AAS and Cardiovascular/Pulmonary Function

[Michael Scally MD]

Sun H, Oh Y, Ding M, Yang P. More Caution Is Required for the Iatrogenic Short QT: Additional Concerning on Shortened QTc by Testosterone Treatment. Pacing Clin Electrophysiol. http://onlinelibrary.wiley.com/doi/10.1111/pace.12659/abstract

We read with great interest the article by Jorgensen et al. (1) published on PACE recently. http://onlinelibrary.wiley.com/doi/10.1111/pace.12580/abstract

Although short QT in addition to long QT are closely related cardiopathic conditions, which could both ultimately increase the risk of arrhythmias and sudden death, risk related to acquired short QT syndrome is relatively underestimated.

Here the authors reported a new potential electrophysiological feature characterizing KS patients demonstrated in their electrocardiogram(ECG) recordings; the study showed a decrease in the corrected QT interval (QTc) in Klinefelter Syndrome (KS) patients, illustrated by multiple linear regressions.

Surprisingly, testosterone (T) treated KS patients displayed even shorter QTc compared to untreated and controls.

These findings are of significant importance as they imply that caution is needed for the iatrogenic short QT internals. We believe additional aspects should be taken into account.


Jorgensen IN, Skakkebaek A, Andersen NH, Pedersen LN, Hougaard DM, et al. Short QTc Interval in Males with Klinefelter Syndrome-Influence of CAG Repeat Length, Body Composition, and Testosterone Replacement Therapy. Pacing Clin Electrophysiol. 2015;38(4):472-82. http://onlinelibrary.wiley.com/doi/10.1111/pace.12580/abstract

BACKGROUND: Klinefelter syndrome (KS) is a sex chromosomal aneuploidy (47,XXY) affecting 1/660 males. Based on findings in Turner syndrome, we hypothesized that electrocardiogram (ECG) abnormalities would be present in males with KS.

OBJECTIVE: To investigate ECGs in males with KS and compare with controls. METHODS: Case control study of 62 males with KS and 62 healthy males matched on age. The primary outcome parameter was a difference in the ECG presentation between the two groups. The ECGs were analyzed by one blinded examiner (intraobserver variability 0.2-2.1%). The QT-interval was measured using "teach-the-tangent" method excluding the U-wave. QTc was calculated using Bazett's equation, Hodges' equation, and a linear regression model. Body mass index, abdominal fat, and muscle mass as well as sex hormone levels were secondary parameters. The prevalence of mutations in genes related to short QT syndrome was determined in participants with a QTc < 330 ms.

RESULTS: Compared to controls, the QTc-interval was shorter (P = 0.02-0.06) in males with KS depending on the applied correction method. QTc was shortest among testosterone (T)-treated males with KS, while untreated and thus hypogonadal KS had QTc interval comparable to controls. No mutations in genes related to short QT syndrome were found.

CONCLUSION: We found short QTc interval in males with KS, with further shortening of the QTc interval by T. These results suggest that genes on the X chromosome could be involved in regulation of the QTc interval and that T treatment may aggravate this mechanism.

 

[Michael Scally MD]

Defining the Incidence of Polycythemia in Men Using Intramuscular Testosterone Supplementation
http://www.aua2015.org/abstracts/abstractprint.cfm?id=MP51-05

Introduction and Objectives - Polycythemia (PCT) is well-recognized adverse effect of testosterone supplementation. However, widely disparate rates exist in the literature (2-24%) based on varied definitions of PCT and modality of T supplementation. We attempted to determine the rate of PCT in patients in our intramuscular testosterone (IMT) program.

Methods - Symptomatic men with two low total T (TT) levels (<350 ng/dl), using IMT for at least 6 months comprised the study cohort. Men used 200mg IM every 2 weeks and had peak (day 1-2) and trough T (day 13-14) levels checked after two cycles, and every 6 months.

PCT was defined as hematocrit (HCT) ≥52%. Patients were excluded from IMT if they had baseline HCT >48%. A multivariate model was constructed to define predictors of PCT development.

Factors assessed included: patient age, mean BMI, cigarette smoking history, baseline HCT, mean per patient peak TT level, mean per patient trough TT level,

Results - 176 men were analyzed. 24% were diabetic, 48% prior or current cigarette smokers.

