AAS and Cardiovascular/Pulmonary Function

[Michael Scally MD]

Yoshida S, Ikeda Y, Aihara KI. Roles of the Androgen - Androgen Receptor System in Vascular Angiogenesis. J Atheroscler Thromb. https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_31047/_article

Although many clinical studies have shown that a low testosterone level is associated with cardiovascular diseases, the role of androgens in cardiovascular physiology and pathophysiology remains controversial. Androgens exert various actions in their target organs, and the androgen receptor (AR) is widely distributed in several tissues, including endothelial cells, smooth muscle cells, and fibroblasts, in the vascular system. Biological activities of androgens are predominantly mediated through the AR by the transcriptional control of target genes and interaction with multiple signaling pathways. To clarify the molecular mechanisms of androgens in cardiovascular disease, we examined a pathological model using AR knockout mice and showed that the androgen-AR system has protective effects on cardiovascular remodeling against cardiovascular stress. In this review, we focus on the role of the androgen-AR system in angiogenesis after ischemic stress.

 

[Dave202000]

Good he should post these findings on Facebook where 18 year old scientists seem to think aas do nothing to cardiac tissue lmfao

 

[heady muscle]

D-Ribose and the Heart:

http://onlinelibrary.wiley.com/doi/10.1016/S1388-9842(03)00060-6/full

 

[Dr JIM]

Good he should post these findings on Facebook where 18 year old scientists seem to think aas do nothing to cardiac tissue lmfao

I would caution you about passing judgement on a medical ailment that is of multifactorial causation.

Whether AAS has an adverse effect (or any effect) on the myocardium is largely UNKNOWN at present, and using studies on rodents to support or refute a particular assertion in humans is shortsighted to say the least.

 

[Michael Scally MD]

Xinfang Xie, Emily Atkins, Jicheng Lv, et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. The Lancet, November 6, 2015. http://www.thelancet.com/pb/assets/raw/Lancet/pdfs/S0140673615008053.pdf

Background - Recent hypertension guidelines have reversed previous recommendations for lower blood pressure targets in high-risk patients, such as those with cardiovascular disease, renal disease, or diabetes. This change represents uncertainty about whether more intensive blood pressure-lowering strategies are associated with greater reductions in risk of major cardiovascular and renal events. We aimed to assess the efficacy and safety of intensive blood pressure-lowering strategies.

Methods - For this updated systematic review and meta-analysis, we systematically searched MEDLINE, Embase, and the Cochrane Library for trials published between Jan 1, 1950, and Nov 3, 2015. We included randomised controlled trials with at least 6 months' follow-up that randomly assigned participants to more intensive versus less intensive blood pressure-lowering treatment, with different blood pressure targets or different blood pressure changes from baseline. We did not use any age or language restrictions.

We did a meta-analysis of blood pressure reductions on relative risk (RR) of major cardiovascular events (myocardial infarction, stroke, heart failure, or cardiovascular death, separately and combined), and non-vascular and all-cause mortality, end-stage kidney disease, and adverse events, as well as albuminuria and progression of retinopathy in trials done in patients with diabetes.

Findings - We identified 19 trials including 44 989 participants, in whom 2496 major cardiovascular events were recorded during a mean 3·8 years of follow-up (range 1·0–8·4 years).

Our meta-analysis showed that after randomisation, patients in the more intensive blood pressure-lowering treatment group had mean blood pressure levels of 133/76 mm Hg, compared with 140/81 mm Hg in the less intensive treatment group.

Intensive blood pressure-lowering treatment achieved RR reductions for major cardiovascular events (14% [95% CI 4–22]), myocardial infarction (13% [0–24]), stroke (22% [10–32]), albuminuria (10% [3–16]), and retinopathy progression (19% [0–34]).

However, more intensive treatment had no clear effects on heart failure (15% [95% CI −11 to 34]), cardiovascular death (9% [–11 to 26]), total mortality (9% [–3 to 19]), or end-stage kidney disease (10% [–6 to 23]).

The reduction in major cardiovascular events was consistent across patient groups, and additional blood pressure lowering had a clear benefit even in patients with systolic blood pressure lower than 140 mm Hg. The absolute benefits were greatest in trials in which all enrolled patients had vascular disease, renal disease, or diabetes.

Serious adverse events associated with blood pressure lowering were only reported by six trials and had an event rate of 1·2% per year in intensive blood pressure-lowering group participants, compared with 0·9% in the less intensive treatment group (RR 1·35 [95% CI 0·93–1·97]). Severe hypotension was more frequent in the more intensive treatment regimen (RR 2·68 [1·21–5·89], p=0·015), but the absolute excess was small (0·3% vs 0·1% per person-year for the duration of follow-up).

