Association of small dense low-density lipoprotein cholesterol with longitudinal trajectories of cardio-kidney-metabolic comorbidity: A prospective cohort study based on multi-state Markov models.

OBJECTIVE

To assess the associations of small dense low-density lipoprotein cholesterol (sdLDL-C) with longitudinal trajectories of cardiovascular-kidney-metabolic multimorbidity (CKMM) in middle-aged and older adults.

METHODS

This prospective cohort study utilized data from the China Health and Retirement Longitudinal Study. Univariate and multivariable Cox proportional hazard models were used to assess the associations of LDL-C and sdLDL-C with two outcomes: onset of cardiovascular, kidney, and metabolic disease (FCKMD) and CKMM. Multi-state Markov models were used to assess the roles of LDL-C and sdLDL-C in the progression of CKMM (from no CKMD to one, two, three and four CKMDs). Stratified analyses further explored the associations based on different LDL-C levels. A sensitivity analysis was conducted to evaluate the robustness of the relationships.

RESULTS

Among 6110 participants followed for a mean of 8.12 years, 2070 (32.88%) developed at least one FCKMD. Of these cases, 349 (16.86%) progressed to CKMM. The transition rate from baseline to FCKMD was 1.72 times that from FCKMD to CKMM. Elevated sdLDL-C levels were linked to an increased risk of FCKMD and CKMM, whereas high LDL-C levels were associated only with higher odds of CKMM. sdLDL-C was associated with the onset of FCKMDs (from baseline to FCKMD, except for chronic kidney disease), and with the transition to heart disease-CKMM. sdLDL-C levels were related to the progression from baseline to FCKMD, regardless of LDL-C levels. Sensitivity analyses confirmed these findings.

CONCLUSION

sdLDL-C may serve as an important lipid-related risk marker in the progression trajectories of CKMM and may provide additional value for early risk stratification and precise prevention beyond traditional LDL-C-based assessment.