AAS and Cardiovascular/Pulmonary Function

[Kimpe]

Incredibly informative thread, thank you for this because it's just what I had been looking for.
Last week I had atrial fibrillation and was taken to the hospital where they had to zap my heart into normal rhythm. Now I'm on blood thinners and have been trying to figure out if I should quit my TRT.

After reading plenty of these studies I think it's best for my heart to just drop the TRT .

 

[Michael Scally MD]

Oxidized phospholipids as a unifying theory for lipoprotein(a) and cardiovascular disease

Key points

· Elevated plasma concentrations of lipoprotein(a) (Lp(a)) are an independent — and possibly causal — risk factor for atherothrombotic cardiovascular disease and calcific aortic valve disease.

· The mechanisms by which Lp(a) accelerates these disorders are not fully understood, but the oxidized phospholipids present on apolipoprotein(a) might have an important role.

· Lp(a) is the major carrier of oxidized phospholipids in human plasma, and interventions that lower plasma Lp(a) levels also reduce the oxidized phospholipid concentration in plasma.

· The oxidized phospholipids on apolipoprotein(a) have been shown to mediate numerous, and partially overlapping, molecular and cellular events underlying atherothrombotic cardiovascular disease and calcific aortic valve disease.

· Direct evidence demonstrating that lowering plasma Lp(a) levels reduces the risk of cardiovascular disease is lacking, as are conclusive data on the specific role of Lp(a)-associated oxidized phospholipids.

· Cardiovascular outcome studies and further basic science investigations will be required to address these important questions.

Epidemiological and clinical studies over the past decade have firmly established that elevated plasma concentrations of lipoprotein(a) (Lp(a)) are an important, independent and probably causal risk factor for the development of cardiovascular diseases.

Whereas a link between Lp(a) levels and atherosclerotic cardiovascular disease (ASCVD) has been appreciated for decades, the role of Lp(a) in calcific aortic valve disease (CAVD) and aortic stenosis has come into focus only in the past 5 years.

ASCVD and CAVD are aetiologically distinct but have several risk factors in common and similar pathological processes at the cellular and molecular levels. Oxidized phospholipids, which modify Lp(a) primarily by covalent binding to its unique apolipoprotein(a) (apo(a)) component, might hold the key to Lp(a) pathogenicity and provide a mechanistic link between ASCVD and CAVD.

Oxidized phospholipids colocalize with apo(a)–Lp(a) in arterial and aortic valve lesions and directly participate in the pathogenesis of these disorders by promoting endothelial dysfunction, lipid deposition, inflammation and osteogenic differentiation, leading to calcification.

The advent of potent Lp(a)-lowering therapies provides the opportunity to address directly the causality of Lp(a) in ASCVD and CAVD and, more importantly, to provide both a novel approach to reduce the residual risk of ASCVD and a long-sought medical treatment for CAVD.

Boffa MB, Koschinsky ML. Oxidized phospholipids as a unifying theory for lipoprotein(a) and cardiovascular disease. Nature Reviews Cardiology 2019;16:305-18. Oxidized phospholipids as a unifying theory for lipoprotein(a) and cardiovascular disease | Nature Reviews Cardiology

 

[Michael Scally MD]

Badran HM, Soliman MA, Elmadbouh I, Ibrahim WA, El Masry SF. Relationship of coronary artery disease with testosterone level in young men undergoing coronary angiography. Menoufia Med J [serial online] 2019 [cited 2019 Apr 17];32:18-24. Available from: http://www.mmj.eg.net/text.asp?2019/32/1/18/256137

Objective - This study aimed to investigate the relation of testosterone level with the extent of coronary artery disease (CAD) in young adult male undergoing coronary angiography.

Materials and methods - Medline databases (PubMed, Journal of Clinical Endocrinology and Metabolism, British Medical Journal, Journal of American College of Cardiology and European Heart Journal) and also materials available in the internet were searched. The search was performed in the electronic databases from 2014 to 2017. The initial search presented 127 articles of which 61 met the inclusion criteria.

The articles studied premature CAD, relation of testosterone level to CAD, and testosterone replacement therapy. If the studies did not fulfill the inclusion criteria, they were excluded. Study quality assessment included whether ethical approval was gained, eligibility criteria specified, appropriate controls, adequate information, and defined assessment measures. Comparisons were made by structured review with the results tabulated.

Findings - In total, 61 potentially relevant publications were included. The studies indicate that the serum levels of both total and free testosterone were significantly lower in young males with CAD, and both were significantly correlated with the severity of CAD as assessed by Gensini score.