Interpretation - Intensive blood pressure lowering provided greater vascular protection than standard regimens. In high-risk patients, there are additional benefits from more intensive blood pressure lowering, including for those with systolic blood pressure below 140 mmHg. The net absolute benefits of intensive blood pressure lowering in high-risk individuals are large.

 

[Michael Scally MD]

[Rabbits] Cardiotoxicity after Long-Term Nandrolone Decanoate Administration

Highlights
· Cardiovascular effects of nandrolone decanoate on young rabbits
· Focal fibrosis and inflammatory infiltrations of cardiac tissue in high dose groups
· Preserved systolic performance, distorted MPI values, diastolic impairment
· TBARS increased in high dose groups, troponin increased in wash-out period
· Heart tissue relative telomerase activity increased dose-dependently

Vasilaki F, Tsitsimpikou C, Tsarouhas K, et al. Cardiotoxicity in rabbits after long-term nandrolone decanoate administration. Toxicol Lett. https://www.sciencedirect.com/science/article/pii/S0378427415300928

Abuse of anabolic androgenic steroids is linked to a variety of cardiovascular complications.

The aim of our study was to investigate the possible cardiovascular effects of nandrolone decanoate on young rabbits using echocardiography, histology and monitoring of telomerase activity, oxidative stress and biochemical markers.

Fourteen rabbits were divided into three administration groups and the control group. Doses of 4mg/kg and 10mg/kg of nandrolone decanoate, given intramuscularly and subcutaneously, two days per week for six months were applied. A 4-months wash-out period followed.

Focal fibrosis and inflammatory infiltrations of cardiac tissue were observed in the high dose groups. Thiobarbituric Acid-Reactive Species (TBARS) levels were significantly increased in the high dose groups, while catalase activity decreased.

Myocardial Performance Index (MPI) is the main echocardiographic index primarily affected by nandrolone administration in rabbits. Despite the preserved systolic performance, histological lesions observed associated with distorted MPI values, point to diastolic impairment of the thickened myocardium due to nandrolone treatment.

Oxidative stress accumulates and telomerase activity in cardiac tissue rises. Subcutaneous administration seems to be more deleterious to the cardiovascular system, as oxidative stress, telomerase activity and biochemical markers do not appear to return into normal values in the wash-out period.

 

[Michael Scally MD]

Prevalence of 'Silent' Heart Attacks

In a multiethnic, middle-aged and older study population, the prevalence of myocardial scars (evidence of a heart attack) was nearly 8 percent, of which nearly 80 percent were unrecognized by electrocardiography or clinical evaluation.

Participants were multiethnic, 45 through 84 years of age and free of clinical cardiovascular disease (CVD) at study entry in 2000-2002. In the 10th year examination (2010-2012), 1,840 participants (average age, 68 years; 52 percent men) underwent Cardiac Magnetic Resonance (CMR) imaging with gadolinium to detect myocardial scar. Cardiovascular disease risk factors and coronary artery calcium (CAC) scores were measured at study entry and year 10.

The overall prevalence of myocardial scar by CMR was 7.9 percent (146 of 1,840). The prevalence of previously unrecognized myocardial scar was 6.2 percent, whereas 1.7 percent had clinically recognized MI. Thus, 78 percent (114 of 146) of myocardial scars were unrecognized by clinical or electrocardiography (ECG) evaluation. Men had a higher prevalence of myocardial scar than women (12.9 percent vs 2.5 percent).

Of individual risk factors, age, male sex, CAC score, body mass index, current smoking, and use of antihypertensive medications at study entry were associated with higher odds of myocardial scar.

Turkbey EB, Nacif MS, Guo M, et al. Prevalence and Correlates of Myocardial Scar in a US Cohort. JAMA. 2015;314(18):1945-1954. http://jama.jamanetwork.com/article.aspx?articleid=2468890

Importance Myocardial scarring leads to cardiac dysfunction and poor prognosis. The prevalence of and factors associated with unrecognized myocardial infarction and scar have not been previously defined using contemporary methods in a multiethnic US population.

Objective To determine prevalence of and factors associated with myocardial scar in middle- and older-aged individuals in the United States.

Design, Setting, and Participants The Multi-Ethnic Study of Atherosclerosis (MESA) study is a population-based cohort in the United States. Participants were aged 45 through 84 years and free of clinical cardiovascular disease (CVD) at baseline in 2000-2002. In the 10th year examination (2010-2012), 1840 participants underwent cardiac magnetic resonance (CMR) imaging with gadolinium to detect myocardial scar. Cardiovascular disease risk factors and coronary artery calcium (CAC) scores were measured at baseline and year 10. Logistic regression models were used to estimate adjusted odds ratios (ORs) for myocardial scar.

