Abstract
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.