“我们所有人”研究项目中通过负荷应激测量的慢性应激与年龄相关性黄斑变性之间的关系
Relationship Between Chronic Stress Measured by Allostatic Load and Age-Related Macular Degeneration in the All of Us Research Program.
作者信息
Yoo Kristy, Wu Linda, Toy Brian, Xu Benjamin Y
机构信息
From the Keck School of Medicine (K.Y., L.W., B.T., B.Y.X.), University of Southern California, Los Angeles, California, USA.
From the Keck School of Medicine (K.Y., L.W., B.T., B.Y.X.), University of Southern California, Los Angeles, California, USA; Roski Eye Institute (B.T., B.Y.X.), Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
出版信息
Am J Ophthalmol. 2025 Apr;272:150-160. doi: 10.1016/j.ajo.2025.01.018. Epub 2025 Jan 31.
PURPOSE
To assess the longitudinal relationship between age-related macular degeneration (AMD) 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 February 1985 to May 2022 and with (cases) or without (controls) AMD 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 earliest or latest biomarker measurements. The main outcome was AMD status (AMD or non-AMD). Logistic regression models assessed the association between AL score and AMD after standardization of age and sex and adjustment for race/ethnicity and pack-years of cigarette smoking. Mediation analysis estimated the relationship between race/ethnicity and AMD as mediated by AL score.
RESULTS
Among 1530 participants (221 cases, 1309 controls) with complete biomarker data, there were 44.6% males, 76.1% non-Hispanic Whites (NHWs), 18.6% other specified race/ethnicity (Asian, Black, or Hispanic race/ethnicity), and 5.3% unspecified race/ethnicity. AL scores measured a median of 9.0 (IQR=5.0-14.0) years prior to diagnosis were higher among cases compared to controls (Median [IQR] = 2 [2-4] versus 2 [1-3]; P = .02). On multivariable analysis, higher baseline AL score (OR=1.11) and greater pack-years (OR=1.15 per 10 pack-years) conferred higher risk of AMD (P ≤ .02). Mediation analysis revealed a significant indirect effect that increased risk of AMD among other specified race/ethnicity participants compared to NHW participants through higher AL score (OR=1.07 per unit [1.01-1.15]).
CONCLUSION
All of Us participants diagnosed with AMD had greater AL score 9.0 years prior to AMD diagnosis. Chronic stress appears to increase risk for AMD and may contribute to racial/ethnic differences in disease prevalence.
目的
评估年龄相关性黄斑变性（AMD）与应激负荷（AL）之间的纵向关系，应激负荷是一种通过测量全身生物标志物来量化慢性应激生理效应的既定框架。
设计
回顾性病例对照研究。
方法
确定美国国立卫生研究院“我们所有人”（AoU）研究项目中在1985年2月至2022年5月期间有完整AL生物标志物数据且患有（病例）或未患有（对照）AMD的参与者。使用由10种全身生物标志物组成的改良Seeman AL量表计算AL评分：体重指数、收缩压、舒张压、总胆固醇、甘油三酯、肾小球滤过率、白蛋白、C反应蛋白和同型半胱氨酸。AL评分定义为处于最高风险四分位数的生物标志物数量。年龄计算为最早或最晚生物标志物测量时的年龄中位数。主要结局是AMD状态（AMD或非AMD）。逻辑回归模型在对年龄和性别进行标准化并对种族/族裔和吸烟包年数进行调整后，评估AL评分与AMD之间的关联。中介分析估计种族/族裔与AMD之间的关系是由AL评分介导的。
结果
在1530名有完整生物标志物数据的参与者（221例病例，1309例对照）中，男性占44.6%，非西班牙裔白人（NHW）占76.1%，其他特定种族/族裔（亚洲、黑人或西班牙裔种族/族裔）占18.6%，未指定种族/族裔占5.3%。病例组在诊断前9.0年（IQR = 5.0 - 14.0）测量的AL评分中位数高于对照组（中位数[IQR] = 2 [2 - 4]对2 [1 - 3]；P = 0.02）。在多变量分析中，较高的基线AL评分（OR = 1.11）和较多的吸烟包年数（每10个吸烟包年OR = 1.15）会增加患AMD的风险（P≤0.02）。中介分析显示，与NHW参与者相比，其他特定种族/族裔参与者通过较高的AL评分增加患AMD风险的间接效应显著（每单位OR = 1.07 [1.01 - 1.15]）。
结论
被诊断患有AMD的“我们所有人”研究项目参与者在AMD诊断前9.0年的AL评分更高。慢性应激似乎会增加患AMD的风险，并可能导致疾病患病率的种族/族裔差异。
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