Exposures Cardiovascular risk factors, CAC scores, left ventricle size and function, and carotid intima-media thickness.

Main Outcomes and Measures Myocardial scar detected by CMR imaging.

Results Of 1840 participants (mean [SD] age, 68 [9] years, 52% men), 146 (7.9%) had myocardial scars, of which 114 (78%) were undetected by electrocardiogram or by clinical adjudication. In adjusted models, age, male sex, body mass index, hypertension, and current smoking at baseline were associated with myocardial scar at year 10. The OR per 8.9-year increment was 1.61 (95% CI, 1.36-1.91; P < .001); for men vs women: OR, 5.76 (95% CI, 3.61-9.17; P < .001); per 4.8-SD body mass index: OR, 1.32 (95% CI, 1.09-1.61, P = .005); for hypertension: OR, 1.61 (95% CI, 1.12-2.30; P = .009); and for current vs never smokers: 2.00 (95% CI, 1.22-3.28; P = .006). Age-, sex-, and ethnicity-adjusted CAC scores at baseline were also associated with myocardial scar at year 10. Compared with a CAC score of 0, the OR for scores from 1 through 99 was 2.4 (95% CI, 1.5-3.9); from 100 through 399, 3.0 (95% CI, 1.7-5.1), and 400 or higher, 3.3 (95% CI, 1.7-6.1) (P ≤ .001). The CAC score significantly added to the association of myocardial scar with age, sex, race/ethnicity, and traditional CVD risk factors (C statistic, 0.81 with CAC vs 0.79 without CAC, P = .01).

Conclusions and Relevance The prevalence of myocardial scars in a US community-based multiethnic cohort was 7.9%, of which 78% were unrecognized by electrocardiography or clinical evaluation. Further studies are needed to understand the clinical consequences of these undetected scars.

 

[Michael Scally MD]

Bair TL, May HT, Le VT, Lappe DL, Anderson JL, Muhlestein JB. Abstract 16401: Cardiovascular Clinical Effects of Testosterone Supplementation Among Healthy Hypo-androgenic Men: Information From the Intermountain Healthcare Health Plans Database. Circulation 2015;132(Suppl 3):A16401. http://circ.ahajournals.org/content/132/Suppl_3/A16401.abstract

Introduction: Epidemiologic studies have identified low serum testosterone (T) levels as an independent risk factor for cardiovascular (CV) and total mortality. However, the cardiovascular safety of T therapy among healthy men with low T levels is unknown.

Hypothesis: We hypothesized that T supplementation among healthy men over the age of 50 yrs with low T levels is not associated with an increased risk of major adverse cardiovascular events (MACE).

Methods: All men in the Intermountain Healthcare Health Plans Database >50 years of age, with no prior history of CV disease, a documented low (<212 ng/dL) baseline T level, at least 1 follow-up (f/u) T level and 3 years of clinical f/u were stratified by whether or not they received at least 90 days of T supplementation (topical gel or injection) or not.

Cox hazard regression analysis, adjusting for 17 baseline variables, was performed to determine any association between T supplementation and 3 year MACE (death [D], non-fatal MI, and stroke).

Results: A total of 1,472 men (age 57.0 ± 5.5 y, diabetes: 20%, hypertension: 41%, hyperlipidemia: 43%, smokers: 13%) were studied. Event rates at 1 and 3-y by supplementation status, and adjusted HRs, are shown in the Table. Overall 3-y rates of MACE, D, MI and stroke were low consistent with the baseline age and health of the population.

After adjustment, subjects supplemented with T had statistically reduced 1 and 3 year rates of D and total MACE, including numerically reduced rates of MI and stroke compared to those receiving no supplementation.

Conclusions: Among a generally healthy and relatively young population of hypo-androgenic men, T therapy was associated with reduced MACE and D over 3-y compared to no T supplementation. These findings provide further observational evidence of the CV safety associated with T supplementation in this population.

 

[Michael Scally MD]

Akdis D, Saguner AM, von Eckardstein A, Chen HSV, Brunckhorst C, Duru F. Abstract 11027: Elevated Serum Testosterone Levels are Associated With Adverse Events in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia. Circulation 2145;132(Suppl 3):A11027. http://circ.ahajournals.org/content/132/Suppl_3/A11027.abstract

Introduction: Sex hormones have been reported to play a role in the pathophysiology of ventricular arrhythmias.

