Safety First
New Member
This is so sad. I am so happy you're making these kinds of posts. Honestly you're saving lives just educating people on what's out there.
MESO-Rx
Anabolic Steroids
AAS and Cardiovascular/Pulmonary Function
- Thread starter Michael Scally MD
- Start date
Old
New Member
It is doubtful that he was perfectly healthy with no heart or vascular issues 6 months earlier. Unless he was already lean by nature, it is doubtful that he lost so much subcutaneous fat in just 6 months as well.
Don't underestimate clenbuterol being a factor ... plenty die using such stimulants.
As for LVH, that is common enough for athletes even without ever touching an AAS. LVH can be cause by both aerobics as well as strength training. In those instances it is not normally considered life threatening.
[OA] Mechanisms of Testosterone Deficiency-Related Endothelial Dysfunction
Evidence from clinical studies suggests that patients with low testosterone levels are at increased cardiovascular disease risk. Even though the exact mechanisms remain poorly understood, a low plasma testosterone level is associated with a pro-atherogenic lipid profile, insulin resistance and increased levels of pro-inflammatory mediators and vascular dysfunction, which is typically observed in patients with hypogonadism.
Furthermore, recent evidence suggests that testosterone deficiency has also direct adverse effects on the endothelium and nitric oxide (NO) bioavailability. Observations from studies in patients with hypogonadal hypogonadism imply that the mechanisms of endothelial dysfunction related to testosterone deficiency may involve changes in asymmetric dimethylarginine (ADMA) levels, a known endogenous inhibitor of NO synthase.
Evidence suggests that testosterone replacement therapy is not only a safe but also an effective means to reduce atherosclerotic risk and reverse endothelial dysfunction in patients with hypogonadal hypogonadism. Further research in the field is expected to clarify whether changes in ADMA metabolism constitute the central mechanism through which a low testosterone level leads to endothelial dysfunction.
Antonopoulos AS, Antoniades C. Mechanisms of testosterone deficiency-related endothelial dysfunction: Invited commentary for the Hellenic Journal of Cardiology on: Tsikas et al. "Associations between asymmetric dimethylarginine, nitrite-dependent renal carbonic anhydrase activity and plasma testosterone levels in hypogonadal men". Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese 2018;59:207-8. https://www.sciencedirect.com/science/article/pii/S1109966618301684?via=ihub
Evidence from clinical studies suggests that patients with low testosterone levels are at increased cardiovascular disease risk. Even though the exact mechanisms remain poorly understood, a low plasma testosterone level is associated with a pro-atherogenic lipid profile, insulin resistance and increased levels of pro-inflammatory mediators and vascular dysfunction, which is typically observed in patients with hypogonadism.
Furthermore, recent evidence suggests that testosterone deficiency has also direct adverse effects on the endothelium and nitric oxide (NO) bioavailability. Observations from studies in patients with hypogonadal hypogonadism imply that the mechanisms of endothelial dysfunction related to testosterone deficiency may involve changes in asymmetric dimethylarginine (ADMA) levels, a known endogenous inhibitor of NO synthase.
Evidence suggests that testosterone replacement therapy is not only a safe but also an effective means to reduce atherosclerotic risk and reverse endothelial dysfunction in patients with hypogonadal hypogonadism. Further research in the field is expected to clarify whether changes in ADMA metabolism constitute the central mechanism through which a low testosterone level leads to endothelial dysfunction.
Antonopoulos AS, Antoniades C. Mechanisms of testosterone deficiency-related endothelial dysfunction: Invited commentary for the Hellenic Journal of Cardiology on: Tsikas et al. "Associations between asymmetric dimethylarginine, nitrite-dependent renal carbonic anhydrase activity and plasma testosterone levels in hypogonadal men". Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese 2018;59:207-8. https://www.sciencedirect.com/science/article/pii/S1109966618301684?via=ihub
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Effect of Transdermal Testosterone and Oral Progesterone on Drug-Induced QT Interval Lengthening in Older Men
Although female sex is a risk factor for torsades de pointes,1 29% to 44% of drug-induced cases occur in men. Older age is also a risk factor. Preclinical studies have shown that testosterone and progesterone protect against drug-induced prolongation of ventricular repolarization, early afterdepolarizations, and arrhythmias. Oral progesterone shortens QT intervals and attenuates drug induced QT lengthening in young women. We hypothesized that transdermal testosterone and oral progesterone attenuate drug-induced QT interval lengthening in older men.
…
In conclusion, despite a small sample, our results suggest that transdermal testosterone attenuates drug induced QT lengthening in older men. We cannot rule out an effect of oral progesterone on attenuation of drug-induced QT lengthening. These findings support larger studies investigating the efficacy, safety, and feasibility of transdermal testosterone and oral progesterone for attenuating drug-induced QT interval lengthening in older men with risk factors who require therapy with QT-prolonging drugs.
Muensterman ET, Jaynes HA, Sowinski KM, et al. Effect of Transdermal Testosterone and Oral Progesterone on Drug-Induced QT Interval Lengthening in Older Men: A Randomized, Double-Blind, Placebo-Controlled Crossover-Design Study. Circulation 2019;140:1127-9. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.041395
Although female sex is a risk factor for torsades de pointes,1 29% to 44% of drug-induced cases occur in men. Older age is also a risk factor. Preclinical studies have shown that testosterone and progesterone protect against drug-induced prolongation of ventricular repolarization, early afterdepolarizations, and arrhythmias. Oral progesterone shortens QT intervals and attenuates drug induced QT lengthening in young women. We hypothesized that transdermal testosterone and oral progesterone attenuate drug-induced QT interval lengthening in older men.
