Abstract
Background
Hypertension (HTN), a primary driver of cardiovascular disease (CVD) progression, shares etiological links with dyslipidemia. While low-density lipoprotein cholesterol (LDL-C) remains a cornerstone biomarker for CVD risk, emerging evidence implicates remnant cholesterol (RC)-a triglyceride-rich lipoprotein component-in HTN pathogenesis. This study aimed to examine the association between RC (independent of LDL-C) and incident HTN among Chinese adults aged 45 years and older.Methods
We analyzed 4,508 normotensive participants from the China Health and Retirement Longitudinal Study (CHARLS). Incident HTN served as the primary endpoint. RC was derived by subtracting directly measured LDL-C from non-high-density lipoprotein cholesterol (non-HDL-C). Adjusted Cox proportional hazards models evaluated the relationship between natural log-transformed RC (ln RC) levels and HTN risk. Discordance analyses categorized participants into RC-LDL-C concordant/discordant groups using percentile differences (> 15 units), median splits, and guideline-based LDL-C thresholds. Subgroup analyses validated the robustness of the results.Results
During a median follow-up of 9 years, 39.88% (n = 1,798) of participants developed incident HTN. RC-LDL-C discordance was observed in 58.23% of the cohort, comprising 37.18% with discordantly low RC and 21.05% with discordantly high RC. After multivariable adjustment, each 1 standard deviation increase in baseline ln RC was associated with a 7% elevated HTN risk (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.02-1.12). Restricted cubic spline (RCS) analysis revealed a linear dose-response relationship between continuous ln RC levels and HTN risk (P for trend = 0.013; P for nonlinearity = 0.233). Participants in the discordantly high RC group exhibited a 17% higher HTN risk compared with the discordantly low group (HR 1.17, 95% CI 1.04-1.32). Stratification by three LDL-C clinical thresholds and the median value showed that low LDL-C/high RC individuals had higher HTN risk than the low LDL-C/low RC reference group in the fully adjusted model, with statistically significant associations at 113 and 130 mg/dL. Subgroup analyses supported these findings.Conclusions
In normotensive populations, higher RC concentrations were independently linked to incident HTN, irrespective of LDL-C levels. The pathophysiological pathways underlying this RC-HTN association-distinct from LDL-C-mediated mechanisms-and the clinical utility of RC-targeted interventions in primary prevention strategies warrant further investigation.