Hypothesis: We hypothesized that there may be a relationship between sex hormones and cardiovascular adverse events in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D).

Methods: Serum levels of testosterone, dehydroepiandrosterone, sex steroid-binding globulin, androstendione, estradiol, and progesterone were measured along with routine biochemical markers in 44 patients (33 male) from the Swiss ARVC/D Registry with a definite (n=29) or borderline (n=15) diagnosis of ARVC/D. Sex hormone levels were correlated with major adverse cardiovascular events (MACE), defined as the occurrence of cardiac death, heart transplantation, survived sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia or arrhythmogenic syncope.

Results: Twenty-four patients experienced MACE within the last six months prior to determination of sex hormone levels. Testosterone levels were significantly higher in patients with MACE (mean±SD: 14nmol/l±9.6 versus 8.6nmol/l±5.9;p=0.03). In male patients with MACE, testosterone levels (18.7nmol/l±5.8 versus 11.3nmol/l±3.8; p=0.001) and sex steroid-binding globulin levels (48.9nmol/l±20.8 versus 32nmol/l±12.2; p=0.01) were significantly increased, whereas dehydroepiandrosterone levels were significantly decreased (4.0 micromol/l±2.6 versus 7.0 micromol/l±4.4; p=0.03). In females estradiol was lower in patients with MACE (14.1pmol/l±3.8 versus 396.6pmol/l±336.2; p=0.007). In bivariable analysis after adjusting for confounders such as body mass index, sports activity, and reduced RV/LV function, increased testosterone levels remained a significant independent predictor of MACE in males (odds ratio 1.4 per 1 nmol/l increase, 95% confidence interval 1.1-1.8, p=0.005). A cut-off value for testosterone at 13.45 nmol/l predicted MACE with a sensitivity of 0.8 and a specificity of 0.7.

Conclusion: In conclusion, our study suggests that sex hormones, in particular testosterone, are associated with adverse clinical events in patients with ARVC/D, and therefore, may play a role in risk stratification of this disease.

 

[Michael Scally MD]

A Randomized Trial of Intensive versus Standard Blood-Pressure Control

Treating to a systolic blood pressure target of 120 mm Hg lowered the incidence of adverse cardiovascular events in a high-risk population, according to the SPRINT study published in the New England Journal of Medicine and presented at the American Heart Association's annual meeting.

Researchers enrolled roughly 9400 patients (age 50 or older) with a systolic BP of 130 to 180 mm Hg and high cardiovascular risk but without diabetes or stroke. Patients were randomized to either intensive or standard treatment (systolic BP targets, 120 or 140 mm Hg, respectively). The researchers were permitted discretion in choosing drug regimens.

The trial was terminated early after a median follow-up of 3.3 years, during which participants' average systolic BPs were 121.5 mm Hg and 134.6 mm Hg in the intensive- and standard-treatment groups, respectively. The primary composite outcome (myocardial infarction, non-MI acute coronary syndrome, stroke, heart failure, or CV-related death) occurred in 5.2% of intensive-treatment patients and 6.8% of standard-treatment patients.

Two individual components of the composite outcome were significantly lower with intensive treatment — heart failure (1.3% vs. 2.1%) and CV-related death (0.8% vs. 1.4%). All-cause mortality also was significantly lower with intensive treatment (3.3% vs. 4.5%).

Several serious adverse events were significantly more common with intensive than with standard treatment: incidences of hypotension, syncope, and electrolyte abnormalities were each about 1 percentage point higher, and incidence of acute kidney injury was about 2 percentage points higher. Among patients without CKD at baseline, the incidence of a >30% decline in glomerular filtration rate was significantly greater with intensive treatment (3.8% vs. 1.1%).

SPRINT has demonstrated that aiming for a systolic BP of 120 mm Hg can lower the rate of adverse cardiovascular events; to prevent 1 event, 61 patients had to be treated for 3.3 years. Keep in mind that SPRINT was limited to middle-aged and older patients at above-average CV risk and that diabetic patients were excluded. Whether the decline in GFR associated with intensive treatment represents a harmless hemodynamic effect or more-serious renal injury is unclear.

Clinicians must understand that BP measurements in this study were based on the average of the three readings, taken automatically at 5-minute intervals with no clinician in the room. This method yields substantially lower readings than does a single measurement by a clinician. If SPRINT is applied without attention to proper BP measurement, substantial overtreatment — with a higher rate of adverse events — likely will occur.

