AAS and Cardiovascular/Pulmonary Function

[Michael Scally MD]

Pietri P, Vlachopoulos C, Ioakeimidis N, Aggelis A, Terentes-Printzios D, et al. 5b.06: Association of Plasma Testosterone with Central Haemodynamics in Hypertensive Men. J Hypertens.33 Suppl 1 - ESH 2015 Abstract Book:e67. http://journals.lww.com/jhypertensi...OCIATION_OF_PLASMA_TESTOSTERONE_WITH.179.aspx

OBJECTIVE: There is evidence for an inverse association between plasma testosterone and blood pressure. Recently, low plasma testosterone was associated with increased risk of major cardiovascular events in middle-aged hypertensive men.

Central (aortic) blood pressures predict cardiovascular mortality with equal ability compared to peripheral (brachial) blood pressures.

The aim of the present study was to assess the relationship of plasma total testosterone (TT) with peripheral and central haemodynamics in hypertensive men.

DESIGN AND METHOD: We studied 70 non-diabetic, hypertensive men (mean age = 60 years old). Office brachial systolic (bSBP) and diastolic (bDBP) blood pressures were measured according to the ESH guidelines. Pulse pressure (bPP) was calculated as SBP minus DBP.

All patients were subject to measurement of aortic systolic (aoSBP), diastolic (aoDBP) and pulse pressures (aoPP) by pulse wave analysis using the Sphygmocor device. Wave reflections were assessed by the measurement of heart-rate corrected augmentation index (AIx75).

Plasma TT was measured in all subjects by enzyme immunoassay.

RESULTS: The mean value of TT in the whole population was 4.6 ng/ml (hypogonadism was defined as TT < 3.4 ng/ml).

Plasma TT was inversely and significantly related to aoSBP (r = -0.26, p = 0.03), aoPP (r = -0.30, p = 0.01) and AIx75 (r = -0.31, p = 0.01) but only marginally related to bSBP (r = -0.22, p = 0.07) and bPP (r = -0.23, p = 0.06).

In linear regression analysis, after adjustment for age, smoking, BMI, plasma glucose, total cholesterol and presence of antihypertensive treatment, aoSBP (b = -0.29, p = 0.03), aoPP (b = -0.31, p = 0.02) and AIx75 (b = -0.30, p = 0.03) were independently associated with TT but the relationship of TT with bSBP (b = -0.25, p = 0.06) and bPP (b = -0.23, p = 0.07) remained weak.

CONCLUSIONS: In hypertensive men, plasma TT is independently and inversely associated with central blood pressures and wave reflections.

Considering the adverse prognostic role of central blood pressures on cardiovascular outcomes, the present finding might explain part of the increased cardiovascular risk associated with low testosterone.

Whether measurement of central haemodynamics may improve risk stratification in men with low testosterone, warrants further investigation.

 

[Michael Scally MD]

Gianatti EJ, Hoermann R, Lam Q, Dupuis P, Zajac JD, et al. Effect of testosterone treatment on cardiac biomarkers in a randomised controlled trial of men with type 2 diabetes. Clinical Endocrinology. http://onlinelibrary.wiley.com/doi/10.1111/cen.12842/abstract

Objective To assess the effect of testosterone treatment on cardiac biomarkers in men with type 2 diabetes (T2D).

Design Randomized double-blind, parallel, placebo-controlled trial.

Patients Men aged 35-70 years with T2D and a total testosterone level < 12.0 nmol/L (346 ng/dl) at high risk of cardiovascular events, median 10-year United Kingdom Prospective Diabetes Study (UKPDS) coronary heart disease (CHD) risk 21% (IQR 16%, 27%). 88 participants were randomly assigned to 40 weeks of intramuscular testosterone undecanoate (n= 45) or matching placebo (n= 43).

Main Outcome Measures N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT).

Results Testosterone treatment reduced NT-proBNP (mean adjusted difference (MAD) in change over 40 weeks across the testosterone and placebo groups, -17.9 ng/L [95% CI -32.4, -3.5], p=0.047), but did not change hs-cTnT (MAD, 0.41 ng/L [95% CI -0.56, 1.39], p=0.62).