Conclusion - The low testosterone level is associated with both the incidence and severity of premature CAD in young adult males.

 

[Michael Scally MD]

Sex Differences in Coronary Artery Disease

Cardiovascular disease is the leading cause of death in women in the United States. Although awareness of coronary artery disease (CAD) risk and presentation in women has increased over the last 3 decades, sex-related disparities persist.

Women continue to be underrepresented in clinical trials, and this affects the accuracy of cardiovascular risk assessment models, diagnostic modalities, and treatments for this population. More women than men present with atypical symptoms during an acute coronary syndrome, and this may be attributed to a gender-specific pathophysiology of disease.

Nonobstructive CAD and plaque erosion is more common in women who present with acute myocardial infarction compared to men. Further studies are needed to determine whether sex-based diagnostic modalities and therapy can improve the morbidity and mortality of women with CAD.

However, until these studies are performed, it is imperative that the current, gender-neutral guidelines be applied for women just as for men. This chapter reviews the differences in awareness, risk factors, pathophysiology, clinical presentation, diagnostic evaluation, and management between men and women with CAD.

Kawamoto K, Duvernoy CS, Davis MB. Chapter 12 - Sex Differences in Coronary Artery Disease. In: LaMarca B, Alexander BT, eds. Sex Differences in Cardiovascular Physiology and Pathophysiology: Academic Press; 2019:185-201. https://www.sciencedirect.com/science/article/pii/B9780128131978000129

 

[Michael Scally MD]

[OA] Clinical Significance of Low Blood Testosterone Concentration in Men as a Cardiovascular Risk Factor From the Perspective of Blood Rheology

Background: Recent clinical studies have indicated the importance of low blood testosterone concentration or whole blood passage time (WBPT) which reflects blood rheology as a cardiovascular risk factor. On the contrary, there are no reports regarding the association of blood testosterone concentrations and WBPT.

This cross-sectional study aimed to elucidate the clinical significance of low blood testosterone concentration in men as a cardiovascular risk factor from the perspective of blood rheology using WBPT.

Methods: In total, 382 male patients with traditional cardiovascular risk factor and no history of cardiovascular disease (age (mean +/- standard deviation (SD)), 64 +/- 10 years) were enrolled. Serum total testosterone concentration (TT) was measured as a marker of testosterone level in vivo, and WBPT was also measured using microchannel array flow analyzer as a commercial device. The relationship between TT and WBPT was evaluated.

Results: There was a significantly negative correlation between TT and WBPT (r = -0.45; P < 0.001). Furthermore, multiple regression analysis revealed that TT (beta = -0.25; P < 0.001) could be selected as an independent variable when WBPT was used as a subordinate factor.

According to receiver operating characteristic curve analysis and the result of the previous report that determined WBPT of > 72.4 s as a risk for incidence of primary cardiovascular disease, TT of < 551.4 ng/dL is the optimal cut-off point for discriminating high WBPT.

Conclusions: The study results showed that TT is independently and inversely associated with WBPT in male patients with traditional cardiovascular risk factor and no history of cardiovascular disease. In addition, this study suggests that the incidence of primary cardiovascular events can be prevented by maintaining TT at approximately >/= 550 ng/dL from the perspective of blood rheology.

Hitsumoto T. Clinical Significance of Low Blood Testosterone Concentration in Men as a Cardiovascular Risk Factor From the Perspective of Blood Rheology. Cardiology research 2019;10:106-13. https://cardiologyres.org/index.php/Cardiologyres/article/view/858/911

 

[Michael Scally MD]

Potential Relation Between Soluble Growth Differentiation Factor-15 and Testosterone Deficiency in Male Patients with Coronary Artery Disease

BACKGROUND: There is a mutual interaction between inflammation and endocrine disorders in the development of coronary artery disease (CAD). Growth differentiation factor-15 (GDF-15) is associated with CAD, and the effects of testosterone on CAD as reported in literature have been considered as anti-atherosclerotic. The present study aimed to examine the possible association between serum GDF-15 and testosterone in male CAD patients.

METHODS: GDF-15 and testosterone concentrations were determined in blood samples of 426 male patients with CAD and 220 male controls. Serum concentrations of hs-CRP, and other baseline characteristics were also measured.

RESULTS: Serum levels of GDF-15 were higher in CAD patients when compared to controls, and testosterone concentrations were lower (p < 0.001). Patients with low testosterone levels had higher concentrations of GDF-15 (p < 0.001).