Finally, note that the average achieved systolic BP in the intensive-treatment group (121.5 mm Hg) remained higher than the 120 mm target. This likely represents judicious balancing by treating clinicians who tried to approximate the 120 mm goal while avoiding side effects and excessive polypharmacy.

The SPRINT Research Group. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. New England Journal of Medicine. http://www.nejm.org/doi/full/10.1056/NEJMoa1511939

 

[Michael Scally MD]

Bress AP, Tanner RM, Hess R, Colantonio LD, Shimbo D, Muntner P. Generalizability of results from the Systolic Blood Pressure Intervention Trial (SPRINT) to the US adult population. J Am Coll Cardiol. 2015. http://content.onlinejacc.org/article.aspx?articleid=2468917

Background In the Systolic Blood Pressure Intervention Trial (SPRINT), a systolic blood pressure (SBP) goal of <120 mmHg resulted in lower cardiovascular disease (CVD) risk compared with a SBP goal of <140 mmHg.

Objectives To estimate the prevalence, number, and characteristics of US adults meeting SPRINT eligibility criteria and a broader population to whom SPRINT could be generalized.

Methods We conducted a cross-sectional, population-based study using data from the National Health and Nutrition Examination Survey 2007-2012. SPRINT eligibility included the following: inclusion criteria were age ≥ 50 years, SBP of 130 to 180 mmHg depending on the number of antihypertensive medication classes being taken, high CVD risk (history of coronary heart disease, estimated glomerular filtration rate of 20 to 59 ml/min/1.73 m2, 10-year CVD risk ≥15%, or age ≥ 75 years); exclusion criteria were diabetes, history of stroke, >1 gram of proteinuria daily, heart failure, estimated glomerular filtration rate < 20 ml/min/1.73m2 or receiving dialysis. Treated hypertension was defined by self-reported use of medication to lower blood pressure with one or more classes of antihypertensive medication identified through a pill bottle review.

Results Overall, 7.6% (95%CI 7.0%-8.3%) or 16.8 million (95%CI 15.7-17.8) of US adults, and 16.7% (95%CI 15.2%-18.3%) or 8.2 million (95%CI 7.6-8.8) of those with treated hypertension, met the SPRINT eligibility criteria. Among both the overall US population and adults with treated hypertension, the percentage meeting SPRINT eligibility criteria increased with older age, was higher among males than females, and was higher among non-Hispanic whites compared with non-Hispanic blacks or Hispanics. Of US adults eligible for SPRINT, 51.0% (95%CI 47.8%-54.1%) or 8.6 million (95%CI 8.0-9.1) were not treated for hypertension.

Conclusions A substantial percentage of US adults meet the eligibility criteria for SPRINT.

 

[Michael Scally MD]

Merck Reveals That Its 30,000 Patient CETP Trial Will Continue
http://cardiobrief.org/2015/11/13/merck-reveals-that-its-30000-patient-cetp-trial-will-continue/

Despite rumors to the contrary the story of the CETP inhibitors isn’t quite over. Merck today announced that the REVEAL trial will continue. After a series of disappointing and often spectacular failures, REVEAL is the last remaining phase 3 trial of a CETP inhibitor still underway.

REVEAL is a 30,000 patient trial studying Merck’s anacetrapib. In the announcement Merck said the decision to continue the trial was based on a planned review of unblinded data by the study’s independent data monitoring committee. The review “included an assessment of futility.” http://www.mercknewsroom.com/news-r...s/merck-provides-update-reveal-outcomes-study

Three previous CETP inhibitors have failed. First, and most spectacularly, Pfizer’s torcetrapib, which the company had hoped would preserve its cholesterol franchise, was found to have off target negative effects. Expectations for the CETP inhibitor class were further damaged by the failure of Roche’s dalcetrapib and, more recently, Lilly’s evacetrapib. With this string of failures many experts gave up hope for the drugs and many speculated that Merck would end development of anacetrapib and terminate REVEAL.

Initial interest in CETP inhibitors was based on their ability to raise HDL levels. In observational studies HDL has been consistently associated with reduced cardiovascular risk, but a cause and effect relationship has never been demonstrated, and more recent genetic studies have put additional stress on the HDL hypothesis.

The failure of the trials has prompted many experts to question the value of the HDL hypothesis. (Some experts argue that simply raising HDL may not be enough; instead it may be necessary to enhance the purported benefit of HDL’s “reverse cholesterol transport” mechanism.)

One point of confusion and possible ray of light for Merck’s anacetrapib is that there appear to be important differences in the activity of the different CETP inhibitors. In particular, Merck may be pinning its hopes not on the HDL-raising properties of the drug but on its LDL-lowering properties. Some think REVEAL could be successful based solely on the LDL lowering properties of the drug.