Six men, three in each group experienced an adverse cardiac event, displaying already higher baseline NT-proBNP (p<0.01) and hs-cTnT levels (p=0.01).

At baseline, 10-year UKPDS CHD risk was associated positively with NT-proBNP (tau=0.21, p=0.004) and hs-cTnT (tau=0.23, p=0.003), and inversely with testosterone (total testosterone tau=-0.18, p=0.02, calculated free testosterone tau=-0.19, p=0.01), but there was no significant association between testosterone and cardiac biomarkers (p>0.05).

Conclusions In this trial of men with T2D and high cardiovascular risk, testosterone treatment reduced NT-proBNP, and did not change hs-cTnT.

Further studies should determine whether men with increased cardiac biomarkers prior to testosterone therapy are at higher risk of testosterone-treatment associated adverse cardiac events.

 

[Michael Scally MD]

Brasil GA, de Lima EM, do Nascimento AM, Caliman IF, de Medeiros AR, et al. Nandrolone decanoate induces cardiac and renal remodeling in female rats, without modification in physiological parameters: The role of ANP system. Life Sci. https://www.sciencedirect.com/science/article/pii/S0024320515003574

Anabolic-androgenic steroids are misused, including women, but little is known about the cardiovascular effects of these drugs on females.

Aim: Evaluated the effects of nandrolone decanoate (ND), physical exercise and estrogen deficiency on female rats.

Main Methods: Female Wistar rats were divided into 8 groups:
S and OVX: (SHAM: sham surgery; OVX: ovariectomy), SE and OVXE (resistance exercise 5 times a week), SD and OVXD (treated with ND, 20 mg/kg/week for 4 weeks); and SDE and OVXDE.

Treatments were initiated 21 days after surgery. The Bezold-Jarisch reflex was assessed by Phenylbiguanide administration. The right atrium, kidney, and serum were collected for molecular analyses by RT-PCR of atrial natriuretic peptide (ANP), A-type natriuretic peptide receptor (NPR-A) and NPR-C. ELISA assay to estradiol and testosterone concentrations. The gastrocnemius muscle, heart and kidney weights/tibia length were measured. Morphometric analysis of heart was made (H/E) and collagen content of heart and kidney were evaluated using Pirossirius Red.

Key findings: ND treatment increased ANP expression on atrium and decreased NPR-A expression in kidney. Physical exercise and ovariectomy did not alter this parameter. NPR-C level was reduced in the SDE and OVXDE. Renal and cardiac hypertrophy was observed after ND treatment, with collagen deposition. Plasma estrogen concentrations were reduced and serum testosterone concentrations were increased after ND treatment.

Significance: ANP has an important role in modulating the cardiovascular effects of ND in females. This modulating may have occurred by the increasing ANP expression, reducing NPR-A and NPR-C expression levels, and changing sex hormone levels.

 

[Michael Scally MD]

Francomano D, Fattorini G, Gianfrilli D, Paoli D, Sgro P, et al. Acute endothelial response to testosterone gel administration in men with severe hypogonadism and its relationship to androgen receptor polymorphism: a pilot study. J Endocrinol Invest. http://www.ncbi.nlm.nih.gov/pubmed/26162521

PURPOSE: Testosterone (T) exerts different effects on the cardiovascular system. Despite this knowledge, the acute vascular effect of androgen remains still poorly understood.

METHODS: We investigated the acute effects of T on vascular function in ten men (18-40 years age) with hypogonadism and severe hypotestosteronemia [serum total testosterone (TT) = 0.6 +/- 0.3 ng/mL].

In a 4-day double-blind, randomized, placebo-controlled crossover study, we administered 80 mg daily dose of transdermal-T gel (TG) and evaluated endothelial variations with Endopat2000 (reactive hyperemia index, RHI and the augmentation index, AI); also, CAG repeat polymorphism in exon 1 of the androgen receptor gene was investigated.

RESULTS: After TG administration, RHI significantly improved at 4 h (p < 0.05), while AI improvement was recorded at 4 and 96 h, also when adjusted for heart rate (AI@75; p < 0.01 and p < 0.001, respectively).