…
In conclusion, despite a small sample, our results suggest that transdermal testosterone attenuates drug induced QT lengthening in older men. We cannot rule out an effect of oral progesterone on attenuation of drug-induced QT lengthening. These findings support larger studies investigating the efficacy, safety, and feasibility of transdermal testosterone and oral progesterone for attenuating drug-induced QT interval lengthening in older men with risk factors who require therapy with QT-prolonging drugs.
Muensterman ET, Jaynes HA, Sowinski KM, et al. Effect of Transdermal Testosterone and Oral Progesterone on Drug-Induced QT Interval Lengthening in Older Men: A Randomized, Double-Blind, Placebo-Controlled Crossover-Design Study. Circulation 2019;140:1127-9. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.041395
[OA] Androgens and Blood Pressure Control: Sex Differences and Mechanisms
Article Outline
I. Androgens in Men
II. Androgens and Male Obese Zucker Rats (OZR)
III. Androgens in Women
IV. Mechanisms Responsible for Hypertension in Hyperandrogenemic Female Rats
A. Role of the Sympathetic Nervous System and Melanocortin-4 Receptor
B. Role of 20-Hydroxyeicosatetraenoic Acid
C. Role of the Renin-Angiotensin System
V. Postmenopausal Hyperandrogenemia and Blood Pressure
VI. The Consequences of Androgens in Transgender Humans
VII. The 4-Core Chromosome Mouse as a Model for Future Studies
VIII. Conclusion
A. Grant Support
IX. References
The role that androgens play in mediating elevated blood pressure is unclear. Low levels of androgens in men and increased levels of androgens in women, as occurs with polycystic ovary syndrome (PCOS), are both associated with increased risk for cardiovascular disease and elevated blood pressure.
We have used animal models to evaluate the potential mechanisms by which men and women have differential responses to androgens that affect regulation of blood pressure and the implications these may have for the health of men and women.
Reckelhoff JF. Androgens and Blood Pressure Control: Sex Differences and Mechanisms. Mayo Clin Proc 2019;94:536-43. https://www.mayoclinicproceedings.org/article/S0025-6196(18)30927-3/fulltext
Article Outline
I. Androgens in Men
II. Androgens and Male Obese Zucker Rats (OZR)
III. Androgens in Women
IV. Mechanisms Responsible for Hypertension in Hyperandrogenemic Female Rats
A. Role of the Sympathetic Nervous System and Melanocortin-4 Receptor
B. Role of 20-Hydroxyeicosatetraenoic Acid
C. Role of the Renin-Angiotensin System
V. Postmenopausal Hyperandrogenemia and Blood Pressure
VI. The Consequences of Androgens in Transgender Humans
VII. The 4-Core Chromosome Mouse as a Model for Future Studies
VIII. Conclusion
A. Grant Support
IX. References
The role that androgens play in mediating elevated blood pressure is unclear. Low levels of androgens in men and increased levels of androgens in women, as occurs with polycystic ovary syndrome (PCOS), are both associated with increased risk for cardiovascular disease and elevated blood pressure.
We have used animal models to evaluate the potential mechanisms by which men and women have differential responses to androgens that affect regulation of blood pressure and the implications these may have for the health of men and women.
Reckelhoff JF. Androgens and Blood Pressure Control: Sex Differences and Mechanisms. Mayo Clin Proc 2019;94:536-43. https://www.mayoclinicproceedings.org/article/S0025-6196(18)30927-3/fulltext
Vascular Mechanisms of Testosterone: The Non-Genomic Point of View
Highlights
· The main non-genomic vascular mechanism of Testosterone (T) is vasorelaxation.
· T causes dependent-endothelium vasodilation by Gi/o protein and PKA activation.
· T causes independent-endothelium vasodilation by pGC and PKG activation.
· T-induced PKG activation activate Kv and BKCa and inactivate L-Type VOCC channels.
· T is beneficial to the cardiovascular system and TRT may become a CVD treatment.
Testosterone (T) is the predominant endogenous androgen in the bloodstream. At the vascular level, T presents genomic and non-genomic effects, and both effects may overlap.
The genomic actions assume that androgens can freely cross the plasma membrane of target cells and bind to nuclear androgen receptors, inducing gene transcription and protein synthesis.
The non-genomic effects have a more rapid onset and may be related to the interaction with protein/receptor/ion channels of the plasma membrane.
The key T effect at the vascular level is vasorelaxation, which is primarily due to its rapid effect. Thus, the main purpose of this review is to discuss the T non-genomic effects at the vascular level and the molecular pathways involved in its vasodilator effect observed in in vivo and in vitro studies.
In this sense, the nuclear receptor activation, the influence of vascular endothelium and the activation or inhibition of ion channels (potassium and calcium channels, respectively) will be reviewed regarding all the data that corroborated or not.
Moreover, this review also provides a brief update on the association of T with the risk factors for cardiovascular diseases, namely metabolic syndrome, type 2 diabetes mellitus, obesity, atherosclerosis, dyslipidaemia, and hypertension.
In summary, in this paper we consider the non-genomic vascular mode of action of androgen in physiological conditions and the main risk factors for cardiovascular diseases.
