Anabolic deficiencies in men with systolic heart failure: do co-morbidities and therapies really contribute significantly?

Figures & data

Table 1. Baseline characteristics of the studied men with systolic HF.

Variables	All men with systolic HF (N = 382)	Men with systolic HF aged <60 years (N = 179)	Men with systolic HF aged ≥60 years (N = 203)	p
Clinical and laboratory variables
BMI, kg/m^2	27.0 (24.15–29.93)	27.22 (23.67–30.42)	26.75 (24.22–29.39)	0.75
BMI ≥30 kg/m^2, n (%)	93 (24.3%)	51 (28.5%)	42 (20.5%)	0.08
HF aetiology, CAD, n (%)	247 (71.7%)	99 (55.3%)	175 (86.2%)	<0.0001
NYHA class, III-IV, n (%)	136 (35.6%)	56 (31.3%)	80 (39.4%)	0.098
LVEF, %	30.7 ± 7.4	29.8 ± 7.9	31.5 ± 6.8	0.03
LVEF ≤35%, n (%)	277 (72.5%)	130 (72.6%)	147 (72.4%)	0.96
NT-proBNP, pg/mL	1550.5 (542–4029)	1541 (447–4583)	1595 (658–3850)	0.63
NT-proBNP ≥2000 pg/mL, n (%)	169 (44.2%)	81 (45.2%)	88 (43.3%)	0.71
hsCRP, mg/L	3.49 (1.40–7.78)	3.49 (1.38–8.36)	3.39 (1.40–7.11)	0.52
hsCRP ≥7.78 mg/L (upper quartile), n (%)	92 (24.1%)	48 (26.8%)	44 (21.4%)	0.31
eGFR, mL/min/1.73 m^2	71.2 ± 20.9	75.8 ± 19.6	67.0 ± 21.1	<0.0001
eGFR MDRD ≤60 ml/min/1.73m^2, n (%)	110 (28.8%)	33 (18.4%)	77 (37.9%)	<0.0001
Haemoglobin, g/dL	14.2 ± 1.6	14.4 ± 1.5	14.0 ± 1.7	0.01
Anaemia, haemoglobin <13.0 g/dL, n (%)	14 (3.7%)	4 (2.2%)	10 (4.9%)	0.08
Diabetes mellitus, yes, n (%)	103 (26.9%)	34 (18.9%)	69 (33.9%)	<0.0001
Atrial fibrillation, yes, n (%)	151 (39.5%)	65 (36.3%)	86 (42.3%)	0.21
Hypertension, yes, n (%)	206 (53.9%)	81 (45.2%)	125 (61.5%)	0.001
Thyroid dysfunction, yes, n (%)	23 (6.0%)	11 (6.1%)	12 (5.9%)	0.91
Stroke, yes, n (%)	36 (9.4%)	18 (10.1%)	18 (8.9%)	0.69
COPD, yes, n (%)	31 (8.1%)	8 (4.5%)	23 (11.3%)	0.01
Applied treatment
ACEI or/and ARB, yes, n (%)	361 (94.5%)	171 (95.5%)	190 (93.6%)	0.41
βblocker, yes, n (%)	355 (92.9%)	171 (95.5%)	184 (90.6%)	0.06
Spironolactone, yes, n (%)	113 (29.6%)	53 (29.6%)	60 (29.5%)	0.99
CRT, yes, n (%)	16 (4.2%)	7 (3.9%)	9 (4.4%)	0.79
Furosemide, yes, n (%)	208 (54.4%)	93 (51.9%)	115 (56.6%)	0.36
Digoxin, yes, n(%)	102 (26.7%)	51 (28.5%)	51 (25.1%)	0.46

Data are presented as an arithmetic mean ± a standard deviation of a mean, a median (with lower and upper quartiles), or a number (with a percentage), where appropriate.

BMI – body mass index, HF – heart failure, CAD – coronary artery disease, NCAD – non-coronary artery disease, NYHA – New York Heart Association, LVEF – left ventricular ejection fraction, NTproBNP – N-terminal pro-brain natriuretic peptide, hs CRP – high sensitivity C-reactive protein, eGFR – estimated glomerular filtration rate, COPD- chronic obstructive pulmonary disease, ACEI- angiotensin converting enzyme inhibitor, BB – beta-blocke, CRT – cardiac resynchronization therapy, eFT – estimated free testosterone, TT – total testosterone, DHEAS – dehydroepiandrosterone sulphate, IGF-1 – insulin-like growth factor type 1.