 

[Michael Scally MD]

D'Andrea A, Limongelli G, Morello A, et al. Anabolic-androgenic steroids and athlete's heart: When big is not beautiful...! Int J Cardiol 2015;203:486-8. https://www.sciencedirect.com/science/article/pii/S0167527315307506

Anabolic–androgenic steroids (AASs) are synthetic derivatives of testosterone. Their abuse has been linked with numerous toxic and hormonal effects (1–5). In particular, although data are conflicting, healthy athletes abusing AAS may show increased levels of low-density lipoproteins and low levels of high-density lipoproteins, elevated systolic and diastolic arterial blood pressure values and left ventricular (LV) hypertrophy that may persist even after AAS cessation (5–7).

We describe the case of a 35-year-old bodybuilder with a 20-year history of strength training, presenting with increasing exertional dyspnoea and fatigue during mild dynamic effort. The athlete revealed a more than 15-year history of illicit use of supraphysiologic doses of AAS (weekly dose of 675 mg of testosterone-equivalent).

Patient's past medical history was negative for cardiac disease, and he had a normal physical examination (body surface area: 1.9m2). Resting blood pressure was within normal limits. The laboratory tests showed normal liver and renal functions and serum electrolytes, normal creatine phosphokinase and thyroid functions, and elevated low density lipoprotein values.

Resting ECG showed LV hypertrophy with widespread abnormalities of ventricular repolarization and a ventricular ectopic beats. Standard transthoracic echocardiography demonstrated severe concentric LV hypertrophy (septal wall thickness: 17 mm; posterior wall thickness: 13.5 mm), with mildly impaired systolic function (ejection fraction by Simpson biplane: 50%). There was no LV outflow tract obstruction at rest or after Valsalva maneuver.

Conversely, transmitral flow pattern showed an impairment of global and regional diastolic functions, with a mean E/Ea ratio of 14. By speckle tracking strain analysis, a severe and diffuse impairment of both radial and longitudinal myocardial deformation was evidenced.

Cardiopulmonary exercise test revealed severe reduction of functional capacity: maximal watts reached 100 (65% of target); maximal VO2 24.9 ml/kg/min (50% of target); VE/VCO2 slope 31; and VO2/work 7.

Cardiac magnetic resonance confirmed severe LV hypertrophy, revealing also focal areas of delayed enhancement with pattern of nonischemic distribution localized at the level of septal and inferior-lateral wall of the left ventricle.

After 6 months from discontinuation of steroids, the athlete showed by cardiac magnetic resonance a mild reduction of LV volumes and hypertrophy, with improvement of speckle-tracking measurements by echocardiography and a better functional capacity by cardiopulmonary test: maximal watts reached 125 (71% of target); maximal VO2 31.8 ml/kg/min (65% of target); VE/VCO2 slope 29; VO2/ work 10.

Athletes abusing AAS often exhibit severe LV hypertrophy. However, since physiologic LV hypertrophy may be related to the increased afterload typical of isometric exercise (1) the adequate cardiac evaluation of elite athletes who admit chronic AAS abuse can be really complex (8–10). Possible associations between AAS and LV hypertrophy can be related to secondary arterial hypertension or to a direct effect on the myocardium.

Notably, studies in isolated human myocytes have shown that AASs bind to androgen receptors and may directly cause hypertrophy (2–3), potentially via tissue up-regulation of the renin– angiotensin system (4). Indeed, clinical studies suggest a distinct form of LV hypertrophy in AAS abusers, with textural changes in the myocardium on echocardiography before the onset of overt LVH (5–7).

The present case illustrates that several years after chronic abuse of AAS, strength athletes can show LV hypertrophy with a sub-clinical impairment of both systolic and diastolic myocardial functions, strongly associated with mean dosage and time duration of AAS use.

The combined use of standard echocardiography, speckle-tracking strain and cardiac magnetic resonance may be useful for early identification of patients with more diffused cardiac involvement, and eventually to investigate the reversibility of such myocardial effect after discontinuation of the drug in AAS users.