Lorigo M, Mariana M, Lemos MC, Cairrao E. Vascular mechanisms of testosterone: the non-genomic point of view. J Steroid Biochem Mol Biol 2019:105496. Vascular mechanisms of testosterone: the non-genomic point of view - ScienceDirect
Highlights
· The main non-genomic vascular mechanism of Testosterone (T) is vasorelaxation.
· T causes dependent-endothelium vasodilation by Gi/o protein and PKA activation.
· T causes independent-endothelium vasodilation by pGC and PKG activation.
· T-induced PKG activation activate Kv and BKCa and inactivate L-Type VOCC channels.
· T is beneficial to the cardiovascular system and TRT may become a CVD treatment.
Testosterone (T) is the predominant endogenous androgen in the bloodstream. At the vascular level, T presents genomic and non-genomic effects, and both effects may overlap.
The genomic actions assume that androgens can freely cross the plasma membrane of target cells and bind to nuclear androgen receptors, inducing gene transcription and protein synthesis.
The non-genomic effects have a more rapid onset and may be related to the interaction with protein/receptor/ion channels of the plasma membrane.
The key T effect at the vascular level is vasorelaxation, which is primarily due to its rapid effect. Thus, the main purpose of this review is to discuss the T non-genomic effects at the vascular level and the molecular pathways involved in its vasodilator effect observed in in vivo and in vitro studies.
In this sense, the nuclear receptor activation, the influence of vascular endothelium and the activation or inhibition of ion channels (potassium and calcium channels, respectively) will be reviewed regarding all the data that corroborated or not.
Moreover, this review also provides a brief update on the association of T with the risk factors for cardiovascular diseases, namely metabolic syndrome, type 2 diabetes mellitus, obesity, atherosclerosis, dyslipidaemia, and hypertension.
In summary, in this paper we consider the non-genomic vascular mode of action of androgen in physiological conditions and the main risk factors for cardiovascular diseases.
Lorigo M, Mariana M, Lemos MC, Cairrao E. Vascular mechanisms of testosterone: the non-genomic point of view. J Steroid Biochem Mol Biol 2019:105496. Vascular mechanisms of testosterone: the non-genomic point of view - ScienceDirect
hurricane
Well-known Member
Man if T has all these great vascular effects i need to get on some asap!!
Fuk ivabradine and amlodipine and coreg. I'll settle for T.
[OA] Cardiovascular and Cerebrovascular Safety of Testosterone Therapy
To the Editor:
We read with great interest the study by Loo et al1 concerning testosterone (T) therapy increasing the risk of cerebral and cardiovascular disease. Cardiovascular and Cerebrovascular Safety of Testosterone Replacement Therapy Among Aging Men with Low Testosterone Levels: A Cohort Study - ScienceDirect
Unfortunately, the authors’ conclusions are not supported by the results, raising serious concerns. Here we highlight some of these concerns:
1. The single most important finding of this study is that almost twice as many men in the untreated group DIED vs the treatment group, in agreement with previous studies. If we were to counsel a symptomatic hypogonadal patient based on this study and the results of the T trials, we would advise him that T therapy will improve sexual function, walking distance, mood, bone mineral density, anemia, lean muscle mass, insulin sensitivity, and significantly increase his chances of being alive in 5-10 years’ time.
A major critical confounder, inadequately recognized by authors, is that T deficiency itself is a risk for increased cardiovascular events. For this reason, some investigators have elected to censor major adverse cardiovascular events during the first 12 months because those events may be related to the underlying condition rather than T treatment. Failing to take measures like this may account for differences in results between studies. Considerable published data contradict the findings of this study.
2. A careful look at the crude hazard ratios reported in Tables 2-4 suggests that there were no significant statistical differences between the treated and nontreated groups, except in Table 4, where all-cause mortality was significantly reduced in the treated group when compared with both the nontreated group and the “past use” group. The absence of statistically significant results was surprising, because the sample sizes are quite large.
Examining the forest plot, it is clear that there is a lot of variability in the estimates, and even with the large sample size, the authors did not claim any significant differences and most importantly, if these differences are clinically important. There appears to be a lack of evidence of probable clinical significance.
3. It is disturbing that the authors had a preconceived view that only men with classical hypogonadism should be treated, yet they present no evidence as to how results from a “classical” cohort would have been different from those men with nonclassical hypogonadism. On the contrary, the benefits from the T trial were seen in men with “functional” hypogonadism.
4. The authors dismissed symptoms of hypogonadism as due to “aging” and suggested that these symptoms should be tolerated, even for men in their 50s. If this were the case, then hypertension, cataracts, retinal degeneration, and hearing loss should be left untreated and accepted as a consequence of aging.
In addition, the inclusion of a comparative cohort taking 5α-reductase inhibitors is completely irrelevant and bears no basis for comparison. The authors appeared to have preconceived views and seem determined to ensure that their findings are interpreted to fit these views.
