氯离子是人体细胞外液中最丰富的阴离子，在维持体内平衡中发挥着至关重要的作用。先前的研究表明，低氯血症可以作为各种临床环境中不良结果的独立危险因素。然而，一般人群中血清氯的方差与长期死亡风险之间的关联很少被研究。本研究旨在评估美国成年人群中血清氯与全因和特定原因死亡率的关联。数据收集自国家健康和营养检查调查的 10 个调查周期（1999 年至 2018 年）。全因死亡率、心血管疾病 (CVD) 死亡率、癌症死亡率和呼吸道疾病死亡率数据是通过与截至 2019 年 12 月 31 日的国家死亡指数关联获得的。在调整人口因素和相关生活方式、实验室项目和共病因素后，构建加权 Cox 比例风险模型来估计全因和特定原因死亡率的风险比和 95% CI。总共纳入了 51,060 名成年参与者，在中位随访 111 个月期间，记录了 7582 例死亡、 CVD 2388 例、癌症 1639 例、呼吸系统疾病 567 例。加权卡普兰-迈耶生存分析显示，血清氯化物最低四分位数的个体始终具有最高的死亡风险。血清氯从最低到最高四分位数（≤101.2、101.3-103.2、103.2-105.0 和≥105.1 mmol/L）的多变量调整风险比分别为 1.00（95% CI 参考）、0.77（95% CI 0.67-0.89）全因死亡率分别为 0.72 (95% CI 0.63-0.82) 和 0.77 (95% CI 0.65-0.90)（线性趋势 P<.001）； CVD 死亡率为 1.00（95% CI 参考）、0.63（95% CI 0.51-0.79）、0.56（95% CI 0.43-0.73）和 0.67（95% CI 0.50-0.89）（线性趋势 P=0.004） ;癌症死亡率为 1.00（95% CI 参考）、0.67（95% CI 0.54-0.84）、0.65（95% CI 0.50-0.85）和 0.65（95% CI 0.48-0.87）（线性趋势 P=0.004） ;呼吸系统疾病死亡率为 1.00（95% CI 参考）、0.68（95% CI 0.41-1.13）、0.59（95% CI 0.40-0.88）和 0.51（95% CI 0.31-0.84）（线性趋势 P=. 004）。受限三次样条分析揭示了血清氯与全因和特定原因死亡率的非线性和L形关联（所有非线性P<0.05），其中较低的血清氯与较高的死亡风险显着相关。血清氯与死亡风险的关联性很强，并且对于全因死亡率和 CVD 死亡率没有检测到显着的额外交互作用（交互作用 P>0.05）。在美国成年人中，血清氯浓度降低与所有原因死亡风险增加独立相关。 - 原因死亡率、CVD 死亡率、癌症死亡率和呼吸系统疾病死亡率。我们的研究结果表明，血清氯化物可能作为普通成年人群中一种有前途的、具有成本效益的健康指标。需要进一步的研究来探索血清氯与死亡率之间潜在的病理生理学机制。©侯欣然，徐伟，张成亮，宋宗斌，朱茂恩，郭曲连，王健。最初发表于 JMIR 公共卫生和监测 (https://publichealth.jmir.org)，2023 年 11 月 13 日。

Chloride is the most abundant anion in the human extracellular fluid and plays a crucial role in maintaining homeostasis. Previous studies have demonstrated that hypochloremia can act as an independent risk factor for adverse outcomes in various clinical settings. However, the association of variances of serum chloride with long-term mortality risk in general populations has been rarely investigated.This study aims to assess the association of serum chloride with all-cause and cause-specific mortality in the general American adult population.Data were collected from 10 survey cycles (1999-2018) of the National Health and Nutrition Examination Survey. All-cause mortality, cardiovascular disease (CVD) mortality, cancer mortality, and respiratory disease mortality data were obtained by linkage to the National Death Index through December 31, 2019. After adjusting for demographic factors and relevant lifestyle, laboratory items, and comorbid factors, weighted Cox proportional risk models were constructed to estimate hazard ratios and 95% CIs for all-cause and cause-specific mortality.A total of 51,060 adult participants were included, and during a median follow-up of 111 months, 7582 deaths were documented, 2388 of CVD, 1639 of cancer, and 567 of respiratory disease. The weighted Kaplan-Meier survival analyses showed consistent highest mortality risk in individuals with the lowest quartiles of serum chloride. The multivariate-adjusted hazard ratios from lowest to highest quartiles of serum chloride (≤101.2, 101.3-103.2, 103.2-105.0, and ≥105.1 mmol/L) were 1.00 (95% CI reference), 0.77 (95% CI 0.67-0.89), 0.72 (95% CI 0.63-0.82), and 0.77 (95% CI 0.65-0.90), respectively, for all-cause mortality (P for linear trend<.001); 1.00 (95% CI reference), 0.63 (95% CI 0.51-0.79), 0.56 (95% CI 0.43-0.73), and 0.67 (95% CI 0.50-0.89) for CVD mortality (P for linear trend=.004); 1.00 (95% CI reference), 0.67 (95% CI 0.54-0.84), 0.65 (95% CI 0.50-0.85), and 0.65 (95% CI 0.48-0.87) for cancer mortality (P for linear trend=.004); and 1.00 (95% CI reference), 0.68 (95% CI 0.41-1.13), 0.59 (95% CI 0.40-0.88), and 0.51 (95% CI 0.31-0.84) for respiratory disease mortality (P for linear trend=.004). The restricted cubic spline analyses revealed the nonlinear and L-shaped associations of serum chloride with all-cause and cause-specific mortality (all P for nonlinearity<.05), in which lower serum chloride was prominently associated with higher mortality risk. The associations of serum chloride with mortality risk were robust, and no significant additional interaction effect was detected for all-cause mortality and CVD mortality (P for interaction>.05).In American adults, decreased serum chloride concentrations were independently associated with increased all-cause mortality, CVD mortality, cancer mortality, and respiratory disease mortality. Our findings suggested that serum chloride may serve as a promising cost-effective health indicator in the general adult population. Further studies are warranted to explore the potential pathophysiological mechanisms underlying the association between serum chloride and mortality.©Xinran Hou, Wei Xu, Chengliang Zhang, Zongbin Song, Maoen Zhu, Qulian Guo, Jian Wang. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 13.11.2023.