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Cardiovascular Effects of Androgenic Anabolic Steroids in Male Bodybuilders Determined by Tissue Doppler Imaging
Cardiovascular Effects of Androgenic Anabolic Steroids in Male Bodybuilders Determined by Tissue Doppler Imaging Stéphane Nottin, PhDa,*, Long-Dang Nguyen, MDb, Mohamed Terbah, MDb, and Philippe Obert, PhDa The effects of anabolic androgenic steroids (AASs) on left ventricular (LV) diastolic function in strength-trained athletes are controversial. The main objective of this study was to evaluate the effects of regular AAS administration in bodybuilders using pulsed tissue Doppler imaging (TDI) to evaluate LV relaxation properties. Fifteen male bodybuilders with a history of intensive, long-term strength training and 16 age-matched sedentary controls were recruited. Six of the bodybuilders reported regular use of AASs, and 9 were drug free. To assess LV diastolic function, each subject underwent standard Doppler echocardiography and pulsed TDI. Drug-using bodybuilders exhibited altered LV diastolic filling characterized by a smaller contribution of passive filling to LV filling compared with their drug-free counterparts. TDI measurements indicated that drug-using bodybuilders had smaller peak Em than drug-free bodybuilders and sedentary controls, except at the level of the anterior wall, at which peak Em was significantly smaller than in drug-free bodybuilders only. The E/Em ratio, an index of LV filling pressures, was not affected by strength training or by AAS use. Drug-using bodybuilders exhibited larger LV end-diastolic diameters, volumes, and masses than their drug-free counterparts. However, no difference was found in LV wall thickness between the groups. In conclusion, drug-using bodybuilders showed a decrease in the contribution in LV passive filling to LV filling associated with a decrease in LV relaxation properties. Because no wall thickening was obtained in drug-using bodybuilders, the decrease in LV relaxation properties might have been be due to an alteration in the active properties of the myocardium, but that has yet to be confirmed. © 2006 Elsevier Inc. All rights reserved. (Am J Cardiol 2006;97: 912–915) The self-administration of anabolic androgenic steroids (AASs) is a widespread practice among athletes to increase lean body mass and muscular strength. In recent years, a strong body of evidence has revealed the cardiovascular toxicity of AASs.1–3 In the present study, considering the deleterious effects of AASs observed on animal myocardium,4 – 6 we hypothesized that the repeated use of AASs would negatively alter left ventricular (LV) relaxation properties of athletes with a long-term history of strength training. To test this hypothesis, we used Doppler echocardiography, especially tissue Doppler imaging (TDI), to evaluate LV relaxation properties in drug-free bodybuilders, drug-using bodybuilders, and age-matched sedentary control subjects. •••
Fifteen male bodybuilders were recruited from local clubs. Six men reported current self-administration of AASs, and 9 reported never having used these drugs. All strength-
a
Laboratory of Cardiovascular Adaptations to Exercise, Faculty of Sciences, Avignon; and bCardiology Department, Regional Hospital Center, Orléans, France. Manuscript received May 3, 2005; revised manuscript received and accepted October 3, 2005. * Corresponding author: Tel: 33-0-4-32-74-32-02; fax: 33-0-4-90-1444-09. E-mail address: [email protected] (S. Nottin). 0002-9149/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2005.10.026
trained athletes had been training for 5 to 12 hours/week for ⱖ10 years. For admission into the study, bodybuilders in the steroid group were required to have used the drugs for the past 2 years. Sixteen age-matched sedentary controls were also enrolled. None of the subjects in either group had clinical or historical evidence of cardiovascular disease or hypertension. This study received approval from the local ethics committee, and written informed consent was obtained from subjects. A biometric evaluation was performed before each test. Height was measured with a height gauge and body mass with a balance beam scale. Body fat mass was assessed by skinfold thickness measurements according to Durnin and Rahaman.7 After a 15-minute rest period, standard Doppler echocardiography and TDI measurements were performed with the subjects in a partial left decubitus position using a HDI 5000 system (Phillips Ultrasound system, Phillips Medical System, Best, The Netherlands). A variable-frequency phasedarray transducer (2.5 to 4 Mhz) was used for Doppler echocardiographic and TDI measurements. Doppler echocardiographic and TDI tracings were recorded digitally on a hard drive for further analyses. All measurements were averaged on 3 to 5 measurements obtained during the end-expiratory stage of normal respiration. Standard echocardiograms consisted of 2-dimensional, www.AJConline.org
Congenital Heart Disease/Anabolic Steroids in Bodybuilders Table 2 Standard Doppler echocardiographic data
Table 1 Anthropometric data and blood pressures of the subjects Variable
Age (yrs) Height (cm) Body mass (kg) Fat mass (%) Body surface area (m2) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg)
Sedentary Men Drug-Free (n ⫽ 16) Bodybuilders (n ⫽ 9) 42 ⫾ 10 177 ⫾ 5 76 ⫾ 9 19 ⫾ 3 1.93 ⫾ 0.10 125 ⫾ 10
38 ⫾ 6 174 ⫾ 8 78 ⫾ 10 16 ⫾ 3* 1.92 ⫾ 0.16 122 ⫾ 11
78 ⫾ 8
77 ⫾ 12
913
Drug-Using Bodybuilders (n ⫽ 6)
Variable
41 ⫾ 6 180 ⫾ 6 97 ⫾ 7†§ 15 ⫾ 3† 2.16 ⫾ 0.12†§ 132 ⫾ 10
Septal wall thickness (mm) Posterior wall thickness (mm) LV end-diastolic diameter (mm) LV end-systolic diameter (mm) LV mass (g) LV end-diastolic volume LV end-systolic volume Ejection fraction (%) Stroke volume (ml) Heart rate (beats/min) Cardiac output (L)
87 ⫾ 8
Significantly different from sedentary men: * p ⬍0.05; † p ⬍0.01. Significantly different from drug-free bodybuilders: ‡ p ⬍0.05; § p ⬍0.01.
