The association between the estimated small dense low-density lipoprotein cholesterol and multimorbidity: a national longitudinal study

OBJECTIVE: To investigate the relationship between E-sdLDL-C and the risk of multimorbidity and to explore whether E-sdLDL-C is a stronger predictor of multimorbidity than the traditional lipid profiles. METHODS: This study included 10,763 participants in the cross-sectional analysis and 7,321 in the longitudinal analysis from the China Health and Retirement Longitudinal Study, all of whom were aged over 45 years. E-sdLDL-C was calculated using the formula: E-sdLDL-C (mg/dL) = LDL-C -(1.43 × LDL-C -(0.14 × (ln (TG) × LDL-C)) - 8.99). Multimorbidity was defined as the coexistence of at least two chronic diseases. Logistic regression and Cox proportional hazards models were used to evaluate the cross-sectional and longitudinal relationships between E-sdLDL-C and traditional lipid profiles and multimorbidity, respectively. Additionally, cumulative E-sdLDL-C (CumE-sdLDL-C) exposure was analyzed to assess its long-term impact on multimorbidity development. RESULTS: Compared to individuals with lower E-sdLDL-C levels, those with higher E-sdLDL-C levels had a significantly increased risk of multimorbidity in both cross-sectional (odds ratio [OR] 1.223, 95% confidence interval [CI] 1.095-1.366) and cohort analyses (hazard ratio [HR] 1.278, 95% CI 1.163-1.404). Discordantly high E‑sdLDL‑C had a higher risk of multimorbidity in discordance analyses with triglycerides (HR 1.251, 95% CI 1.094-1.429) as compared with the respective concordantly low groups. Furthermore, higher CumE-sdLDL-C exposure was associated with an increased risk of incident multimorbidity (HR 1.335, 95% CI 1.098-1.623). CONCLUSIONS: Elevated E-sdLDL-C levels were associated with an increased risk of multimorbidity in middle‑aged and older adults, both at baseline and over time.