U-shaped association of platelet-to-lymphocyte ratio with all-cause and cardiovascular mortality in hypertension: mediating role of renal dysfunction in a nationwide cohort (NHANES 2005–2018)

To evaluate the association between the platelet-to-lymphocyte ratio (PLR) and all-cause and cardiovascular mortality among adults with hypertension in the National Health and Nutrition Examination Survey (NHANES). We conducted a prospective cohort analysis using NHANES 2005–2018 data linked to National Death Index mortality records through December 31, 2019. The study included 6,109 adults with hypertension. PLR was calculated as the absolute platelet count divided by the absolute lymphocyte count. Data-driven cut points identified by maximum rank statistics were used to define low, intermediate, and high PLR groups. Nonlinear associations were examined using restricted cubic spline models. Survey-weighted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. Mediation analysis was used to quantify the statistical contribution of estimated glomerular filtration rate (eGFR) to the observed PLR-mortality associations. During follow-up, PLR showed a nonlinear association with all-cause mortality. Compared with the intermediate PLR group, the high PLR group was associated with increased all-cause mortality in the fully adjusted model (HR, 1.29; 95% CI, 1.10–1.51). The association for the low PLR group was attenuated and was not statistically significant after full adjustment (HR, 1.15; 95% CI, 0.97–1.36). For cardiovascular mortality, the association was also nonlinear, with a significantly higher risk among participants in the high PLR group (HR, 1.71; 95% CI, 1.27–2.31), whereas the association for the low PLR group was not statistically significant (HR, 0.91; 95% CI, 0.64–1.30). eGFR statistically mediated approximately 16.0% of the association between PLR and all-cause mortality and 5.9% of the association between PLR and cardiovascular mortality. Among adults with hypertension, higher PLR was associated with increased all-cause and cardiovascular mortality, and the exposure-outcome associations were nonlinear. The low PLR group was not independently associated with mortality after comprehensive adjustment. eGFR accounted for a modest proportion of the observed associations. PLR may have potential value as an accessible risk-stratification marker, but the data do not establish a causal relationship or support its use as a stand-alone clinical decision-making tool.