M-mode, and Doppler blood flow measurements. Acquisitions were made in harmonic imaging mode. M-mode measurements were obtained according to the recommendations of the American Society of Echocardiography in the parasternal long-axis view.8 The parameters measured were interventricular septal thickness, LV diameter, and LV posterior wall thickness. LV mass was calculated according to Penn’s convention.9 The LV ejection fraction was calculated from LV volumes measured by the biplane Simpson’s method.10 Pulsed Doppler LV inflow recordings were performed in the apical 4-chamber view, with the sample volume at the tip level of the mitral valves. E and A peak velocities (m · s⫺1), E-wave deceleration time (milliseconds), and isovolumetric relaxation time (milliseconds) were measured as indexes of global diastolic function. Stroke volume was estimated as the product of the aortic root area and the integral of aortic blood velocity and time. The maximal systolic diameter of the ascending aorta was measured from the 2-dimensional parasternal long-axis view. Measurements were performed from inner to inner edge at the level of the insertion of the aortic valve leaflets. The velocity of blood in the aorta was recorded from a 5-chamber view. The outline contour of the velocity curve overtime was traced manually. Cardiac output was calculated as the product of stroke volume and heart rate. TDI was performed at a transducer frequency of 3.5 to 4 Mhz, adjusting the spectral pulsed Doppler signal filters to a Nyquist limit of 15 to 20 cm · s⫺1 and using the minimal optimal gain. Wall motion velocities were assessed at the mitral annulus level on the septal, lateral, inferior, and anterior walls in 4- and 2-chamber views. Pulsed TDI was characterized by a myocardial systolic wave (Sm) and 2 diastolic waves (early [Em] and atrial [Am]), expressed in centimeters per second. The peak velocity of Sm was considered a systolic index. Em and Am peak velocities, the Em/Am ratio, and regional isovolumetric relaxation time were determined as diastolic measurements. The ratio of the transmitral E velocity to peak Em velocity recorded on the septal wall at the level of the mitral annulus was used as an index of LV filling pressures.11
Sedentary Men Drug-Free Drug-Using (n ⫽ 15) Bodybuilders Bodybuilders (n ⫽ 9) (n ⫽ 6) 9.5 ⫾ 1.9
9.7 ⫾ 1.7
10.8 ⫾ 1.3
9.3 ⫾ 0.12
10.3 ⫾ 0.9
10.0 ⫾ 1.4
52 ⫾ 5
53 ⫾ 5
58 ⫾ 4*‡
33 ⫾ 3
34 ⫾ 4
37 ⫾ 5
182 ⫾ 53 92 ⫾ 22 34 ⫾ 8 62 ⫾ 3 99 ⫾ 19 66 ⫾ 7 6.6 ⫾ 0.7
202 ⫾ 52 106 ⫾ 27 40 ⫾ 10 62 ⫾ 3 114 ⫾ 18 68 ⫾ 14 7.6 ⫾ 1.8
249 ⫾ 33*‡ 124 ⫾ 25† 49 ⫾ 12† 61 ⫾ 3 111 ⫾ 20 72 ⫾ 6 8.0 ⫾ 0.9
Significantly different from sedentary men: * p ⬍0.05; † p ⬍0.01. Significantly different from drug-free bodybuilders: ‡ p ⬍0.05.
