血清生长分化因子 15 水平可预测合并心血管代谢疾病患者的虚弱发生风险。

Serum Growth Differentiation Factor 15 Levels Predict the Incidence of Frailty among Patients with Cardiometabolic Diseases.

机构信息

Department of Diabetes, Metabolism, and Endocrinology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan.

Department of Cardiology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan.

出版信息

Gerontology. 2024;70(5):517-525. doi: 10.1159/000536150. Epub 2024 Mar 15.

DOI:10.1159/000536150

PMID:38286122

Abstract

INTRODUCTION

Frailty is a crucial health issue among older adults. Growth differentiation factor 15 (GDF15) is associated with inflammation, oxidative stress, insulin resistance, and mitochondrial dysfunction, which are possible pathogeneses of frailty. However, few longitudinal studies have investigated the association between GDF15 and the incidence of frailty. Therefore, we investigated whether high serum GDF15 levels are associated with the incidence of frailty.

METHODS

A total of 175 older adults (mean age: 77 ± 6 years; 63% women) with cardiometabolic diseases and no frailty out of the two criteria at baseline participated. Individuals with severe renal impairment or severe cognitive impairment were excluded. Serum GDF15 levels were measured at baseline. Patients were asked to assess frailty status at baseline and annually during follow-up using the modified version of the Cardiovascular Health Study (mCHS) and the Kihon Checklist (KCL). We examined the association between GDF15 tertiles and each frailty measure during follow-up (median 38-39 months). In the multivariate Cox regression analysis, with the GDF15 tertile groups as the explanatory variables, hazard ratios (HRs) and 95% confidence intervals (CIs) for incident frailty were calculated after adjusting for covariates and using the lowest tertile group as the reference.

RESULTS

During the follow-up period, 25.6% and 34.0% of patients developed frailty, as defined by the mCHS and KCL, respectively. The highest GDF15 tertile group had a significantly higher incidence of mCHS- or KCL-defined frailty than the lowest GDF15 tertile group. Multivariate Cox regression analysis revealed that the adjusted HRs for incident mCHS- and KCL-defined frailty in the highest GDF15 tertile group were 3.9 (95% CI: 1.3-12.0) and 2.7 (95% CI: 1.1-6.9), respectively.

CONCLUSION

High serum GDF15 levels predicted the incidence of frailty among older adults with cardiometabolic diseases and could be an effective marker of the risk for frailty in interventions aimed at preventing frailty, such as exercise and nutrition.

摘要

简介

衰弱是老年人的一个重要健康问题。生长分化因子 15（GDF15）与炎症、氧化应激、胰岛素抵抗和线粒体功能障碍有关，这些可能是衰弱的发病机制。然而，很少有纵向研究调查 GDF15 与衰弱发生之间的关系。因此，我们研究了高血清 GDF15 水平是否与衰弱的发生有关。

方法

共纳入 175 名患有心血管代谢疾病且基线时无两项标准的衰弱老年人（平均年龄：77±6 岁，63%为女性）。排除严重肾功能不全或严重认知障碍的患者。在基线时测量血清 GDF15 水平。患者在基线和随访期间每年使用修改后的心血管健康研究（mCHS）和 Kihon 清单（KCL）评估衰弱状态。我们在随访期间（中位数 38-39 个月）检查了 GDF15 三分位组与每个衰弱测量之间的关系。在多变量 Cox 回归分析中，以 GDF15 三分位组为解释变量，在调整协变量后，计算 GDF15 三分位组发生衰弱的风险比（HR）和 95%置信区间（CI），并以最低三分位组为参考。

结果

在随访期间，分别有 25.6%和 34.0%的患者根据 mCHS 和 KCL 定义发生衰弱。最高 GDF15 三分位组发生 mCHS 或 KCL 定义的衰弱的发生率明显高于最低 GDF15 三分位组。多变量 Cox 回归分析显示，最高 GDF15 三分位组发生 mCHS 和 KCL 定义的衰弱的调整 HR 分别为 3.9（95%CI：1.3-12.0）和 2.7（95%CI：1.1-6.9）。