Associations between lipid parameters and incident cardio-renal-metabolic multimorbidity: The Tehran Lipid and...

To evaluate the association between lipid parameters and incident Cardio-Renal-Metabolic (CRM) multimorbidity in a large prospective cohort.

We used multivariable Cox regression models to assess the association between lipid parameters and the risk of incident CRM multimorbidity, defined as the presence of ≥2 of type 2 diabetes (T2DM), cardiovascular disease (CVD), and chronic kidney disease (CKD), in individuals initially free of these conditions. Data from 5721 participants in the Tehran Lipid and Glucose Study (TLGS) (mean age 44.4 years; 3075 women) were analyzed. During a median follow-up of 15.4 years, 332 cases of CRM multimorbidity were identified. The combinations of coexisting CRM conditions, in order of frequency, were CVD and T2DM (49.2%), CKD and T2DM (19.9%), CVD and CKD (18.0%), and all three conditions (12.8%). Multivariable-adjusted hazard ratios (HRs) per standard deviation (SD) increase in TC, non-HDL-C, LDL-C, and log(TG) were 1.24 (1.12-1.37), 1.26 (1.14-1.39), 1.20 (1.08-1.34), and 1.29 (1.15-1.45), respectively. HRs per SD increase in TC/HDL-C, LDL-C/HDL-C, and log(TG/HDL-C) were 1.21 (1.10-1.33), 1.18 (1.07-1.30), and 1.26 (1.12-1.43), respectively. HDL-C was associated with a 17% lower risk (95% CI: 0.73-0.93); however, not after adjustment for metabolic risk factors. No evidence of nonlinearity was observed (all P_nonlinearity >0.05).

These findings underscore the important role of lipid abnormalities in cardio-renal-metabolic multimorbidity, particularly CVD-T2DM multimorbidity. However, they should be interpreted in light of composite heterogeneous outcomes with shared pathophysiological pathways, and the likelihood that the analytic sample represented a relatively healthier subset of the original cohort.