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Background <p>The association of neutrophil-to-lymphocyte ratio (NLR) and depressive symptoms with stroke risk, mortality, and major adverse cardiovascular events (MACE) is currently unknown. This study aimed to investigate the effects of neutrophil-to-lymphocyte ratio (NLR) and depressive symptoms on stroke risk, mortality, and MACE in NHANES 2005–2018.</p> Methods <p>The National Health and Nutrition Examination Survey (NHANES) was conducted by the National Center for Health Statistics between 2005 and 2018, recruiting a nationally representative sample of participants aged 20 years and older. The NLR reflects inflammatory status and the Patient Health Questionnaire 9 (PHQ-9) indicates depressive symptoms. Independent and joint associations between NLR, depressive symptoms, and stroke and mortality were then examined, and relative risk was calculated using weight-based Cox regression analyses. Finally, mediation analysis was used to explore the indirect impact of the PHQ-9 score on stroke and mortality mediated through NLR.</p> Results <p>NLR and depressive symptoms were positively associated with stroke risk (<i>p</i> &lt; 0.05). Participants with higher NLR levels had an increased risk of all-cause mortality and MACE (HR, 1.406; 95% CI 1.261–1.567; HR, 1.927; 95% CI 1.518–2.447), while those with higher PHQ-9 score were associated with an elevated risk of all-cause mortality and MACE (HR, 1.762; 95% CI 1.516–2.047; HR, 1.755; 95% CI 1.396–2.206). In addition, joint analyses indicated that participants with PHQ-9 score ≥ 10 and high NLR levels had the highest risk of all-cause mortality and MACE (HR, 2.079; 95% CI 1.673–2.585; HR, 2.858, 95% CI 2.007–4.069). Specifically, participants with elevated NLR levels and moderate-severe depressive symptoms faced the greatest risk of mortality. Mediation analyses revealed that NLR partially mediated the association between PHQ-9 score and stroke risk, all-cause mortality, and MACE by0.6%, 5.9%, and 4.8%, respectively.</p> Conclusion <p>Our research indicates that elevated NLR levels and more severe depressive symptoms were associated with increased risk of stroke, all-cause mortality and MACE. In addition, NLR plays a mediation role in linking depressive symptoms to stroke, MACE, and all-cause mortality.</p>

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Higher PHQ-9 score levels and neutrophil-to-lymphocyte ratio are associated with increased risks of stroke, all-cause mortality, and MACE in NHANES 2005–2018

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  • 发表日期：

    2025年9月14日

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  • Junqi Liao,
  • Aimei Zhang,
  • Yujun Cong,
  • Wanhui Peng,
  • Xiaogang Tang,
  • Qing Zhu,
  • Li Li,
  • Yunze Li,
  • Yan Liu,
  • Hui Jiang,
  • Jingyi Chen,
  • Yang Han,
  • Zhaoyao Chen,
  • Wenlei Li,
  • Yuan Zhu,
  • Hongquan Liu,
  • Minghua Wu

摘要

Background

The association of neutrophil-to-lymphocyte ratio (NLR) and depressive symptoms with stroke risk, mortality, and major adverse cardiovascular events (MACE) is currently unknown. This study aimed to investigate the effects of neutrophil-to-lymphocyte ratio (NLR) and depressive symptoms on stroke risk, mortality, and MACE in NHANES 2005–2018.

Methods

The National Health and Nutrition Examination Survey (NHANES) was conducted by the National Center for Health Statistics between 2005 and 2018, recruiting a nationally representative sample of participants aged 20 years and older. The NLR reflects inflammatory status and the Patient Health Questionnaire 9 (PHQ-9) indicates depressive symptoms. Independent and joint associations between NLR, depressive symptoms, and stroke and mortality were then examined, and relative risk was calculated using weight-based Cox regression analyses. Finally, mediation analysis was used to explore the indirect impact of the PHQ-9 score on stroke and mortality mediated through NLR.

Results

NLR and depressive symptoms were positively associated with stroke risk (p < 0.05). Participants with higher NLR levels had an increased risk of all-cause mortality and MACE (HR, 1.406; 95% CI 1.261–1.567; HR, 1.927; 95% CI 1.518–2.447), while those with higher PHQ-9 score were associated with an elevated risk of all-cause mortality and MACE (HR, 1.762; 95% CI 1.516–2.047; HR, 1.755; 95% CI 1.396–2.206). In addition, joint analyses indicated that participants with PHQ-9 score ≥ 10 and high NLR levels had the highest risk of all-cause mortality and MACE (HR, 2.079; 95% CI 1.673–2.585; HR, 2.858, 95% CI 2.007–4.069). Specifically, participants with elevated NLR levels and moderate-severe depressive symptoms faced the greatest risk of mortality. Mediation analyses revealed that NLR partially mediated the association between PHQ-9 score and stroke risk, all-cause mortality, and MACE by0.6%, 5.9%, and 4.8%, respectively.

Conclusion

Our research indicates that elevated NLR levels and more severe depressive symptoms were associated with increased risk of stroke, all-cause mortality and MACE. In addition, NLR plays a mediation role in linking depressive symptoms to stroke, MACE, and all-cause mortality.