In stratified analyses, inverse relations between GDF-15 levels and testosterone were noted for almost all strata, stratified by categories of hs-CRP, leukocytes, neutrophils, neutrophil to lymphocyte ratio, glucose, HDL-c, and LDL-c, and whether had hypertension, diabetes, and underwent percutaneous coronary intervention (PCI).

Furthermore, in the linear regression models with bootstrap resampling with 1000 replications, high GDF-15 levels were independently associated with testosterone deficiency in male patients with CAD.

CONCLUSIONS: In male patients with CAD, high GDF-15 levels were associated with testosterone deficiency. These results support that upregulation of GDF-15 in the presence of low testosterone levels during CAD progression is a potential mechanism by which GDF-15 affects CAD.

Liu H, Lyu Y, Li D, et al. Potential relation between soluble growth differentiation factor-15 and testosterone deficiency in male patients with coronary artery disease. Cardiovasc Diabetol 2019;18:21. https://cardiab.biomedcentral.com/articles/10.1186/s12933-019-0823-3

 

[Michael Scally MD]

[Rats] Cardiac Electrical and Contractile Disorders Promoted by Anabolic Steroid Overdose are Associated with Late Autonomic Imbalance and Impaired Ca(2+) Handling

[AS overdose was induced by weekly intramuscular injection of nandrolone decanoate (DECAgroup, Deca Durabolin, Organon®, n = 29) at 10 mg/kg for 8 weeks.]

Highlights
· Nandrolone decanoate (DECA) promoted autonomic imbalance with decreased M2R mRNA expression.
· QTc interval and cardiomyocyte action potential were prolonged by DECA.
· Ito density of rat cardiomyocytes was decreased by DECA.
· ICaL density was up-regulated in cardiomyocytes of DECA-treated rats.
· Sarcoplasmic reticulum Ca+2 mobilization and Ca+2-induced tension were impaired by DECA.

AIM: Investigate cardiac electrical and mechanical dysfunctions elicited by chronic anabolic steroid (AS) overdose.

METHODS: Male Wistar rats were treated with nandrolone decanoate (DECA) or vehicle (CTL) for 8 weeks. Electrocardiography and heart rate variability were assessed at weeks 2, 4, and 8.

Cardiac reactivity to isoproterenol was investigated in isolated rat hearts. Action potential duration (APD) was measured from left ventricular (LV) muscle strips. L-type Ca(2+) current (ICaL), and transient outward potassium current (Ito) were recorded by whole-cell patch-clamp in LV cardiomyocytes.

Sarcoplasmic reticulum (SR) Ca(2+) mobilization and Ca(2+)-induced contractile response sensitivity were evaluated in skinned cardiac fibers. Muscarinic type 2 receptor (M2R), beta1-adrenergic receptor (beta1AR), sarcoplasmic Ca(2+) ATPase (SERCA-2a), type 2 ryanodine receptor (RyR2), L-type Ca(2+) channel (CACNA1), Kv4.2 (KCND2), and Kv4.3 (KCND3) mRNA expression levels were measured by quantitative RT-PCR.

RESULTS: Compared with CTL group, DECA group exhibited decreased high frequency band power density (HF) and increased low frequency power density (LF), Cardiac M2R mRNA level was decreased. QTc interval at 2(nd), 4(th), and 8(th) week as well as APD30 and APD90 were increased by DECA. Ito density was decreased, while ICaL density was increased by DECA. SR Ca(2+) loading and release were decreased by DECA, while contractile sensitivity to Ca(2+) was increased versus CTL group.

CONCLUSION: DECA overdose induced cardiac rhythmic and mechanical abnormalities that can be associated with autonomic imbalance, up-regulated ICaL and down-regulated Ito, abnormal SR Ca(2+) mobilization, and increased contractile sensitivity to Ca(2+).

Seara FAC, Arantes PC, Domingos AE, et al. Cardiac electrical and contractile disorders promoted by anabolic steroid overdose are associated with late autonomic imbalance and impaired Ca(2+) handling. Steroids 2019. https://www.sciencedirect.com/science/article/pii/S0039128X19300662?via=ihub

 

[Michael Scally MD]

Go Beyond LDL
CV Risk Beyond LDL Content Hub - American College of Cardiology

Cardiovascular (CV) disease is the leading cause of mortality in the US and globally contributing to more than 17 million deaths worldwide.

For years, lowering LDL-cholesterol has been one of the primary targets for reducing CV risk, with statins as the established treatment.

