U-shaped association between lymphocyte-to-high-density lipoprotein ratio and all-cause mortality in patients with chronic obstructive pulmonary disease: insights from a population-based cohort study.

Background: Chronic obstructive pulmonary disease (COPD) represents a leading cause of mortality worldwide, characterized by systemic inflammation and metabolic dysregulation. While identifying reliable prognostic biomarkers remains crucial for COPD management, the lymphocyte-to-high-density lipoprotein ratio (LHR), an integrated marker of inflammation and metabolism, has shown promise in various conditions but remains unexplored in COPD. This investigation aimed to evaluate LHR's relationship with mortality outcomes in COPD patients using National Health and Nutrition Examination Survey (NHANES) data, exploring its potential role in clinical risk assessment. Methods: We analyzed 2,167 COPD patients from NHANES (1999-2018) with mortality follow-up through December 2019 (median 7.7 years). LHR was calculated as absolute lymphocyte count (ALC) divided by high-density lipoprotein (HDL) level. Cox proportional hazards models with progressive adjustment and restricted cubic spline analysis were employed. Results: LHR showed a U-shaped relationship with all-cause mortality. After full adjustment, moderate LHR levels demonstrated the strongest protective effect [Q3: hazard ratio (HR) =0.60; 95% confidence interval (CI): 0.45-0.82]. Two-piecewise regression identified 1.75 as the threshold, below which LHR increased associated with reduced mortality risk (HR =0.50; 95% CI: 0.35-0.72), while higher values showed slightly increased risk (HR =1.05; 95% CI: 1.01-1.10). Conclusions: LHR is a readily available biomarker with significant prognostic value in COPD. The U-shaped association highlights the importance of optimal immune-metabolic balance, with 1.75 as a key reference point for risk stratification. Future studies should validate these findings and explore LHR-based interventions.