Anabolic Steroids And The Cardiovascular System

Introduction

The abuse of Androgenic Anabolic Steroids (AAS) has been linked to a variety of different cardiovascular side effectsin athletes, including the development of left ventricular hypertrophy, cardiomyopathy, arrhythmias, myocardial infarction, heart failure, hypertension, arterial thrombosis and pulmonary embolism.[1-4]

Effects of AAS Abuse

AAS disturb serum levels of high density lipoprotein (HDL), low density lipoprotein (LDL), lipoprotein A (Lp-A), total cholesterol (TC), triglycerides and homocysteine. Significant reduction of HDL and elevation of LDL and Lp-A increases the risk of atherogenesis (plack formation), leading to atheromatosis and coronary heart disease. The elevation of LDL parallels the decrease of HDL levels.  Reduction of HDL increased LDL/TC results in atheromatic index distortion (> 5) and increased risk of acute myocardial infarction (AMI). Studies suggest that serum LDL levels may increase through the induction of the enzyme hepatic triglyceride lipase and catabolism of very low density lipoprotein. Hepatic triglyceride lipase induction may also catabolize HDL and reduce its serum levels. By some estimates, these lipoprotein abnormalities increase the risk for coronary artery disease by three- to six fold. [4] Hyperhomocysteinemia induces endothelial injury and endothelial dysfunction, increased platelet aggregation at the site of microvascular injury, leading to the development of atherosclerosis. The adverse effect on serum lipids and homocysteine depends on the type of AAS used, the route of administration, combination of drugs, dosage and time of abuse. However, studies have shown that the recovery on serum lipids after AAScessationis strongly dependent on duration of the AAS abuse rather than the dosage. It should be noted that, although the AAS cessation leads to reduced homocysteine levels, the damage of the vascular endothelium is irreversible. [1-4,8]

Steroids have been also associated with arrhythmias (atrial fibrillation, ventricular fibrillation, and tachycardia). One of the reasons is electrolyte imbalance and hypercalcemia in particular, since it has been well established that under supraphysiological dosages, AAS increase electrolytes and minerals absorption (sodium, calcium, phosphorus, magnesium).[1-3] Furthermore, the use of AAS appears to confer an increased risk of life-threatening arrhythmia leading to sudden death. [1] 

Echocardiographic studies show that supraphysiologic doses of AAS lead to both morphologic and functional changes of the heart. These include a tendency to produce myocardial hypertrophy, a possible increase of heart chamber diameters, and most likely a subclinically compromised left ventricular contractile function. These changes lead to left ventricular hypertrophy (LVH), cardiomegaly and increase the risk of chronic heart failure, hypertension and arrhythmias. It should be noted that, the adverse effects in heart structure and function are expected after prolonged AAS abuse. [1] Furthermore, studies suggest that AAS-using strength athletes have a slight concentric left ventricular hypertrophy, with some indication of decreased diastolic function several years after ceasing AAS abuse, compared with steroid-free strength athletes.

AAS abuse and especially androgens may increase blood pressure (BP), since they stimulate the production of aldosterone hormone from kidneys. [1,4,7]The amount of increase is associated with duration of abuse. Some AAS also do aromatize, converted to estrogen, by the aromatase enzyme. Estrogenic activity is linked with water retention and edema. Therefore a bodybuilder under off season, who abuses steroids that aromatize, has greater chances of developing hypertension. However, few AAS that do not aromatize are capable to increase BP.  Flyoxymesterone and trenbolone are among them. Both of them suppress the catabolic glucocorticosteroid cortisol (this is the reason of their high anabolic effect). But they also suppress the mineral corticosteroid aldosterone. So this is the reason they have zero water retention.

Nevertheless, other mechanisms that involve inhibition of the enzyme 11-hydroxylase, will eventually lead to increased BP. Kidneys have this specific enzyme, in order to protect them from increased BP from cortisol. This enzyme converts cortisol into the inactive cortisone (synthetic form).The reason of that is the fact aldosterone’s receptors are sometimes bound by cortisol and the problem initiates. When inhibition of 11 hydroxylase occurs, the overproduction of 11-β-deoxycorticosterone by adrenal cortex may be responsible forincreased BP. [7]

AAS influence hemopoiesis leading to erythrocytosis and finally polycytemia. The later could become a risk factor for cardiovascular disease, since blood viscosity increases dramatically. AAS also influence platelet aggregation, as a result of the increased production of thromboxane A2 and decreased production of prostacyclin. In addition, changes in the coagulation cascade may occur, including increased thrombin activity, which also contributes to a hypercoagulable state. These adverse effects are exacerbated by dehydration and catecholaminergic stress, which often occur in association with intense physical activities.  Hypercoagulable stateincreases the risk of cardiovascular events (myocardial infarction, thrombotic stroke, cerebrovascular hemorrhage).

AAS prolong bleeding time and sabotage hemostasis, while INR, APTT increase and enhance fibrinolysis. This mechanism is contradictive with the platelets aggregation effect. In the bottom line, AAS break down coagulation processing, but on the other hand they induce clot formation, through hematocrit elevation and fibrinogen elevation.

Prevention of Cardiovascular Risk

 Since AAS users are at an increased risk of cardiovascular morbidity and mortality when compared to non-users, cardiovascular physical activity is important for the following reasons:

1) The bodybuilder strongman, or weightlifter has to perform 30′ of slow pace aerobic activity at 60% of MHR. This kind of exercise will eventually improve myocardium’s shape and size.LVF will be diminished and ventricles will shift to the model of an endurance athlete’s heart; as long as AAS are ceased or at least taken with moderation and wisely. BMI is also a factor that has to be taken under consideration, as an overweight person, even at low fat percentage, has greater O2 demands for his myocardium. Therefore, heart has to perform harder and this is risky for an ischemic episode.