Direct relationships between DeltaT, DeltaDHT and DeltaRHI variations (r = 0.37, p < 0.01; r = 0.17, p < 0.05, respectively) as well as between "CAG repeats" length and DeltaLnRHI at 96 h (p < 0.03, r 2 = 0.47) were found.

An inverse relationship between DeltaT and DeltaAI (p < 0.01, r = -0.35) and DeltaAI@75 (p < 0.01, r = -0.38) were found.

CONCLUSION: Administration of TG causes an acute vasodilation and improves arterial stiffness probably due to non-genomic actions of T. Endothelial vasodilatory response was more pronounced depending on higher plasma TT and DHT levels attained. Clinical implications in elderly frail populations are discussed.

 

[Michael Scally MD]

Emer E, Yildiz O, Seyrek M, Demirkol S, Topal T, et al. High-dose testosterone and dehydroepiandrosterone induce cardiotoxicity in rats: Assessment of echocardiographic, morphologic, and oxidative stress parameters. Hum Exp Toxicol. http://het.sagepub.com/content/early/2015/07/20/0960327115595706.abstract

The aim of this study is to assess cardiotoxic effect of testosterone (TES) and dehydroepiandrosterone (DHEA) in Sprague Dawley rats. We compared the impact of subacute (14 days) and subchronic (90 days) administration of suprapharmacologic doses of TES and DHEA on body weight, locomotor activity, muscle strength, echocardiographic parameters, heart histopathology, and oxidative stress markers with the control group.

Testosterone (10, 30, and 100 mg/100 g body weight) and DHEA (10 mg/100 g body weight) administration decreased the body weights and locomotor activity (p < 0.05), and the combination of both increased muscle strength (p < 0.05) in rats.

In our histopathological evaluation, misshapen cell nuclei, disorganized myocardial fibers, and leukocytic infiltrates were observed in high-dose TES (100 mg/100 g)-treated rats, especially on day 14. On day 90, mild changes such as misshapen cell nuclei, disorganized myocardial fibers, and leukocytic infiltrates were observed in TES and DHEA-treated groups. According to our echocardiographic study on day 14 and day 90, TES, especially at high doses, induced increase in left ventricular posterior wall diameter and ejection fraction (p < 0.05).

In this study, blood oxidative stress marker malondialdehyde was increased slightly but not significantly in TES and DHEA groups. On the other hand, antioxidant enzymes such as SOD and glutathione peroxidase (GSH-Px) levels were slightly but not significantly increased in TES and DHEA groups.

These data demonstrate that the potential risk to cardiac health due to exogenous androgen use may be related to oxidative stress in rats.

 

[Michael Scally MD]

Santos MR, Sayegh AL, Groehs RV, Fonseca G, Trombetta IC, et al. Testosterone Deficiency Increases Hospital Readmission and Mortality Rates in Male Patients with Heart Failure. Arq Bras Cardiol. http://www.arquivosonline.com.br/2015/english/aop/AOP_6793_i.pdf

BACKGROUND: Testosterone deficiency in patients with heart failure (HF) is associated with decreased exercise capacity and mortality; however, its impact on hospital readmission rate is uncertain. Furthermore, the relationship between testosterone deficiency and sympathetic activation is unknown.

OBJECTIVE: We investigated the role of testosterone level on hospital readmission and mortality rates as well as sympathetic nerve activity in patients with HF.

METHODS: Total testosterone (TT) and free testosterone (FT) were measured in 110 hospitalized male patients with a left ventricular ejection fraction < 45% and New York Heart Association classification IV. The patients were placed into low testosterone (LT; n = 66) and normal testosterone (NT; n = 44) groups. Hypogonadism was defined as TT < 300 ng/dL and FT < 131 pmol/L. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography in a subpopulation of 27 patients.

RESULTS: Length of hospital stay was longer in the LT group compared to in the NT group (37 +/- 4 vs. 25 +/- 4 days; p = 0.008). Similarly, the cumulative hazard of readmission within 1 year was greater in the LT group compared to in the NT group (44% vs. 22%, p = 0.001).

