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

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

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.

FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Dietary salt, Gene-environment interaction, Glaucoma, Intraocular pressure, Urinary sodium
2589-4234
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Modifiable Risk Factors for Glaucoma Collaboration
UK Biobank Eye and Vision Consortium
International Glaucoma Genetics Consortium
Stuart, Kelsey V.
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Biradar, Mahantesh I.
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Sun, Zihan
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Stuart, Kelsey V., Biradar, Mahantesh I., Luben, Robert N., Dhaun, Neeraj, Wagner, Siegfried K., Warwick, Alasdair N., Sun, Zihan, Madjedi, Kian M., Pasquale, Louis R., Wiggs, Janey L., Kang, Jae H., Lentjes, Marleen A.H., Aschard, Hugues, Kim, Jihye, Foster, Paul J. and Khawaja, Anthony P. , Modifiable Risk Factors for Glaucoma Collaboration, UK Biobank Eye and Vision Consortium and International Glaucoma Genetics Consortium (2024) The association of urinary sodium excretion with glaucoma and related traits in a large United Kingdom population. Ophthalmology Glaucoma. (doi:10.1016/j.ogla.2024.04.010).

Record type: Article

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.

FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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Accepted/In Press date: 30 April 2024
e-pub ahead of print date: 8 May 2024
Published date: 8 May 2024
Additional Information: Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Keywords: Dietary salt, Gene-environment interaction, Glaucoma, Intraocular pressure, Urinary sodium

Identifiers

Local EPrints ID: 491895
URI: http://eprints.soton.ac.uk/id/eprint/491895
ISSN: 2589-4234
PURE UUID: 02cc8ea6-7498-4807-a10c-8ad443e4cb8d
ORCID for Roxana Carare: ORCID iD orcid.org/0000-0001-6458-3776
ORCID for Sarah Ennis: ORCID iD orcid.org/0000-0003-2648-0869
ORCID for Jane Gibson: ORCID iD orcid.org/0000-0002-0973-8285
ORCID for Andrew Lotery: ORCID iD orcid.org/0000-0001-5541-4305
ORCID for Jay Self: ORCID iD orcid.org/0000-0002-1030-9963
ORCID for Angela Cree: ORCID iD orcid.org/0000-0002-1987-8900

Catalogue record

Date deposited: 05 Jul 2024 16:45
Last modified: 12 Jul 2024 01:43

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Contributors

Author: Kelsey V. Stuart
Author: Mahantesh I. Biradar
Author: Robert N. Luben
Author: Neeraj Dhaun
Author: Siegfried K. Wagner
Author: Alasdair N. Warwick
Author: Zihan Sun
Author: Kian M. Madjedi
Author: Louis R. Pasquale
Author: Janey L. Wiggs
Author: Jae H. Kang
Author: Marleen A.H. Lentjes
Author: Hugues Aschard
Author: Jihye Kim
Author: Paul J. Foster
Author: Anthony P. Khawaja
Author: Mark Chia
Author: Sharon Chua
Author: Ron Do
Author: Paul Foster
Author: Jae Kang
Author: Alan Kastner
Author: Anthony Khawaja
Author: Marleen Lentjes
Author: Robert Luben
Author: Kian Madjedi
Author: Giovanni Montesano
Author: Louis Pasquale
Author: Kelsey Stuart
Author: Alasdair Warwick
Author: Janey Wiggs
Author: Naomi Allen
Author: Tariq Aslam
Author: Denize Atan
Author: Sarah Barman
Author: Jenny Barrett
Author: Paul Bishop
Author: Graeme Black
Author: Tasanee Braithwaite
Author: Roxana Carare ORCID iD
Author: Sarah Ennis ORCID iD
Author: Jane Gibson ORCID iD
Author: Andrew Lotery ORCID iD
Author: James Morgan
Author: Jay Self ORCID iD
Author: Irene Stratton
Author: Li Chen
Author: Ching Yu Cheng
Author: Angela Cree ORCID iD
Author: James Wilson
Corporate Author: Modifiable Risk Factors for Glaucoma Collaboration
Corporate Author: UK Biobank Eye and Vision Consortium
Corporate Author: International Glaucoma Genetics Consortium

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