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

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.

Retrospective case-control study.

Participants of the National Institutes of Health All of Us (AoU) Research Program with complete AL biomarker data between December 1984 and 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, glycated hemoglobin, 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 the time of biomarker measurements. Logistic regression analysis was performed to assess the association between the earliest possible AL score and glaucoma adjusted for race or ethnicity. Mediation analysis was performed to estimate the relationship between race or ethnicity and glaucoma mediated by AL score.

The study cohort consisted of 349 cases (16.1%) and 1819 controls (83.9%) with 52.7% females, 2.2% Asians, 10.7% Blacks, 10.0% Hispanics, and 72.5% non-Hispanic Whites. At the earliest time point (median [interquartile range (IQR)] = 6.4 [1.9-12.2] years prior to diagnosis), cases had higher AL score than controls (3 [1-4] vs 2 [1-3], respectively; P < .001). On multivariable analysis, a 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 ≤ .02). The AL score partially mediated higher glaucoma risk among Blacks (7.5%) and Hispanics (5.0%) compared with non-Hispanic Whites. On subgroup analysis, higher AL score was significantly associated with primary open angle glaucoma (OR=1.11; P = .01) but not primary angle closure glaucoma (P = .87).

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