At baseline, mean TT = 224±104 ng/dl. mean HCT = 38±6%, mean BMI = 32±6. Mean duration on IMT = 17±23 months. Mean peak TT level = 1164±240 ng/dl, mean trough TT level = 324±180 ng/dl. Mean HCT for entire cohort on IMT = 44±9 (39-57)%, representing a mean per patient change of 4.7±3.9 (2-11)%.

17% met the definition of HCT on IMT with a mean HCT = 54.2±1.8%. 23/30 patients with PCT developed it after 6 months on IMT. Factors found to be a predictor on multivariate analysis are listed in the Tables 1and 2, however cigarette smoking was not a predictor.

Conclusions - Almost one fifth of men on IMT experience PCT. Most men appear to develop it after 6 months of treatment. Predictors of PCT development are higher baseline HCT and higher peak TT levels.

 

[Michael Scally MD]

Lai J, Ge Y, Shao Y, Xuan T, Xia S, et al. Low serum testosterone level was associated with extensive coronary artery calcification in elderly male patients with stable coronary artery disease. Coron Artery Dis. http://journals.lww.com/coronary-ar...osterone_level_was_associated_with.99412.aspx

BACKGROUND: Coronary artery calcification (CAC) is a pandemic condition in elderly patients with coronary artery disease (CAD) and associated with a worse prognosis.

Although available data have shown an association between testosterone levels in men and CAD, the association between testosterone and CAC in elderly male patients with CAD remains unknown.

METHODS: A total of 211 consecutive male patients (age>/=65 years) who underwent first multidetector computed tomography and following angiography were enrolled from our institution between March 2009 and September 2014. CAD was angiographically documented as significant stenoses (reduction>/=50% of the lumen diameter) on any major coronary vessel. The standard Agatston calcium score was calculated.

The relationship of serum testosterone level with the CAC score measured by multidetector computed tomography in elderly male patients with stable CAD was evaluated.

For data analyses, the CAC score was divided into four categories: </=10, 11-99, 100-399, and >/=400, corresponding to minimal, moderate, increased, and extensive calcification.

RESULTS: Patients with higher CAC scores had significantly lower testosterone levels than patients with lower CAC scores (P=0.048). In logistic regression analysis, testosterone level remained an independent predictor of extensive CAC (odds ratio 0.997, 95% confidence interval 0.994-0.999, P=0.043).

CONCLUSION: Our findings indicate an inverse association between testosterone level and the susceptibility to extensive CAC in elderly men with stable CAD.

 

[Michael Scally MD]

Chung CC, Hsu RC, Kao YH, Liou JP, Lu YY, et al. Androgen attenuates cardiac fibroblasts activations through modulations of transforming growth factor-beta and angiotensin II signaling. Int J Cardiol. 2014;176(2):386-93. http://linkinghub.elsevier.com/retrieve/pii/S0167-5273(14)01287-X

BACKGROUND: Androgen deficiency produces heart failure, which can be ameliorated by testosterone supplementation. Cardiac fibrosis plays a critical role in the pathophysiology of heart failure. This study aimed to evaluate whether testosterone can attenuate cardiac fibroblast activity through modulating transforming growth factor (TGF)-beta and angiotensin (Ang) II signaling.

METHODS: Migration, proliferation, myofibroblast differentiation, collagen production, and transcription signaling were evaluated in adult male rat (weighing 300-350 g) cardiac fibroblasts with and without incubation with testosterone (10nM) and co-administration of TGF-beta1 (10 ng/ml) or Ang II (100 nM) by cell migration analysis, proliferation assay, soluble collagen measurement, zymographic analysis, immunofluorescence microscopy, real-time PCR and Western blot.

RESULTS: Compared to those without testosterone, testosterone-treated fibroblasts exhibited less collagen production. Testosterone-treated fibroblasts also had less migration, proliferation, myofibroblast differentiation, and collagen production in the presence of TGF-beta1, or had less collagen production with Ang II. Testosterone-treated fibroblasts had decreased phosphorylated Akt, mammalian target of rapamycin, and 4E binding protein-1 irrespective of TGF-beta1 treatment and had increased matrix metalloproteinase (MMP)-2 in the presence of TGF-beta1 treatment, and had decreased phosphorylated P38 and Smad 2/3 levels in the presence of Ang II. Cardiac fibroblasts with and without testosterone had similar mRNA and protein expressions of total Akt and total Smad 2/3 irrespective of TGF-beta1 or Ang II treatment.

