Cardiovascular Toxicity of Illicit Anabolic-Androgenic Steroid Use

Editor's Note: Commentary based on Baggish AL, Weiner RB, Kanayama G, et al. Cardiovascular toxicity of illicit anabolic-androgenic steroid use. Circulation 2017;135:1991-2002.

The following are ten summary points about cardiovascular toxicity of illicit anabolic-androgenic steroid (AAS) use:

  1. An estimated 2.9 to 4.0 million Americans, mostly male recreational weightlifters, have used AAS for athletic performance or personal appearance. Widespread AAS use began in the 1980s, and therefore most AAS users are still relatively young.
  2. The long-term cardiovascular impact of AAS use is not completely understood. Previous studies have suggested that AAS exposure can lead to cardiomyopathy and accelerated atherosclerotic disease, but these studies have been small in participant number and methodologically limited.
  3. In preclinical studies, AAS exposure at supraphysiologic doses has been found to cause dyslipidemia, stimulate cardiomyocyte hypertrophy, impair coronary arterial function, reduce cardiac β-adrenoreceptor sensitivity, potentiate oxidative cardiac stress, lower arrhythmic thresholds, and induce myocyte apoptosis.
  4. In this observational cross-sectional cohort study, 140 male weightlifters between 34 and 54 years old were analyzed. The final analysis compared 86 AAS users (>2 years of AAS use) with 54 non-AAS users. All subjects were assessed with transthoracic echocardiography and coronary computed tomography angiography. Baseline characteristics were similar in both groups with the exception that AAS users had higher body mass index and fat-free mass index consistent with the known effects of AAS. Primary outcomes assessed were left ventricular (LV) systolic function (ejection fraction, EF), LV diastolic function (early relaxation, E' velocity), and coronary atherosclerosis (coronary artery plaque volume).
  5. Individuals with current or past AAS use were found to have relatively reduced LV systolic function (LV EF 52 ± 11% versus 63 ± 8%; P < 0.001) and diastolic function (E' = 9.3 ± 2.4 cm/s versus 10.1 ± 2.4 cm/s; P < 0.001) compared to non-users. AAS users also exhibited higher LV mass index, LV wall thickness and more concentric LV geometry compared to non-users. Importantly, LV mass increase among AAS users was associated with decrements in LV EF and E' velocity, suggesting a mechanistic and pathologic link between AAS-associated cardiac hypertrophy and functional deterioration. Finally, AAS users had higher blood pressure (mean ± SD systolic, 118 ± 11 versus 115 ± 10 mm Hg; diastolic, 76 ± 9 versus 72 ± 9 mm Hg) and a higher prevalence of dyslipidemia (N [%] as evidenced by LDL cholesterol >160 mg/dL: 20 [23%] versus 7 [13%]).
  6. Interestingly, with discontinuation of AAS use, LV systolic function appears to normalize however, changes in diastolic function persist. On-drug AAS users (N = 58) showed significantly reduced LV systolic function (LV EF = 49 ± 10% versus 58 ± 10%; P < 0.001) compared to off-drug AAS users. While 41 out of 58 (71%) on-drug AAS users demonstrated LV EF below the normal threshold of 52%, there was no significant difference in LV EF between off-drug AAS users and non-users. In contrast, while 29 out of 58 (50%) on-drug AAS users exhibited E' <8.5 cm/sec, diastolic function achieved only partial normalization in off-drug users and thus remained diminished compared to non-users (E' = 10.1 ± 2.4 versus 11.1 ± 2.0 cm/s; P = 0.035).
  7. AAS users demonstrated higher coronary artery plaque volume than nonusers, and the lifetime AAS dose was strongly associated with coronary atherosclerotic plaque volume for each 10-year increase in cumulative duration of AAS use. No significant association was found with currency of use and plaque volume. Notably, three AAS users had experienced myocardial infarction before the age of 50 and another was diagnosed with congestive heart failure and found to have significant coronary artery disease requiring percutaneous intervention at the age of 42. None of the non-users experienced myocardial infarction or were diagnosed with congestive heart failure.
  8. Overall, long-term AAS use appears to be associated with myocardial dysfunction and accelerated coronary atherosclerosis. Thus, knowledge of the results from this study may deter future potential youthful AAS users.
  9. When clinicians encounter young to middle-aged men who exhibit otherwise unexplained LV systolic or diastolic dysfunction or premature coronary artery disease, AAS-induced cardiotoxicity should be considered in the differential diagnosis.
  10. Results from the current study set the stage for important future longitudinal studies of the impact of AAS use on cardiovascular outcomes. Future work should aim to further characterize changes in cardiovascular phenotypes as a function of currency of use and include hard clinical outcomes. Interventions to impact drug exposure and treatment options are also important areas that are yet to be defined.

Clinical Topics: Cardio-Oncology, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Sports and Exercise Cardiology, Lipid Metabolism, Nonstatins, Novel Agents, Acute Heart Failure, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Echocardiography/Ultrasound, Nuclear Imaging, Sports & Exercise and Imaging

Keywords: Coronary Artery Disease, Cholesterol, LDL, Plaque, Atherosclerotic, Cardiotoxicity, Drug Users, Apoptosis, Blood Pressure, Body Mass Index, Angiography, Myocytes, Cardiac, Stroke Volume, Systole, Diastole, Echocardiography, Myocardial Infarction, Cardiomyopathies, Heart Failure, Cardiomegaly, Dyslipidemias, Athletic Performance, Athletes, Phenotype, Longitudinal Studies, Sports


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