Discordance between remnant cholesterol and low-density lipoprotein cholesterol predicts incident hypertension: a 9-year prospective cohort study in Chinese adults

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.