Table 2. Mean serum hormone levels and the prevalence of hormone deficiencies in the studied men with systolic HF.

Serum hormone levels and the prevalence of hormone deficiencies	All men with systolic HF (N = 382)	Men with systolic HF aged <60 years (N = 179)	Men with systolic HF aged ≥60 years (N = 203)	p
Total testosterone, ng/ml	4.24 ± 1.94	4.49 ± 1.95	4.01 ± 1.90	0.02
Total testosterone deficiency, yes, n (%)	88 (23.0%)	41 (22.9%)	47 (23.2%)	0.95
eFT, pg/ml	83.4 ± 48.7	91.6 ± 51.7	76.1 ± 44.7	0.002
eFT deficiency, yes, n (%)	122 (31.9%)	53 (29.6%)	69 (33.9%)	0.36
DHEAS, ng/ml	556.3 (249–1129)	681 (301–1380)	442 (192–887)	<0.0001
DHEAS deficiency, yes, n (%)	209 (54.7%)	112 (62.5%)	97 (47.8%)	0.004
IGF-1, ng/ml	136.8 ± 61.5	137.7 ± 64.1	136 ± 59.2	0.78
IGF-1 deficiency, yes, n (%)	313 (81.9%)	164 (91.6%)	149 (73.4%)	<0.0001

Data are presented as an arithmetic mean ± a standard deviation of a mean, a median (with lower and upper quartiles), or a number (with a percentage), where appropriate, DHEAS – dehydroepiandrosterone sulphate, IGF-1 – insulin-like growth factor type 1, eFT – estimated free testosterone [39].

Table 3. Risk factors predisposing to the prevalence of total testosterone deficiency in younger versus older men with systolic HF.

Determining variables	Men with systolic HF aged <60 years			Men with systolic HF aged ≥60 years
	OR (±95% Cl)	χ^2	p	OR(±95%Cl)	χ^2	p
BMI ≥versus <30 kg/m^2	1.41 (0.67–3.00)	0.83	0.36	1.22 (0.55–2.68)	0.25	0.61
HF aetiology, CAD versus non-CAD	1.59 (0.79–3.23)	1.71	0.19	1.39 (0.57–3.43)	0.53	0.47
NYHA class ≥ versus <III-IV	2.36 (1.14–4.87)	5.45	0.02	0.94 (0.48–1.85)	0.03	0.86
LVEF ≤versus >35%	2.64 (1.03–6.79)	4.12	0.04	1.33 (0.62–2.85)	0.53	0.47
NTproBNP ≥ versus <2000 pg/ml	1.55 (0.77–3.14)	1.51	0.22	1.07 (0.55–2.08)	0.04	0.83
hsCRP ≥ versus <7.78 mg/l	0.848 (0.38–1.91)	0.16	0.69	1.32 (0.62–2.86)	0.53	0.47
eGFR MDRD ≤versus >60 ml/min/m^2	1.61 (0.69–3.76)	1.24	0.27	0.80 (0.40–1.59)	0.39	0.53
Haemoglobin < versus ≥13 g/dl	1.57 (0.65–3.77)	1.02	0.31	1.27 (0.60–2.68)	0.41	0.52
Diabetes mellitus, yes versus no	1.53 (0.66–3.56)	0.99	0.32	1.82 (0.93–3.56)	3.07	0.08
Atrial fibrillation, yes versus no	1.16 (0.56–2.39)	0.17	0.68	0.79 (0.40–1.55)	0.46	0.49
Hypertension, yes versus no	1.04 (0.52–2.11)	0.02	0.90	1.26 (0.63–2.5)	0.43	0.51
Thyroid dysfunction, yes versus no	1.28 (0.32–5.12)	0.13	0.72	0.96 (0.41–2.23)	0.01	0.92
Stroke, yes versus no	1.33 (0.44–4.03)	0.27	0.60	0.64 (0.18–2.33)	0.46	0.49
COPD, yes versus no	1.13 (0.22–5.87)	0.02	0.88	2.38 (0.95–5.96)	3.49	0.06
ACEI, yes versus no	0.87 (0.17–4.62)	0.02	0.88	0.51 (0.16–1.63)	1.29	0.26
BB, yes versus no	0.89 (0.17–4.62)	0.02	0.88	0.43 (0.16–1.19)	2.63	0.11
Spironolactone, yes versus no	1.14 (0.53–2.43)	0.11	0.74	2.22 (1.12–4.41)	5.26	0.02
CRT, yes versus no	0.38 (0.08–1.78)	1.53	0.22	1.06 (0.20–5.57)	0.004	0.95
Furosemide, yes versus no	2.10 (1.01–4.37)	4.02	0.046	2.42 (1.18–4.96)	5.92	0.02
Digoxin, yes versus no	2.14 (1.03–4.42)	4.24	0.04	1.78 (0.87–3.65)	2.55	0.11