Recently, new science has emerged and is changing the landscape of how cardiologists and the broader CV team reduce CV risk in their patients.

The goal of this page is to provide a resource to highlight the most relevant content on the emerging science in CV risk beyond LDL.

Curated content will include new cutting-edge science along with foundational policy, education, and tools.

[Supported by: Amarin]

 

[Michael Scally MD]

An Update on Heart Disease Risk Associated with Testosterone Boosting Medications

INTRODUCTION: The cardiovascular (CV) safety of testosterone replacement therapy (TRT) remains a crucial issue in the management of subjects with late-onset hypogonadism. The authors systematically reviewed and discussed the available evidence focusing our analysis on heart-related issues.

AREAS COVERED: All the available data from prospective observational studies evaluating the role endogenous T levels on the risk of acute myocardial infarction (AMI) were collected and analyzed. In addition, the impact of TRT on heart-related diseases, as derived from pharmaco-epidemiological studies as well as from randomized placebo-controlled trials (RCTs), was also investigated.

EXPERT OPINION: Available evidence indicates that endogenous low T represents a risk factor of AMI incidence and its related mortality. TRT in hypogonadal patients is able to improve angina symptoms in subjects with ischemic heart diseases and exercise ability in patients with heart failure (HF). In addition, when prescribed according to the recommended dosage, TRT does not increase the risk of heart-related events.

Corona G, Rastrelli G, Guaraldi F, et al. An update on heart disease risk associated with testosterone boosting medications. Expert opinion on drug safety 2019;18:321-32. https://www.tandfonline.com/doi/abs/10.1080/14740338.2019.1607290?journalCode=ieds20

 

[Michael Scally MD]

Predictive Value of Low Testosterone Concentrations Regarding Coronary Heart Disease and Mortality

INTRODUCTION: The relevance of low testosterone concentrations for incident coronary heart disease (CHD) and mortality has been discussed in various studies. Here we evaluate the predictive value of low baseline testosterone levels in a large population-based cohort.

METHODS: We measured the serum levels of testosterone in 7,671 subjects (3,710 male, 3,961 female) of the population-based FINRISK97 study.

RESULTS: The median follow-up (FU) was 13.8 years. During the FU a total of 779 deaths from any cause, and 395 incident CHD events were recorded.

The age-adjusted baseline testosterone levels were similar in subjects suffering incident events during FU and those without incident events during FU (men: 15.80 vs 17.01 nmol/L; p= 0.69, women: 1.14 vs 1.15 nmol/L; p= 0.92).

Weak correlations of testosterone levels were found with smoking (R= 0.09; p<0.001), HDL-cholesterol levels (R= 0.22, p<0.001), systolic blood pressure (R= -0.05; p=0.011), BMI (R= -0.23; p<0.001), and waist-hip-ratio (R= -0.21; p<0.001) in men, and with eGFR (R= -0.05; p=0.009) in women.

Kaplan-Meier analyses did not reveal a positive association of testosterone levels with incident CHD or mortality. Accordingly, also in Cox regression analyses, testosterone levels were not predictive for incident CHD or mortality -neither in men (HR 1.02 [95%CI: 0.70-1.51]; p= 0.79 for lowest versus highest quarter regarding CHD and HR 1.06 [95%CI: 0.80-1.39]; p= 0.67 regarding mortality), nor in women (HR 1.13 [95%CI: 0.69-1.85]; p= 0.56 for lowest versus highest quarter regarding CHD and HR 0.99 [95%CI: 0.71-1.39]; p= 0.80 regarding mortality).

CONCLUSIONS: Low levels of testosterone are not predictive regarding future CHD or mortality -neither in men, nor in women.

Zeller T, Appelbaum S, Kuulasmaa K, et al. Predictive Value of Low Testosterone Concentrations Regarding Coronary Heart Disease and Mortality in Men and Women - Evidence From The FINRISK97 Study. J Intern Med 2019. Error - Cookies Turned Off

 

[Michael Scally MD]

Testosterone Replacement Therapy and Cardiovascular Risk

Key points

· Population studies suggest that low serum levels of endogenous testosterone are a risk factor for cardiovascular events, although these studies cannot establish causality or exclude reverse causality, and some of these associations might result from residual confounding.

· Although many retrospective studies show no association, some retrospective studies of prescription databases have shown a higher risk of cardiovascular events in men receiving testosterone, with the risk increasing early after treatment initiation.

· Meta- analyses of randomized, controlled trials of testosterone replacement therapy report conflicting findings, probably because the included trials lacked power or the duration was too short to assess cardiovascular events.

