Association of urinary sodium excretion with glaucoma and related traits

Abstract

Purpose : Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may in turn influence intraocular pressure (IOP) and glaucoma risk. We performed cross-sectional and gene-environment interaction analyses of UK Biobank participants to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits.

Methods : Participants (aged 40–72 years) provided a midstream urine sample at baseline from which the urine sodium:creatinine ratio (UNa:Cr), a validated measure of dietary sodium intake normalized for urinary concentration, was calculated. We included participants with data on IOP (n=109,537), inner retinal OCT measurements (n=46,411) and glaucoma (n=173,718). Ocular parameters were measured as part of a comprehensive eye examination and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Multivariable linear and logistic regression were used to model associations. Genetic susceptibility to glaucoma was assessed through use of a glaucoma polygenic risk score (PRS) comprising 2,673 variants.

Results : In maximally-adjusted regression models, a one standard deviation increase in UNa:Cr was associated with higher IOP (0.12mmHg; 95% CI, 0.10 to 0.15; P<0.001), thinner macular retinal nerve fiber layer thickness (-0.05µm, 95% CI, -0.10 to 0.00; P=0.040) and greater prevalence of glaucoma (OR, 1.06; 95% CI, 1.02 to 1.10; P=0.002). Compared to those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.46mmHg; 95% CI, 0.37 to 0.54, P<0.001) and prevalence of glaucoma (OR, 1.35; 95% CI, 1.21 to 1.50; P<0.001). Stronger associations with IOP (P_interaction=0.031) and glaucoma (P_interaction=0.009) were noted in participants at the highest underlying genetic risk for glaucoma.

Conclusions : Dietary sodium intake may represent a new and important modifiable risk factor for glaucoma, potentially through an effect on IOP – an association which proved substantial on a population level – and this relationship may be modified by genetic susceptibility to glaucoma. This may have important clinical and public health implications should further studies support a causal relationship.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Gene-environment interaction analyses illustrating the effect of the glaucoma PRS on the association of urinary sodium excretion with IOP and glaucoma