Abstract
Purpose :
Allostatic load (AL) is an established framework for measuring the physiologic effects of chronic stress through measurement of systemic biomarkers. We propose a longitudinal, retrospective case-control study to investigate the relationship between chronic stress and age-related macular degeneration (AMD), a leading cause of permanent vision loss worldwide with few modifiable risk factors.
Methods :
Participants of the National Institutes of Health All of Us (AoU) Research Program with complete AL biomarker data with (cases) and without (controls) AMD were identified. We utilized the adapted Seeman AL scale, a validated method of quantifying chronic stress using 10 systemic biomarkers: body mass index, systolic and diastolic blood pressure, total cholesterol, triglycerides, glomerular filtration rate, albumin, C-reactive protein, and homocysteine. AL scores were calculated by adding the number of biomarkers that met component-specific cutoffs determined by Youden index maximizing sensitivity and specificity for AMD. Age was calculated as the mean age at time of biomarker measurements, and controls were age- and sex-standardized to cases. Smoking history was obtained from participant questionnaires. Logistic regression models were developed to assess the association between baseline or time-of-diagnosis AL score and AMD.
Results :
Of 1,778 eligible participants (213 cases, 1,565 controls), there 47.5% males, 70.8% non-Hispanic Whites, and 24.1% non-Whites. Non-Hispanic Whites reported longer smoking history compared to non-Whites (11.1±20.3 pack years versus 6.9±14.4 pack years; 0.04). At baseline (6.7±6.5 years prior to age of diagnosis), cases had higher AL score (4.5±1.7 versus 4.0±1.7; p<0.001). On multivariable analysis, higher AL score (OR=1.18 per point) and greater pack years (OR=1.08 per 10 pack years) conferred higher risk of AMD (p≤0.02) after adjusting for race/ethnicity. Non-Whites had lower risk of AMD (OR=0.68; p=0.04) only on univariable analysis. The difference in AL between cases (4.4±1.6) and controls (4.1±1.5) persisted through the time of AMD diagnosis (p=0.01).
Conclusions :
Chronic stress appears to increase risk of AMD even after controlling for age, sex, race/ethnicity, and smoking history. This relationship highlights the potential benefit of holistic, stress-reducing lifestyle interventions in preventing onset of AMD.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.