References

Ø [1] J. Payne, P.J. Kotwinski, H.E. Montgomery, Cardiac effects of anabolic steroids, Heart 90 (2004) 473–475.
Ø [2] S. Nottin, L.-D. Nguyen, M. Terbah, P. Obert, Cardiovascular effects of androgenic anabolic steroids in male bodybuilders determined by tissue Doppler imaging, Am. J. Cardiol. (2006).
Ø [3] L. Fanton, D. Belhani, F. Vaillant, A. Tabib, L. Gomez, J. Descotes, et al., Heart lesions associated with anabolic steroid abuse: comparison of post-mortem findings in athletes and norethandrolone-induced lesions in rabbits, Exp. Toxicol. Pathol. (2009).
Ø [4] P.D. Thompson, A. Sadaniantz, E. Cullinane, K. Bodziony, D. Catlin, G. Torek-Both, et al., Left ventricular function is not impaired in weight-lifters who use anabolic steroids, J. Am. Coll. Cardiol. (1992) 19.
Ø [5] N.A. Hassan, M.F. Salem, M.A.E.L. Sayed, Doping and effects of anabolic androgenic steroids on the heart: histological, ultrastructural, and echocardiographic assessment in strength athletes, Hum. Exp. Toxicol. (2009).
Ø [6] J. Marsh, M.H. Lehmann, R.H. Ritchie, J.K.Gwathmey, G.E. Green, R.J. Schiebinger, Androgen receptors mediate hypertrophy in cardiac myocytes, Circulation 98 (1998) 256–261.
Ø [7] P. Liu, A.K. Death, D.J. Handelsman, Androgens and cardiovascular disease, Endocr. Rev. 24 (2003) 313–340.
Ø [8] A. D'Andrea, P. Caso, G. Salerno, R. Scarafile, G. De Corato, C. Mita, et al., Left ventricular early myocardial dysfunction after chronic misuse of anabolic androgenic steroids: a Doppler myocardial and strain imaging analysis, Br. J. Sports Med. 41 (3) (2007) 149–155.
Ø [9] S. Sharma, Athlete's heart—effect of age, sex, ethnicity and sporting discipline, Exp. Physiol. 88 (2003) 665–669.
Ø [10] M. Galderisi, N. Cardim, A. D'Andrea, O. Bruder, B. Cosyns, L. Davin, et al., The multimodality cardiac imaging approach to the Athlete's heart: an expert consensus of the European Association of Cardiovascular Imaging, Eur. Heart J. Cardiovasc. Imaging 16 (4) (2015) 353.

 

[Michael Scally MD]

Special Report: SPRINT Trial -- Implications for Hypertension Management
http://www.medscape.com/viewcollection/33554

[Access might require membership, which is free.]

 

[Michael Scally MD]

AHA: HDL – the waters grow muddier
http://www.clinicalendocrinologynew...muddier/66bdef5d2b497c21aa780dcb35cd9f6c.html


AHA: New emphasis on percent LDL reduction on-treatment
http://www.clinicalendocrinologynews.com/specialty-focus/lipid-metabolic-disorders/single-article-page/aha-new-emphasis-on-percent-ldl-reduction-on-treatment/6201621685a6e52aeec8fd896d857cf2.html

 

[Michael Scally MD]

Hu Z, Ma R, Gong J. Investigation of testosterone-mediated non-transcriptional inhibition of Ca2+ in vascular smooth muscle cells. Biomedical Reports. Investigation of testosterone-mediated non-transcriptional inhibition of Ca2+ in vascular smooth muscle cells

The aim of the present study was to observe the effect of short-term testosterone treatment on Ca2+ in vascular smooth muscle cells (VSMCs) of male rats.

Cells were loaded with the Ca2+‑sensitive fluorescent indicator Fura-2 and intracellular Ca2+ signals of VSMCs were measured using a Nikon TE2000-E live cell imaging workstation.

The baseline level of cytosolic Ca2+ concentration ([Ca2+]i) in resting state VSMCs was ~100 nmol/l.

Testosterone alone led to a slow increase in [Ca2+]i, but there was no significant difference compared with the ethanol vehicle control.

When VSMCs were stimulated with a high‑potassium solution (containing 42 mmol/l of K+), [Ca2+]i rose rapidly and remained at a high plateau level.

Short‑term treatment using physiological (40 nmol/l) or supraphysiological (4 µmol/l) levels of testosterone at either the plateau phase or the pretreatment stage could significantly inhibit the [Ca2+]i increase induced by high‑potassium solutions.

Testosterone coupled to bovine serum albumin also had a similar effect and repetitive testosterone interventions over a short time‑frame led to inhibition.

Testosterone has a non-transcriptional inhibition effect on the [Ca2+]i of VSMCs and acts with the cell membranes of VSMCs to inhibit voltage-gated Ca2+ channel‑mediated Ca2+ influx, which may be one of the mechanisms underlying testosterone-mediated vasodilation.

