Discordant LDL-C and Estimated LDL-Triglycerides in Predicting Hypertension Risk: A Prospective Analysis From Charls

Objective: While elevated low-density lipoprotein cholesterol (LDL-C) is a well-established cardiovascular risk factor, its association with hypertension (HTN) remains ambiguous. Estimated LDL-triglycerides (eLDL-TG), a novel biomarker reflecting triglyceride-enriched LDL particles which has been strongly linked to atherosclerotic cardiovascular disease (ASCVD), may offer improved predictive insight into HTN development, particularly in individuals with optimal LDL-C levels.Design and method: This prospective study included 4,746 middle-aged and older adults from the China Health and Retirement Longitudinal Study (CHARLS). We employed multi-adjusted Cox models to compare hazard ratios (HRs) per standard deviation (SD) increase in eLDL-TG and other lipid parameters (non-HDL-C, LDL-C, remnant cholesterol [RC]). Restricted cubic splines (RCS) were used to evaluate dose-response relationships. Discordance analyses were conducted using cohort-derived medians (LDL-C: 113 mg/dL; eLDL-TG: 36 mg/dL) and guideline-based clinical thresholds (LDL-C <100 mg/dL and <130 mg/dL, with corresponding eLDL-TG thresholds of 33 mg/dL and 42 mg/dL matched by distribution percentiles). Joint effects of eLDL-TG (median: 36 mg/dL) and high-sensitivity C-reactive protein (hsCRP; clinical cutoff: 2 mg/L) were also assessed. Results: After multivariable adjustment, eLDL-TG demonstrated the strongest association with incident HTN (HR per SD: 1.10, 95% confidence interval [CI]: 1.05–1.16). RCS revealed a nonlinear positive relationship between eLDL-TG and HTN risk (P for trend < 0.001; P for nonlinearity = 0.035). Discordance analyses consistently identified the group with high eLDL-TG but low LDL-C as having the highest HTN risk (e.g., at LDL-C <130 mg/dL, HR: 1.32, 95% CI: 1.14–1.54; at LDL-C <100 mg/dL, HR: 1.44, 95% CI: 1.20–1.74). Notably, individuals with optimal LDL-C but elevated eLDL-TG exhibited markedly elevated HTN risk, suggesting residual risk undetected by conventional LDL-C. Joint analysis showed synergistic effects between high eLDL-TG and elevated hsCRP (HR: 1.42, 95% CI: 1.21–1.61). Conclusions: eLDL-TG is an independent predictor of HTN, especially in adults with optimal LDL-C levels. Its integration with hsCRP enhances risk stratification, supporting a potential role of lipid-driven inflammation in HTN pathogenesis. These findings advocate for targeted assessment of eLDL-TG to identify high-risk individuals who may benefit from early intervention.