· The TRAVERSE trial, the first trial of testosterone therapy that is adequately powered to assess cardiovascular events, began in 2018, and its findings might take a decade to become available.

· Until the results of the TRAVERSE trial are available, clinicians should individualize testosterone treatment after having an informed discussion with their patients about the risks and benefits of testosterone replacement therapy.

Testosterone is the main male sex hormone and is essential for the maintenance of male secondary sexual characteristics and fertility. Androgen deficiency in young men owing to organic disease of the hypothalamus, pituitary gland or testes has been treated with testosterone replacement for decades without reports of increased cardiovascular events.

In the past decade, the number of testosterone prescriptions issued for middle-aged or older men with either age-related or obesity-related decline in serum testosterone levels has increased exponentially even though these conditions are not approved indications for testosterone therapy.

Some retrospective studies and randomized trials have suggested that testosterone replacement therapy increases the risk of cardiovascular disease, which has led the FDA to release a warning statement about the potential cardiovascular risks of testosterone replacement therapy. However, no trials of testosterone replacement therapy published to date were designed or adequately powered to assess cardiovascular events; therefore, the cardiovascular safety of this therapy remains unclear.

In this Review, we provide an overview of epidemiological data on the association between serum levels of endogenous testosterone and cardiovascular disease, prescription database studies on the risk of cardiovascular disease in men receiving testosterone therapy, randomized trials and meta-analyses evaluating testosterone replacement therapy and its association with cardiovascular events and mechanistic studies on the effects of testosterone on the cardiovascular system. Our aim is to help clinicians to make informed decisions when considering testosterone replacement therapy in their patients.

Gagliano-Jucá T, Basaria S. Testosterone replacement therapy and cardiovascular risk. Nature Reviews Cardiology 2019. https://doi.org/10.1038/s41569-019-0211-4

 

[Michael Scally MD]

Fat or Fiction: The Diet-Heart Hypothesis

The concept that diet, serum cholesterol and cardiovascular disease are causally related and gave rise to the diet-heart hypothesis nearly 70 years ago.

This hypothesis postulates that reducing dietary saturated fat reduces serum cholesterol, thereby reducing the risk of cardiovascular disease.

Today, this concept has been transformed from a hypothesis into public health policy as current guidelines recommend reducing the intake of dietary saturated fat.

Not all practitioners agree, however, and a reappraisal of the evidence may help resolve this controversy.

…

The preponderance of evidence indicates that low-fat diets that reduce serum cholesterol do not reduce cardiovascular events or mortality. Specifically, diets that replace saturated fat with polyunsaturated fat do not convincingly reduce cardiovascular events or mortality. These conclusions stand in contrast to current opinion.

There are several possible explanations. Foremost, we must consider that the diet-heart hypothesis is invalid or requires modification. Moreover, some experts may selectively cite evidence that validates their own viewpoint while disregarding evidence to the contrary, a behaviour called confirmation bias.

Others have noted the limitations of targeting a single risk factor in a multifactorial disease. Alternatively, the degree and/or duration of cholesterol reduction achieved with diet may simply be inadequate.

Finally, the concept that one can simply replace one macronutrient with another to prevent cardiovascular disease risks oversimplifying an extremely complex disease process.

DuBroff R, de Longeril M. Fat or fiction: the diet-heart hypothesis. BMJ Evidence-Based Medicine 2019:bmjebm-2019-111180. Fat or fiction: the diet-heart hypothesis

 

[Michael Scally MD]

[OA] Strong Muscles, Weak Heart: Testosterone-Induced Cardiomyopathy

Exogenous anabolic androgen steroid use is associated with adverse cardiovascular outcomes. A 53-year-old bodybuilder presented with 3 months of exertional dyspnoea. Physical examination showed tachycardia and pan-systolic murmur; an echocardiogram showed a left ventricular ejection fraction (EF) of 15%.

Evaluations included normal coronary angiogram, iron panel and thyroid studies, a negative viral panel (human immunodeficiency virus, Lyme disease, and hepatitis), and urine toxicology.

He admitted to intramuscular anabolic steroid use; his testosterone level was 30,160.0 ng/dL (normal 280-1100 ng/dL). In addition to discontinuation of anabolic steroid use, he was treated with guideline-directed heart failure medical therapy.

Repeat echocardiogram at 6 months showed an EF of 54% and normalized testosterone level of 603.7 ng/dL. Anabolic steroid use is a rare, reversible cause of cardiomyopathy in young, otherwise healthy athletes; a high index of suspicion is required to prevent potentially fatal side effects.

