Findings from a study published in the American Journal of Ophthalmology (AJO) evaluated the longitudinal relationship between age-related macular degeneration (AMD) and allostatic load (AL).
First of all, what is allostatic load?
AL is an established framework for quantifying the cumulative physiological burden of chronic stress through measurements of systemic biomarkers.
In fact: A similar study recently published in the AJO demonstrated that participants with glaucoma had a greater AL 6.4 years before diagnosis.
- Further: Each point of AL score was associated with an 11% greater odds of primary open-angle glaucoma (POAG) after adjusting for race or ethnicity.
Now talk about the study.
In this retrospective case-control study, investigators included participants of the National Institutes of Health All of Us Research Program with complete AL biomarker data between February 1985 and May 2022 who did (case) and did not (control) have AMD.
- Quick reminder: The All of Us Research Program is a nationwide, longitudinal research initiative with an emphasis on recruiting populations underrepresented in biomedical research.
Main outcome measure of this study: AMD status (i.e., AMD or non-AMD)
How did they calculate AL?
AL scores were calculated using the adapted Seeman AL scale, which comprises 10 systemic biomarkers:
- Body mass index (BMI)
- Systolic blood pressure
- Diastolic blood pressure
- Glycated hemoglobin
- Total cholesterol
- Triglycerides
- Glomerular filtration rate
- Albumin
- C-reactive protein
- Homocysteine
In addition: The AL score was defined as the number of biomarkers with measurements in the highest risk quartiles, and age was calculated as the median age at the time of earliest or latest biomarker measurements.
Findings?
The demographic breakdown of the 1,530 participants (221 cases, 1,309 controls) with complete biomarker data was as follows:
- Males: 44.6%
- Non-Hispanic Whites (NHWs): 76.1%
- Other specified race/ethnicity (Asian, Black, or Hispanic): 18.6%
- Unspecified race/ethnicity: 5.3%
AL scores measured a median of 9.0 years (interquartile range [IQR] 5.0-14.0) before AMD diagnosis were higher among cases compared to controls (median [IQR] 2 [2-4] vs 2 [1-3], respectively, P=0.02).
Anything else?
Multivariable analyses demonstrated that a higher baseline AL score (odds ratio [OR 1.11) and greater pack-years (OR 1.15 per 10 pack-years) conferred a higher risk of AMD (P≤0.02).
Additional analyses revealed a significant indirect effect that increased the risk of AMD among other specified race/ethnicity participants compared to NHW participants through higher AL score (OR 1.07 per unit).
Expert opinion?
The study authors reported that the effect of AL was more pronounced in early and intermediate AMD compared to more severe stages—suggesting that other risk factors may dominate in later stages of the disease course.
Further, the investigators pointed out that racial and ethnic minorities (who often have higher AL) also showed increased susceptibility to AMD, indicating that “Asian, Black, and Hispanic race/ethnicity may confer greater protection from AMD if disparities in AL are addressed.”
Take home.
These findings suggest that All of Us participants diagnosed with AMD had greater AL scores 9.0 years prior to AMD diagnosis.
In addition: Chronic stress appears to increase the risk of AMD and may contribute to racial/ethnic differences in disease prevalence.
Next steps?
Although this analysis proposes chronic stress as a potential novel risk factor for AMD, it is critical to recognize that “stress is a complex physiologic process mediated by a wide range of internal and external factors that cannot be fully represented by a single number like AL score,” the study authors highlighted.
As such: Future research could expand on existing efforts to elucidate the impact of chronic stress on ocular health and disease outcomes—such as AMD progression—to determine effective and accessible stress-reducing approaches for reducing ocular and visual morbidity.