In the single-predictor analysis, TT (hazard ratio

---

, 2.77; 95% confidence interval [CI], 1.58-4.85; p = 0.02) predicted hospital readmission within 90 days. In addition, TT (HR, 4.65; 95% CI, 2.67-8.10; p = 0.009) and readmission within 90 days (HR, 3.27; 95% CI, 1.23-8.69; p = 0.02) predicted increased mortality. Neurohumoral activation, as estimated by MSNA, was significantly higher in the LT group compared to in the NT group (65 +/- 3 vs. 51 +/- 4 bursts/100 heart beats; p < 0.001).

CONCLUSION: These results support the concept that LT is an independent risk factor for hospital readmission within 90 days and increased mortality in patients with HF. Furthermore, increased MSNA was observed in patients with LT.

 

[BuccanAy]

isn't the drug trimetedazine supposed to help this...avail at ADC

 

[Michael Scally MD]

Daka B, Langer RD, Larsson CA, Rosen T, Jansson PA, et al. Low concentrations of serum testosterone predict acute myocardial infarction in men with type 2 diabetes mellitus. BMC Endocr Disord. 2015;15(1):35. http://www.biomedcentral.com/1472-6823/15/35

BACKGROUND: The aim of the present study was to investigate the associations between endogenous testosterone concentrations and the incidence of acute myocardial infarction (AMI) in men and women with and without type 2 diabetes.

METHODS: The study comprised 1109 subjects >/=40 years of age (mean age 62 +/- 12 years) participating in a baseline survey in Sweden in 1993-94. Information about smoking habits and physical activity was obtained using validated questionnaires. Serum concentrations of testosterone and sex hormone-binding globulin (SHBG) were obtained using radioimmunoassay. Diagnosis of type 2 diabetes was based on WHO's 1985 criteria. Individual patient information on incident AMI was ascertained by record linkage with national inpatient and mortality registers from baseline through 2011.

RESULTS: The prevalence of type 2 diabetes at baseline was 10.0 % in men and 7.5 % in women. During a mean follow-up of 14.1 years (+/-5.3), there were 74 events of AMI in men and 58 in women. In age-adjusted Cox models, a significant inverse association between concentrations of testosterone and AMI-morbidity was found in men with type 2 diabetes (HR = 0.86 CI (0.75-0.98)). In a final model also including waist-to-hip ratio, systolic blood pressure, total cholesterol and active smoking, the association still remained statistically significant (HR = 0.754 CI (0.61-0.92)).

CONCLUSION: Low concentrations of testosterone predicted AMI in men with type 2 diabetes independent of other risk factors. Trials with testosterone investigating the effect regarding cardiovascular outcome are still lacking. Future trials in this field should take into account a modification effect of diabetes.

 

[Michael Scally MD]

Kereiakes DJ, Robinson JG, Cannon CP, Lorenzato C, Pordy R, et al. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study. Am Heart J. 2015;169(6):906-15 e13. https://www.sciencedirect.com/science/article/pii/S0002870315001684

BACKGROUND: The ODYSSEY COMBO I study (http://clinicaltrials.gov/show/NCT01644175) evaluated efficacy and safety of alirocumab as add-on therapy to stable maximally tolerated daily statin with or without other lipid-lowering therapy in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia.

METHODS: This multicenter, phase 3, randomized (2:1 alirocumab vs placebo), double-blind, 52-week trial enrolled 316 patients with established coronary heart disease or coronary heart disease risk equivalents and hypercholesterolemia.

Alirocumab (75 mg every 2 weeks [Q2W]) or placebo Q2W was self-administered subcutaneously via 1 mL prefilled pen. The alirocumab dose was increased to 150 mg Q2W (also 1 mL) at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was >/=70 mg/dL.

The primary efficacy end point was percent change in LDL-C from baseline to week 24 (intention-to-treat analysis).

RESULTS: At week 24, estimated mean (95% CI) changes in LDL-C from baseline were -48.2% (-52.0% to -44.4%) and -2.3% (-7.6% to 3.1%) for alirocumab and placebo, respectively, an estimated mean (95% CI) difference of -45.9% (-52.5% to -39.3%) (P < .0001).

