Ma Jun, Song Yingda, Zhang Shaochen, Feng Weirong, Wei Ziqing, Shen Zengqiang, Tong Zhiqiang, Bai Xiaoming
The Thoracic Surgery Department of Shanxi Provincial People's Hospital, Shanxi Medical University, Taiyuan, Shanxi Province, China.
Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi Province, China.
PLoS One. 2025 Jun 5;20(6):e0324849. doi: 10.1371/journal.pone.0324849. eCollection 2025.
Accumulating evidence supports the important role of inflammation in disease outcomes. Derived neutrophil-to-lymphocyte ratio (dNLR) is broadly identified as potential prognostic marker in clinical trials or daily clinical practice, but dNLR has never been verified in cardiovascular and all-cause mortality.
Overall, 34,392 participants from the National Health and Nutrition Examination Survey (NHANES) were included. The exposure variable was Log-dNLR (dNLR Logarithmic transformation). Participants were categorized according to Log-dNLR quartiles and followed through 31st December 2019. Weighted univariable and multivariable Cox regression were applied to assess the relationship between Log-dNLR evaluated as categorical variables, with cardiovascular and all-cause mortality. Restricted cubic spline (RCS) regression, subgroup analysis, and threshold effect were applied to assess nonlinear relationship between Log-dNLR with cardiovascular and all-cause mortality as well as the effects of special populations. We used multiple sensitivity analyses to reduce selection bias and validate these relationships. Last, the time-dependent weighted receiver operating characteristic (ROC) curve analysis was used to assess predictive accuracy of the Log-dNLR for survival outcomes.
During a median follow-up duration of 116.90 months, a total of 4,939 all-cause deaths occurred, of which 1,327 were cardiovascular deaths. After adjusting for multiple confounders, compared to the quartile 1, the hazard ratios (HRs) (95% confidence interval, CI) for quartile 4 were 1.38 (95% CI, 1.14-1.68) for cardiovascular mortality and 1.16 (95% CI, 1.06-1.27) for all-cause mortality was identified using RCS regression, with a threshold point of 0.370. Significant differences were observed before and after this threshold point. In addition, there were significant interactions between sex, hypertension status and Log-dNLR (P for interaction = 0.025, 0.005, respectively) for the all-cause mortality risk and significant interactions between age groups, diabetes status and Log-dNLR (P for interaction = 0.007, 0.004, respectively) for the cardiovascular mortality risk. Lastly, ROC analysis revealed that Log-dNLR showed moderate predictive power for all-cause and cardiovascular mortality in the short and long term.
In summary, elevated dNLR levels are significantly associated with an increased risk of both cardiovascular and all-cause mortality.
越来越多的证据支持炎症在疾病转归中发挥重要作用。衍生中性粒细胞与淋巴细胞比值（dNLR）在临床试验或日常临床实践中被广泛认为是潜在的预后标志物，但dNLR从未在心血管死亡率和全因死亡率方面得到验证。
总共纳入了来自美国国家健康与营养检查调查（NHANES）的34392名参与者。暴露变量为Log-dNLR（dNLR的对数转换值）。参与者根据Log-dNLR四分位数进行分类，并随访至2019年12月31日。应用加权单变量和多变量Cox回归来评估作为分类变量的Log-dNLR与心血管死亡率和全因死亡率之间的关系。采用限制性立方样条（RCS）回归、亚组分析和阈值效应来评估Log-dNLR与心血管死亡率和全因死亡率之间的非线性关系以及特殊人群的影响。我们进行了多项敏感性分析以减少选择偏倚并验证这些关系。最后，采用时间依赖性加权受试者工作特征（ROC）曲线分析来评估Log-dNLR对生存结局的预测准确性。
在中位随访期116.90个月内，共发生4939例全因死亡，其中1327例为心血管死亡。在调整多个混杂因素后，与第一四分位数相比，第四四分位数的心血管死亡率风险比（HRs）（95%置信区间，CI）为1.38（95%CI，1.14 - 1.68），全因死亡率的HRs为1.16（95%CI，1.06 - 1.27），通过RCS回归确定阈值点为0.370。在该阈值点前后观察到显著差异。此外，在全因死亡风险方面，性别、高血压状态与Log-dNLR之间存在显著交互作用（交互作用P值分别为0.025、0.005），在心血管死亡风险方面，年龄组、糖尿病状态与Log-dNLR之间存在显著交互作用（交互作用P值分别为0.007、0.004）。最后，ROC分析显示Log-dNLR在短期和长期对全因死亡率和心血管死亡率均具有中等预测能力。
总之，dNLR水平升高与心血管死亡率和全因死亡率风险增加显著相关。