 

[Michael Scally MD]

We Shouldn’t SPRINT to Lower Blood Pressure Targets
http://internalmedicineblog.jamainternalmed.com/2015/12/16/we-shouldnt-sprint-to-lower-blood-pressure-targets/

Full results of the Systolic Blood Pressure Intervention Trial (SPRINT) have been released. Much acclaim has followed along with numerous calls to lower blood pressure targets. The main conclusion of SPRINT is that in patients 50 years or older with an increased risk of cardiovascular events, those assigned to intensive blood pressure (BP) control (<120 mmHg) compared to standard control (<140 mmHg) had a significantly lower rate of cardiovascular events including death. Despite these results there are several reasons to pause in the race to lower BP targets.

 

[Michael Scally MD]

[Open Access] Heart Disease and Stroke Statistics-2016 Update

Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics related to heart disease, stroke, and other cardiovascular and metabolic diseases and presents them in its Heart Disease and Stroke Statistical Update.

The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, healthcare administrators, researchers, and others seeking the best available data on these conditions.

Together, cardiovascular disease (CVD) and stroke produce immense health and economic burdens in the United States and globally.

The Statistical Update brings together in a single document up-to-date information on the core health behaviors (including diet, physical activity [PA], smoking, and energy balance) and health factors (including blood pressure, cholesterol, and glucose) that define cardiovascular health; a range of major clinical disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, and peripheral arterial disease); and the associated outcomes (including quality of care, procedures, and economic costs).

Mozaffarian D, Benjamin EJ, Go AS, et al. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. http://circ.ahajournals.org/content/early/2015/12/16/CIR.0000000000000350.full.pdf

 

[Michael Scally MD]

Highlights
· Use of anabolic steroids in athletes is growing.
· We tested the effect of severe exercise + nandrolone on arrhythmia occurrence.
· Nandrolone + severe exercise increased the ventricular fibrillation incidence.
· Nandrolone + severe exercise decreased the ventricular fibrillation latency.
· This effects cannot be explained by the changes of redox system.

Abdollahi F, Joukar S, Najafipour H, Karimi A, Masumi Y, Binayi F. The risk of life-threatening ventricular arrhythmias in presence of high -intensity endurance exercise along with chronic administration of nandrolone decanoate. Steroids. The risk of life-threatening ventricular arrhythmias in presence of high-intensity endurance exercise along with chronic administration of nandrolone decanoate

Anabolic steroids used to improve muscular strength and performance in athletics. Its long-term consumption may induce cardiovascular adverse effects. We assessed the risk of ventricular arrhythmias in rats which subjected to chronic nandrolone plus high-intensity endurance exercise.

Animals were grouped as; control (CTL), Exercise (Ex): 8 weeks under exercise, vehicle group (Arach): received arachis oil, and Nan group: received nandrolone decanoate 5 mg/kg twice a week for 8 weeks, Arach + Ex group, and Nan + Ex. Finally, under anesthesia, arrhythmia was induced by infusion of 1.5 mug/0.1 mL/min of aconitine IV and ventricular arrhythmias were recorded for 15 minutes. Then, animals' hearts were excised and tissue samples were taken.

Nandrolone plus exercise had no significant effect on blood pressure but decreased the heart rate (P<0.01) and increased the RR (P<0.01) and JT intervals (P<0.05) of electrocardiogram. Nandrolone + exercise significantly increased the ventricular fibrillation (VF) frequency and also decreased the VF latency (P<0.05 versus CTL group). Combination of exercise and nandrolone could not recover the decreasing effects of nandrolone on animals weight gain but, it enhanced the heart hypertrophy index (P<0.05). In addition, nandrolone increased the level of Hydroxyproline (HYP) and malondialdehyde (MDA) but had not significant effect on Glutathione peroxidase of heart. Exercise only prevented the effect of nandrolone on HYP.

Nandrolone plus severe exercise increases the risk of VF that cannot be explained only by the changes in redox system. The intensification of cardiac hypertrophy and prolongation of JT interval may be a part of involved mechanisms.

 

[Michael Scally MD]

[Open Access] Low High-Density Lipoprotein and Risk of Myocardial Infarction

Low HDL is an independent risk factor for myocardial infarction.

This paper reviews our current understanding of HDL, HDL structure and function, HDL subclasses, the relationship of low HDL with myocardial infarction, HDL targeted therapy, and clinical trials and studies.

Furthermore potential new agents, such as alirocumab (praluent) and evolocumab (repatha) are discussed.

Ramirez A, Hu PP. Low High-Density Lipoprotein and Risk of Myocardial Infarction. Clin Med Insights Cardiol 2015;9:113-7. Low High-Density Lipoprotein and Risk of Myocardial Infarction