CONCLUSION: Physiological level of testosterone attenuated Akt and Smad 2/3 phosphorylation mediated by TGF-beta1 and angiotensin II respectively, which can result in decreased cardiac fibroblast activation and potentially contribute to beneficial effects in heart failure.

 

[Michael Scally MD]

Anabolic Steroids And Cardiovascular Risk: A National Population-Based Cohort Study


Highlights
· This is a nationwide population study
· We examine cardiac events and general mortality in anabolic androgenic steroids (AAS) user.
· Our results suggest that use of anabolic steroids is an independent risk factor for cardiac disease

Thiblin I, Garmo H, Garle M, Holmberg L, Byberg L, et al. Anabolic steroids and cardiovascular risk: A national population-based cohort study. Drug and Alcohol Dependence. https://www.sciencedirect.com/science/article/pii/S0376871615002094

Background Non-therapeutic use of anabolic androgenic steroids (AAS) has been associated with various adverse effects; one of the most serious being direct cardiovascular effects with unknown long-term consequences. Therefore, large studies of the association between AAS and cardiovascular outcomes are warranted. We investigated cardiovascular morbidity and mortality in individuals who tested positive for AAS.

Methods and Results Between 2002 and 2009, a total of 2013 men were enrolled in a cohort on the date of their first AAS test. Mortality and morbidity after cohort entry was retrieved from national registries. Of the 2013 individuals, 409 (20%) tested positive for AAS. These men had twice the cardiovascular morbidity and mortality rate as those with negative tests (adjusted hazard ratio (aHR) 2.0; 95% confidence interval (CI) 1.2-3.3). Compared to the Swedish population, all tested men had an increased risk of premature death from all causes (standardized mortality ratio for AAS-positive: 19.3, 95% CI 12.4-30.0; for AAS-negative: 8.3, 95% CI 6.1-11.0).

Conclusion Non-therapeutic exposure to AAS appears to be an independent risk factor for cardiovascular morbidity and premature death.

 

[Michael Scally MD]

Gheshlaghi F, Piri-Ardakani MR, Masoumi GR, Behjati M, Paydar P. Cardiovascular manifestations of anabolic steroids in association with demographic variables in body building athletes. J Res Med Sci. 2015;20(2):165-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400712/

BACKGROUND: The most common drug abuse among athletes is anabolic steroids which lead to the development of cardiovascular diseases and sudden death. Thus, the aim of this study was to evaluate cardiovascular outcomes of anabolic consumption in body building athletes.

MATERIALS AND METHODS: Totally, 267 male athletes at the range of 20-45 years old with the regular consumption of anabolic steroids for >2 months with at least once weekly. High-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), and hematocrit (Hct) levels were measured after 10 h of fasting. Data analysis was performed using K2, t-test, ANOVA and correlation coefficient through SPSS 17.

RESULTS: There was a nonsignificant difference between groups regarding HDL, TG, and total cholesterol. There was a significant decrease in the total and categorized LDL and Hct levels in consumers of anabolic steroid versus nonusers (P = 0.01 and P = 0.041, respectively). Results showed a significant increase in systolic and diastolic blood pressure (SBP and DBP) in anabolic steroid users which associates with duration of abuse (P = 0.02 and P = 0.03, respectively). No significant electrocardiography changes were found within the follow-up period.

CONCLUSION: Increase in SBP or DBP is a common complication of these drugs which can lead serious vascular disorders. The lower LDL cholesterol level might be due to the higher amounts of lipid consumption in these athletes.

 

[Michael Scally MD]

Semsarian C, Sweeting J, Ackerman MJ. Sudden cardiac death in athletes. BMJ. 2015;350:h1218. http://www.bmj.com/content/350/bmj.h1218.long

Sudden cardiac death is defined as an unexpected death, occurring usually within one hour from onset of symptoms in cases where the death is witnessed and in unwitnessed cases within 24 hours of the individual last being seen alive and well.

Sudden cardiac death in athletes is the leading cause of medical death in this subgroup, with an estimated incidence of 1 in 50 000 to 1 in 80 000 athletes per year, although a wide range has been reported, from 1 in 3000 in some subpopulations to 1 in 1 000 000. Males, black or African Americans, and basketball players seem to be at a higher risk than other subgroups.

Although rare, sudden cardiac death in athletes is important because of its impact within both the sporting community and the general community. The widely held perception is that athletes represent examples of health and vitality, so the sudden cardiac death of an athlete can evoke strong emotions and disbelief.

