Department of Epidemiology and Public Health, University College London, UK.
UCL Brain Sciences, University College London, UK; Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Brain Behav Immun. 2023 Nov;114:46-51. doi: 10.1016/j.bbi.2023.07.026. Epub 2023 Aug 4.
While systemic inflammation has been implicated in the etiology of selected neurodegenerative disorders, its role in the development of amyotrophic lateral sclerosis (ALS), a condition with high case-fatality, is untested. Accordingly, we quantified the relationship of C-reactive protein (CRP), an acute-phase reactant and marker of systemic inflammation, with subsequent ALS occurrence.
We used data from UK Biobank, a prospective cohort study of 502,649 participants who were aged 37 to 73 years when examined at research centers between 2006 and 2010. Venous blood was collected at baseline in the full cohort and assayed for CRP, and repeat measurement was made 3-7 years later in a representative subgroup (N = 14,514) enabling correction for regression dilution. ALS was ascertained via national hospitalization and mortality registries until 2021. We computed multivariable hazard ratios with accompanying 95% confidence intervals for log-transformed CRP expressed as standard deviation and tertiles.
In an analytical sample of 400,884 initially ALS-free individuals (218,203 women), a mean follow-up of 12 years gave rise to 231 hospitalizations and 223 deaths ascribed to ALS. After adjustment for covariates which included health behaviors, 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 hospitalizations (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 hospitalizations (1.37; 1.05, 1.76).
Higher levels of CRP, a blood-based biomarker widely captured in clinical practice, is associated with moderately increased future risk of amyotrophic lateral sclerosis.
虽然全身炎症与某些神经退行性疾病的病因有关，但它在高病死率的肌萎缩侧索硬化症（ALS）的发展中的作用尚未得到验证。因此，我们量化了 C 反应蛋白（CRP），一种急性期反应物和全身炎症标志物，与随后发生的 ALS 之间的关系。
我们使用了英国生物库的数据，这是一项针对 502649 名参与者的前瞻性队列研究，这些参与者在 2006 年至 2010 年期间在研究中心接受检查时年龄在 37 至 73 岁之间。在整个队列中采集基线时的静脉血，并检测 CRP，在一个具有代表性的亚组（N=14514）中进行 3-7 年的重复测量，从而纠正回归稀释。通过国家住院和死亡率登记处确定肌萎缩侧索硬化症，直到 2021 年。我们计算了以标准偏差和三分位表示的对数转换 CRP 的多变量危害比，并附有 95%置信区间。
在一个最初无 ALS 的 400884 人分析样本中（218203 名女性），平均随访 12 年导致 231 例住院和 223 例归因于 ALS 的死亡。在调整了包括健康行为、合并症和社会经济地位在内的混杂因素后，CRP 的一个标准差升高与 ALS 死亡率（危害比；95%置信区间：1.32；1.13，1.53）和住院率（1.20；1.00，1.39）的升高相关。CRP 三分位的剂量-反应关系均有证据（趋势检验的 p 值≤0.05）。回归稀释的校正使 CRP 与死亡率（1.62；1.27，2.08）和住院率（1.37；1.05，1.76）的关系得到加强。
CRP 水平较高，这是一种在临床实践中广泛捕获的基于血液的生物标志物，与肌萎缩侧索硬化症未来风险的适度增加相关。