Traish AM, Hackett G, Miner M, Morgentaler A. Cardiovascular and Cerebrovascular Safety of Testosterone Therapy. Am J Med 2019. https://www.amjmed.com/article/S0002-9343(19)30433-4/fulltext
To the Editor:
We read with great interest the study by Loo et al1 concerning testosterone (T) therapy increasing the risk of cerebral and cardiovascular disease. Cardiovascular and Cerebrovascular Safety of Testosterone Replacement Therapy Among Aging Men with Low Testosterone Levels: A Cohort Study - ScienceDirect
Unfortunately, the authors’ conclusions are not supported by the results, raising serious concerns. Here we highlight some of these concerns:
1. The single most important finding of this study is that almost twice as many men in the untreated group DIED vs the treatment group, in agreement with previous studies. If we were to counsel a symptomatic hypogonadal patient based on this study and the results of the T trials, we would advise him that T therapy will improve sexual function, walking distance, mood, bone mineral density, anemia, lean muscle mass, insulin sensitivity, and significantly increase his chances of being alive in 5-10 years’ time.
A major critical confounder, inadequately recognized by authors, is that T deficiency itself is a risk for increased cardiovascular events. For this reason, some investigators have elected to censor major adverse cardiovascular events during the first 12 months because those events may be related to the underlying condition rather than T treatment. Failing to take measures like this may account for differences in results between studies. Considerable published data contradict the findings of this study.
2. A careful look at the crude hazard ratios reported in Tables 2-4 suggests that there were no significant statistical differences between the treated and nontreated groups, except in Table 4, where all-cause mortality was significantly reduced in the treated group when compared with both the nontreated group and the “past use” group. The absence of statistically significant results was surprising, because the sample sizes are quite large.
Examining the forest plot, it is clear that there is a lot of variability in the estimates, and even with the large sample size, the authors did not claim any significant differences and most importantly, if these differences are clinically important. There appears to be a lack of evidence of probable clinical significance.
3. It is disturbing that the authors had a preconceived view that only men with classical hypogonadism should be treated, yet they present no evidence as to how results from a “classical” cohort would have been different from those men with nonclassical hypogonadism. On the contrary, the benefits from the T trial were seen in men with “functional” hypogonadism.
4. The authors dismissed symptoms of hypogonadism as due to “aging” and suggested that these symptoms should be tolerated, even for men in their 50s. If this were the case, then hypertension, cataracts, retinal degeneration, and hearing loss should be left untreated and accepted as a consequence of aging.
In addition, the inclusion of a comparative cohort taking 5α-reductase inhibitors is completely irrelevant and bears no basis for comparison. The authors appeared to have preconceived views and seem determined to ensure that their findings are interpreted to fit these views.
Traish AM, Hackett G, Miner M, Morgentaler A. Cardiovascular and Cerebrovascular Safety of Testosterone Therapy. Am J Med 2019. https://www.amjmed.com/article/S0002-9343(19)30433-4/fulltext
[OA] Abuse of Anabolic Steroids: A Dangerous Indulgence
Anabolic androgenic drugs include testosterone and its synthetic steroidal derivatives [also known as anabolic androgenic steroids (AAS)], as well as nonsteroidal selective androgen receptor modulators (SARMs), which exert tissue-specific androgenic effects by binding to the androgen receptor.
As these agents increase muscle mass and strength, they have been widely abused by professional athletes to seek competitive advantage. Recently the use of these compounds have also increased among amateur athletes and also among men who are not athletes but want to enhance their body image. The use of AAS is associated with many adverse effects, some of which are serious and difficult to manage.
In this paper, we briefly review the types of AAS, the mechanism behind their ergogenic effects and lastly discuss their adverse effects in some detail.
Gagliano-Jucá T, Basaria S. Abuse of Anabolic Steroids: A Dangerous Indulgence. Current Opinion in Endocrine and Metabolic Research 2019. Abuse of Anabolic Steroids: A Dangerous Indulgence - ScienceDirect
Anabolic androgenic drugs include testosterone and its synthetic steroidal derivatives [also known as anabolic androgenic steroids (AAS)], as well as nonsteroidal selective androgen receptor modulators (SARMs), which exert tissue-specific androgenic effects by binding to the androgen receptor.
As these agents increase muscle mass and strength, they have been widely abused by professional athletes to seek competitive advantage. Recently the use of these compounds have also increased among amateur athletes and also among men who are not athletes but want to enhance their body image. The use of AAS is associated with many adverse effects, some of which are serious and difficult to manage.
In this paper, we briefly review the types of AAS, the mechanism behind their ergogenic effects and lastly discuss their adverse effects in some detail.
Gagliano-Jucá T, Basaria S. Abuse of Anabolic Steroids: A Dangerous Indulgence. Current Opinion in Endocrine and Metabolic Research 2019. Abuse of Anabolic Steroids: A Dangerous Indulgence - ScienceDirect
hurricane
Well-known Member
Great read. Kind of scary.
hurricane
Well-known Member
I really enjoyed how this study talked about psychiatric implications and arrhythmias.
I think many users greatly underestimate the mind fuk that AAS use may cause. No doubt it exacerbated some of my issues.
I can 100% say afib was prevelant during many of my workouts since i had an implantable loop recorder before my ablation.
Dr. Marieb or his staff would call me during or after my workouts and tell me what they were seeing.
Really enjoyed this study.
Good stuff Doc.
[OA] Combined Effects of Growth Hormone and Testosterone Replacement Treatment in Heart Failure
AIMS: Although preliminary studies have demonstrated safety and effectiveness of single replacement therapy for growth hormone deficiency or testosterone deficiency in heart failure (HF), no data are available regarding the combined treatment with both GH and T in this setting. Thus, the aim of the present hypothesis generating pilot study was to evaluate the effectiveness and safety of multiple hormonal replacement therapies in chronic HF.