2) HDL increases with prolonged-sustained aerobic exercise, thus atheromatic index (HDL/LDL) is improved and atherothrombotic cardiovascular disease (CVD) risk can be diminished.

3) Low pace aerobic activity establishes the so called ”collateral circulation”. This fact is practically translated into a vast vascular network that surrounds the myocardium and provides oxygen to the heart muscle. Through this kind of vessels, someone could survive under a heart attack ischemic episode (AMI). [8,9]

Many studies have shown that cardiac adjustment varies, depending on the type of training (dynamic or static) and the type of sport. It appears that more than three hours of exercise is required per week, in order to observe adaptive changes; such as the reduction in heart rate and increase in mass of the left ventricle (LV). Marathon and triathlon runners have a “drop heart” shape, with enlarged ventricles and thin ventricular walls. This helps hemodynamically-functionally providing a greater ejection fraction (EF) and stroke volume (the ability of the heart muscle to pump blood and the volume of blood in each pulse).

On the other hand, exercising with weights-resistance training, in combination with chemical enhancement with Performance Enhancing Drugs (PED’s) leads to specific hemodynamic changes in the heart. In particular, increase in heart rate, decrease in stroke volume and ejection fraction (EF).

The LV becomes adapted to these hemodynamic changes, resulting in thickening of the wall with smaller ventricular cavities.[8,9]

A steroid user, who smokes, avoids cardiovascular aerobic physical activity and consumes saturated-trans fat, develops poor physical condition, with inadequate collateral circulation, high blood pressure and is more likely to develop coronary heart disease, due to atherosclerosis.

VO2max and cardio respiratory capacity are significantly dropped.

All current guidelines on the prevention of CVD in clinical practice recommend the assessment of total CVD risk because atherosclerotic CVD is usually the product of a number of risk factors. The higher the risk the more intensive the action should be. So AAS abusers are high risk population and should follow certain rules for longevity and medical prevention. [9] These include:

  1. Moderate aerobic physical activity of 60% MHR pace for 30′ on a daily basis.
  2. Avoidance of excessive saturated fat and trans fat/refined carbohydrates-sugars
  3. Diet rich in white meat, fish, egg whites, vegetables, fruits, nuts, oats and fiber that prevent oxidation of LDL and raise of triglycerides, Total Cholesterol too, while they contribute to a low insulin resistance and decrease glycemic effect.
  4. Use of anti-clotting agents (EPA, DHA, salicylic acid) as hematocrite (Htc) is raised and blood viscosity increases, due to AAS abuse.Use of salicylic acid preferable with breakfast, not post workout.
  5. Use of niacin (B3), phytosterols % red rice yeast to improve HDL/LDL ratio and regular use of coenzyme Q10, that has the ability to increase aerobic energy production of myocardium, along with magnesium and L-carnitine  acting as a mild anti-arrhythmic agent and energy enhancement .
  6. Monitoring BP and HR on a weekly basis, while performing a stress test, a U/S and a Holter 24hrs examination once a year. Elevated BP is one of the most powerful modifiable risk factors for CVD. The beneficial effects of BP-lowering therapies to reduce stroke, myocardial infarction, heart failure and death have been shown in numerous meta-analyses. 
  7. Regular assessment of Hematocrite, Hemoglobin, Platelets, HDL, LDL, Total Cholesterol, Triglycerides, Fasting blood glucose. These evaluations will ensure that there is no evidence of Metabolic Syndrome, Dislipidemia, Polycytemia, andtype 2 diabetes mellitus. Optimal control of the LDL-C level and of the BP is of great importance in all AAS abusers.

References:

  1. Androgenic anabolic steroid abuse and the cardiovascular system. Vanberg P, Atar D, et al.Handb Exp Pharmacol. 2010; (195):411-57.
  2. Cardiovascular disease and androgens: A review.Manu Kaushik, Siva P. Sontineni, et al. International Journal of Cardiology2010;142: 8–14
  3. Cardiovascular Toxicity of Illicit Anabolic-Androgenic Steroid Use. Aaron L. Baggish, Rory B. Weiner, et al. 2017; 135:1991–2002.
  4. Cardiac and Metabolic Effects of Anabolic-Androgenic Steroid Abuse on Lipids, Blood Pressure, Left Ventricular Dimensions, and Rhythm. Suraj Achar, Armand Rostamian, et al. Am J Cardiol.2010 Sep 15; 106(6):893-901.
  5. Performance enhancing drug abuse and cardiovascular risk in athletes: implications for the clinician.  Peter J Angell, Neil Chester, et al. Br J Sports Med 2012; 46: i78-i84
  6. Anabolic Steroids and Cardiovascular Risk. Peter Angell, Chester N, et al. Sports Med 2012; 42 (2): 119-134
  7. Cardiovascular manifestations of anabolic steroids in association with demographic variables in bodybuilding athletes. Farzad Gheshlaghi, Mohammad-Reza Piri-Ardakani, et al. J Res Med Sci. 2015 Feb; 20(2): 165–168.
  8. Prospective echocardiographic assessment of androgenic-anabolic steroids effects on cardiac structure and function in strength athletes. H Kuipers, et al. Int J Sports Med 2003; 24: 344-351
  9. Prevention of cardiovascular disease: recent achievements and remaining challenges. Guy De Backer. E-Journal of Cardiology Practice. https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-15/prevention-of-cardiovascular-disease-recent-achievements-and-remaining-challeng