Association of Biomarker and Physiologic Indices With Mortality in Older Adults: Cardiovascular Health Study
Association of Biomarker and Physiologic Indices With Mortality in Older Adults: Cardiovascular Health Study
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DOI：
10.1093/gerona/gly075
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发表时间：
2019-01-01
影响因子：
5.1
通讯作者：
Newman, Anne B.
中科院分区：
文献类型：
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作者：
Sanders, Jason L.;Arnold, Alice M.;Newman, Anne B.
老年学的一个目标是发现老化表型，反映生物老化与疾病发病机制不同。与死亡率密切相关且独立相关的生物标志物和统计学上衰减的年龄可以用来定义这种表型。我们确定了生物标志物指数（BI）与死亡率的相关性，并将其与经验证的老年人生理指数（PI）进行了比较。这些指数是在心血管健康研究中构建的，平均（SD）年龄为74.5（5.1）岁。BI纳入了新生物标志物的循环水平，包括胰岛素样生长因子-1、胰岛素样生长因子结合蛋白3、氨基末端B型利钠肽前体、硫酸脱氢表雄酮和白细胞介素-6，并在试验（N = 2，197）和验证（N = 1，124）样本中构建。PI包括颈动脉内膜中层厚度、肺容量、脑白色物质分级、胱抑素C和空腹血糖。预测死亡的多变量考克斯比例风险模型计算了10年的随访。在单独的年龄调整模型中，BI每点死亡率的风险比为1.30（95%置信区间1.25，1.34），BI使年龄衰减25%。PI的风险比为1.28（1.24，1.33; 29%年龄衰减）。在同一模型中，BI的风险比为1.23（1.18，1.28），PI的风险比为1.22（1.17，1.26），年龄衰减42.5%。进一步校正后，相关性仍然存在，BI和PI与死亡率显著独立相关。两者都大大减弱了年龄对死亡率的影响。这些指数可能是可行的表型，用于开发希望改变衰老轨迹的干预措施。
A goal of gerontology is discovering aging phenotypes that reflect biological aging distinct from disease pathogenesis. Biomarkers that strongly and independently associated with mortality and that statistically attenuated chronologic age could be used to define such a phenotype. We determined the association of a Biomarker Index (BI) with mortality and compared it with a validated Physiologic Index (PI) in older adults.The indices were constructed in the Cardiovascular Health Study, mean (SD) age 74.5 (5.1) years. The BI incorporated circulating levels of new biomarkers, including insulin-like growth factor-1, insulin-like growth factorbinding protein 3, amino-terminal pro-B-type natriuretic peptide, dehydroepiandrosterone sulfate, and interleukin-6, and was built in test (N = 2,197) and validation (N = 1,124) samples. The PI included carotid intimamedia thickness, pulmonary capacity, brain white matter grade, cystatin-C, and fasting glucose. Multivariable Cox proportional hazards models predicting death were calculated with 10 years of follow-up.In separate age-adjusted models, the hazard ratio for mortality per point of the BI was 1.30 (95% confidence interval 1.25, 1.34) and the BI attenuated age by 25%. The hazard ratio for the PI was 1.28 (1.24, 1.33; 29% age attenuation). In the same model, the hazard ratio for the BI was 1.23 (1.18, 1.28) and for the PI was 1.22 (1.17, 1.26), and age was attenuated 42.5%. Associations persisted after further adjustment.The BI and PI were significantly and independently associated with mortality. Both attenuated the age effect on mortality substantially. The indices may be feasible phenotypes for developing interventions hoping to alter the trajectory of aging.