METHODS AND RESULTS: Five stable HF with reduced ejection fraction patients, with a concomitant diagnosis of growth hormone deficiency and testosterone deficiency, on top of guideline-based HF treatment underwent 1 year of GH replacement therapy by subcutaneous injections of somatotropin at a dose of 0.012 mg/kg every second day. After 12 months, a T replacement treatment was added at a dosage of 1000 mg every 3 months.
Each patient underwent a complete M-mode, two-dimensional, and Doppler echocardiographic examination, and an incremental symptom-limited cardiopulmonary exercise test on a bicycle ergometer at baseline (BL), after 1 year of GH treatment (V1), and after 1 year of combined GH + T treatments (V2).
One-year of GH treatment resulted in a significant improvement in left ventricular ejection fraction (+5.4%, P < 0.01), New York Heart Association functional class (P < 0.05), and peak oxygen consumption (VO2 peak) (+19.3%, P < 0.01), and in a significant reduction in NT-proBNP levels (-35.1%, P < 0.01).
Notably, one additional year of combined GH and T replacement therapy induced a further increase in VO2 peak (+27.7%, final delta change + 52.44%, P < 0.01), as well as a significant improvement in muscular strength, as assessed by handgrip dynamometry (+17.5%, final delta change + 25.8%, P < 0.01).
These beneficial effects were paralleled with an improvement of the overall clinical status (as assessed by New York Heart Association class). Of note, neither adverse effects nor cardiovascular events were reported during the follow-up period.
CONCLUSIONS: Our preliminary data suggest for the first time that combined replacement therapy with GH and T could be considered safe and therapeutic in HF patients with multiple hormone deficiencies, supporting the hypothesis that multiple hormone deficiencies syndrome can be considered as a novel and promising therapeutic target in HF. Further studies with a more robust design and larger population are needed.
Salzano A, Marra AM, Arcopinto M, et al. Combined effects of growth hormone and testosterone replacement treatment in heart failure. ESC heart failure 2019. Error - Cookies Turned Off
AIMS: Although preliminary studies have demonstrated safety and effectiveness of single replacement therapy for growth hormone deficiency or testosterone deficiency in heart failure (HF), no data are available regarding the combined treatment with both GH and T in this setting. Thus, the aim of the present hypothesis generating pilot study was to evaluate the effectiveness and safety of multiple hormonal replacement therapies in chronic HF.
METHODS AND RESULTS: Five stable HF with reduced ejection fraction patients, with a concomitant diagnosis of growth hormone deficiency and testosterone deficiency, on top of guideline-based HF treatment underwent 1 year of GH replacement therapy by subcutaneous injections of somatotropin at a dose of 0.012 mg/kg every second day. After 12 months, a T replacement treatment was added at a dosage of 1000 mg every 3 months.
Each patient underwent a complete M-mode, two-dimensional, and Doppler echocardiographic examination, and an incremental symptom-limited cardiopulmonary exercise test on a bicycle ergometer at baseline (BL), after 1 year of GH treatment (V1), and after 1 year of combined GH + T treatments (V2).
One-year of GH treatment resulted in a significant improvement in left ventricular ejection fraction (+5.4%, P < 0.01), New York Heart Association functional class (P < 0.05), and peak oxygen consumption (VO2 peak) (+19.3%, P < 0.01), and in a significant reduction in NT-proBNP levels (-35.1%, P < 0.01).
Notably, one additional year of combined GH and T replacement therapy induced a further increase in VO2 peak (+27.7%, final delta change + 52.44%, P < 0.01), as well as a significant improvement in muscular strength, as assessed by handgrip dynamometry (+17.5%, final delta change + 25.8%, P < 0.01).
These beneficial effects were paralleled with an improvement of the overall clinical status (as assessed by New York Heart Association class). Of note, neither adverse effects nor cardiovascular events were reported during the follow-up period.
CONCLUSIONS: Our preliminary data suggest for the first time that combined replacement therapy with GH and T could be considered safe and therapeutic in HF patients with multiple hormone deficiencies, supporting the hypothesis that multiple hormone deficiencies syndrome can be considered as a novel and promising therapeutic target in HF. Further studies with a more robust design and larger population are needed.
Salzano A, Marra AM, Arcopinto M, et al. Combined effects of growth hormone and testosterone replacement treatment in heart failure. ESC heart failure 2019. Error - Cookies Turned Off
hurricane
Well-known Member
Incredible results.
Ouch!
[OA] Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction
BACKGROUND - Experimental and clinical evidence support the role of INFLAMMATION in atherosclerosis and its complications. Colchicine is an orally administered, potent ANTIINFLAMMATORY medication that is indicated for the treatment of gout and pericarditis.
METHODS - We performed a randomized, double-blind trial involving patients recruited within 30 days after a myocardial infarction. The patients were randomly assigned to receive either low-dose colchicine (0.5 mg once daily) or placebo.
The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. The components of the primary end point and safety were also assessed.
RESULTS - A total of 4745 patients were enrolled; 2366 patients were assigned to the colchicine group, and 2379 to the placebo group. Patients were followed for a median of 22.6 months.
The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P=0.02).
The hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for myocardial infarction, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization.
Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P=0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P=0.03).
CONCLUSIONS - Among patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo.