All data were measured on digital recordings. The intraand interobserver variabilities of data analysis were assessed in a previous study conducted in our laboratory. Data from 12 subjects were analyzed blindly on 2 separate days by 2 experienced cardiologists. Because intra- and interobserver variabilities were low (⬍5% for all echocardiographic variables), values presented in the present report were those obtained by only 1 cardiologist. Auscultatory cuff blood pressures were obtained in the right arm using manual sphygmanometry (mean of 2 measurements). The appearance of the first Korotkoff sound was used as a criterion for systolic blood pressure, and the fourth Korotkoff sound (i.e., muffling of the sound) defined diastolic blood pressure. The results are presented as mean ⫾ SD. Each variable was compared among the 3 groups using a 1-way analysis of variance. When an overall difference was found at p ⬍0.05, a post hoc test of Fisher’s protected least-significant difference was performed. Statistical significance for all analyses was defined as p ⬍0.05. The characteristics of the subjects are listed in Table 1. No differences were observed in age, height, or blood pressure among sedentary men and drug-free and drug-using bodybuilders. However, the 2 groups of bodybuilders exhibited a smaller percentage of body fat mass than sedentary subjects. Moreover, drug-using bodybuilders had greater body mass and body surface area than drug-free bodybuilders and age-matched sedentary men. The standard echocardiographic data are listed in Table 2. No differences were found in LV morphologic parameters (i.e., LV internal diameter, LV wall thickness, and LV mass) between drug-free bodybuilders and their sedentary counterparts. An effect of AAS use was observed on LV morphology, because drug-using bodybuilders exhibited greater LV enddiastolic diameters, LV volumes, and LV mass compared with
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Table 3 Doppler echocardiographic data on left ventricular diastolic function Variable
Peak E velocity (cm · s⫺1) Peak A velocity (cm · s⫺1) Peak E/A ratio Isovolumetric relaxation time (ms)
Sedentary Men (n ⫽ 15)
Drug-Free Bodybuilders (n ⫽ 9)
Drug-Using Bodybuilders (n ⫽ 6)
69 ⫾ 12
76 ⫾ 8
63 ⫾ 15†
54 ⫾ 10
62 ⫾ 10
57 ⫾ 6
1.35 ⫾ 0.44 86 ⫾ 17
1.25 ⫾ 0.21 84 ⫾ 19
1.12 ⫾ 0.34 107 ⫾ 28*†
Significantly different from sedentary men: * p ⬍0.05. Significantly different from drug-free bodybuilders: † p ⬍0.05.
ment (i.e., septal, lateral, inferior, and anterior walls), no differences were observed in peak Em, peak Am, the peak Em/Am ratio, and peak Sm between drug-free bodybuilders and age-matched sedentary controls. However, whatever the site of measurement, drug-using bodybuilders had smaller peak Em and smaller peak Em/Am ratios than drug-free bodybuilders and sedentary counterparts, except at the level of the anterior wall, at which peak Em was significantly smaller than in drug-free bodybuilders only. The E/Em ratio, an index of LV filling pressures, was not affected by strength training or AAS use (5.8 ⫾ 1.1, 6.2 ⫾ 1.2, and 6.5 ⫾ 1.5 in sedentary men, drug-free bodybuilders, and drug-using bodybuilders, respectively; p ⫽ NS). •••
Table 4 Tissue Doppler imaging measurements recorded at the level of the mitral annulus Variable
Septal wall Peak Em (cm · s⫺1) Peak Am (cm · s⫺1) Em/Am ratio Peak Sm (cm · s⫺1) Lateral wall Peak Em (cm · s⫺1) Peak Am (cm · s⫺1) Em/Am ratio Peak Sm (cm · s⫺1) Inferior wall Peak Em (cm · s⫺1) Peak Am (cm · s⫺1) Em/Am ratio Peak Sm (cm · s⫺1) Anterior wall Peak Em (cm · s⫺1) Peak Am (cm · s⫺1) Em/Am ratio Peak Sm (cm · s⫺1)
Sedentary Men (n ⫽ 15)
Drug-Free Bodybuilders (n ⫽ 9)
Drug-Using Bodybuilders (n ⫽ 6)
12.1 ⫾ 2.1 10.6 ⫾ 1.8 1.18 ⫾ 0.34 9.1 ⫾ 1.5
12.6 ⫾ 2.1 9.5 ⫾ 1.2 1.33 ⫾ 0.22 8.8 ⫾ 1.1
9.6 ⫾ 0.7†§ 10.8 ⫾ 0.6 0.89 ⫾ 0.08*§ 8.4 ⫾ 1.0
17.5 ⫾ 3.5 9.8 ⫾ 3.1 1.99 ⫾ 0.88 11.3 ⫾ 2.8
17.8 ⫾ 1.2 9.8 ⫾ 2.7 1.95 ⫾ 0.59 10.0 ⫾ 2.2
12.7 ⫾ 1.7†§ 10.9 ⫾ 2.7 1.19 ⫾ 0.27*‡ 10.7 ⫾ 2.9
16.0 ⫾ 2.7 11.5 ⫾ 3.4 1.53 ⫾ 0.60 9.1 ⫾ 1.5
15.2 ⫾ 1.3 11.2 ⫾ 2.8 1.44 ⫾ 0.36 8.8 ⫾ 1.1
12.3 ⫾ 2.9†‡ 11.6 ⫾ 3.6 1.24 ⫾ 0.71*§ 8.4 ⫾ 1.0
12.0 ⫾ 3.0 8.2 ⫾ 1.4 1.50 ⫾ 1.1 9.8 ⫾ 1.9
13.5 ⫾ 3.5 8.9 ⫾ 1.8 1.55 ⫾ 3.5§ 9.7 ⫾ 1.8
9.8 ⫾ 2.4† 9.2 ⫾ 0.8 1.06 ⫾ 0.25*† 8.6 ⫾ 1.9
Significantly different from sedentary men: * p ⬍0.05; † p ⬍0.01. Significantly different from drug-free bodybuilders: ‡ p ⬍0.05; § p ⬍0.01.
