Joint association of the non-traditional lipid parameters and hs-CRP with cardiometabolic multimorbidity: a nationwide prospective cohort study

Cardiometabolic multimorbidity (CMM), defined as the presence of at least two of diabetes, coronary heart disease and stroke, is increasingly common worldwide and poses a substantial burden on healthcare systems. However, the joint association of CMM with non-traditional lipids and inflammation remains unexplored. We included 8,141 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study (CHARLS). Non-traditional lipid parameters were calculated. hs-CRP (high-sensitivity C-reactive protein) was categorised as < 1 and ≥ 1 mg/L. Cox regression, restricted cubic spline (RCS), Kaplan–Meier (K-M), interaction, age-stratified, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses were used to assess associations, joint effects, age differences, and incremental values. During a median follow-up of 9.0 years (IQR, 7.0–9.0), 961 (11.8%) participants developed incident CMM. In fully adjusted models, each 1-standard deviation (SD) increment in non-traditional lipid parameters was associated with a 14%-25% higher risk (all P < 0.05). When categorised by the median, participants with high levels of non-traditional lipid parameters had a 19% to 46% higher risk than those with low levels. Furthermore, relative to the group with both low lipid levels and low hs-CRP, participants with concurrent high lipid levels and elevated hs-CRP had a 57% to 82% relative increase in risk, with a significant dose–response trend across the combined categories ( P < 0.05). RCS analyses revealed a non-linear positive association between LCI and hs-CRP, whereas linear relationships were observed for the other parameters. No significant interaction was observed between non-traditional lipid parameters and hs-CRP levels. The addition of non-traditional lipid parameters and hs-CRP levels to the basic model improved the C-statistic from 0.681 to 0.707, with significant NRI and IDI values (all P < 0.001), indicating a modest but statistically significant incremental discriminative value beyond conventional risk factors. Age-stratified analyses showed stronger associations in participants aged < 60 years, with significant interactions observed for most non-traditional lipid parameters. Non-traditional lipids and hs-CRP levels were individually associated with CMM risk in separate multivariate-adjusted models. Notably, when assessed jointly, participants with concurrent elevation of both markers exhibited a higher risk, with more pronounced effects in younger participants (<60 years). However, the absolute incremental value was modest, so these markers are not yet ready to change clinical practice. These findings support the combined assessment of lipid parameters and inflammatory status for CMM risk stratification in high-risk populations.