Cardiovascular and metabolic effects of hyperbilirubinemia in a cohort of italian olympic athletes

Introduction: Bilirubin was supposed to have cardio-metabolic protective role by signaling functions. Indeed, mild hyperbilirubinemia has immunosuppressive and endocrine activities and may offer protection against oxidative stress-mediated diseases. Gilbert syndrome (GS) has been hypothesized to provide cardio-metabolic benefits. Objective: To investigate the prevalence of hyperbilirubinemia and its cardio-metabolic effects in a cohort of elite Italian athletes engaged in different sports disciplines. Methods: We enrolled 1492 elite athletes (age 25.8 ± 5.1) practising different disciplines (power, skills, endurance, and mixed) underwent blood, echocardiographic, and exercise tests. GS was diagnosed per exclusionem in athletes with isolated asymptomatic unconjugated hyperbilirubinemia. Results: GS was highlighted in 91 athletes (6%; globally 9% male and 2.4% female); 82% were males (p < 0.0001) showing higher indirect bilirubin (0.53 ± 0.4 vs. 0.36 ± 0.24 mg/dL in females, p < 0.0001). GS athletes had fewer platelets (201 ± 35 vs. 214 ± 41, p = 0.01), higher iron (male: 124 ± 44 vs. 100.9 ± 34 mcg/dL, p < 0.0001; female: 143.3 ± 35 vs. 99.9 ± 42 mcg/dL, p < 0.0001), and lower erythrocyte sedimentation rate, (1.93 ± 0.9 vs. 2.80 ± 2.7 mm/H, p = 0.03). At multivariate analysis, male (OR 3.89, p = 0.001) and iron (OR 3.47, p = 0.001) were independently associated with GS. No significant differences were found in cardiac remodeling, heart rate, blood pressure, arrhythmias, or power capacity at stress test. Endurance athletes (313) presented higher total (p = 0.003) and indirect bilirubin (p = 0.001). Conclusion: Bilirubin has several metabolic effects (including immunosuppressive and endocrine) and plays a role in regulating antioxidant pathways exercise-related with hematological consequences but seems not to affect significantly cardiovascular remodeling. Endurance athletes present higher bilirubin concentrations, likely as an adaptive mechanism to counteract increased oxidative stress.