the 2 other groups. No significant differences were found in stroke volume, heart rate, cardiac output, and the ejection fraction among the 3 groups, indicating that strength training and AAS use had no effect on LV systolic function. Transmitral Doppler echocardiography data of LV diastolic function are listed in Table 3. No significant differences were found in peak E, peak A, the peak E/A ratio, and isovolumetric relaxation time between drug-free bodybuilders and age-matched sedentary men. However, drug-using bodybuilders exhibited smaller peak E and longer isovolumetric relaxation times than their drug-free counterparts. The peak E/A ratio did not reach statistical significance but tended to be smaller in drug-using bodybuilders. TDI measurements recorded at the level of the mitral annulus are listed in Table 4. Whatever the site of measure-
The main objective of the present study was to evaluate the effects of the repeated use of AASs on LV diastolic function in athletes with a long-term history of bodybuilding. In addition to standard echocardiography, we used TDI, a new Doppler tool to evaluate LV relaxation properties. Our results indicated that drug-using bodybuilders exhibited depressed LV diastolic function that was characterized by a decrease in the contribution of LV passive filling to LV filling. Alteration in intrinsic LV relaxation properties could be responsible for this phenomenon. The effects of AASs on LV diastolic function in strength-trained athletes have been studied exclusively by cross-sectional studies (i.e., drug-free vs drug-using subjects) using transmitral flow velocities. From these data, controversy exists as to whether LV diastolic function is altered by the use of AAS in strength-trained athletes. Palatini et al12 showed normal LV diastolic function in a group of 10 bodybuilders using AASs. Thompson et al13 also failed to confirm LV diastolic dysfunction in weightlifters. However, it must be emphasized that in these 2 studies, drug-using athletes had been training for only 5.3 ⫾ 3.0 and 3.3 ⫾ 2.5 years, respectively. In other studies, evidence of moderate alteration in LV diastolic function has been established. Pearson et al14 observed reduced Doppler indexes of LV diastolic filling in a group of 5 elite weightlifters (a national team) using AASs. Urhausen et al15 reported that the regular intake of AASs in highly trained bodybuilders (6.3 ⫾ 2.9 years of training, 11.4 ⫾ 2.6 hours/week) induced an increase in LV isovolumetric relaxation time. The discrepancies between these studies could be attributed to the duration and/or the intensity of the training programs. In the present study, our trained subjects were on average 40 years old, with a very long-term history of strength training, contrary to most previous studies, in which subjects were younger (about 25 to 30 years old).12–15 Our results indicated that the contribution of LV passive filling to LV filling (i.e., the E/A ratio) was less and isovolumetric relaxation time greater in our bodybuilders with a long-term history of AAS administration compared with the 2 other groups. It must be emphasized that from TDI measurements, we were able to evaluate the underlying mechanisms responsible for
Congenital Heart Disease/Anabolic Steroids in Bodybuilders
this altered diastolic function. Unlike transmitral flow evaluation, TDI measurements recorded at the level of the mitral annulus are relatively preload independent and constitute a good index of LV relaxation properties.11,16 To the best of our knowledge, no study has evaluated the effects of AASs on LV diastolic function by TDI in a population of strength-trained athletes to date. Whatever the site of measurement (i.e., septal, lateral, posterior, and anterior walls), the peak Em recorded at the level of the mitral annulus (and thus the LV relaxation properties) was significantly smaller in drug-using bodybuilders than their drugfree counterparts and sedentary subjects. This constitutes additional evidence of depressed diastolic function in drugusing bodybuilders. No evidence was found, however, that LV filling pressures, a key element of LV filling, were affected by AAS use, because no difference was obtained in the peak E/Em ratio. The mechanisms responsible for the alteration of LV relaxation properties remain unclear. A trend toward greater blood pressures in the AAS users may have negatively affected LV relaxation. Another explanation could be structural and/or functional alteration of the myocardium.4 – 6 On the whole, our results clearly indicate that long-term strength training associated with regular AAS administration negatively alters diastolic function through mechanisms involving reduced LV relaxation properties. Because of the obvious difficulty in conducting a precise history of AAS administration, these results should be interpreted carefully. Moreover, TDI has several intrinsic limitations, such as the angle dependence of pulsed TDI, the possible presence of artifacts, and the motion of the entire heart in space. To deal with these methodologic problems, we paid specific attention to having the LV wall as close as possible to the direction of the beam, and all measurements were averaged on 3 to 5 measurements of good quality obtained during the end-expiratory stage of normal respiration. 1. Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes. Sports Med 2004;34:513–554. 2. Sullivan ML, Martinez CM, Gennis P, Gallagher EJ. The cardiac toxicity of anabolic steroids. Prog Cardiovasc Dis 1998;41:1–15.