BMI – body mass index, HF – heart failure, CAD – coronary artery disease, NCAD – non-coronary artery disease, NYHA – New York Heart Association, LVEF–left ventricular ejection fraction, NTproBNP- N-terminal pro-brain natriuretic peptide, hs CRP – high sensitivity C-reactive protein, eGFR – estimated glomerular filtration rate, COPD – chronic obstructive pulmonary disease, ACEI – angiotensin converting enzyme inhibitor, BB – beta-blocker, CRT – cardiac resynchronization therapy.

Table 4. Risk factors predisposing to the prevalence of estimated free testosterone deficiency in younger versus. older men with systolic HF.

	Men with systolic HF aged <60 years			Men with systolic HF aged ≥ 60 years
Determining variables	OR (±95% Cl)	χ^2	p	OR (±95%Cl)	χ^2	p
BMI ≥ versus <30 kg/m^2	1.64 (0.82–3.29)	1.98	0.16	0.64 (0.29–1.37)	1.31	0.25
HF aetiology, CAD versus. non-CAD	1.59 (0.83–3.05)	2.00	0.16	1.09 (0.47–2.59)	0.04	0.83
NYHA ≥ versus <III-IV	1.51 (0.77–2.99)	1.45	0.23	1.08 (0.59–1.95)	0.06	0.81
LVEF ≤ versus > 35%	1.93 (0.87–4.25)	2.68	0.10	1.25 (0.64–2.44)	0.45	0.50
NTproBNP ≥ versus <2000 pg/ml	1.72 (0.87–3.29)	2.69	0.10	1.10 (0.61–1.98)	0.11	0.74
hsCRP ≥ versus <7.78 mg/l	0.97 (0.47–2.01)	0.01	0.94	1.47 (0.73–2.93)	1.19	0.28
GFR MDRD ≤ versus >60 ml/min/m^2	1.04 (0.45–2.39)	0.01	0.92	0.74 (0.40–1.36)	0.93	0.33
Haemoglobin < versus ≥13 g/dl	1.76 (0.77–3.99)	1.84	0.18	1.66 (0.85–3.22)	2.24	0.13
Diabetes mellitus yes versus.no	2.59 (1.19–5.63)	5.89	0.02	1.41 (0.76–2.59)	1.23	0.27
Atrial fibrillation yes versus.no	1.37 (0.705–2.66)	0.88	0.35	0.81 (0.44–1.46)	0.51	0.48
Hypertension yes versus.no	1.22 (0.64–2.34)	0.38	0.54	0.94 (0.51–1.71)	0.05	0.83
Thyroid dysfunction yes versus.no	0.88 (0.22–3.51)	0.03	0.86	0.63 (0.16–2.43)	0.45	0.50
Stroke yes versus. No	1.59 (0.57–4.39)	0.82	0.37	0.36 (0.09–1.30)	2.46	0.19
COPD yes versus no	1.45 (0.33–6.37)	0.35	0.62	2.33 (0.97–5.64)	3.59	0.06
ACEI, yes versus.no	0.69 (0.16–3.02)	0.25	0.62	0.36 (0.12–1.08)	3.35	0.07
BB, yes versus. no	0.69 (0.16–3.02)	0.25	0.62	0.61 (0.23–1.65)	0.95	0.33
Spironolactone, yes versus. no	1.18 (0.59–2.37)	0.22	0.64	1.36 (0.72–2.56)	0.92	0.34
CRT, yes versus. no	0.29 (0.06–1.39)	2.38	0.12	1.85 (0.37–9.22)	0.56	0.45
Furosemide, yes versus.no	1.81 (0.94–3.51)	3.17	0.08	1.42 (0.78–2.59)	1.36	0.24
Digoxin, yes versus no	2.25 (1.14–4.44)	5.55	0.02	0.76 (0.38–1.51)	0.63	0.43