Doleeb S, Kratz A, Salter M, Thohan V. Strong muscles, weak heart: testosterone-induced cardiomyopathy. ESC heart failure 2019. Error - Cookies Turned Off

 

[Michael Scally MD]

Five-Year Prospective Study on Cardiovascular Events, In Patients with Erectile Dysfunction and Hypotestosterone

OBJECTIVE: Testosterone levels play a role in cardiac and vascular pathology. In the present study we investigated the prognostic significance of this hormone for cardiovascular outcome, in a 5-year follow-up.

MATERIALS AND METHODS: Our cohort included 802 adult subjects, from 40 to 80 years. Patients were excluded if they had a past history of peripheral or coronary artery disease, and revascularization. A blood sample was drawn to valuate testosterone level, and we considered normal testosterone levels 300 ng/dl.

FMD (flow mediated dilatation) of the brachial artery was assessed by measuring the increase of the brachial artery diameter during reactive hyperemia after transient forearm ischemia. B-mode longitudinal images of the brachial artery were obtained at the level of the antecubital fossa. The FMD was defined as the percentage change in the brachial artery diameter 60 s after releasing the ischemic cuff.

Erectile dysfunction (ERD) was assessed by the International Index of Erectile Function-5 (IIEF-5) score questionnaire. We considered composite end points including the following major adverse cardiovascular events (MACEs)

RESULTS: Subjects with lower serum testosterone levels (n = 332) had higher prevalence of traditional cardiovascular risk factors, such as hypertension (p = 0.009), diabetes (p = 0.03), dyslipidemia (p < 0.0001), obesity (p = 0.002), and endothelial function score (p < 0.0001).

AMI, death after AMI, major stroke and all clinical events were more frequent (p < 0.001) in patients with testosterone levels < 300 ng/dl.

Further, by multiple logistic regression analysis we found that only dyslipidemia (p = 0,001), obesity (p = 0,007), testosterone < 300 ng/dl (p < 0,0001) and ED (p < 0,0001) were independent predictors of future events.

CONCLUSIONS: A therapeutic intervention on testosterone may not only have a positive effect on the cardiovascular system but also an important role in preventing new cardiovascular events.

Iacona R, Bonomo V, Di Piazza M, et al. Five-year prospective study on cardiovascular events, in patients with erectile dysfunction and hypotestosterone. Archivio italiano di urologia, andrologia: organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica 2017;89:313-5. https://www.pagepressjournals.org/index.php/aiua/article/view/aiua.2017.4.313

 

[Michael Scally MD]

Asztalos BF, Niisuke K, Horvath KV. High-density lipoprotein: our elusive friend. Curr Opin Lipidol 2019;30:314-9. https://journals.lww.com/co-lipidol...ensity_lipoprotein__our_elusive_friend.8.aspx

PURPOSE OF REVIEW: Despite advances in the research on HDL composition (lipidomics and proteomics) and functions (cholesterol efflux and antioxidative capacities), the relationship between HDL compositional and functional properties is not fully understood. We have reviewed the recent literature on this topic and pointed out the difficulties which limit our understanding of HDL's role in cardiovascular disease (CVD).

RECENT FINDINGS: Though current findings strongly support that HDL has a significant role in CVD, the underlying mechanisms by which HDL mitigates CVD risk are not clear. This review focuses on studies that investigate the cell-cholesterol efflux capacity and the proteomic and lipidomic characterization of HDL and its subfractions especially those that analyzed the relationship between HDL composition and functions.

SUMMARY: Recent studies on HDL composition and HDL functions have greatly contributed to our understanding of HDL's role in CVD. A major problem in HDL research is the lack of standardization of both the HDL isolation and HDL functionality methods. Data generated by different methods often produce discordant results on the particle number, size, lipid and protein composition, and the various functions of HDL.

 

[hurricane]

[OA] Strong Muscles, Weak Heart: Testosterone-Induced Cardiomyopathy

Exogenous anabolic androgen steroid use is associated with adverse cardiovascular outcomes. A 53-year-old bodybuilder presented with 3 months of exertional dyspnoea. Physical examination showed tachycardia and pan-systolic murmur; an echocardiogram showed a left ventricular ejection fraction (EF) of 15%.

Evaluations included normal coronary angiogram, iron panel and thyroid studies, a negative viral panel (human immunodeficiency virus, Lyme disease, and hepatitis), and urine toxicology.