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3. Kutscher EC, Lund BC, Perry PJ. Anabolic steroids: a review for the clinician. Sports Med 2002;32:285–296. 4. Appell HJ, Heller-Umpfenbach B, Feraudi M, Weicker H. Ultrastructural and morphometric investigations on the effects of training and administration of anabolic steroids on the myocardium of guinea pigs. Int J Sports Med 1983;4:268 –274. 5. Trifunovic B, Norton GR, Duffield MJ, Avraam P, Woodiwiss AJ. An androgenic steroid decreases left ventricular compliance in rats. Am J Physiol 1995;268:H1096 –H1105. 6. Woodiwiss AJ, Trifunovic B, Philippides M, Norton GR. Effects of an androgenic steroid on exercise-induced cardiac remodeling in rats. J Appl Physiol 2000;88:409 – 415. 7. Durnin JV, Rahaman MM. The assessment of the amount of fat in the human body from measurements of skinfold thickness. Br J Nutr 1967;21:681– 689. 8. Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58:1072–1083. 9. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986;57:450 – 458. 10. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989;2:358 –367. 11. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol 1997;30:1527–1533. 12. Palatini P, Giada F, Garavelli G, Sinisi F, Mario L, Michieletto M, Baldo-Enzi G. Cardiovascular effects of anabolic steroids in weighttrained subjects. J Clin Pharmacol 1996;36:1132–1140. 13. Thompson PD, Sadaniantz A, Cullinane EM, Bodziony KS, Catlin DH, Torek-Both G, Douglas PS. Left ventricular function is not impaired in weight-lifters who use anabolic steroids. J Am Coll Cardiol 1992;19:278 –282. 14. Pearson AC, Schiff M, Mrosek D, Labovitz AJ, Williams GA. Left ventricular diastolic function in weight lifters. Am J Cardiol 1986;58: 1254 –1259. 15. Urhausen A, Holpes R, Kindermann W. One- and two-dimensional echocardiography in bodybuilders using anabolic steroids. Eur J Appl Physiol Occup Physiol 1989;58:633– 640. 16. Sohn DW, Chai IH, Lee DJ, Kim HC, Kim HS, Oh BH, Lee MM, Park YB, Choi YS, Seo JD, et al. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol 1997;30:474 – 480.
Fifteen male bodybuilders were recruited from local clubs. Six men reported current self-administration of AASs, and 9 reported never having used these drugs. All strength-
a
Laboratory of Cardiovascular Adaptations to Exercise, Faculty of Sciences, Avignon; and bCardiology Department, Regional Hospital Center, Orléans, France. Manuscript received May 3, 2005; revised manuscript received and accepted October 3, 2005. * Corresponding author: Tel: 33-0-4-32-74-32-02; fax: 33-0-4-90-1444-09. E-mail address: [email protected] (S. Nottin). 0002-9149/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2005.10.026
trained athletes had been training for 5 to 12 hours/week for ⱖ10 years. For admission into the study, bodybuilders in the steroid group were required to have used the drugs for the past 2 years. Sixteen age-matched sedentary controls were also enrolled. None of the subjects in either group had clinical or historical evidence of cardiovascular disease or hypertension. This study received approval from the local ethics committee, and written informed consent was obtained from subjects. A biometric evaluation was performed before each test. Height was measured with a height gauge and body mass with a balance beam scale. Body fat mass was assessed by skinfold thickness measurements according to Durnin and Rahaman.7 After a 15-minute rest period, standard Doppler echocardiography and TDI measurements were performed with the subjects in a partial left decubitus position using a HDI 5000 system (Phillips Ultrasound system, Phillips Medical System, Best, The Netherlands). A variable-frequency phasedarray transducer (2.5 to 4 Mhz) was used for Doppler echocardiographic and TDI measurements. Doppler echocardiographic and TDI tracings were recorded digitally on a hard drive for further analyses. All measurements were averaged on 3 to 5 measurements obtained during the end-expiratory stage of normal respiration. Standard echocardiograms consisted of 2-dimensional, www.AJConline.org
Congenital Heart Disease/Anabolic Steroids in Bodybuilders Table 2 Standard Doppler echocardiographic data
Table 1 Anthropometric data and blood pressures of the subjects Variable
Age (yrs) Height (cm) Body mass (kg) Fat mass (%) Body surface area (m2) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg)
Sedentary Men Drug-Free (n ⫽ 16) Bodybuilders (n ⫽ 9) 42 ⫾ 10 177 ⫾ 5 76 ⫾ 9 19 ⫾ 3 1.93 ⫾ 0.10 125 ⫾ 10
38 ⫾ 6 174 ⫾ 8 78 ⫾ 10 16 ⫾ 3* 1.92 ⫾ 0.16 122 ⫾ 11
78 ⫾ 8
77 ⫾ 12
913
Drug-Using Bodybuilders (n ⫽ 6)
Variable
41 ⫾ 6 180 ⫾ 6 97 ⫾ 7†§ 15 ⫾ 3† 2.16 ⫾ 0.12†§ 132 ⫾ 10
Septal wall thickness (mm) Posterior wall thickness (mm) LV end-diastolic diameter (mm) LV end-systolic diameter (mm) LV mass (g) LV end-diastolic volume LV end-systolic volume Ejection fraction (%) Stroke volume (ml) Heart rate (beats/min) Cardiac output (L)
87 ⫾ 8
Significantly different from sedentary men: * p ⬍0.05; † p ⬍0.01. Significantly different from drug-free bodybuilders: ‡ p ⬍0.05; § p ⬍0.01.
