SdLDL‑C/LDL‑C discordance as a practical surrogate for triglyceride‑associated cardiovascular risk: identification of at‑risk lipid phenotypes in the CHARLS prospective cohort.

Abstract

BACKGROUND: Discordance between small dense low-density lipoprotein cholesterol (sdLDL-C) and low-density lipoprotein cholesterol (LDL-C) levels is common. Whether this easily calculated parameter, derived from routine lipid profiles using the triglyceride (TG)-dependent Sampson equation, can serve as a practical surrogate for TG-associated cardiovascular disease (CVD) risk and improve risk stratification remains unclear. METHODS: This prospective analysis included 7736 CVD-free participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study (CHARLS). The sdLDL-C level was estimated using the Sampson equation and discordance was defined as a ≥ 10 percentile difference. Cox proportional hazards models were used to evaluate associations with incident CVD. Net reclassification improvement (NRI) was used to assess the incremental predictive value, and risk stratification was performed using clinically relevant cutoff points. RESULTS: During a median follow-up of 84 months, 1390 incident CVD events were documented. After multivariable adjustment, elevated sdLDL-C was associated with an increased CVD risk (hazard ratio [HR] = 1.392, 95% confidence interval [CI]:1.175–1.649). The high-discordance group exhibited a higher CVD risk (HR = 1.158, 95% CI: 1.007–1.332); this association was fully attenuated in the TG-stratified analyses, indicating that discordance mainly reflects TG-related risk. Notably, 13.3% of individuals with normal TG levels (< 150 mg/dL) showed high discordance, corresponding to a high-normal TG phenotype. Including sdLDL-C into traditional risk factors yielded a significant NRI (0.103, P < 0.05). Using paired clinical thresholds (LDL-C 130 mg/dL; sdLDL-C 40 mg/dL), individuals with dual-high LDL-C and sdLDL-C levels had the highest CVD risk (HR = 1.215, 95% CI: 1.067–1.384), whereas isolated high LDL-C level was not associated with an elevated risk. CONCLUSIONS: In this Chinese cohort, the sdLDL-C/LDL-C discordance derived from routine lipid measurements represented a significant CVD risk marker consistent with TG-associated atherogenic dyslipidaemia. This parameter provides a modest incremental prognostic value without additional costs and identifies two clinically actionable high-risk subgroups: the high-normal TG phenotype and the dual-high phenotype. Evaluating the sdLDL-C/LDL-C discordance may help refine CVD risk stratification as an auxiliary tool in current lipid management strategies.