Phenotypic Age and Neutrophil-to-Lymphocyte Ratio mediate the association between the triglyceride glucose-body mass index and the cardiovascular mortality risk in hypertensive patients.

BackgroundThe triglyceride glucose-body mass index (TyG-BMI) has emerged as a novel marker for insulin resistance and metabolic syndrome. However, its relationship with prognosis in hypertensive patients remains uncertain. This study investigates the association between TyG-BMI and all-cause and cardiovascular mortality in hypertensive patients. Additionally, it explores the mediating roles of the neutrophil-to-lymphocyte ratio (NLR) and Phenotypic Age (PhenoAge) in these associations. MethodsData from 5164 hypertensive adults participating in the National Health and Nutritional Examination Surveys (NHANES) from 1999 to 2018 were analyzed. Mortality details were obtained from the National Death Index (NDI). Restricted cubic spline (RCS) was used to assess potential nonlinear associations, and weighted Cox proportional hazards models assessed the independent association of TyG-BMI with mortality risk. Time-dependent ROC curve analysis evaluated the predictive ability of TyG-BMI for survival. Structural equation modeling (SEM) explored indirect effects of NLR and PhenoAge on mortality associations. ResultsOver a median follow-up of 8.33 years, there were 1005 deaths, including 398 from cardiovascular causes. Participants were stratified by TyG-BMI classes using K-means clustering. Higher TyG-BMI levels were associated with increased risks of all-cause (HR 1.28, 95% CI 1.02-1.60, P = 0.03) and cardiovascular mortality (HR 1.62, 95% CI 1.06-2.46, P = 0.025). Time-dependent ROC analysis showed increasing TyG-BMI predictive accuracy for both all-cause and cardiovascular mortality over 10-, 15-, and 20-years, respectively. RCS analysis revealed a U-shaped relationship between TyG-BMI and mortality risk, with an inflection point at TyG-BMI = 239; deviations below or above this threshold significantly impacted mortality risk. SEM identified NLR and PhenoAge as mediators in high-risk hypertensive individuals (TyG-BMI >239). ConclusionTyG-BMI predicts all-cause and cardiovascular mortality in hypertensive patients, mediated by NLR and PhenoAge. Incorporating TyG-BMI, NLR, and PhenoAge into clinical practice may help improve risk stratification and guide targeted interventions for high-risk individuals. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/25331891v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@f8e24aorg.highwire.dtl.DTLVardef@1d0740eorg.highwire.dtl.DTLVardef@735aa1org.highwire.dtl.DTLVardef@143294a_HPS_FORMAT_FIGEXP M_FIG C_FIG