Low-density lipoprotein cholesterol <70 mg/dL was achieved by 75% alirocumab versus 9% placebo patients at week 24. At week 12, 83.2% of evaluable alirocumab-treated patients remained on 75-mg Q2W. Treatment-emergent adverse events were comparable between groups.

CONCLUSIONS: Alirocumab treatment achieved a significantly greater reduction in LDL-C and allowed a greater proportion of patients to achieve LDL-C goals, versus placebo after 24 weeks in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia at baseline despite receiving maximally tolerated statin with or without other lipid-lowering therapy. The frequency of treatment-emergent adverse events and study medication discontinuations were generally comparable between treatment groups.

 

[Michael Scally MD]

Sharma R, Oni OA, Gupta K, Chen G, Sharma M, et al. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. European Heart Journal. http://eurheartj.oxfordjournals.org/content/early/2015/07/27/eurheartj.ehv346

Aims There is a significant uncertainty regarding the effect of testosterone replacement therapy (TRT) on cardiovascular (CV) outcomes including myocardial infarction (MI) and stroke. The aim of this study was to examine the relationship between normalization of total testosterone (TT) after TRT and CV events as well as all-cause mortality in patients without previous history of MI and stroke.

Methods and Results We retrospectively examined 83 010 male veterans with documented low TT levels. The subjects were categorized into (Gp1: TRT with resulting normalization of TT levels), (Gp2: TRT without normalization of TT levels) and (Gp3: Did not receive TRT).

By utilizing propensity score-weighted Cox proportional hazard models, the association of TRT with all-cause mortality, MI, stroke, and a composite endpoint was compared between these groups.

The all-cause mortality [hazard ratio (HR): 0.44, confidence interval (CI) 0.42–0.46], risk of MI (HR: 0.76, CI 0.63–0.93), and stroke (HR: 0.64, CI 0.43–0.96) were significantly lower in Gp1 (n = 43 931, median age = 66 years, mean follow-up = 6.2 years) vs. Gp3 (n = 13 378, median age = 66 years, mean follow-up = 4.7 years) in propensity-matched cohort.

Similarly, the all-cause mortality (HR: 0.53, CI 0.50–0.55), risk of MI (HR: 0.82, CI 0.71–0.95), and stroke (HR: 0.70, CI 0.51–0.96) were significantly lower in Gp1 vs. Gp2 (n = 25 701, median age = 66 years, mean follow-up = 4.6 years). There was no difference in MI or stroke risk between Gp2 and Gp3.

Conclusion In this large observational cohort with extended follow-up, normalization of TT levels after TRT was associated with a significant reduction in all-cause mortality, MI, and stroke.

 

[Michael Scally MD]

Basaria S, Harman S, Travison TG, et al. Effects of Testosterone Administration for 3 Years on Subclinical Atherosclerosis Progression in Older Men With Low or Low-Normal Testosterone Levels: A Randomized Clinical Trial. JAMA. 2015;314(6):570-581. http://jama.jamanetwork.com/article.aspx?articleid=2425744

Importance Testosterone use in older men is increasing, but its long-term effects on progression of atherosclerosis are unknown.

Objective To determine the effect of testosterone administration on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels.

Design, Setting, and Participants Testosterone’s Effects on Atherosclerosis Progression in Aging Men (TEAAM) was a placebo-controlled, double-blind, parallel-group randomized trial involving 308 men 60 years or older with low or low-normal testosterone levels (100-400 ng/dL; free testosterone <50 pg/mL), recruited at 3 US centers. Recruitment took place between September 2004 and February 2009; the last participant completed the study in May 2012.

Interventions One hundred fifty-six participants were randomized to receive 7.5 g of 1% testosterone and 152 were randomized to receive placebo gel packets daily for 3 years. The dose was adjusted to achieve testosterone levels between 500 and 900 ng/dL.

Main Outcomes and Measures Coprimary outcomes included common carotid artery intima-media thickness and coronary artery calcium; secondary outcomes included sexual function and health–related quality of life.

