Anabolic-androgenic steroid use tied to adverse cardiovascular phenotypes
Long-term exposure to anabolic-androgenic steroids (AAS) may result in both systolic and diastolic myocardial dysfunction, as well as coronary atherosclerosis, a study has found.
Compared with systolic functional deficit that appears to be reversible once AAS is discontinued, diastolic myocardial dysfunction persists. Further, atherosclerotic disease shows a strong association with lifetime duration of AAS use.
“Millions of individuals have used AAS to gain muscle for athletic purposes or personal appearance,” the authors said. “[The] AAS-associated adverse cardiovascular phenotypes [characterized by both myocardial and coronary artery pathologies] may represent a previously under-recognized public-health problem.”
“Our findings may inform public health initiatives to curb drug exposure and provide clinicians with information that will translate into improved patient care,” they added.
The cross-sectional cohort study included 140 experienced male weightlifters aged 34 to 54 years. Of these, 86 reported a median of 7.4 years of cumulative lifetime AAS use (median cumulative lifetime AAS dose, 366 g), while the remaining 54 were nonusers. [Circulation 2017;135:1991–2002]
Primary outcome measures were left ventricular (LV) systolic function (left ventricular ejection fraction [LVEF]), LV diastolic function (early relaxation velocity) and coronary atherosclerosis (coronary artery plaque volume). Assessments were performed using transthoracic echocardiography and coronary computed tomography angiography.
Results showed that AAS users had a significantly reduced LV systolic function (mean LVEF, 52 vs 63 percent in nonusers; p<0.001) and diastolic function (mean early relaxation velocity, 9.3 vs 11.1 cm/second; p<0.001). Among users, those currently taking AAS at the time of evaluation (n=58) had significantly reduced LV systolic (mean LVEF, 49 vs 58 percent; p<0.001) and diastolic function (early relaxation velocity, 8.9 vs 10.1 cm/second; p=0.035) compared with those currently off-drug (n=28).
Moreover, compared with nonusers, AAS users were found to have higher coronary artery plaque volume (median, 3 mL3; interquartile range [IQR], 0 to 174 vs 0 mL3; IQR, 0 to 69; p=0.012). Lifetime AAS dose had a strong association with coronary atherosclerotic burden, and the increase in rank of plaque volume for each 10-year increase in cumulative duration of AAS use was 0.60 SD units (95 percent CI, 0.16 to 1.03; p=0.008).
The finding of substantial LV systolic function impairment in AAS users was driven almost entirely by those AAS users who were on-drug at the time of evaluation, the authors explained. This indicates that LV dysfunction may be dynamically related to AAS use patterns.
“In contrast to systolic function, which appeared largely normal among off-drug AAS users, LV diastolic function was impaired in both on-drug and off-drug users, suggesting a more permanent form of acquired pathology,” they continued.
Other notable findings include the potential effect of AAS on cardiac muscle mass as indicated by AAS users having significantly more LV hypertrophy (measured by LV mass index) vs nonusers, and a possible mechanistic link between LV hypertrophy and functional deterioration, with the magnitude of LV hypertrophy among AAS users being directly related to the degrees of both systolic and diastolic function.
“Widespread illicit AAS use first appeared in the general population in the 1980s, and most AAS users are still young or middle-aged today,” the authors noted.
“Thus, when clinicians encounter young or middle-aged men who exhibit evidence of unexplained left ventricular dysfunction or premature coronary artery disease, the possibility of cardiotoxicity because of long-term AAS use should be considered in the differential diagnosis,” they said.
They pointed out that most contemporary AAS users (about 80 percent) are simply recreational weightlifters rather than competitive athletes, underscoring the importance of considering the possibility of AAS use even in individuals who do not identify as athletes.
The authors acknowledged the presence of limitations inherent to studies with a cross-sectional design, adding that the results might not be generalizable to other AAS-using groups (eg, elite athletes).