyte growth, especially if the growth is sped up due to AAS.
Thus, supporting angiogenesis in the myocardium appears to be crucial in order to ensure that the AAS induced growth in the heart muscle is compensatory in nature and does not lead to pathological changes such as necrosis of areas with insufficient blood flow.
How does a beta-blocker help
Simple. The slower heart rate allows for more filling time of the ventricles, resulting in less force and frequency needed to pump the blood out to the rest of the body.
Why Nebivolol and not another cardioselective beta blocker like atenolol?
As it turns out, Nebivolol has powerful vasodilating effects which among other things contributes to its ability to lower blood pressure. Thus, for a given level of blood pressure reduction, Nebivolol will require less beta blockage in the heart, thereby maintaining exercise capacity:
Patients treated with beta-blocking agents often complain of fatigue during exercise. Exercise capacity is decreased under this condition. Nebivolol is a new beta 1-adrenoceptor antagonist with a particular hemodynamic profile, which might be due to an ancillary property. Five milligrams once daily seems the optimal dose for antihypertensive treatment. In a double-blind, placebo-controlled crossover study, the effects of nebivolol on maximal and endurance exercise capacity are compared with those of atenolol in healthy volunteers. The hemodynamic and metabolic effects during exercise are also studied. Nebivolol 5 mg once daily and atenolol 100 mg once daily decrease blood pressure at rest similarly. At these dosages nebivolol shows a smaller decrease in heart rate than atenolol. During exercise, the rise in systolic blood pressure and heart rate is less depressed with nebivolol than with atenolol. In contrast to atenolol, nebivolol does not decrease maximal and endurance exercise capacity, and does not increase perceived exertion significantly Changes in hemodynamics influence maximal exercise capacity. Since nebivolol has less effect on exercise hemodynamics than atenolol, this might explain why maximal work capacity is not changed during nebivolol. During endurance exercise metabolic effects are thought to be more important. Under nebivolol glycerol and NEFA production is less depressed during exercise and might explain the preserved endurance capacity. These data suggest less beta blockade during nebivolol than during atenolol at the dosages used in this study. In conclusion, at a dose known to be antihypertensive, nebivolol does not alter exercise capacity significantly in healthy volunteers.
Exercise tolerance with nebivolol and atenolol - PubMed
Patients treated with beta-blocking agents often complain of fatigue during exercise. Exercise capacity is decreased under this condition. Nebivolol is a new beta 1-adrenoceptor antagonist with a particular hemodynamic profile, which might be due to an ancillary property. Five milligrams once...
pubmed.ncbi.nlm.nih.gov
Takeaway:
Bystolic blocks beta-1, lowers heart rate increasing ventricle filling time, lessens the effects of norepinephrine synthesis of the heart, and lowers BP by increasing nitric oxide content cause vasodilation.
Nitric oxide increases our pumps and vascularity. As well as our erectile strength. (Anabolic doc swears by this effect, I don’t agree with him on a lot of things but this makes a lot of sense to me.
Now as far as what other benefit does this bring us? @Aude_Aliquid_Dignu
If you are someone with a low resting heart rate, but hypertensive I’d say start with an ARB preferably telmisartan. It has more overall lifestyle and health benefits on its own.
If you are someone with a high resting heart rate, with or without hypertension Bystolic may be for you. We see improved lipid profile, increase insulin sensitivity, and defense against cardiac Hypertrophy.
If telmisartan isn’t cutting it for you with BP control, low dose telmisartan and Bystolic is a go to in BP control and the combo seems to block the gambit of negative health consequences we see from AAS use.
Minor points:
- Because of its impact on norepi synthesis sometimes beta blockers are used as a treatment for anxiety with great success.
- Improved sleep quality is usually reported by users.
- Most beta blockers are banned by WDA because of its ability to increase cardiac output and dull the body’s fight or flight response. If you are tested as an athlete always check with your governing body.
- Consult your physician before starting a new medication.
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