Systemic inflammation and subsequent risk of amyotrophic lateral sclerosis: prospective cohort study
Systemic inflammation and subsequent risk of amyotrophic lateral sclerosis: prospective cohort study
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DOI：
10.1101/2023.03.06.23286852
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发表时间：
2023-03
期刊：
影响因子：
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通讯作者：
G. D. Batty;Mika Kivimäki;Philipp Frank;C. Gale;L. Wright
中科院分区：
文献类型：
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作者：
G. D. Batty;Mika Kivimäki;Philipp Frank;C. Gale;L. Wright
重要性：虽然全身性炎症与选定的神经退行性疾病的病因有关，但其在肌萎缩侧索硬化症（ALS）发展中的作用尚未得到证实。目的：探讨肌萎缩侧索硬化（ALS）患者急性时相反应物和全身炎症标志物C反应蛋白（CRP）与ALS发病的关系。设计、设置、参与者：UK Biobank是一项前瞻性队列研究，研究对象为502，649名参与者，他们在2006年至2010年期间在研究中心接受检查时年龄在37岁至73岁之间。暴露：在基线时采集整个队列的静脉血，并测定CRP。3-7年后，在代表性亚组（N= 14，514）中进行重复测量，以校正回归稀释。主要结局和指标：通过国家住院和死亡登记确定的ALS。我们计算了多变量风险比，并将对数转换的CRP的95%置信区间表示为标准差和三分位数。结果如下：在400，884人（218，203名女性）的分析样本中，平均随访12年，导致231人住院，223人死于ALS。在对包括健康行为、合并症和社会经济状况在内的协变量进行校正后，log-CRP升高一个标准差与ALS死亡率（风险比; 95%置信区间：1.32; 1.13，1.53）和住院率（1.20; 1.00，1.39）升高相关。对于两种结局，有证据表明CRP三分位数之间存在剂量反应效应（趋势p [≤]0.05）。回归稀释校正导致与CRP的相关性加强，包括ALS的死亡率（1.62; 1.27，2.08）和住院率（1.37; 1.05，1.76）。结论和相关性：CRP是一种在临床实践中广泛捕获的血液生物标志物，其水平较高与ALS的后续风险较高相关。
Importance: While systemic inflammation has been implicated in the aetiology of selected neurodegenerative disorders, its role in the development of amyotrophic lateral sclerosis (ALS) is untested. Objective: To quantify the relationship of C-reactive protein (CRP), an acute-phase reactant and marker of systemic inflammation, with ALS occurrence. Design, Setting, Participants: UK Biobank, a prospective cohort study of 502,649 participants who were aged 37 to 73 years when examined at research centres between 2006 and 2010. Exposure: Venous blood was collected at baseline in the full cohort and assayed for CRP. Repeat measurement was made 3-7 years later in a representative subgroup (N=14,514) enabling correction for regression dilution. Main Outcome(s) and Measure(s): ALS as ascertained via national hospitalisation and mortality registries. We computed multi-variable hazard ratios with accompanying 95% confidence intervals for log-transformed CRP expressed as standard deviation and tertiles. Results: In an analytical sample of 400,884 individuals (218,203 women), a mean follow-up of 12 years gave rise to 231 hospitalisations and 223 deaths ascribed to ALS. After adjustment for covariates which included health behaviours, comorbidity, and socio-economic status, a one standard deviation higher log-CRP was associated with elevated rates of both ALS mortality (hazard ratios; 95% confidence intervals: 1.32; 1.13, 1.53) and hospitalisations (1.20; 1.00, 1.39). There was evidence of dose-response effects across tertiles of CRP for both outcomes (p for trend[≤]0.05). Correction for regression dilution led to a strengthening of the relationship with CRP for both mortality (1.62; 1.27, 2.08) and hospitalisations (1.37; 1.05, 1.76) ascribed to ALS. Conclusions and Relevance: Higher levels of CRP, a blood-based biomarker widely captured in clinical practice, were associated with a higher subsequent risk of ALS.