BMI – body mass index, HF – heart failure, CAD – coronary artery disease, NCAD – non-coronary artery disease, NYHA – New York Heart Association, LVEF – left ventricular ejection fraction, NTproBNP – N-terminal pro-brain natriuretic peptide, hs CRP-high sensitivity C-reactive protein, eGFR – estimated glomerular filtration rate, COPD – chronic obstructive pulmonary disease, ACEI – angiotensin converting enzyme inhibitor, BB – beta-blocker, CRT – cardiac resynchronization therapy

Table 5. Risk factors predisposing to the prevalence of DHEAS deficiency in younger versus older men with systolic HF.

	Men with systolic HF aged <60 years			Men with systolic HF aged≥ 60 years
Determining variables	OR (±95% Cl)	χ^2	p	OR (±95%Cl)	χ^2	p
BMI ≥ vs < 30 kg/m^2	0.89 (0.56–1.76)	0.10	0.76	1.13 (0.57–2.24)	0.13	0.72
HF aetiology, CAD vs. non-CAD	0.91 (0.49–1.69)	0.09	0.77	1.31 (0.58–2.93)	0.43	0.51
NYHA class ≥ vs < III-IV	0.49 (0.25–1.00)	3.87	0.05	1.91 (1.08–3.39)	4.95	0.03
LVEF ≤ vs > 35%	0.65 (0.33–1.27)	1.60	0.21	1.78 (0.95–3.36)	3.24	0.07
NTproBNP ≥ vs < 2000 pg/ml	2.05 (1.09–3.86)	5.03	0.02	1.27 (0.72–2.22)	0.69	0.40
hsCRP ≥ vs < 7.78 mg/l	0.69 (0.34–1.40)	1.06	0.30	2.02 (1.02–4.01)	4.07	0.045
GFR MDRD ≤ vs > 60 ml/min/m^2	0.57 (0.24–1.32)	1.75	0.19	1.42 (0.80–2.52)	1.48	0.23
Haemoglobin < vs. ≥ 13 g/dl	2.77 (1.06–7.23)	4.40	0.04	1.47 (0.77–2.82)	1.38	0.24
Diabetes mellitus yes vs.no	0.64 (0.28–1.45)	1.14	0.29	1.70 (0.94–3.07)	3.17	0.08
Atrial fibrillation yes vs.no	0.57 (0.29–1.09)	2.90	0.09	1.15 (0.65–2.01)	0.24	0.63
Hypertension yes vs.no	1.62 (0.87–3.00)	2.38	0.13	0.71 (0.40–1.26)	1.36	0.25
Thyroid dysfunction yes vs.no	0.61 (0.15–2.40)	0.51	0.48	1.57 (0.48–5.16)	0.56	0.45
Stroke yes vs. no	0.30 (0.08–1.10)	3.34	0.07	3.54 (1.11–11.2)	4.65	0.03
COPD yes vs.no	0.54 (0.105–2.81)	0.54	0.46	1.47 (0.61–3.55)	0.75	0.39
ACEI, yes vs.no	1.84 (0.36–9.49)	0.54	0.46	0.81 (0.27–2.44)	0.15	0.70
BB, yes vs. no	2.93 (0.67–12.80)	2.07	0.15	0.55 (0.20–1.49)	1.37	0.24
Spironolactone, yes vs. no	0.90 (0.46–1.78)	0.08	0.78	2.02 (1.09–3.74)	5.01	0.03
CRT, yes vs. no	0.43 (0.09–2.02)	1.15	0.28	0.44 (0.11–1.83)	1.28	0.26
Furosemide, yes vs.no	2.12 (1.14–3.95)	5.74	0.02	1.77 (1.01–3.12)	3.97	0.048
Digoxin, yes vs.no	1.51 (0.76–2.98)	1.43	0.23	2.41 (1.24–4.68)	6.79	0.009

BMI – body mass index, HF – heart failure, CAD – coronary artery disease, NCAD – non-coronary artery disease, NYHA – New York Heart Association, LVEF – left ventricular ejection fraction, NTproBNP – N-terminal pro-brain natriuretic peptide, hs CRP-high sensitivity C-reactive protein, eGFR – estimate glomerular filtration rate, COPD – chronic obstructive pulmonary disease, ACEI – angiotensin converting enzyme inhibitor, BB – beta-blocker, CRT – cardiac resynchronization therapy.