Tardif J-C, Kouz S, Waters DD, et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. New England Journal of Medicine 2019. https://doi.org/10.1056/NEJMoa1912388
BACKGROUND - Experimental and clinical evidence support the role of INFLAMMATION in atherosclerosis and its complications. Colchicine is an orally administered, potent ANTIINFLAMMATORY medication that is indicated for the treatment of gout and pericarditis.
METHODS - We performed a randomized, double-blind trial involving patients recruited within 30 days after a myocardial infarction. The patients were randomly assigned to receive either low-dose colchicine (0.5 mg once daily) or placebo.
The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. The components of the primary end point and safety were also assessed.
RESULTS - A total of 4745 patients were enrolled; 2366 patients were assigned to the colchicine group, and 2379 to the placebo group. Patients were followed for a median of 22.6 months.
The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P=0.02).
The hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for myocardial infarction, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization.
Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P=0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P=0.03).
CONCLUSIONS - Among patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo.
Tardif J-C, Kouz S, Waters DD, et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. New England Journal of Medicine 2019. https://doi.org/10.1056/NEJMoa1912388
Effect of Testosterone Level on Mortality in Patients With Left Ventricular Assist Device
BACKGROUND AND OBJECTIVES: Testosterone deficiency is associated with mortality in patients with heart failure; however, its effects on patients undergoing Left Ventricular Assist Device (LVAD) implantation are unclear. We investigated the role of total testosterone (TT) and free testosterone (FT) levels on mortality undergoing LVAD implantation.
METHODS: Between December 2010 and December 2014, 101 consecutive male patients who underwent LVAD implantation and had plasma testosterone measurement (TT and FT) in the last month before operation were included in the study. Demographics, follow-up, and mortality data were analyzed retrospectively.
RESULTS: The mean age of the patients was 51.7 +/- 11 years. TT and FT levels were in the below normal range of 31.6% (n = 32) and 65.3% (n = 66) of the patients, respectively. The mean follow-up time was 355 +/- 268 days, and 32 (31%) patients died during follow-up. Cumulative survival rates were significantly worse in patients with low TT and FT than patients in the normal range (P < .001 and P = .029, respectively).
Multivariate analysis after adjustment for clinical variables, age, albumin, C-reactive protein, total cholesterol, chronic kidney disease, diabetes mellitus (DM), and leukocytosis showed that low TT and FT were independently associated with poor survival (HR, 3.680; 95% CI, 1.615-8.385 P = .002 and HR, 3.816; 95% CI, 1.279-11.383, P = .016, respectively).
CONCLUSION: Low TT and FT levels were independent risk factors for mortality in patients with LVAD.
Simsek E, Kilic S, Kemal HS, et al. Effect of Testosterone Level on Mortality in Patients With Left Ventricular Assist Device. Transplantation proceedings 2019. Effect of Testosterone Level on Mortality in Patients With Left Ventricular Assist Device - ScienceDirect
BACKGROUND AND OBJECTIVES: Testosterone deficiency is associated with mortality in patients with heart failure; however, its effects on patients undergoing Left Ventricular Assist Device (LVAD) implantation are unclear. We investigated the role of total testosterone (TT) and free testosterone (FT) levels on mortality undergoing LVAD implantation.
METHODS: Between December 2010 and December 2014, 101 consecutive male patients who underwent LVAD implantation and had plasma testosterone measurement (TT and FT) in the last month before operation were included in the study. Demographics, follow-up, and mortality data were analyzed retrospectively.
RESULTS: The mean age of the patients was 51.7 +/- 11 years. TT and FT levels were in the below normal range of 31.6% (n = 32) and 65.3% (n = 66) of the patients, respectively. The mean follow-up time was 355 +/- 268 days, and 32 (31%) patients died during follow-up. Cumulative survival rates were significantly worse in patients with low TT and FT than patients in the normal range (P < .001 and P = .029, respectively).
Multivariate analysis after adjustment for clinical variables, age, albumin, C-reactive protein, total cholesterol, chronic kidney disease, diabetes mellitus (DM), and leukocytosis showed that low TT and FT were independently associated with poor survival (HR, 3.680; 95% CI, 1.615-8.385 P = .002 and HR, 3.816; 95% CI, 1.279-11.383, P = .016, respectively).
CONCLUSION: Low TT and FT levels were independent risk factors for mortality in patients with LVAD.
Simsek E, Kilic S, Kemal HS, et al. Effect of Testosterone Level on Mortality in Patients With Left Ventricular Assist Device. Transplantation proceedings 2019. Effect of Testosterone Level on Mortality in Patients With Left Ventricular Assist Device - ScienceDirect
Anabolic Deficiencies in Heart Failure: Ready for Prime Time?
KEY POINTS
· Many patients with chronic heart failure show some hormonal deficiency that might worsen morbidity and mortality.
· Chronic heart failure development might be explained by the imbalance between catabolic and anabolic pathways present in the disease.
· Multiple hormonal deficiency is associated with a relevant worsening of prognosis in patients with chronic heart failure and patients should be screened for it.
· Replacement hormonal therapy in patients with chronic heart failure has shown promising beneficial results.
"Chronic heart failure (CHF) is a complex syndrome characterized by symptoms and signs supported by different forms of cardiac impairment.
The link between multiple hormonal and metabolic derangements and the development of CHF and the beneficial effects seen with hormonal replacement therapy suggest that a reduction of anabolic pathways might contribute to the onset of CHF.