M-mode, and Doppler blood flow measurements. Acquisitions were made in harmonic imaging mode. M-mode measurements were obtained according to the recommendations of the American Society of Echocardiography in the parasternal long-axis view.8 The parameters measured were interventricular septal thickness, LV diameter, and LV posterior wall thickness. LV mass was calculated according to Penn’s convention.9 The LV ejection fraction was calculated from LV volumes measured by the biplane Simpson’s method.10 Pulsed Doppler LV inflow recordings were performed in the apical 4-chamber view, with the sample volume at the tip level of the mitral valves. E and A peak velocities (m · s⫺1), E-wave deceleration time (milliseconds), and isovolumetric relaxation time (milliseconds) were measured as indexes of global diastolic function. Stroke volume was estimated as the product of the aortic root area and the integral of aortic blood velocity and time. The maximal systolic diameter of the ascending aorta was measured from the 2-dimensional parasternal long-axis view. Measurements were performed from inner to inner edge at the level of the insertion of the aortic valve leaflets. The velocity of blood in the aorta was recorded from a 5-chamber view. The outline contour of the velocity curve overtime was traced manually. Cardiac output was calculated as the product of stroke volume and heart rate. TDI was performed at a transducer frequency of 3.5 to 4 Mhz, adjusting the spectral pulsed Doppler signal filters to a Nyquist limit of 15 to 20 cm · s⫺1 and using the minimal optimal gain. Wall motion velocities were assessed at the mitral annulus level on the septal, lateral, inferior, and anterior walls in 4- and 2-chamber views. Pulsed TDI was characterized by a myocardial systolic wave (Sm) and 2 diastolic waves (early [Em] and atrial [Am]), expressed in centimeters per second. The peak velocity of Sm was considered a systolic index. Em and Am peak velocities, the Em/Am ratio, and regional isovolumetric relaxation time were determined as diastolic measurements. The ratio of the transmitral E velocity to peak Em velocity recorded on the septal wall at the level of the mitral annulus was used as an index of LV filling pressures.11
Sedentary Men Drug-Free Drug-Using (n ⫽ 15) Bodybuilders Bodybuilders (n ⫽ 9) (n ⫽ 6) 9.5 ⫾ 1.9
9.7 ⫾ 1.7
10.8 ⫾ 1.3
9.3 ⫾ 0.12
10.3 ⫾ 0.9
10.0 ⫾ 1.4
52 ⫾ 5
53 ⫾ 5
58 ⫾ 4*‡
33 ⫾ 3
34 ⫾ 4
37 ⫾ 5
182 ⫾ 53 92 ⫾ 22 34 ⫾ 8 62 ⫾ 3 99 ⫾ 19 66 ⫾ 7 6.6 ⫾ 0.7
202 ⫾ 52 106 ⫾ 27 40 ⫾ 10 62 ⫾ 3 114 ⫾ 18 68 ⫾ 14 7.6 ⫾ 1.8
249 ⫾ 33*‡ 124 ⫾ 25† 49 ⫾ 12† 61 ⫾ 3 111 ⫾ 20 72 ⫾ 6 8.0 ⫾ 0.9
Significantly different from sedentary men: * p ⬍0.05; † p ⬍0.01. Significantly different from drug-free bodybuilders: ‡ p ⬍0.05.
