Cardiac Health & Changes Associated With Anabolic Steroid Usage

The rising incidence of sudden unexpected death in certain subsets of athletes has sparked an increasing discussion on cardiac health in sports. Cardiac disease is the primary etiology of sudden death; both among the general population and athletes [1]. Given that the athlete population engages in ongoing rigorous physical activity, there is a general assumption that they are in optimal cardiac health. While this can be generally true, the usage of performance enhancing drugs (PEDs), can distort the health outcomes of this population. The types of PEDs that athletes use is heavily dependent on their sport. They include anabolic androgenic steroids (AAS), peptide hormones, stimulants, erythropoietin (EPO) and other agents. Many of the unexpected deaths seen over the past decade have occurred among those competing in sports where AAS use is highly prominent. Furthermore, these sports feature abuse of these drugs (very high dose usage) among many other agents. The purpose of this article is to evaluate the use of AAS among athletes in the context of cardiac health as well as other confounding variables.

Sudden Cardiac Death & Differential Diagnosis

The most common cause of sudden cardiac death in the general population is a lethal arrhythmia due to coronary artery disease (CAD). Similarly, older athletes with risk factors for CAD will carry elevated risks of suffering an ischemic cardiac event which can then induce a dangerous and/or lethal arrhythmia [2]. Younger athletes can also be at risk of a lethal arrhythmia if they carry any of the congenital risk factors. In contrast to older athletes where acquired CAD is prominent, younger athletes rarely experience the same events with the exceptions of coronary vasospasm and vasculitis. It is important to note that the most common final cause of a fatal cardiac event is ventricular fibrillation or pulseless electrical activity. While CAD is the most common pathologic cause that leads to a fatal arrhythmia, there are a broad range of etiologies that should be considered.

Acute Etiologies [3]

  • Acute myocardial infarction
  • Hypokalemia/hyperkalemia
  • Hypothermia
  • Acidosis
  • Hypoglycemia
  • Hypoxia
  • Hypovolemia
  • Drug overdose
  • Unstable tachycardia
  • Cardiac tamponade
  • Trauma
  • Aortic rupture

 

Acquired Structural Heart Disease

  • Coronary artery disease/atherosclerosis
  • Left ventricular hypertrophy (LVH)
  • Mitral valve prolapse (MVP)
  • Dilated cardiomyopathy
  • Myocarditis

 

Congenital Structural Heart Disease

  • Hypertrophic obstructive cardiomyopathy (HOCM)
  • Coronary artery anomaly
  • Left ventricular noncompaction
  • Dilated cardiomyopathy
  • Arrhythmogenic right ventricular dysplasia
  • Congenital aortic stenosis

 

Congenital Electrophysiologic Disease

  • Long QT syndrome
  • Short QT syndrome
  • Catecholaminergic polymorphic ventricular tachycardia (CPVT)
  • Wolff-Parkinson White syndrome
  • Brugada syndrome
  • Idiopathic ventricular tachycardia
  • Mixed sodium channel disease
  • Atrioventricular block(s)

 

These different acute events, structural issues and electrophysiologic defects can lead to episodes of unstable and potentially fatal arrhythmias. Understanding the different etiologies of sudden cardiac death is important for providing clinical context for PED induced cardiac arrest.
As such, the bolded clinical conditions highlight potential causes of sudden cardiac death in athletes [4]. While certain acute causes (Ex. trauma or aortic rupture) can be incidental, the others are generally self-induced. Electrolyte alterations such as hypokalemia can occur from diuretic abuse. Hypoglycemia can happen from improper insulin usage. As well, stimulant overdoses can lead to unstable tachycardia.


While other acquired conditions will be discussed in detail in this article, it is important to understand that all of the other listed conditions can elevate one’s risk of a cardiac event over a long athletic career. This occurs independently of any PED use and therefore abuse of PEDs would only further elevate one’s risk in the presence of pre-existing (and possibly unknown) cardiac disease.

 

Performance Enhancing Drugs & Cardiac Arrest

There are several long term mechanisms in PED users that can elevate the risk of sudden cardiac death. These cardiac mechanisms can be categorized as: direct structural changes, indirect structural changes, arrhythmogenicity and atherosclerotic disease. While the usage of AAS is primarily linked to these potential changes, there are confounding variables that are often underappreciated. These include peptide hormones, stimulants and diuretics. It is important to note that while peptide hormones (ex. human growth hormone) can play a significant role in cardiac structural changes, the use of stimulants and diuretics can be triggering variable for a cardiac event as previously mentioned.  

Direct Structural Changes

The use of AAS has been extensively tied to left ventricular hypertrophy in literature. As these hormones bind to the myocardial androgenic receptors on the heart, they induce ongoing growth. Certain agents induce less significant growth, such as testosterone. Other agents, such as Trenbolone, will lead to significant LVH in the long term. A lot of the left ventricular growth can also be credited to intensive exercise, but mechanism differs from AAS-induced LVH. Concurrent usage of certain peptide hormones, which is relatively common, is another major factor in left ventricular growth. Unfortunately, most of the evidence suggests irreversibility of these changes in the presence of long term abuse [5][6].
A pathologic state of LVH generally means that the hypertrophied myocytes are not accompanied by a relatively equal increase of capillaries. The result is a mismatch of oxygen and nutrient supply relative to the demand. As well, myocyte apoptosis may occur along with shifts in intracellular calcium. The clinical result of increased oxygen and metabolic demands along with other micro-level changes can lead to decompensation and heart failure.  

