Clinical Medicine and Hepatology Department, Campus Bio-Medico University, Rome, Italy.
National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
J Gerontol A Biol Sci Med Sci. 2018 Jun 14;73(7):925-930. doi: 10.1093/gerona/glx126.
Although low alanine aminotransferase (ALT) levels have been associated with poor outcomes in the elderly population, the determinants subtending this association have been poorly explored. To gain insight into this topic, we analyzed data from a prospective population-based database (InCHIANTI study) in which frailty, disability, sarcopenia, and pyridoxine levels were systematically assessed.
Data are from 765 participants aged more than 65 years (mean age 75.3 years, women 61.8%), without chronic liver disease, malignancies, or alcohol abuse. Frailty was defined according to Fried criteria, sarcopenia through peripheral Quantitative-Computed-Tomography (lowest gender-specific tertile of the residuals of a linear regression of muscle mass from height and fat mass), and disability as self-reported need for help in at least one basic daily living activity. Associations of ALT with overall and cardiovascular mortality were assessed by Cox-models with time-dependent covariates.
ALT activity was inversely associated with frailty, sarcopenia, disability, and pyridoxine deficiency; however, higher ALT was confirmed to be protective with respect of overall and cardiovascular mortality even in multiple-adjusted models including all these covariates (overall: hazard ratio [HR] 0.98 [0.96-1], p = .02; cardiovascular: 0.94 [0.9-0.98], p < .01). The association between ALT activity and mortality was nonlinear (J-shaped), and subjects in the lower quintiles of ALT levels showed a sharply increased overall and cardiovascular mortality.
These results suggest that reduced ALT levels in older individuals can be considered as a marker of frailty, disability, and sarcopenia, and as an independent predictor of adverse outcomes. The possible relationship between reduced ALT and impaired hepatic metabolic functions should be explored.
尽管低丙氨酸氨基转移酶(ALT)水平与老年人群的不良结局相关,但该关联的决定因素尚未得到充分探索。为了深入了解这一主题,我们分析了一项前瞻性基于人群的数据库(InCHIANTI 研究)的数据,其中系统评估了虚弱、残疾、肌肉减少症和吡哆醇水平。
数据来自 765 名年龄在 65 岁以上(平均年龄 75.3 岁,女性 61.8%)、无慢性肝病、恶性肿瘤或酗酒的参与者。根据 Fried 标准定义虚弱,通过外周定量计算机断层扫描(肌肉质量从身高和脂肪质量的线性回归残差的最低性别特定三分位数)定义肌肉减少症,通过自我报告的至少一项基本日常生活活动需要帮助来定义残疾。使用时间依赖性协变量的 Cox 模型评估 ALT 与全因和心血管死亡率的相关性。
ALT 活性与虚弱、肌肉减少症、残疾和吡哆醇缺乏呈负相关;然而,即使在包括所有这些协变量的多调整模型中,较高的 ALT 仍被证实对全因和心血管死亡率具有保护作用(全因:风险比 [HR] 0.98 [0.96-1],p =.02;心血管:0.94 [0.9-0.98],p <.01)。ALT 活性与死亡率之间的关系是非线性的(J 形),ALT 水平较低五分位的受试者全因和心血管死亡率明显升高。
这些结果表明,老年人中 ALT 水平降低可被视为虚弱、残疾和肌肉减少症的标志物,也是不良结局的独立预测因子。应探讨 ALT 降低与肝脏代谢功能受损之间的可能关系。