Nonlinear Multisystem Physiological Dysregulation Associated With Frailty in Older Women: Implications for Etiology and Treatment
Nonlinear Multisystem Physiological Dysregulation Associated With Frailty in Older Women: Implications for Etiology and Treatment
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DOI：
10.1093/gerona/glp076
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发表时间：
2009-10-01
影响因子：
5.1
通讯作者：
Bandeen-Roche, Karen
中科院分区：
文献类型：
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作者：
Fried, Linda P.;Xue, Qian-Li;Bandeen-Roche, Karen
老年人的虚弱被定义为一系列体征和症状，与个体生理系统的异常水平有关。我们检验了这一假设，即与虚弱相关的是生理系统异常的临界质量，而不是每个个体系统的状态，并且这种关系是非线性的。使用来自妇女健康和老龄化研究I和II的70-79岁妇女的数据，多种分析方法评估了虚弱与八种生理指标的横截面关联。（贫血、炎症、胰岛素样生长因子-1、硫酸脱氢表雄酮、血红蛋白A1 c、微量营养素、肥胖和精细运动速度）与虚弱状态显著相关。然而，调整每个系统措施的水平，系统受损的平均数显着和非线性预测脆弱。那些有三个或更多系统受损的人最有可能虚弱，虚弱的几率随着系统异常水平的数量而增加，对于那些有一个到两个，三个到四个，五个或更多系统异常的人，比值比（OR）为4.8到11到26（所有p <0.05）。最后，确定了两个亚组，一个为孤立或无系统异常，另一个（30%）为多个系统异常。后一组与虚弱独立相关（OR = 2.6，p <0.05），调整混杂因素和慢性疾病，然后控制个体系统。总的来说，这些发现表明虚弱的可能性与生理系统异常的数量呈非线性关系增加，并且异常系统的数量比个体异常系统更具预测性。这些发现支持了这样一种理论，即随着年龄的增长，生理系统中复杂性的总损失是脆弱的一个重要原因。其含义是，阈值损失的复杂性，所示的系统异常的数量，可能会破坏稳态的适应能力，导致发展的脆弱性及其相关的风险，随后的不良后果。它进一步表明，更换任何一个有缺陷的系统可能不足以防止或改善脆弱性。
Frailty in older adults, defined as a constellation of signs and symptoms, is associated with abnormal levels in individual physiological systems. We tested the hypothesis that it is the critical mass of physiological systems abnormal that is associated with frailty, over and above the status of each individual system, and that the relationship is nonlinear.Using data on women aged 70-79 years from the Women's Health and Aging Studies I and II, multiple analytic approaches assessed the cross-sectional association of frailty with eight physiological measures.Abnormality in each system (anemia, inflammation, insulin-like growth factor-1, dehydroepiandrosterone-sulfate, hemoglobin A1c, micronutrients, adiposity, and fine motor speed) was significantly associated with frailty status. However, adjusting for the level of each system measure, the mean number of systems impaired significantly and nonlinearly predicted frailty. Those with three or more systems impaired were most likely to be frail, with odds of frailty increasing with number of systems at abnormal level, from odds ratios (ORs) of 4.8 to 11 to 26 for those with one to two, three to four, and five or more systems abnormal (p < .05 for all). Finally, two subgroups were identified, one with isolated or no systems abnormal and a second (in 30%) with multiple systems abnormal. The latter group was independently associated with being frail (OR = 2.6, p < .05), adjusting for confounders and chronic diseases and then controlling for individual systems.Overall, these findings indicate that the likelihood of frailty increases nonlinearly in relationship to the number of physiological systems abnormal, and the number of abnormal systems is more predictive than the individual abnormal system. These findings support theories that aggregate loss of complexity, with aging, in physiological systems is an important cause of frailty. Implications are that a threshold loss of complexity, as indicated by number of systems abnormal, may undermine homeostatic adaptive capacity, leading to the development of frailty and its associated risk for subsequent adverse outcomes. It further suggests that replacement of any one deficient system may not be sufficient to prevent or ameliorate frailty.