The association of urinary sodium excretion with glaucoma and related traits in a large United Kingdom population

Kelsey Stuart, Mahantesh I. Biradar, Robert Luben, Neeraj Dhaun, Siegfried K. Wagner, Alasdair N. Warwick, Zihan Sun, Kian Madjedi, Louis R. Pasquale, Janey Wiggs, Jae Kang, Marleen Lentjes, Hugues Aschard, Jihye Kim, Paul J. Foster, Anthony Khawaja, Mark Chia, Sharon Chua, Ron Do, Paul FosterJae Kang, Alan Kastner, Anthony Khawaja, Marleen Lentjes, Robert Luben, Kian Madjedi, Giovanni Montesano, Louis Pasquale, Kelsey Stuart, Alasdair Warwick, Janey Wiggs, Naomi Allen, Tariq Aslam, Denize Atan, Sarah Barman, Jenny Barrett, Paul Bishop, Graeme Black, Tasanee Braithwaite, Roxana Carare, Usha Chakravarthy, Michelle Chan, Alexander Day, Ruth Hogg, Bernadette McGuinness, Gareth McKay, Euan Paterson, Tunde Peto, David Steel, Jayne Woodside, Modifiable Risk Factors for Glaucoma Collaboration, UK Biobank Eye and Vision Consortium, International Glaucoma Genetics Consortium

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Abstract

Purpose
Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and determine whether this relationship is modified by genetic susceptibility to disease.

Design
Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study.

Participants
Up to 103 634 individuals (mean age: 57 years; 51% women) with complete urinary, ocular, and covariable data.

Methods
Urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. 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. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score comprising 2673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions.

Main Outcome Measures
Corneal-compensated IOP, OCT derived macular retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma.

Results
In maximally adjusted regression models, a 1 standard deviation increase in UNa:Cr was associated with higher IOP (0.14 mmHg; 95% confidence interval [CI], 0.12–0.17; P < 0.001) and greater prevalence of glaucoma (odds ratio, 1.11; 95% CI, 1.07–1.14; P < 0.001) but not macular retinal nerve fiber layer or ganglion cell-inner plexiform layer thickness. Compared with those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45 mmHg; 95% CI, 0.36–0.53, P < 0.001) and prevalence of glaucoma (odds ratio, 1.30; 95% CI, 1.17–1.45; P < 0.001). Stronger associations with glaucoma (P interaction = 0.001) were noted in participants with a higher glaucoma polygenic risk score.

Conclusions
Urinary sodium excretion, a biomarker of dietary intake, may represent an important modifiable risk factor for glaucoma, especially in individuals at high underlying genetic risk. These findings warrant further investigation because they may have important clinical and public health implications.

Original languageEnglish
Pages (from-to)499-511
Number of pages13
JournalOphthalmology Glaucoma
Volume7
Issue number5
DOIs
Publication statusPublished - 19 Sept 2024

Keywords

  • dietary salt
  • gene-environment interaction
  • glaucoma
  • intraocular pressure
  • urinary sodium

ASJC Scopus subject areas

  • Ophthalmology

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