The esteem in which athletes are held, in combination with often highly emotive reporting from the media, means that these events are tragedies not only on a personal family level but also at a public level.

This review summarises the common causes of sudden cardiac death in athletes and examines whether systematic training can confer increased risk for the condition. Also considered are the measures that can be undertaken to prevent sudden cardiac death.

 

[Millard]

Polycythemia (pct) is well-recognized adverse effect of testosterone supplementation

But that acronym is already taken...

 

[Michael Scally MD]

Pongkan W, Chattipakorn SC, Chattipakorn N. Roles of Testosterone Replacement in Cardiac Ischemia-Reperfusion Injury. J Cardiovasc Pharmacol Ther. http://cpt.sagepub.com/content/early/2015/05/25/1074248415587977.abstract

Testosterone is an anabolic steroid hormone, which is the major circulating androgen hormone in males. Testosterone levels decreasing below the normal physiological levels lead to a status known as androgen deficiency.

Androgen deficiency has been shown to be a major risk factor in the development of several disorders, including obesity, metabolic syndrome, and ischemic heart disease.

In the past decades, although several studies from animal models as well as clinical studies demonstrated that testosterone exerted cardioprotection, particularly during ischemia-reperfusion (I/R) injury, other preclinical and clinical studies have shown an inverse relationship between testosterone levels and cardioprotective effects. As a result, the effects of testosterone replacement on the heart remain controversial.

In this review, reports regarding the roles of testosterone replacement in the heart following I/R injury are comprehensively summarized and discussed.

At present, it may be concluded that chronic testosterone replacement at a physiological dose demonstrated cardioprotective effects, whereas acute testosterone replacement can cause adverse effects in the I/R heart.

 

[Michael Scally MD]

Corrigan FE, 3rd, Al Mheid I, Eapen DJ, Hayek SS, Sher S, et al. Low testosterone in men predicts impaired arterial elasticity and microvascular function. Int J Cardiol. 2015;194:94-9. https://www.sciencedirect.com/science/article/pii/S0167527315011110

BACKGROUND: A low testosterone level in men is associated with increased adiposity, insulin resistance, and dyslipidemia. Whether low testosterone level is associated with arterial stiffness and endothelial and microvascular dysfunction remains unknown and was investigated in this study.

METHODS: Serum testosterone was measured in 237 healthy men aged 50years (SD 12). Endothelial and microvascular function were assessed as brachial artery flow-mediated dilation (FMD) and digital reactive hyperemia index (RHI), respectively. Arterial stiffness was evaluated by tonometry-derived pulse wave velocity (PWV) and central augmentation index (AIX).

RESULTS: Mean total testosterone level was 16.3nmol/L (SD 6.11) and 25% of subjects had low levels (<12.0nmol/L). Testosterone level correlated positively with RHI (r=0.24, p<0.001) and inversely with AIX (r=-0.14, p=0.033) but not with FMD or PWV, indicating impaired microvascular hyperemia and arterial elasticity with lower testosterone levels. After multivariate adjustment for the Framingham Risk Score and weight, testosterone level remained an independent predictor of RHI and AIX (beta=0.23, -0.13; p=0.001, 0.04, respectively).

CONCLUSION: In men with few co-morbidities, lower serum testosterone level is associated with microvascular dysfunction and increased pulse wave reflections, mechanisms by which lower testosterone levels may confer increased cardiovascular risk. Whether normalization of low testosterone level improves vascular function needs further investigation.

 

[Michael Scally MD]

MicroRNA are a growing field. Watch for them!!!

miR-222 Is Necessary for Exercise-Induced Cardiac Growth and Protects against Pathological Cardiac Remodeling [How does exercise improve cardiac health?]

Highlights

• MicroRNAs concordantly regulated by distinct forms of exercise were identified
• miR-222 induces cellular hypertrophy and proliferation in vitro via distinct targets
• Inhibition of miR-222 in vivo completely blocks exercise-induced cardiac growth
• Cardiac expression of miR-222 reduces adverse remodeling after ischemic injury

Liu X, Xiao J, Zhu H, Wei X, Platt C, et al. miR-222 Is Necessary for Exercise-Induced Cardiac Growth and Protects against Pathological Cardiac Remodeling. Cell Metabolism. 2015;21(4):584-95. http://www.cell.com/cell-metabolism/abstract/S1550-4131(15)00066-2

Exercise induces physiological cardiac growth and protects the heart against pathological remodeling.