Therefore, an imbalance between anabolic and catabolic forces could be responsible for the development of CHF.
There are sufficient evidence to support the screening in patients with CHF of hormonal deficiencies and their correction with replacement therapy."
Napoli R, D'Assante R, Miniero M, Salzano A, Cittadini A. Anabolic Deficiencies in Heart Failure: Ready for Prime Time? Heart failure clinics 2020;16:11-21. Anabolic Deficiencies in Heart Failure: Ready for Prime Time? - ScienceDirect
KEY POINTS
· Many patients with chronic heart failure show some hormonal deficiency that might worsen morbidity and mortality.
· Chronic heart failure development might be explained by the imbalance between catabolic and anabolic pathways present in the disease.
· Multiple hormonal deficiency is associated with a relevant worsening of prognosis in patients with chronic heart failure and patients should be screened for it.
· Replacement hormonal therapy in patients with chronic heart failure has shown promising beneficial results.
"Chronic heart failure (CHF) is a complex syndrome characterized by symptoms and signs supported by different forms of cardiac impairment.
The link between multiple hormonal and metabolic derangements and the development of CHF and the beneficial effects seen with hormonal replacement therapy suggest that a reduction of anabolic pathways might contribute to the onset of CHF.
Therefore, an imbalance between anabolic and catabolic forces could be responsible for the development of CHF.
There are sufficient evidence to support the screening in patients with CHF of hormonal deficiencies and their correction with replacement therapy."
Napoli R, D'Assante R, Miniero M, Salzano A, Cittadini A. Anabolic Deficiencies in Heart Failure: Ready for Prime Time? Heart failure clinics 2020;16:11-21. Anabolic Deficiencies in Heart Failure: Ready for Prime Time? - ScienceDirect
[OA] Testosterone To Oestradiol Ratio Reflects Systemic And Plaque Inflammation And Predicts Future Cardiovascular Events In Men With Severe Atherosclerosis
Aims: The effects of testosterone on cardiovascular disease (CVD) as reported in literature have been ambiguous. Recently, the interplay between testosterone and oestradiol as assessed by testosterone/oestradiol (T/E2) ratio was suggested to be better informative on the normal physiological balance.
Considering the role in CVD, we hypothesized that a low T/E2 ratio in men with CVD is associated with increased inflammation, a more unstable plaque and a worse cardiovascular outcome.
Methods and results: Testosterone and oestradiol concentrations were determined in blood samples of 611 male carotid endarterectomy patients included in the Athero-Express Biobank Study. T/E2 ratio was associated with baseline characteristics, atherosclerotic plaque specimens, inflammatory biomarkers, and 3 year follow-up information.
Patients with low T/E2 ratio had more unfavourable inflammatory profiles compared with patients with high T/E2 as observed by higher levels of C-reactive protein [2.81 mug/mL vs. 1.22 mug/mL (P < 0.001)] and higher leucocyte counts [8.98*109/L vs. 7.75*109/L (P = 0.001)] in blood. In atherosclerotic plaques, a negative association between T/E2 ratio and number of neutrophils [B = -0.366 (P = 0.012)], plaque calcifications [OR: 0.816 (P = 0.044)], interleukin-6 (IL-6) [B = -0.15 (P = 0.009)], and IL-6 receptor [B = -0.13 (P = 0.024)] was found.
Furthermore, in multivariate Cox regression analysis, low T/E2 ratio was independently associated with an increased risk for major cardiovascular events (MACE) during 3 year follow-up [hazard ratio 1.67 (95% confidence interval 1.02-2.76), P = 0.043]. In men with elevated body mass index (BMI), these effects were strongest.
Conclusion: In male patients with manifest atherosclerotic disease, low T/E2 ratio was associated with increased systemic inflammation, increased inflammatory plaque proteins, and an increased risk of future MACE as compared to men with normal T/E2 ratio.
These effects are strongest in men with elevated BMI and are expected to be affected by aromatase activity in white fat tissues. Normalization of T/E2 ratio may be considered as target for the secondary prevention of CVD in men.
van Koeverden ID, de Bakker M, Haitjema S, et al. Testosterone to oestradiol ratio reflects systemic and plaque inflammation and predicts future cardiovascular events in men with severe atherosclerosis. Cardiovasc Res 2019;115:453-62. https://academic.oup.com/cardiovascres/article/115/2/453/5056751
Aims: The effects of testosterone on cardiovascular disease (CVD) as reported in literature have been ambiguous. Recently, the interplay between testosterone and oestradiol as assessed by testosterone/oestradiol (T/E2) ratio was suggested to be better informative on the normal physiological balance.
Considering the role in CVD, we hypothesized that a low T/E2 ratio in men with CVD is associated with increased inflammation, a more unstable plaque and a worse cardiovascular outcome.
Methods and results: Testosterone and oestradiol concentrations were determined in blood samples of 611 male carotid endarterectomy patients included in the Athero-Express Biobank Study. T/E2 ratio was associated with baseline characteristics, atherosclerotic plaque specimens, inflammatory biomarkers, and 3 year follow-up information.
Patients with low T/E2 ratio had more unfavourable inflammatory profiles compared with patients with high T/E2 as observed by higher levels of C-reactive protein [2.81 mug/mL vs. 1.22 mug/mL (P < 0.001)] and higher leucocyte counts [8.98*109/L vs. 7.75*109/L (P = 0.001)] in blood. In atherosclerotic plaques, a negative association between T/E2 ratio and number of neutrophils [B = -0.366 (P = 0.012)], plaque calcifications [OR: 0.816 (P = 0.044)], interleukin-6 (IL-6) [B = -0.15 (P = 0.009)], and IL-6 receptor [B = -0.13 (P = 0.024)] was found.