Results Baseline characteristics were similar between groups: patients were a mean age of 67.6 years; 42% had hypertension; 15%, diabetes; 15%, cardiovascular disease; and 27%, obesity. The rate of change in intima-media thickness was 0.010 mm/year in the placebo group and 0.012 mm/year in the testosterone group (mean difference adjusted for age and trial site, 0.0002 mm/year; 95% CI, −0.003 to 0.003, P = .89). The rate of change in the coronary artery calcium score was 41.4 Agatston units/year in the placebo group and 31.4 Agatston units/year in the testosterone group (adjusted mean difference, −10.8 Agatston units/year; 95% CI, −45.7 to 24.2; P = .54). Changes in intima-media thickness or calcium scores were not associated with change in testosterone levels among individuals assigned to receive testosterone. Sexual desire, erectile function, overall sexual function scores, partner intimacy, and health-related quality of life did not differ significantly between groups. Hematocrit and prostate-specific antigen levels increased more in testosterone group.

Conclusions and Relevance Among older men with low or low-normal testosterone levels, testosterone administration for 3 years vs placebo did not result in a significant difference in the rates of change in either common carotid artery intima-media thickness or coronary artery calcium nor did it improve overall sexual function or health-related quality of life. Because this trial was only powered to evaluate atherosclerosis progression, these findings should not be interpreted as establishing cardiovascular safety of testosterone use in older men.

 

[Michael Scally MD]

Khera AV, Natarajan P, Kathiresan S. The future of low-density lipoprotein cholesterol lowering therapy: An end to statin exceptionalism? European Journal of Preventive Cardiology. http://www.kathiresanlab.org/wp-content/uploads/2015/08/Khera-Statin-Exceptionalism-EJPC-20151.pdf

A screen of microbial culture broths led by Akira Endo in the 1970s led to the discovery of compactin, a competitive inhibitor of the rate-limiting enzyme in cholesterol synthesis HMG-CoA reductase (HMGCR).

Subsequent development of closely related compounds gave rise to statin medications.

Numerous clinical trials of statin therapy demonstrate robust reductions in both low-density lipoprotein cholesterol (LDL-C) and cardiovascular events, reinforcing statins’ role as the pharmacologic backbone of current hyperlipidemia treatment strategies.

These striking clinical trial results led researchers to seek evidence for pleiotropic cholesterol-independent effects of statins; the impact of statins on metrics of inflammation, endothelial dysfunction, oxidative stress, and immunomodulation were carefully examined.

Favorable results from these studies gave rise to the ‘‘statin exceptionalism’’ hypothesis, the notion that statins exert clinical gain beyond that which would be predicted by the LDL-C reduction achieved.

Recent advances in the realms of both clinical trials and human genetics provide an opportunity to test this hypothesis.

 

[Michael Scally MD]

Rouver WN, Delgado NT, Menezes JB, Santos RL, Moyses MR. Testosterone Replacement Therapy Prevents Alterations of Coronary Vascular Reactivity Caused by Hormone Deficiency Induced by Castration. PLoS One. 2015;10(8):e0137111. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137111

The present study aimed to determine the effects of chronic treatment with different doses of testosterone on endothelium-dependent coronary vascular reactivity in male rats.

Adult male rats were divided into four experimental groups:
control (SHAM),
castrated (CAST),
castrated and immediately treated subcutaneously with a physiological dose (0.5 mg/kg/day, PHYSIO group) or
supraphysiological dose (2.5 mg/kg/day, SUPRA group) of testosterone for 15 days.

Systolic blood pressure (SBP) was assessed at the end of treatment through tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed using the Langendorff retrograde perfusion technique.

A dose-response curve for bradykinin (BK) was constructed, followed by inhibition with 100 muM L-NAME, 2.8 muM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 muM clotrimazole (CLOT).

We observed significant endothelium-dependent, BK-induced coronary vasodilation, which was abolished in the castrated group and restored in the PHYSIO and SUPRA groups.

Furthermore, castration modulated the lipid and hormonal profiles and decreased body weight, and testosterone therapy restored all of these parameters.

Our results revealed an increase in SBP in the SUPRA group.

In addition, our data led us to conclude that physiological concentrations of testosterone may play a beneficial role in the cardiovascular system by maintaining an environment that is favourable for the activity of an endothelium-dependent vasodilator without increasing SBP.

