Beyond LDL-C: discordant small dense LDL cholesterol stratifies hypertension risk in a Chinese longitudinal cohort

BACKGROUND: This longitudinal study investigated small dense low-density lipoprotein cholesterol (sdLDL-C) and its discordance with ‌low-density lipoprotein cholesterol (LDL-C) as predictors of hypertension (HTN) incidence in a Chinese population. METHODS: Sampson's equation was used to calculate sdLDL-C‌. Using data from 4,574 adults aged ≥ 45 from the ‌China Health and Retirement Longitudinal Study (CHARLS)‌, participants were stratified into three groups by sdLDL-C‌/LDL-C‌ percentile divergence (≥ 10%): discordantly low sdLDL-C, concordant, and discordantly high sdLDL-C. Cox regression analyses were performed to examine the relationship between sdLDL-C and HTN, adjusting for potential confounders. Additionally, we compared the LDL-C values derived from the Sampson equation with those measured by the homogeneous assay employed in this study. RESULTS: Over 9 years, 1,826 (39.9%) developed HTN‌. Cox regression adjusted for confounders showed baseline log-transformed sdLDL-C independently predicted HTN risk (hazard ratio [HR]‌ = 1.36, 95% confidence interval [CI]‌:1.17-1.57). The discordantly high sdLDL-C group had 24% higher HTN risk versus the discordantly low group (‌HR‌ = 1.28, 95% ‌CI‌:1.13-1.45). Stratification by three LDL-C clinical thresholds and median values revealed individuals with low LDL-C but high sdLDL-C had the highest HTN risk (vs. low LDL-C/low sdLDL-C reference group in fully adjusted models). Despite strong correlation (Spearman's r = 0.956), systematic biases between direct LDL-C and Sampson methods may limit clinical interchangeability. CONCLUSION: sdLDL-C, particularly its discordance with LDL-C, is independently associated with incident HTN risk in Chinese adults. These findings underscore sdLDL-C's potential to refine cardiovascular risk stratification and enhance precision prevention strategies.