Recent work suggests exercise also enhances the heart’s capacity for repair, which could be important for regenerative therapies.

While microRNAs are important in certain cardiac pathologies, less is known about their functional roles in exercise-induced cardiac phenotypes.

We profiled cardiac microRNA expression in two distinct models of exercise and found microRNA-222 (miR-222) was upregulated in both.

Downstream miR-222 targets modulating cardiomyocyte phenotypes were identified, including HIPK1 and HMBOX1.

Inhibition of miR-222 in vivo completely blocked cardiac and cardiomyocyte growth in response to exercise while reducing markers of cardiomyocyte proliferation. Importantly, mice with inducible cardiomyocyte miR-222 expression were resistant to adverse cardiac remodeling and dysfunction after ischemic injury.

These studies implicate miR-222 as necessary for exercise-induced cardiomyocyte growth and proliferation in the adult mammalian heart and show that it is sufficient to protect the heart against adverse remodeling.





Maladaptive and Adaptive Cardiac Growth

Physiological stress, such as exercise, promotes adaptive growth of the heart. Conversely, disease-related stress triggers maladaptive cardiac remodeling.

Current evidence suggests that these two types of cardiac growth are mutually antagonistic and that the promotion of adaptive growth can mitigate disease-related change.

In a recent study, the microRNA miR-222 was unveiled as a “brake” on pathways promoting maladaptive cardiac remodeling.

 

[Michael Scally MD]

Wickramatilake CM, Mohideen MR, Pathirana C. Association of serum testosterone with the complications of acute myocardial infarction. Pak Heart J 2015;48(01):28-35. http://www.pkheartjournal.com/index.php/pkheart/article/view/871

Objective: The objectives of the study were to assess (1) if serum levels of testosterone differ between men with and those without ST-elevation myocardial infarction, and (2) to determine the association of testosterone with the outcome of ST-elevation myocardial infarction (STEMI).

Methodology: This was hospital based case control study, conducted at Coronary Care Unit of Teaching Hospital, Karapitiya, Galle, Sri Lanka from January 2010 to December 2011. Two hundred and six males (103 patients with STEMI and 103 controls without a history of CAD) were studied. Serum total testosterone, lipids and plasma glucose were estimated.

Results: The basal serum total testosterone in patients was significantly lower compared to controls (11.47 ± 3.3 vs. 18.15 ± 7.2 nmol/L, P = 0.001). The results showed that total testosterone (P = 0.001; OR = 0.75; 95 % CI = 0.66 -0.85) was a significant independent predictor of STEMI and it was a significant independent predictors of in-hospital complications (P = 0.003, OR = 1.68, 95% CI = 1.2 - 2.36).

Conclusion: Men with STEMI have significantly lower basal serum total testosterone compared to controls. Low testosterone is a risk factor of STEMI. Testosterone was independently related to the development of in-hospital complications of STEMI.

 

[Michael Scally MD]

Krysiak R, Gilowski W, Okopien B. The effect of testosterone and fenofibrate, administered alone or in combination, on cardiometabolic risk factors in men with late-onset hypogonadism and atherogenic dyslipidemia. Cardiovascular Therapeutics. http://onlinelibrary.wiley.com/doi/10.1111/1755-5922.12139/abstract

Introduction Oral testosterone was found to reduce plasma levels of HDL cholesterol. No previous study has examined the effect of fibrates, known to increase HDL cholesterol, in patients with low testosterone levels requiring testosterone replacement.

Aims The study included three age-, weight- and lipid-matched groups of older men with atherogenic dyslipidemia and late-onset hypogonadism, treated with oral testosterone undecanoate (120 mg daily, n=15), micronized fenofibrate (200 mg daily, n=15) or testosterone plus fenofibrate (n=18).

Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were assessed before and after 16 weeks of therapy.

Results Apart from an increase in plasma testosterone and a reduction in HDL cholesterol, testosterone undecanoate tended to decrease hsCRP and to improve insulin sensitivity. Fenofibrate administered alone increased HDL cholesterol, reduced triglycerides, decreased insulin resistance, reduced circulating levels of uric acid, hsCRP and fibrinogen, as well as increased plasma levels of homocysteine.

The strongest effect on testosterone, HOMA1-IR, uric acid, hsCRP and fibrinogen was observed if fenofibrate was administered together with testosterone.

Testosterone-fenofibrate combination therapy was also devoid of unfavorable effect on HDL cholesterol and homocysteine.

