Cumulative lipid-inflammatory indices and the risk of cardiometabolic multimorbidity: a prospective cohort study.

Background: Cardiometabolic multimorbidity (CMM) has become a major global public health challenge. Although dyslipidemia and chronic low-grade inflammation are known to contribute to cardiometabolic diseases, their long-term cumulative combined effects on the risk of CMM remain poorly understood. This study aimed to evaluate the associations of cumulative lipid-inflammatory indices with incident CMM in a large prospective cohort. Methods: A total of 25,376 participants from the Kailuan cohort were included and followed up until December 31, 2023. Nine cumulative lipid-inflammatory exposure indices were constructed via trapezoidal area-under-the-curve calculation using repeated measurements from 2006 to 2010. The primary outcome was incident CMM, defined as the concurrence of at least two cardiometabolic diseases including type 2 diabetes, ischemic heart disease and stroke. Multivariable Cox regression, restricted cubic spline analyses, competing-risk models, and subgroup analyses were applied. Results: During a median follow-up of 13.0 years, 481 incident CMM events were documented. All nine cumulative lipid-inflammatory indices were independently and positively associated with an elevated risk of CMM in a dose-response manner. Incorporating these indices into conventional risk model improved risk reclassification and discriminatory ability. Conclusions: Elevated cumulative lipid-inflammatory indices are associated with a higher risk of incident CMM. These composite markers may serve as auxiliary indicators for preliminary risk stratification, while causal relationships cannot be confirmed based on this observational cohort alone.