All data were measured on digital recordings. The intraand interobserver variabilities of data analysis were assessed in a previous study conducted in our laboratory. Data from 12 subjects were analyzed blindly on 2 separate days by 2 experienced cardiologists. Because intra- and interobserver variabilities were low (⬍5% for all echocardiographic variables), values presented in the present report were those obtained by only 1 cardiologist. Auscultatory cuff blood pressures were obtained in the right arm using manual sphygmanometry (mean of 2 measurements). The appearance of the first Korotkoff sound was used as a criterion for systolic blood pressure, and the fourth Korotkoff sound (i.e., muffling of the sound) defined diastolic blood pressure. The results are presented as mean ⫾ SD. Each variable was compared among the 3 groups using a 1-way analysis of variance. When an overall difference was found at p ⬍0.05, a post hoc test of Fisher’s protected least-significant difference was performed. Statistical significance for all analyses was defined as p ⬍0.05. The characteristics of the subjects are listed in Table 1. No differences were observed in age, height, or blood pressure among sedentary men and drug-free and drug-using bodybuilders. However, the 2 groups of bodybuilders exhibited a smaller percentage of body fat mass than sedentary subjects. Moreover, drug-using bodybuilders had greater body mass and body surface area than drug-free bodybuilders and age-matched sedentary men. The standard echocardiographic data are listed in Table 2. No differences were found in LV morphologic parameters (i.e., LV internal diameter, LV wall thickness, and LV mass) between drug-free bodybuilders and their sedentary counterparts. An effect of AAS use was observed on LV morphology, because drug-using bodybuilders exhibited greater LV enddiastolic diameters, LV volumes, and LV mass compared with
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Table 3 Doppler echocardiographic data on left ventricular diastolic function Variable
Peak E velocity (cm · s⫺1) Peak A velocity (cm · s⫺1) Peak E/A ratio Isovolumetric relaxation time (ms)
Sedentary Men (n ⫽ 15)
Drug-Free Bodybuilders (n ⫽ 9)
Drug-Using Bodybuilders (n ⫽ 6)
69 ⫾ 12
76 ⫾ 8
63 ⫾ 15†
54 ⫾ 10
62 ⫾ 10
57 ⫾ 6
1.35 ⫾ 0.44 86 ⫾ 17
1.25 ⫾ 0.21 84 ⫾ 19
1.12 ⫾ 0.34 107 ⫾ 28*†
Significantly different from sedentary men: * p ⬍0.05. Significantly different from drug-free bodybuilders: † p ⬍0.05.
ment (i.e., septal, lateral, inferior, and anterior walls), no differences were observed in peak Em, peak Am, the peak Em/Am ratio, and peak Sm between drug-free bodybuilders and age-matched sedentary controls. However, whatever the site of measurement, drug-using bodybuilders had smaller peak Em and smaller peak Em/Am ratios than drug-free bodybuilders and sedentary counterparts, except at the level of the anterior wall, at which peak Em was significantly smaller than in drug-free bodybuilders only. The E/Em ratio, an index of LV filling pressures, was not affected by strength training or AAS use (5.8 ⫾ 1.1, 6.2 ⫾ 1.2, and 6.5 ⫾ 1.5 in sedentary men, drug-free bodybuilders, and drug-using bodybuilders, respectively; p ⫽ NS). •••
Table 4 Tissue Doppler imaging measurements recorded at the level of the mitral annulus Variable
Septal wall Peak Em (cm · s⫺1) Peak Am (cm · s⫺1) Em/Am ratio Peak Sm (cm · s⫺1) Lateral wall Peak Em (cm · s⫺1) Peak Am (cm · s⫺1) Em/Am ratio Peak Sm (cm · s⫺1) Inferior wall Peak Em (cm · s⫺1) Peak Am (cm · s⫺1) Em/Am ratio Peak Sm (cm · s⫺1) Anterior wall Peak Em (cm · s⫺1) Peak Am (cm · s⫺1) Em/Am ratio Peak Sm (cm · s⫺1)
Sedentary Men (n ⫽ 15)
Drug-Free Bodybuilders (n ⫽ 9)
Drug-Using Bodybuilders (n ⫽ 6)
12.1 ⫾ 2.1 10.6 ⫾ 1.8 1.18 ⫾ 0.34 9.1 ⫾ 1.5
12.6 ⫾ 2.1 9.5 ⫾ 1.2 1.33 ⫾ 0.22 8.8 ⫾ 1.1
9.6 ⫾ 0.7†§ 10.8 ⫾ 0.6 0.89 ⫾ 0.08*§ 8.4 ⫾ 1.0
17.5 ⫾ 3.5 9.8 ⫾ 3.1 1.99 ⫾ 0.88 11.3 ⫾ 2.8
17.8 ⫾ 1.2 9.8 ⫾ 2.7 1.95 ⫾ 0.59 10.0 ⫾ 2.2
12.7 ⫾ 1.7†§ 10.9 ⫾ 2.7 1.19 ⫾ 0.27*‡ 10.7 ⫾ 2.9
16.0 ⫾ 2.7 11.5 ⫾ 3.4 1.53 ⫾ 0.60 9.1 ⫾ 1.5
15.2 ⫾ 1.3 11.2 ⫾ 2.8 1.44 ⫾ 0.36 8.8 ⫾ 1.1
12.3 ⫾ 2.9†‡ 11.6 ⫾ 3.6 1.24 ⫾ 0.71*§ 8.4 ⫾ 1.0
12.0 ⫾ 3.0 8.2 ⫾ 1.4 1.50 ⫾ 1.1 9.8 ⫾ 1.9
13.5 ⫾ 3.5 8.9 ⫾ 1.8 1.55 ⫾ 3.5§ 9.7 ⫾ 1.8
9.8 ⫾ 2.4† 9.2 ⫾ 0.8 1.06 ⫾ 0.25*† 8.6 ⫾ 1.9
Significantly different from sedentary men: * p ⬍0.05; † p ⬍0.01. Significantly different from drug-free bodybuilders: ‡ p ⬍0.05; § p ⬍0.01.