Conclusions Our study shows that fenofibrate produces a stronger effect on cardiometabolic risk factors in men with late-onset hypogonadism and atherogenic dyslipidemia than oral testosterone undecanoate. The obtained results suggest that this group of patients may benefit the most from the combined treatment with oral testosterone undecanoate and micronized fenofibrate.

 

[Michael Scally MD]

Xiao FY, Nheu L, Komesaroff P, Ling S. Testosterone protects cardiac myocytes from superoxide injury via NF-kappaB signalling pathways. Life Sci. https://www.sciencedirect.com/science/article/pii/S0024320515002854

AIMS: Cellular and molecular mechanisms underlying the effects of androgenic hormone testosterone on the heart remain unclear. This study examined the impact of testosterone on viability of cardiac myocytes and the role of NF-kappaB signalling pathways.

MATERIALS AND METHODS: Rat H9c2 myocytes were cultured in steroid-free media and incubated with hydrogen peroxide (H2O2, 200muM, 6h). NF-kappaB expression was knocked down by RelA (p65) siRNA interference. Testosterone (5-100nM, 24-48h) was provided into the media and androgen receptor (AR) blocked by flutamide (100nM). Cell apoptotic/necrotic death was determined by morphological examination and flow-cytometric analysis. Gene expression was examined by Western blotting analysis.

KEY FINDINGS: Testosterone supplements reduced the superoxide-induced apoptotic/necrotic death, stimulated NF-kappaB (RelA) expression, activated Akt activity, and inhibited Caspase-3 expression in the cardiac myocytes. The hormonal effects were abolished by either AR blocker flutamide or NF-kappaB-knockdown. Testosterone also induced ERK1/2 activation, which was not affected by flutamide or NF-kappaB knockdown, and blocking the ERK activity did not affect the protective effect of the hormone on the cells.

SIGNIFICANCE: This study demonstrates that exogenous testosterone supplementation protects cardiac myocytes from superoxide injury via AR mediation and dependent on normally functional canonical NF-kappaB (RelA/p50) signalling pathways. The NF-kappaB signalling may be an important key molecular basis for myocardial benefits of hormone (testosterone) therapy.

 

[Michael Scally MD]

Lusetti M, Licata M, Silingardi E, Reggiani Bonetti L, Palmiere C. Pathological changes in anabolic androgenic steroid users. J Forensic Leg Med. 2015;33:101-4. http://www.ncbi.nlm.nih.gov/pubmed/26048507
http://linkinghub.elsevier.com/retrieve/pii/S1752-928X(15)00077-3

Several classes of recreational and prescription drugs have additional effects on the heart and vasculature, which may significantly contribute to morbidity and mortality in chronic users.

The study presented herein focuses on pathological changes involving the heart possibly due to anabolic androgenic steroid use. The role these hormones may play in their occurrence of sudden cardiac death is also investigated.

98 medico-legal cases including 6 anabolic androgenic steroid users were retrospectively reviewed. Autopsies, histology, immunohistochemistry, biochemistry and toxicology were performed in all cases.

Pathological changes consisted of various degrees of interstitial and perivascular fibrosis as well as fibroadipous metaplasia and perineural fibrosis within the myocardium of the left ventricle.

Within the limits of the small number of investigated cases, our results appear to confirm former observations on this topic and suggest anabolic androgenic steroid's potential causative role in the pathogenesis of sudden cardiac deaths in chronic users.

 

[Michael Scally MD]

Sculthorpe N, Taylor L, Grace FM. Prolonged androgenic anabolic steroid (AAS) induced QT interval shortening: a suitable screening tool? Drug Test Anal. http://onlinelibrary.wiley.com/doi/10.1002/dta.1826/abstract

Androgenic anabolic steroid (AAS) abuse is associated with changes in cardiac electrophysiology. Recently heart rate corrected QT interval (QTc) has been suggested as a method of screening for AAS use in athletes despite conflicting reports.

This study aimed to further investigate the effect of AAS on QTc in a cohort of long-term AAS users in whom the affects may be more pronounced.

Using a cross-sectional cohort design with AAS using resistance trained athletes (AS n = 15) and a group of non-AAS using resistance trained, age matched controls (C n = 15). AS had a long history of AAS use (18 +/- 2 yrs) and AS and C both had >19 years of resistance training.

