Gruenewald Tara L, Seeman Teresa E, Ryff Carol D, Karlamangla Arun S, Singer Burton H
Department of Medicine/Geriatrics, University of California, Los Angeles, CA 90095-1687, USA.
Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14158-63. doi: 10.1073/pnas.0606215103. Epub 2006 Sep 18.
A wide range of biomarkers, reflecting activity in a number of biological systems (e.g., neuroendocrine, immune, cardiovascular, and metabolic), have been found to prospectively predict disability, morbidity, and mortality outcomes in older adult populations. Levels of these biomarkers, singly or in combination, may serve as an early warning system of risk for future adverse health outcomes. In the current investigation, 13 biomarkers were examined as predictors of mortality occurrence over a 12-year period in a sample of men and women (n = 1,189) 70-79 years of age at enrollment into the study. Biomarkers examined in analyses included markers of neuroendocrine functioning (epinephrine, norepinephrine, cortisol, and dehydroepiandrosterone), immune activity (C-reactive protein, fibrinogen, IL-6, and albumin), cardiovascular functioning (systolic and diastolic blood pressure), and metabolic activity [high-density lipoprotein (HDL) cholesterol, total to HDL cholesterol ratio, and glycosylated hemoglobin]. Recursive partitioning techniques were used to identify a set of pathways, composed of combinations of different biomarkers, that were associated with a high-risk of mortality over the 12-year period. Of the 13 biomarkers examined, almost all entered into one or more high-risk pathways although combinations of neuroendocrine and immune markers appeared frequently in high-risk male pathways, and systolic blood pressure was present in combination with other biomarkers in all high-risk female pathways. These findings illustrate the utility of recursive partitioning techniques in identifying biomarker combinations predictive of mortal outcomes in older adults, as well as the multiplicity of biological pathways to mortality in elderly populations.
人们发现，多种生物标志物能够前瞻性地预测老年人群的残疾、发病和死亡情况，这些生物标志物反映了多个生物系统（如神经内分泌、免疫、心血管和代谢系统）的活动。这些生物标志物的水平，单独或联合使用，都可能作为未来不良健康结果风险的早期预警系统。在本次调查中，对13种生物标志物进行了检测，以作为12年期间一组年龄在70 - 79岁的男性和女性（n = 1,189）死亡发生的预测指标。分析中检测的生物标志物包括神经内分泌功能标志物（肾上腺素、去甲肾上腺素、皮质醇和脱氢表雄酮）、免疫活性标志物（C反应蛋白、纤维蛋白原、白细胞介素-6和白蛋白）、心血管功能标志物（收缩压和舒张压）以及代谢活性标志物[高密度脂蛋白（HDL）胆固醇、总胆固醇与HDL胆固醇比值和糖化血红蛋白]。使用递归划分技术来确定一组由不同生物标志物组合构成的途径，这些途径与12年期间的高死亡风险相关。在所检测的13种生物标志物中，几乎所有标志物都进入了一个或多个高风险途径，尽管神经内分泌和免疫标志物的组合在高风险男性途径中频繁出现，而收缩压在所有高风险女性途径中都与其他生物标志物联合出现。这些发现说明了递归划分技术在识别预测老年人死亡结果的生物标志物组合方面的实用性，以及老年人群中导致死亡的生物途径的多样性。
