Association of Unhealthy Lifestyles with Cataract Risk, and The Mediating Role of Metabolic Signature: Analysis of the UK Biobank Prospective Cohort.

Emerging evidence has shown an association between certain unhealthy lifestyle factors and cataract risk. However, the synergistic effect of unhealthy lifestyle factors on cataract risk and their underlying mechanisms remains unknown. This study analyzed data from 199,415 baseline cataract-free participants from the UK Biobank prospective cohort study. Multivariable Cox proportional hazards models estimated the associations of individual unhealthy lifestyle factors (smoking, alcohol consumption, physical inactivity, unhealthy diet, and high body mass index) and their synergistic effect with cataract risk. Elastic net regression was performed to identify a metabolic signature reflecting unhealthy lifestyles, and the mediation effect was evaluated. Our results showed that only smoking and physical inactivity significantly increased cataract risk. Compared to the favorable lifestyle group, the cataract risk increased by 6% in the intermediate lifestyle group (95% confidence interval [CI]: 1.02-1.09) and by 14% in the unfavorable lifestyle group (95% CI: 1.08-1.20). The Cox regression model also revealed that the metabolic signature of unhealthy lifestyles was associated with cataract risk (adjusted hazard ratio, 1.31; 95% CI: 1.18-1.45). Mediation analysis demonstrated that the metabolic signature mediated the association between unhealthy lifestyles and cataract risk, with a mediation proportion of 18.01% (95% CI: 8.57-34.70%). Metabolic pathway analysis revealed that two metabolic pathways (fatty acids and lipoprotein particle concentration and size) played a crucial mediating role. Our study underscores novel insights into the effect of unhealthy lifestyle factors on cataract risk and the mediating role of metabolic factors in this process.