the 2 other groups. No significant differences were found in stroke volume, heart rate, cardiac output, and the ejection fraction among the 3 groups, indicating that strength training and AAS use had no effect on LV systolic function. Transmitral Doppler echocardiography data of LV diastolic function are listed in Table 3. No significant differences were found in peak E, peak A, the peak E/A ratio, and isovolumetric relaxation time between drug-free bodybuilders and age-matched sedentary men. However, drug-using bodybuilders exhibited smaller peak E and longer isovolumetric relaxation times than their drug-free counterparts. The peak E/A ratio did not reach statistical significance but tended to be smaller in drug-using bodybuilders. TDI measurements recorded at the level of the mitral annulus are listed in Table 4. Whatever the site of measure-
The main objective of the present study was to evaluate the effects of the repeated use of AASs on LV diastolic function in athletes with a long-term history of bodybuilding. In addition to standard echocardiography, we used TDI, a new Doppler tool to evaluate LV relaxation properties. Our results indicated that drug-using bodybuilders exhibited depressed LV diastolic function that was characterized by a decrease in the contribution of LV passive filling to LV filling. Alteration in intrinsic LV relaxation properties could be responsible for this phenomenon. The effects of AASs on LV diastolic function in strength-trained athletes have been studied exclusively by cross-sectional studies (i.e., drug-free vs drug-using subjects) using transmitral flow velocities. From these data, controversy exists as to whether LV diastolic function is altered by the use of AAS in strength-trained athletes. Palatini et al12 showed normal LV diastolic function in a group of 10 bodybuilders using AASs. Thompson et al13 also failed to confirm LV diastolic dysfunction in weightlifters. However, it must be emphasized that in these 2 studies, drug-using athletes had been training for only 5.3 ⫾ 3.0 and 3.3 ⫾ 2.5 years, respectively. In other studies, evidence of moderate alteration in LV diastolic function has been established. Pearson et al14 observed reduced Doppler indexes of LV diastolic filling in a group of 5 elite weightlifters (a national team) using AASs. Urhausen et al15 reported that the regular intake of AASs in highly trained bodybuilders (6.3 ⫾ 2.9 years of training, 11.4 ⫾ 2.6 hours/week) induced an increase in LV isovolumetric relaxation time. The discrepancies between these studies could be attributed to the duration and/or the intensity of the training programs. In the present study, our trained subjects were on average 40 years old, with a very long-term history of strength training, contrary to most previous studies, in which subjects were younger (about 25 to 30 years old).12–15 Our results indicated that the contribution of LV passive filling to LV filling (i.e., the E/A ratio) was less and isovolumetric relaxation time greater in our bodybuilders with a long-term history of AAS administration compared with the 2 other groups. It must be emphasized that from TDI measurements, we were able to evaluate the underlying mechanisms responsible for
Congenital Heart Disease/Anabolic Steroids in Bodybuilders
this altered diastolic function. Unlike transmitral flow evaluation, TDI measurements recorded at the level of the mitral annulus are relatively preload independent and constitute a good index of LV relaxation properties.11,16 To the best of our knowledge, no study has evaluated the effects of AASs on LV diastolic function by TDI in a population of strength-trained athletes to date. Whatever the site of measurement (i.e., septal, lateral, posterior, and anterior walls), the peak Em recorded at the level of the mitral annulus (and thus the LV relaxation properties) was significantly smaller in drug-using bodybuilders than their drugfree counterparts and sedentary subjects. This constitutes additional evidence of depressed diastolic function in drugusing bodybuilders. No evidence was found, however, that LV filling pressures, a key element of LV filling, were affected by AAS use, because no difference was obtained in the peak E/Em ratio. The mechanisms responsible for the alteration of LV relaxation properties remain unclear. A trend toward greater blood pressures in the AAS users may have negatively affected LV relaxation. Another explanation could be structural and/or functional alteration of the myocardium.4 – 6 On the whole, our results clearly indicate that long-term strength training associated with regular AAS administration negatively alters diastolic function through mechanisms involving reduced LV relaxation properties. Because of the obvious difficulty in conducting a precise history of AAS administration, these results should be interpreted carefully. Moreover, TDI has several intrinsic limitations, such as the angle dependence of pulsed TDI, the possible presence of artifacts, and the motion of the entire heart in space. To deal with these methodologic problems, we paid specific attention to having the LV wall as close as possible to the direction of the beam, and all measurements were averaged on 3 to 5 measurements of good quality obtained during the end-expiratory stage of normal respiration. 1. Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes. Sports Med 2004;34:513–554. 2. Sullivan ML, Martinez CM, Gennis P, Gallagher EJ. The cardiac toxicity of anabolic steroids. Prog Cardiovasc Dis 1998;41:1–15.
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