Relationship Between Glaucoma and Chronic Stress Quantified by Allostatic Load Score in the All of Us Research Program

Kristy Yoo; Connor Lee; Sally L Baxter; Benjamin Y Xu

doi:10.1016/j.ajo.2024.09.009

Relationship Between Glaucoma and Chronic Stress Quantified by Allostatic Load Score in the All of Us Research Program

Am J Ophthalmol. 2024 Sep 11:S0002-9394(24)00429-X. doi: 10.1016/j.ajo.2024.09.009. Online ahead of print.

Authors

Kristy Yoo¹, Connor Lee², Sally L Baxter³, Benjamin Y Xu⁴

Affiliations

¹ Keck School of Medicine at the University of Southern California, Los Angeles, California.
² Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
³ Division of Ophthalmology Informatics and Data Science, Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, CA, USA; Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
⁴ Keck School of Medicine at the University of Southern California, Los Angeles, California; Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: benjamin.xu@med.usc.edu.

PMID: 39271092
DOI: 10.1016/j.ajo.2024.09.009

Abstract

Purpose: To assess the relationship between glaucoma and allostatic load (AL), an established framework for quantifying the physiologic effects of chronic stress through measurements of systemic biomarkers.

Design: Retrospective case-control study.

Methods: Participants of the National Institutes of Health All of Us (AoU) Research Program with complete AL biomarker data between December 1984 to June 2022 and with (cases) or without (controls) primary glaucoma were identified. AL scores were calculated using the adapted Seeman AL scale consisting of 10 systemic biomarkers: body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, glomerular filtration rate, albumin, C-reactive protein, and homocysteine. AL score was defined as the number of biomarkers with measurements in the highest risk quartiles. Age was calculated as the median age at time of biomarker measurements. Logistic regression analysis was performed to assess the association between the earliest possible AL score and glaucoma adjusted for race/ethnicity. Mediation analysis was performed to estimate the relationship between race/ethnicity and glaucoma mediated by AL score.

Results: The study cohort consisted of 349 (16.1%) cases and 1,819 (83.9%) controls with 52.7% females, 2.2% Asians, 10.7% Blacks, 10.0% Hispanics, and 72.5% non-Hispanic Whites. At the earliest timepoint (median [IQR] = 6.4 [1.9-12.2] years prior to diagnosis), cases had higher AL score than controls (3 [1-4] versus 2 [1-3], respectively; p<0.001). On multivariable analysis, higher AL score (OR=1.09 per point), Black race (OR=2.58), and Hispanic ethnicity (OR=2.12) conferred higher risk of glaucoma (p≤0.02). AL score partially mediated higher glaucoma risk among Blacks (7.5%) and Hispanics (5.0%) compared to non-Hispanic Whites. On subgroup analysis, higher AL score was significantly associated with primary open angle glaucoma (POAG; OR=1.11; p=0.01) but not primary angle closure glaucoma (PACG; p=0.87).

Conclusion: AoU participants with glaucoma had greater AL 6.4 years prior to diagnosis, and AL score partially mediated racial/ethnic differences in glaucoma risk. These findings suggest chronic stress may increase risk for glaucoma and contribute to racial disparities in glaucoma burden.