He admitted to intramuscular anabolic steroid use; his testosterone level was 30,160.0 ng/dL (normal 280-1100 ng/dL). In addition to discontinuation of anabolic steroid use, he was treated with guideline-directed heart failure medical therapy.

Repeat echocardiogram at 6 months showed an EF of 54% and normalized testosterone level of 603.7 ng/dL. Anabolic steroid use is a rare, reversible cause of cardiomyopathy in young, otherwise healthy athletes; a high index of suspicion is required to prevent potentially fatal side effects.

Doleeb S, Kratz A, Salter M, Thohan V. Strong muscles, weak heart: testosterone-induced cardiomyopathy. ESC heart failure 2019. Error - Cookies Turned Off

Pretty incredible for his EF to go from 15% to 54%. I never knew this about just testosterone.
Amazing how resilient the heart is. Not that i condone abusing it in the first place.

 

[Michael Scally MD]

[Rats] Chronic High-Dose Testosterone Treatment: Impact on Cardiac Contractile Biology

Androgen therapy provides cardiovascular benefits for hypogonadism. However, myocardial hypertrophy, fibrosis, and infarction have been reported in testosterone or androgenic anabolic steroid abuse. Therefore, better understanding of the factors leading to adverse results of androgen abuse is needed.

The aim of the present study was to examine the impact of high dose of androgen treatment on cardiac biology, and whether exposure duration modulates this response. Male rats were treated with 10 mg/kg testosterone, three times a week, for either 4 or 12 weeks; vehicle injections served as controls.

Four weeks of testosterone treatment induced an increase in ventricular wall thickness, indicative of concentric hypertrophy, as well as increased ejection fraction; in contrast, both parameters were blunted following 12 weeks of high-dose testosterone treatment.

Cardiac myocyte contractile parameters were assessed in isolated electrically stimulated myocytes (sarcomere and intracellular calcium dynamics), and in chemically permeabilized isolated myocardium (myofilament force development and tension-cost).

High-dose testosterone treatment for 4 weeks was associated with increased myocyte contractile parameters, while 12 weeks treatment induced significant depression of these parameters, mirroring the cardiac pump function results.

In conclusion, chronic administration of high-dose testosterone initially induces increased cardiac function. However, this initial beneficial impact is followed by significant depression of cardiac pump function, myocyte contractility, and cardiac myofilament function. Our results indicate that chronic high-testosterone usage is of limited use and may, instead, induce significant cardiac dysfunction.

Wadthaisong M, Witayavanitkul N, Bupha-Intr T, Wattanapermpool J, de Tombe PP. Chronic high-dose testosterone treatment: impact on rat cardiac contractile biology. Physiological Reports 2019;7:e14192. Error - Cookies Turned Off

 

[Michael Scally MD]

Relation of Testosterone Normalization to Mortality and Myocardial Infarction in Men with Prior Myocardial Infarction

The effect of normalization of serum testosterone levels with testosterone replacement therapy (TRT) in patients with a prior history of myocardial infarction (MI) is unknown. The objective of this study was to determine the incidence of recurrent MI and all-cause mortality in subjects with a history of MI and low total testosterone (TT) with and without TRT.

We retrospectively examined 1470 males with documented low TT levels and prior MI, categorized into
· Gp1: TRT with normalization of TT levels (N=755)
· Gp2: TRT without normalization of TT levels (N=542), and
· Gp3: no TRT (N=173).

The association of TRT with all-cause mortality and recurrent MI was compared using propensity score-weighted Cox proportional hazard models.

All-cause mortality was lower in Gp1 vs. Gp2 (HR 0.76, CI 0.64–0.90, P=0.002), and Gp1 vs Gp3 (HR 0.76, CI 0.60–0.98, P=0.031).

There was no significant difference in the risk of death between Gp2 vs. Gp3 (HR: 0.97, CI 0.76–1.24, P=0.81).

Adjusted regression analyses showed no significant differences in the risk of recurrent MI between groups (Gp1 vs. Gp3, HR 0.79, CI 0.12–5.27, P=0.8; Gp1 vs. Gp2 HR 1.10, CI 0.25–4.77, P=0.90; Gp2 vs. Gp3 HR 0.58, CI 0.08–4.06, P=0.58).

In conclusion, in a large observational cohort of male veterans with prior MI, normalization of TT levels with TRT was associated with decreased all-cause mortality compared to those with non-normalized TT levels and the untreated group. Furthermore, in this high-risk population, TRT was not associated with an increased risk of recurrent MI.

