以血清發炎生物指標與共病症預測老年機構住民之衰弱及死亡

Abstract

目的 血中高濃度的發炎生物指標被發現可能與衰弱有關。本研究目的在探討三種血清高濃度發炎生物指標及共病症是否能預測男性機構住民的衰弱與死亡。 研究對象 本研究針對北台灣某榮家進行二年之前瞻性世代研究，共收案386名65歲以上之男性住民。所有研究對象皆納入二年之死亡追蹤研究，其中258名在基礎時沒有衰弱的個案接受衰弱狀態惡化之追蹤研究。 方法 研究採用「衰弱表現型」來定義衰弱，包含體重減輕、耗竭、緩慢、無力，但不包括低度身體活動指標。衰弱定義為滿足3或4個指標，衰弱前期定義為滿足1或2個指標。在收案時抽血檢驗血清之interleukin -6 (IL-6)、tumor necrosis factor-α (TNF-α)、及high sensitivity C-reactive protein (hsCRP)濃度。研究共收集了二年的死亡資料，並且每年評估研究個案衰弱狀態。 結果 研究個案之平均年齡為81.5±4.9歲，其中33.2%在收案時已符合衰弱標準。橫斷性研究中，在校正年齡、身體質量指數、使用抗發炎藥物、吸菸狀態、以及共病症後，IL-6中間 [OR 2.28 (95% CI 1.24-4.18)]和最高三分位 [OR 1.95 (95% CI 1.04-3.64)]與目前衰弱狀態有關。在二年的追蹤研究中，在校正吸菸狀態、使用抗發炎藥物、及基礎時之衰弱狀態後，二項「發炎生物指標數」 [HR(95%CI)= 7.60 (1.01-56.0)]、罹患心血管疾病 [HR(95%CI)= 4.93 (1.23-19.8)]、以及心智障礙 [HR(95%CI)= 20.7 (1.24-344.7)]，為「衰弱狀態惡化」顯著的預測因子，而年齡 [HR (95%CI) =1.09 (1.01-1.17)]，而慢性阻塞性肺病 [HR (95%CI) =2.55 (1.25-5.20)]、糖尿病 [HR (95%CI) =2.39 (1.16-4.93)]、以及心智障礙[HR (95%CI) =2.22 (1.03-4.83)]為死亡的預測因子。 結論 對於機構之老年男性住民，血清中較高的IL-6與目前衰弱狀態有關；對於衰弱狀態惡化及死亡的預測能力而言，共病症可能比單一血清發炎生物指標具有更佳的預測力。

Objectives Higher levels of inflammatory biomarkers have been found to be associated with frailty. The aim of the study was to determine whether three serum inflammatory biomarkers and comorbidity could predict frailty and mortality in the older institutionalized men. Participants We enrolled a cohort of 386 institutionalized men aged 65 and older from a veterans home in northern Taiwan with 2 years of follow-up. All participants were followed up for 2-year mortality. Two hundreds and fifty-eight participants without baseline frailty were followed for deterioration in frailty status. Methods Frailty status was determined basing on the frailty phenotype including weight loss, exhaustion, slowness, and weakness except for physical activity indicator. Frail men met three or four criteria, and intermediate frail met one or two criteria. Serum interleukin -6 (IL-6), tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hsCRP) levels were measured at baseline. We collected 2-year mortality data and assessed the frailty status of the participants annually. Results The mean age of the participants was 81.5±4.9, with 33.2% being frail at baseline. After adjusting for age, body mass index, use of anti-inflammatory drugs, smoking status, and comorbidities, middle and top tertile of IL-6 were associated with current frailty status [OR 2.28 (95% CI 1.24-4.18); 1.95 (1.04-3.64) respectively] in the cross-sectional analysis. During 2-year study period, after adjusting for smoking status, use of anti-inflammatory drugs, and baseline frailty status, two serum inflammatory biomarkers [HR 7.60 (95% CI 1.01-56.0)], underlying cardiovascular disease [4.93 (1.23-19.8)], and mental disorders [20.7 (1.24-344.7)] were the predictors for deterioration in frailty status, and age [1.09 (1.01-1.17)], diabetes [2.39 (1.16-4.93)], chronic obstructive pulmonary disease [2.55 (1.25-5.20)], and mental disorders [2.22 (1.03-4.83)] were for mortality. Conclusion For institutionalized older men, higher serum level of IL-6 was associated with current frailty status. The comorbidity, instead of each inflammatory marker, may be a better predictor for deterioration in frailty status and mortality.