Participants underwent a resting electrocardiogram (ECG), from which, the QTc interval was calculated using the Bazett formula. The main outcome measure was significant differences in mean corrected QTc between groups. A secondary outcome was to calculate a QTc that best differentiated between C and AS.

Results indicated that QTc was shorter in AS than in C (382.0 +/- 21.01 ms versus 409 +/- 18.77 ms for AS and C respectively p < 0.001). Chi squared analyses revealed a greater incidence of QTc < 380 ms in AS versus C p < 0.01, specificity 93% sensitivity 60%).

In conclusion these results supports previous findings that AAS use causes a reduction in QTc, however, the specificity and sensitivity in our sample is lower than reported previously and precludes use as a screening tool. Copyright (c) 2015 John Wiley & Sons, Ltd.

 

[Michael Scally MD]

Chan YX, Knuiman MW, Hung J, Divitini ML, Handelsman DJ, et al. Testosterone, dihydrotestosterone and estradiol are differentially associated with carotid intima-media thickness and the presence of carotid plaque in men with and without coronary artery disease. Endocr J. https://www.jstage.jst.go.jp/article/endocrj/advpub/0/advpub_EJ15-0196/_article

Clarifying the relationship of sex hormones to preclinical atherosclerosis could illuminate pathways by which androgens are associated with cardiovascular events and mortality.

Our aim was to determine hormone profiles associated with carotid intima-media thickness (CIMT) and carotid atheroma, in men with and without known coronary artery disease (CAD). We included 492 community-based men aged 20-70 years (Group A) and 426 men with angiographically proven CAD aged <60 years (Group B).

Fasting early morning sera were assayed for testosterone (T), dihydrotestosterone (DHT) and estradiol (E2) using mass spectrometry. CIMT and carotid plaque were assessed ultrasonographically.

Mean (+/-SD) age was Group A: 53.8+/-12.6 and Group B: 49.6+/-5.1 years.

Higher T was associated with reduced CIMT (-0.011 mm per 1-SD increase, p=0.042) and lower prevalence of carotid plaque (odds ratio [OR] per 1-SD increase, 0.68, p=0.012) in Group A, but not B.

E2 was associated with increased CIMT in Group A (0.013 mm, p=0.011) but not B.

Higher DHT and E2 were associated with reduced carotid plaque in Group B (DHT: OR=0.77, p=0.024; E2: OR=0.75, p=0.008), but not A.

In community-dwelling men, higher T is associated with favourable CIMT and lower prevalence of carotid plaque, while higher E2 is associated with worse CIMT.

In men with CAD, higher DHT or E2 are associated with less carotid plaque.

T, DHT and E2 are differentially associated with preclinical carotid atherosclerosis in a cardiovascular phenotype-specific manner. Interventional studies are needed to examine effects of exogenous T and its metabolites DHT and E2, on atherogenesis.

 

[Michael Scally MD]

[OA] Frati P, Busardo FP, Cipolloni L, Dominicis ED, Fineschi V. Anabolic Androgenic Steroid (AAS) Related Deaths: Autoptic, Histopathological and Toxicological Findings. Curr Neuropharmacol. 2015;13(1):146-59. http://www.eurekaselect.com/126870/article

Anabolic androgenic steroids (AASs) represent a large group of synthetic derivatives of testosterone, produced to maximize anabolic effects and minimize the androgenic ones.

AAS can be administered orally, parenterally by intramuscular injection and transdermally.

Androgens act by binding to the nuclear androgen receptor (AR) in the cytoplasm and then translocate into the nucleus. This binding results in sequential conformational changes of the receptor affecting the interaction between receptor and protein, and receptor and DNA.

Skeletal muscle can be considered as the main target tissue for the anabolic effects of AAS, which are mediated by ARs which after exposure to AASs are up-regulated and their number increases with body building.

Therefore, AASs determine an increase in muscle size as a consequence of a dose-dependent hypertrophy resulting in an increase of the cross-sectional areas of both type I and type II muscle fibers and myonuclear domains.

Moreover, it has been reported that AASs can increase tolerance to exercise by making the muscles more capable to overload therefore shielding them from muscle fiber damage and improving the level of protein synthesis during recovery.

Despite some therapeutic use of AASs, there is also wide abuse among athletes especially bodybuilders in order to improve their performances and to increase muscle growth and lean body mass, taking into account the significant anabolic effects of these drugs.