Table 6. Risk factors predisposing to the prevalence of IGF-1 deficiency in younger versus older men with systolic HF.

	Men with systolic HF aged <60 years			Men with systolic HF aged ≥ 60 years
Determining variables	OR (±95% Cl)	χ^2	p	OR (±95%Cl)	χ^2	p
BMI ≥ versus < 30 kg/m^2	1.76 (0.59–5.27)	1.04	0.31	0.82 (0.37–1.82)	0.23	0.63
HF aetiology, CAD veruss non-CAD	1.09 (0.37–3.17)	0.03	0.87	0.42 (0.14–1.27)	2.38	0.12
NYHA class ≥ versus < III-IV	0.78 (0.24–2.59)	0.16	0.68	1.19 (0.63–2.26)	0.31	0.58
LVEF ≤ versus > 35%	0.53 (0.18–1.59)	1.28	0.26	1.28 (0.62–2.63)	0.45	0.50
NTproBNP ≥ versus < 2000 pg/ml	1.42 (0.49–4.14)	0.43	0.51	1.59 (0.85–2.99)	2.15	0.14
hsCRP ≥ versus < 7.78 mg/l	0.39 (0.08–1.84)	1.42	0.23	2.69 (1.32–5.47)	7.59	0.006
GFR MDRD ≤ versus > 60 ml/min/m^2	1.12 (0.29–4.24)	0.03	0.87	0.95 (0.47–1.81)	0.03	0.87
Haemoglobin < versus ≥ 13 g/dl	0.75 (0.16–3.53)	0.14	0.71	0.75 (0.35–1.60)	0.57	0.45
Diabetes mellitus yes versus no	1.62 (0.48–5.49)	0.62	0.43	1.34 (0.69–2.56)	0.78	0.38
Atrial fibrillation yes versus no	0.61 (0.18–2.03)	0.65	0.42	1.11 (0.59–2.09)	0.11	0.74
Hypertension yes versus no	1.89 (0.64–5.61)	1.35	0.25	0.69 (0.37–1.32)	1.24	0.26
Thyroid dysfunction yes versus no	1.1 (0.13–9.38)	0.01	0.93	0.91 (0.24–3.54)	0.02	0.89
Stroke yes versus no	1.42 (0.29–6.95)	0.19	0.66	1.87 (0.68–5.13)	1.49	0.22
COPD yes versus no	–	–	–	0.54 (0.17–1.69)	1.13	0.28
ACEI, yes versus no	0.62 (0.07–5.53)	0.18	0.67	2.28 (0.49–10.62)	1.11	0.29
BB, yes versus no	–	–	–	0.41 (0.15–1.12)	3.07	0.08
Spironolactone, yes versus no	0.15 (0.02–1.22)	3.17	0.08	1.17 (0.59–2.31)	0.21	0.65
CRT, yes versus no	0.20 (0.04–1.17)	3.22	0.08	1.28 (0.25–6.45)	0.09	0.76
Furosemide, yes versus no	0.79 (0.27–2.31)	0.18	0.67	0.85 (0.45–1.59)	0.26	0.61
Digoxin, yes versus no	0.32 (0.07–1.49)	2.12	0.15	0.93 (0.45–1.92)	0.04	0.84

OR with +/−95% CI is not possible to be calculated for the presence/absence of COPD and the presence/absence of β-blocker therapy due to a lack of subjects in some of categories.

BMI – body mass index, HF – heart failure, CAD – coronary artery disease, NCAD – non-coronary artery disease, NYHA – New York Heart Association, LVEF – left ventricular ejection fraction, NTproBNP – N-terminal pro-brain natriuretic peptide, hs CRP-high sensitivity C-reactive protein, eGFR – estimated glomerular filtration rate, COPD – chronic obstructive pulmonary disease, ACEI – angiotensin converting enzyme inhibitor, BB – beta-blocke, CRT – cardiac resynchronization therapy.

Gao H-B, Ge R-S, Vijaya Lakshmi, et al. Hormonal regulation of oxidative and reductive activities of 11β-hydroxysteroid dehydrogenase in rat Leydig cells. Endocrinology 1997;138: 156–61

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