Ninety-nine ARVC patients (median age, 40 years; 70.7% male) and 96 healthy controls (median age, 41 years; 62.5% male) were enrolled. The circulating levels of
testosterone were measured by
enzyme-linked
immunosorbent assays (ELISA). The median follow-up time of all ARVC male patients was 17 months (interquartile range/IQR 9-29). Cox proportional hazards regression was used to analyse the effect of plasma
testosterone and other well-described risk factors on malignant arrhythmic events in male ARVC patients. The male ARVC patients had significantly elevated levels of total
testosterone [TT, 6.390 (4.438-8.768) ng/mL vs. 3.617 (2.073-4.479) ng/mL, P < 0.0001, data shown as the median with IQR], bioavailable
testosterone [BT, 4.11 (1.990-6.545) ng/mL vs. 1.32 (0.7965-2.0350) ng/mL, P < 0.0001, median with IQR], and free
testosterone [FT, 0.2055 (0.1000-0.4073) ng/mL vs. 0.0768 (0.0405-0.1105) ng/mL, P < 0.0001, median with IQR] than healthy male volunteer, whereas no differences were observed among female counterparts. There was no significant correlation between the baseline clinical characteristics and
testosterone levels in male ARVC patients (Spearman's correlation test, P > 0.05). During the follow-up, the levels of
testosterone were higher in male patients who experienced malignant arrhythmic events (N = 22) than in those who did not (N = 25) [TT, 9.034 (7.222-15.370) ng/mL vs. 4.633 (3.363-6.375) ng/mL, P < 0.001; BT, 7.485 (2.070-9.163) ng/mL vs. 3.300 (1.685-4.690) ng/mL, P < 0.05; FT, 0.453 (0.221-0.758) ng/mL vs. 0.161 (0.075-0.337) ng/mL P < 0.05, data expressed as median (IQR) and adjusted by Dunn's multiple comparisons test], whereas such distinction was not observed among patients with significant structural progression events (N = 16). Through multivariable adjustments, the Cox regression analysis showed the level of plasma total
testosterone (HR = 1.325, 95% confidence interval = 1.171-1.498, P < 0.001) was an independent predictor for malignant arrhythmic events.
CONCLUSIONS: The levels of plasma
testosterone in ARVC male patients are higher than those in healthy males.
Testosterone level, without relation to the baseline cardiac function and future significant structural progression events, is a strong predictor of future adverse arrhythmic events in male patients with ARVC. Therefore, our results suggest that
testosterone may be a useful
biomarker in arrhythmic risk prediction in the ARVC.