The prolonged misuse and abuse of AASs can determine several adverse effects, some of which may be even fatal especially on the cardiovascular system because they may increase the risk of sudden cardiac death (SCD), myocardial infarction, altered serum lipoproteins, and cardiac hypertrophy.

The aim of this review is to focus on deaths related to AAS abuse, trying to evaluate the autoptic, histopathological and toxicological findings in order to investigate the pathophysiological mechanism that underlines this type of death, which is still obscure in several aspects.

The review of the literature allowed us to identify 19 fatal cases between 1990 and 2012, in which the autopsy excluded in all cases, extracardiac causes of death.

 

[Michael Scally MD]

Eat Chocolate!!!


Kwok CS, Boekholdt SM, Lentjes MAH, Loke YK, Luben RN, et al. Habitual chocolate consumption and risk of cardiovascular disease among healthy men and women. Heart. http://heart.bmj.com/content/early/2015/05/20/heartjnl-2014-307050.full

Objective To examine the association between chocolate intake and the risk of future cardiovascular events.

Methods We conducted a prospective study using data from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Habitual chocolate intake was quantified using the baseline food frequency questionnaire (1993–1997) and cardiovascular end points were ascertained up to March 2008. A systematic review was performed to evaluate chocolate consumption and cardiovascular outcomes.

Results A total of 20 951 men and women were included in EPIC-Norfolk analysis (mean follow-up 11.3±2.8 years, median 11.9 years). The percentage of participants with coronary heart disease (CHD) in the highest and lowest quintile of chocolate consumption was 9.7% and 13.8%, and the respective rates for stroke were 3.1% and 5.4%. The multivariate-adjusted HR for CHD was 0.88 (95% CI 0.77 to 1.01) for those in the top quintile of chocolate consumption (16–99 g/day) versus non-consumers of chocolate intake.

The corresponding HR for stroke and cardiovascular disease (cardiovascular disease defined by the sum of CHD and stroke) were 0.77 (95% CI 0.62 to 0.97) and 0.86 (95% CI 0.76 to 0.97). The propensity score matched estimates showed a similar trend. A total of nine studies with 157 809 participants were included in the meta-analysis.

Higher compared to lower chocolate consumption was associated with significantly lower CHD risk (five studies; pooled RR 0.71, 95% CI 0.56 to 0.92), stroke (five studies; pooled RR 0.79, 95% CI 0.70 to 0.87), composite cardiovascular adverse outcome (two studies; pooled RR 0.75, 95% CI 0.54 to 1.05), and cardiovascular mortality (three studies; pooled RR 0.55, 95% CI 0.36 to 0.83).

Conclusions Cumulative evidence suggests that higher chocolate intake is associated with a lower risk of future cardiovascular events, although residual confounding cannot be excluded. There does not appear to be any evidence to say that chocolate should be avoided in those who are concerned about cardiovascular risk.

 

[Michael Scally MD]

Glaudemans AWJM, Dierckx RAJO, Gielen JLMA, Zwerver J, Slart RJA, et al. The Heart as a Special Muscle in Athletes and Anabolic-Androgenic Steroids (Ab)use. In: Nuclear Medicine and Radiologic Imaging in Sports Injuries: Springer Berlin Heidelberg. 2015:971-1006. http://link.springer.com/chapter/10.1007/978-3-662-46491-5_44

Adaptation of the heart muscle in response to exercise has been extensively described. Different forms of sports may imply a different strain to the heart. In this context endurance sports are considered to induce a dynamic, isotonic workload, which is accompanied by an increase in heart rate and stroke volume and a reduction in peripheral vascular resistance.

Sudden athlete death (SAD) is a widely publicised and increasingly reported phenomenon. For many, the athlete population epitomise human physical endeavour and achievement, and their unexpected death comes with a significant emotional impact on the public.

Anabolic–androgenic steroids (AAS) are abused for enhancing muscle mass, strength growth and improving athletic performance. In recent years many observational and interventional studies have shown important adverse cardiovascular effects of AAS abuse.

Imaging with nuclear medicine with or without combined CT techniques, echocardiography and CMR are promising methods to target and image certain biomarkers in the process of cardiovascular pathology that can be used for early detection of sport- and also AAS-associated adverse effects.

This book chapter discusses the physiological background of myocardial (dys)function in athletes and established and novel nuclear molecular imaging techniques, including MRI, that may serve as potential tools for early detection of sport- and AAS-associated cardiovascular disorders and reducing cardiovascular sudden deaths in athletes.