 

[Michael Scally MD]

Niacin Therapy, HDL Cholesterol, and Cardiovascular Disease: Is the HDL Hypothesis Defunct?

High-density lipoprotein cholesterol (HDL-C) has been shown in epidemiologic studies to be associated with cardiovascular (CV) risk and thus significant efforts have been focused on HDL-C modulation.

Multiple pharmaceutical agents have been developed with the goal of increasing HDL-C. Niacin, the most widely used medication to raise HDL-C, increases HDL-C by up to 25 % and was shown in multiple surrogate end point studies to reduce CV risk.

However, two large randomized controlled trials of niacin, AIM-HIGH and HPS2-THRIVE, have shown that despite its effects on HDL-C, niacin does not decrease the incidence of CV events and may have significant adverse effects.

Studies of other classes of agents such as cholesteryl ester transfer protein (CETP) inhibitors have also shown that even dramatic increases in HDL-C do not necessarily translate to reduction in clinical events.

While these findings have cast doubt upon the importance of HDL-C modulation on CV risk, it is becoming increasingly clear that HDL function-related measures may be better targets for CV risk reduction.

Increasing ApoA-I, the primary apolipoprotein associated with HDL, correlates with reduced risk of events, and HDL particle concentration (HDL-P) inversely associates with incident CV events adjusted for HDL-C and LDL particle measures.

Cholesterol efflux, the mechanism by which macrophages in vessel walls secrete cholesterol outside cells, correlates with both surrogate end points and clinical events.

The effects of niacin on these alternate measures of HDL have been conflicting. Further studies should determine if modulation of these HDL function markers translates to clinical benefits.

Although the HDL cholesterol hypothesis may be defunct, the HDL function hypothesis is now poised to be rigorously tested.

Mani P, Rohatgi A. Niacin Therapy, HDL Cholesterol, and Cardiovascular Disease: Is the HDL Hypothesis Defunct? Current Atherosclerosis Reports C7 – 2015;43.17(8):1-9. http://link.springer.com/article/10.1007/s11883-015-0521-x

 

[heady muscle]

I am sure you saw this @Michael Scally MD or have already posted and I missed it:
http://www.anabolic.org/changes-in-the-heart-as-a-result-of-aas-abuse/

 

[Michael Scally MD]

I am sure you saw this @Michael Scally MD or have already posted and I missed it:
http://www.anabolic.org/changes-in-the-heart-as-a-result-of-aas-abuse/

Yes, ty. It is written by a Greek doctor. A FB friend.

 

[Michael Scally MD]

Lima EM, Nascimento AM, Brasil GA, Kalil IC, Lenz D, et al. Cardiopulmonary reflex, cardiac cytokines, and nandrolone decanoate: response to resistance training in rats. Can J Physiol Pharmacol. 2015. http://www.nrcresearchpress.com/doi/abs/10.1139/cjpp-2015-0014

This study evaluated the effects of nandrolone associated with resistance training (RT) on cardiac cytokines, angiotensin-converting enzyme activity (ACEA), and the sensitivity of the Bezold-Jarisch reflex (BJR). Male Wistar rats were divided into 3 groups: CONT (received vehicle, no training); EXERC (RT: after one week of water adaptation, rats were exercised by jumping into water twice a week for 4 weeks), and ND+EXERC (received nandrolone decanoate 10 mg/kg, twice/week, i.m, associated with RT). The BJR was analysed by measuring bradycardic and hypotensive responses elicited by serotonin administration. Myocyte hypertrophy and matrix collagen deposition were determined by morphometric analysis of H&E and picrosirius red-stained samples, respectively. TNF-alpha and ACEA were also studied. RT promoted physiological myocyte hyrpertrophy but did not cause changes in the other parameters. The association of ND with RT increased myocyte hypertrophy, deposition of matrix type I collagen, TNF-alpha and ACEA; decreased IL-10, and impairment in the BJR were observed in ND+EXERC compared with CONT and EXERC. ND is associated with alterations in cardiac structure and function as a result of the development of pathological cardiac hypertrophy (cardiac cytokine imbalance, elevation of ACEA) and cardiac injury, even when combined with resistance training.