Oni OA, Dehkordi SHH, Jazayeri M-A, et al. Relation of Testosterone Normalization to Mortality and Myocardial Infarction in Men with Prior Myocardial Infarction. The American journal of cardiology 2019. https://www.sciencedirect.com/science/article/pii/S0002914919308161

 

[hurricane]

Relation of Testosterone Normalization to Mortality and Myocardial Infarction in Men with Prior Myocardial Infarction

The effect of normalization of serum testosterone levels with testosterone replacement therapy (TRT) in patients with a prior history of myocardial infarction (MI) is unknown. The objective of this study was to determine the incidence of recurrent MI and all-cause mortality in subjects with a history of MI and low total testosterone (TT) with and without TRT.

We retrospectively examined 1470 males with documented low TT levels and prior MI, categorized into
· Gp1: TRT with normalization of TT levels (N=755)
· Gp2: TRT without normalization of TT levels (N=542), and
· Gp3: no TRT (N=173).

The association of TRT with all-cause mortality and recurrent MI was compared using propensity score-weighted Cox proportional hazard models.

All-cause mortality was lower in Gp1 vs. Gp2 (HR 0.76, CI 0.64–0.90, P=0.002), and Gp1 vs Gp3 (HR 0.76, CI 0.60–0.98, P=0.031).

There was no significant difference in the risk of death between Gp2 vs. Gp3 (HR: 0.97, CI 0.76–1.24, P=0.81).

Adjusted regression analyses showed no significant differences in the risk of recurrent MI between groups (Gp1 vs. Gp3, HR 0.79, CI 0.12–5.27, P=0.8; Gp1 vs. Gp2 HR 1.10, CI 0.25–4.77, P=0.90; Gp2 vs. Gp3 HR 0.58, CI 0.08–4.06, P=0.58).

In conclusion, in a large observational cohort of male veterans with prior MI, normalization of TT levels with TRT was associated with decreased all-cause mortality compared to those with non-normalized TT levels and the untreated group. Furthermore, in this high-risk population, TRT was not associated with an increased risk of recurrent MI.

Oni OA, Dehkordi SHH, Jazayeri M-A, et al. Relation of Testosterone Normalization to Mortality and Myocardial Infarction in Men with Prior Myocardial Infarction. The American journal of cardiology 2019. https://www.sciencedirect.com/science/article/pii/S0002914919308161

Interesting study. I hope i never need trt but it's good to know a study has been done on those like myself.

 

[Michael Scally MD]

[OA] Testosterone and the Heart

The development of a subnormal level of testosterone (T) is not universal in ageing men, with 75% of men retaining normal levels. However, a substantial number of men do develop T deficiency (TD), with many of them carrying a portfolio of cardiovascular (CV) risk factors, including type 2 diabetes (T2D) and the metabolic syndrome. TD increases the risk of CV disease (CVD) and the risk of developing T2D and the metabolic syndrome.

The key symptoms suggesting low T are sexual in nature, including erectile dysfunction (ED), loss of night-time erections and reduced libido. Many men with heart disease, if asked, admit to ED being present; a problem that is often compounded by drugs used to treat CVD. A large number of studies and meta-analyses have provided evidence of the link between TD and an increase in CVD and total mortality. Patients with chronic heart failure (CHF) who have TD have a poor prognosis and this is associated with more frequent admissions and increased mortality compared with those who do not have TD.

Conversely, in men with symptoms and documented TD, T therapy has been shown to have beneficial effects, namely improvement in exercise capacity in patients with CHF, improvement of myocardial ischaemia and coronary artery disease. Reductions in BMI and waist circumference, and improvements in glycaemic control and lipid profiles, are observed in T-deficient men receiving T therapy. These effects might be expected to translate into benefits and there are more than 100 studies showing CV benefit or improved CV risk factors with T therapy.

There are flawed retrospective and prescribing data studies that have suggested increased mortality in treated men, which has led to regulatory warnings, and one placebo-controlled study demonstrating an increase in coronary artery non-calcified and total plaque volumes in men treated with T, which is open for debate. Men with ED and TD who fail to respond to phosphodiesterase type 5 (PDE5) inhibitors can be salvaged by treating the TD. There are data to suggest that T and PDE5 inhibitors may act synergistically to reduce CV risk.

Kirby M, Hackett G, Ramachandran S. Testosterone and the Heart. European cardiology 2019;14:103-10. https://www.ecrjournal.com/testosterone-and-heart