Indirect Structure Changes

Elevated blood pressure is the most common cause of LVH in the general population, and this is a major preceding clinical factor that leads to heart failure [7]. Anabolic steroids carry hypertensive effects depending on the specific agent. Oral steroids which cause extensive water retention will generally be more hypertensive than agents which cause minimal water retention. Certain steroids carry vasoconstricting effects and possibly suppress natriuretic peptides, and this leads to hypertension. These effects are amplified by long term use of stimulants/pre workout supplements that directly elevate blood pressure. Similarly, thyroid drugs and clenbuterol which are used for fat loss, significantly contribute to the ongoing hypertensive state. In summation, these hypertensive effects contribute to the chronic and often irreversible LVH seen in many AAS users [8].

Arrhythmias

Even though lethal arrhythmias are the end outcome that precede full cardiac arrest, there is no significant evidence to suggest that AAS directly can lead to arrhythmias. One study found certain electrophysiologic variables, including the QTc, JTc and Tp-e/QTc, were prolonged. However, it is difficult to truly link these changes to an increased risk of ventricular tachycardia [9]. It is worth noting that testosterone replacement therapy doses used to normalize testosterone have been tied to a lower incidence of atrial fibrillation [10].
The key variables that can lead to arrhythmias in athletes are stimulants and stimulating drugs as well as diuretics. For an athlete who has severe structural impairment of their heart, an increased burden or suboptimal conditions can trigger an arrhythmia. Increasing stimulation directly increases heart rate and contractility which then increases cardiac oxygen demand. Ectopic and irregular heart beats can then be triggered. As well, the use of diuretics can induce an alteration of electrolytes. Specifically, potassium, magnesium and calcium are the important electrolytes. Hypokalemia, hypocalcemia and hypomagnesemia increase the propensity for a dangerous arrhythmia.

Atherosclerosis

The main culprit behind sudden cardiac death in humans is atherosclerotic coronary artery disease. This condition develops due to years of poorly controlled lipid profiles as well as other risk factors. Anabolic steroids have shown a strong link to the lowering of high-density lipoproteins (HDL), slight to moderate elevation of low density lipoprotein (LDL) and overall alterations in cholesterol levels. One mechanism is that AAS can degrade the lipoproteins and also alters apolipoprotein A-I and B synthesis. These poorly controlled lipid profiles lead to the development of plaque inside the arteries and create a longstanding risk of an ischemic cardiac event. It is important to not ignore other lifestyle factors, such as smoking, which play a significant role in this pathological process [11]. Lastly, the prominent use of aromatase inhibitors (AIs) with AAS will decrease estradiol to varying degrees. This can directly worsen the lipid profile, often to significant degrees.  

There are other confounding factors related to AAS that affect the outcome of atherosclerosis. One relatively common effect of anabolic steroids is the development of erythrocytosis, as hemoglobin and hematocrit levels become elevated. The increased blood viscosity, if severe enough, can induce platelet aggregation which elevates the risk of an ischemic cardiac event. Kidney disease is another variable, particularly with the growing prominence of focal segmental glomerulosclerosis (caused by Trenbolone) [12] and cardiorenal syndrome in AAS users. A worsening renal system will be significantly detrimental to the cardiac system.

Solutions & Preventative Measures

The best treatment for cardiac illness is prevention of the disease itself, as sometimes the initial presentation of cardiac disease is sudden death. Given the previously discussed categories of AAS-induced cardiac disease, the management must be comprehensive as these pathological processes often overlap. It is essential to obtain a detailed medical history and conduct a physical examination that adequately assesses the cardiovascular system. As well, patients must be examined for any history of syncope, presyncope, chest pain, shortness of breath or increasing difficulty exercising.  

In the context of cardiac health, patients must have their lipid profiles, complete blood counts (CBC), chemistry panels and kidney function closely monitored (among other lab tests). Frequency of testing is debatable, however bi-annual testing may be warranted. As previously mentioned, distorted lipid profiles are quite common while using AAS. Once there is a recorded value of decreased HDL and/or increased LDL, it would be recommended to initiate statin therapy. There will be obvious hesitance within the medical community to initiate statins in some younger patients who fall under this category but unless the anabolic steroids are discontinued, the patient will be at elevated risk of atherosclerosis. In addition, statins have a therapeutic effect on the coronary arteries themselves. However, usage of statins will deplete coenzyme Q10 levels. This makes supplementation a reasonable choice [13]. Other therapeutic options have mixed efficacy for lipid control. The main exception to that is PCSK9 inhibitors, though given that AAS are known to mainly affect HDL, their use may not be as beneficial since they are highly potent against LDL. Other supplements which may improve the lipid profile are Omega 3s and high dose garlic [14][15]. The literature has consistently shown some improvements in HDL levels following omega 3 use and improvements in LDL levels following higher dose garlic supplementation. As well, they may decrease the likelihood of adverse effects that occur from elevated blood viscosity. The use of other supplements, such as niacin (which can be prescribed for this purpose), is debatable.