Furthermore, in multivariate Cox regression analysis, low T/E2 ratio was independently associated with an increased risk for major cardiovascular events (MACE) during 3 year follow-up [hazard ratio 1.67 (95% confidence interval 1.02-2.76), P = 0.043]. In men with elevated body mass index (BMI), these effects were strongest.
Conclusion: In male patients with manifest atherosclerotic disease, low T/E2 ratio was associated with increased systemic inflammation, increased inflammatory plaque proteins, and an increased risk of future MACE as compared to men with normal T/E2 ratio.
These effects are strongest in men with elevated BMI and are expected to be affected by aromatase activity in white fat tissues. Normalization of T/E2 ratio may be considered as target for the secondary prevention of CVD in men.
van Koeverden ID, de Bakker M, Haitjema S, et al. Testosterone to oestradiol ratio reflects systemic and plaque inflammation and predicts future cardiovascular events in men with severe atherosclerosis. Cardiovasc Res 2019;115:453-62. https://academic.oup.com/cardiovascres/article/115/2/453/5056751
[OA] [Editorial] Testosterone to estradiol ratio and plaque inflammation: mechanistic insights and biomarker potential?
[This editorial refers to ‘Testosterone to oestradiol ratio reflects systemic and plaque inflammation and predicts future cardiovascular events in men with severe atherosclerosis’, by I.D. van Koeverden et al., pp. 453–462.]
Despite the now clear role of inflammation in atherosclerotic plaque development, progression and instability, our understanding of endogenous factors regulating this is limited. Our strategies for measuring inflammation relevant to the arterial wall remains relatively primitive, e.g. the highly sensitive, but non-specific C-reactive protein (CRP).
Improved understanding of the specific factors upstream of inflammation has the potential to identify markers with higher specificity for atherosclerosis risk. New insights may also aid the development of novel therapeutic targets, which may act in a synergistic manner with current standard pharmacotherapy targeting lipids and neurohormonal abnormalities.
Figtree GA, Ngo DTM, Bubb KJ. Testosterone to estradiol ratio and plaque inflammation: mechanistic insights and biomarker potential? Cardiovascular Research 2018;115:255-7. Testosterone to estradiol ratio and plaque inflammation: mechanistic insights and biomarker potential?
Schematic figure illustrating the potential of T:E2 ratio to reflect aromatase activity, and thus abundance of white adipose tissue in males.
Given the role of WAT in production of adipokines related to systemic inflammation, this may have a causal role in atherosclerosis, and may be a better marker of risk than standard markers of obesity such as body mass index. The distribution of WAT is illustrated in the upper panel. Fat, distributed in different locations in the body, is known to have different functions.
Excessive visceral or gut fat, composed of retroperitoneal fat (‘behind the peritoneum’), omental fat (adipose in a sheet of connective tissue hanging as a flap originating at the stomach and draping the intestines), and mesenteric fat (adipose in the sheets of connective tissue holding the intestines in their looping structure), has been shown to be a risk factor for diabetes and cardiovascular disease.
IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein-1; PAI-1, plasminogen activator inhibitor-1; TNF-α, tumour necrosis factor-α.
[This editorial refers to ‘Testosterone to oestradiol ratio reflects systemic and plaque inflammation and predicts future cardiovascular events in men with severe atherosclerosis’, by I.D. van Koeverden et al., pp. 453–462.]
Despite the now clear role of inflammation in atherosclerotic plaque development, progression and instability, our understanding of endogenous factors regulating this is limited. Our strategies for measuring inflammation relevant to the arterial wall remains relatively primitive, e.g. the highly sensitive, but non-specific C-reactive protein (CRP).
Improved understanding of the specific factors upstream of inflammation has the potential to identify markers with higher specificity for atherosclerosis risk. New insights may also aid the development of novel therapeutic targets, which may act in a synergistic manner with current standard pharmacotherapy targeting lipids and neurohormonal abnormalities.
Figtree GA, Ngo DTM, Bubb KJ. Testosterone to estradiol ratio and plaque inflammation: mechanistic insights and biomarker potential? Cardiovascular Research 2018;115:255-7. Testosterone to estradiol ratio and plaque inflammation: mechanistic insights and biomarker potential?
Schematic figure illustrating the potential of T:E2 ratio to reflect aromatase activity, and thus abundance of white adipose tissue in males.
Given the role of WAT in production of adipokines related to systemic inflammation, this may have a causal role in atherosclerosis, and may be a better marker of risk than standard markers of obesity such as body mass index. The distribution of WAT is illustrated in the upper panel. Fat, distributed in different locations in the body, is known to have different functions.
Excessive visceral or gut fat, composed of retroperitoneal fat (‘behind the peritoneum’), omental fat (adipose in a sheet of connective tissue hanging as a flap originating at the stomach and draping the intestines), and mesenteric fat (adipose in the sheets of connective tissue holding the intestines in their looping structure), has been shown to be a risk factor for diabetes and cardiovascular disease.
IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein-1; PAI-1, plasminogen activator inhibitor-1; TNF-α, tumour necrosis factor-α.
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