 

[Michael Scally MD]

[Open Access] Anabolic Drugs and Myocardial Infarction – A Clinical Case Report

In most cases of myocardial infarction (MI) in young people, traditional cardiovascular risk factors continue to be of utmost importance; but at this age, other causes should also be considered, such as drug abuse.

Anabolic steroids are synthetic derivatives of testosterone and are often illegally used by athletes to increase their physical performance. There is a correlation between the use of these drugs and increased cardiovascular risk.

Human growth hormone (hGH) has also been used to increase physical performance, despite the risk of cardiovascular complications.

Clenbuterol is a potent β2-agonist that also has anabolic effects. However, at present, little is known about its potential cardiovascular risk.

Despite reports of MI associated with the use of anabolic steroids, no previous studies have reported the simultaneous use of these three types of medications.

A 25-year-old Caucasian male had no cardiovascular risk factors or history of other known relevant diseases. His practiced bodybuilding and regularly consumed anabolic steroids, hGH, and clenbuterol for the past 6 months.

The last cycle, initiated 6 weeks before the episode described herein, comprised the following:
oxandrolone, 40 mg/day (daily);
clenbuterol, 0.08 mg/day (daily);
mesterolone, 50 mg/day (daily);
hGH, 10 IU/day (daily);
nandrolone, 600 mg/day (twice a week);
testosterone cypionate, 400 mg/day (twice a week);
stanozolol, 100 mg/day (thrice a week);
drostanolone, 200 mg/day (thrice a week);
trenbolone at 200 mg/day (thrice a week);
testosterone propionate, 100 mg/day (thrice a week);
boldenone, 400 mg/day (twice a week); and
methenolone, 200 mg/day (twice a week).

Santos RP, Pereira A, Guedes H, et al. Anabolic Drugs and Myocardial Infarction – A Clinical Case Report. Arq Bras Cardiol. 2015;105(3):316-9. http://www.arquivosonline.com.br/2015/english/10503/pdf/i10503014.pdf

 

[Michael Scally MD]

With such an important BP trial, it would be nice if @nih_nhlbi provides the data right away--beyond @NYT report. It will be a game changer. NHLBI Blood Pressure JNC8 http://jama.jamanetwork.com/article.aspx?articleid=1791497

High Blood Pressure Treatment Should Be More Aggressive
http://www.nytimes.com/2015/09/12/health/blood-pressure-study.html?_r=0

Declaring they had “potentially lifesaving information,” federal health officials said on Friday that they were ending a major study more than a year early because it has already conclusively answered a question cardiologists have puzzled over for decades: how low should blood pressure go?

The answer: way lower than the current guidelines.

The study found that patients who were assigned to reach a systolic blood pressure goal below 120 — far lower than current guidelines of 140, and 150 for people over 60 — had their risk of heart attacks, heart failure and strokes reduced by a third and their risk of death reduced by nearly a quarter.

 

[Michael Scally MD]

[Open Access] Central and Peripheral Testosterone Effects in Men with Heart Failure: An Approach for Cardiovascular Research

Bušić Z, Čulić V. Central and Peripheral Testosterone Effects in Men with Heart Failure: An Approach for Cardiovascular Research. World J Cardiol 2015;7(9):504-10. http://www.wjgnet.com/1949-8462/full/v7/i9/504.htm

Heart failure (HF) is a syndrome recognized as a health problem worldwide. Despite advances in treatment, patients with HF still have increased morbidity and mortality.

Testosterone is one of the most researched hormones in the course of HF. Growing interest regarding the effect of testosterone, on a variety of body systems, has increased the knowledge about its mechanisms of action.

The terms central and peripheral effects are used to distinguish the effects of testosterone on cardiac and extracardiac structures.

Central effects include influences on cardiomyocytes and electrophysiology.

Peripheral effects include influences on blood vessels, baroreceptor reactivity, skeletal muscles and erythropoesis.

Current knowledge about peripheral effects of testosterone may explain much about beneficiary effects in the pathophysiology of HF syndrome. However, central, i.e., cardiac effects of testosterone are to be further explored.