Treating AAS-induced hypertension can pose certain challenges. Discontinuation of the offending medication is always the primary mode of treatment in this context. This requires adequate counselling and the patient should be advised to discontinue the specific drugs that are inducing the hypertension. Often the main culprits are specific oral steroids which induce excessive water retention (ex. Dianabol) and other specific injectables that have major hypertensive properties (ex. Trenbolone). Since these oral agents are cycled for brief periods, they are less concerning than drugs that carry hypertensive effects.  As well, ongoing use of non-caffeine stimulants should be stopped, and the patient should be advised to only utilize caffeine with decreasing doses.
Beyond ceasing offending drugs, it is often imperative to initiate medications to lower blood pressure. Standard guidelines can be utilized for blood pressure management but given the utilization of diuretics among some AAS users, it is critical to obtain an accurate medical history. In some patients, prescribing an ACE inhibitor or ARB medication is quite useful not only to control blood pressure but also to prevent/decrease left ventricular hypertrophy. However, depending on the ethnicity the ACE/ARB medications may not work well for blood pressure control. This makes beta blockers and calcium channel blockers another potential set of options. It’s worth noting that beta blockers can carry additional benefits for select AAS users. If there is existing LVH, beta blockers can improve coronary perfusion and lower the risk of arrhythmias. Besides medications, supplements may provide some benefit. In addition to the beneficial effects on lipids, garlic may also lower blood pressure[14]. Other supplements may provide intermittent improvement of blood pressure but there is very loose evidence behind their use. And as far as lifestyle factors go, AAS users already engage in optimal dietary practices and have sufficient exercise.

The diagnosis and management of left ventricular hypertrophy presents numerous challenges to clinicians. However, given that LVH was a likely contributing factor to the cases of sudden death seen in AAS users, it deserves adequate attention. Since athletes in general will experience physiologic degrees of left ventricular hypertrophy (due to intensive exercise), it can be challenging to diagnosis a pathologic state of LVH. The primary mode of cardiac screening would be an electrocardiogram (ECG); however, there is general hesitance among the medical community to broadly conduct screening ECGs. This is because of the risk of false positives which can then lead to unnecessary testing. Though for the athlete population, the Seattle criteria outlined a methodology which can be used to conduct screening ECGs with minimal false positives. For LVH, the Cornell or Sokolow-Lyon voltage criteria has been used or the Romhilt-Estes point system. Interestingly, one aspect of the Seattle criteria is that a positive ECG test for LVH in an athlete should be ignored. Though with any criteria, clinical judgement must be used [16].  
The most reliable common method of diagnosing LVH is an echocardiogram. However, it is impractical for obvious reasons to conduct an echocardiogram in every AAS user. That’s why a clinician should be selective about who they potentially screen. Common things to look for include: very long standing history of AAS use, co-existing hypertension, extensive use of peptide hormones, and use of specific agents known to induce LVH (ex. Winstrol). Overall, most AAS users should not be screened with an echocardiogram unless several major risk factors and/or symptoms are identified. If the testing is done, then certain markers can be used to differentiate physiologic and pathologic LVH. A left ventricular wall thickness exceeding 15mm is diagnostic of pathologic LVH, whereas 11mm or less is entirely normal. Physiologic LHV is generally within 11-13mm and 13-15mm is a “grey area” that must be evaluated further [17].
Once a diagnosis of pathologic LVH is made, it is imperative to first discontinue the offending agents & also control the patient’s blood pressure. Second, prescribing an ACE/ARB medication and/or a beta blocker should be considered as previously discussed. This blocks Angiotensin II, which is a cardiomyocyte growth factor, thereby regressing the actual LVH & concentric remodeling itself. Also, severe LVH increases the risk of ventricular tachycardia and usage of a beta blocker will lower the risk of an arrhythmia while controlling blood pressure and improving coronary perfusion [18].

Overall, the clinical challenge of preventing and treating cardiac disease in athletes depends on numerous variables, especially in the context of PED use. Identification of congenital issues is a primary background concern as rigorous exercise along with PEDs can exacerbate pre-existing pathologies. Also, prevention of PED-induced cardiac disease is crucial and hence counseling along with adequate screening is essential. Identified issues should be treated early on to prevent long term risks. Achieving optimal outcomes in athletes is a byproduct of a good physician-patient relationship.

DISCLAIMER
The content by Dr. Khash Farzam is strictly intended for academic and educational purposes only. None of the content should ever be taken as medical advice of any form in any context. Khash Farzam does not support or endorse any drug, medication or supplement use of any form that is not prescribed and supervised by an individual’s physician.

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