Impact of lipid accumulation product on cardiometabolic multimorbidity and the mediating effect of leukocytes: evidence from a prospective cohort study among middle-aged and elderly chinese adults.

Abstract

Background: Cardiometabolic multimorbidity (CMM) is a growing public-health burden in ageing populations, yet conventional adiposity measures such as body mass index and waist circumference do not adequately capture the visceral fat and lipid-metabolic disturbances that underlie it. We investigated the association between the lipid accumulation product (LAP) and incident CMM in middle-aged and older Chinese adults, and examined whether systemic inflammation mediates this association.

Methods: We analysed data from five waves (2011-2020) of the China Health and Retirement Longitudinal Study (CHARLS), comprising 7563 participants aged 45 years or older who were free of heart disease, stroke, and diabetes at baseline and had complete LAP and white blood cell (WBC) count data. CMM was defined as the coexistence of two or more cardiometabolic conditions among heart disease, stroke, and diabetes. The association between LAP and incident CMM was assessed using Cox proportional-hazards models with subgroup and restricted cubic spline analyses, and the mediating effects of inflammatory markers (WBC count and C-reactive protein [CRP]) were evaluated by causal mediation analysis.

Results: Over a median follow-up of 9.0 years, 486 participants (6.43%) developed CMM. After multivariable adjustment, LAP was positively associated with CMM: each one-unit increase in the base-10 logarithm of LAP (LgLAP) corresponded to a hazard ratio (HR) of 3.03 (95% CI 2.33-3.93), and risk rose across LAP quartiles (quartile 4 vs. quartile 1 h 3.41, 95% CI 2.49-4.67; P for trend < 0.001). Adding LAP to a base model raised the C-index from 0.624 to 0.674, with corresponding gains in the integrated discrimination improvement (IDI) and net reclassification improvement (NRI); the model including both LAP and WBC had a C-index of 0.677. Restricted cubic spline analysis showed a non-linear, positive dose-response relationship (P for non-linearity = 0.003). The association was stronger in normotensive than in hypertensive participants (HR 4.39 vs. 2.19; P for interaction = 0.020) but remained significant in both. In mediation analysis, WBC count and log-transformed CRP each significantly mediated the association, accounting for 5.1% and 8.4% of the total effect, respectively.

Conclusions: In middle-aged and older Chinese adults, a higher baseline LAP was associated with an increased risk of incident CMM, and systemic inflammation-indexed by WBC count and CRP-partially mediated this association. As an inexpensive and routinely available index, LAP may help identify people at risk of CMM, particularly among those without hypertension.

Clinical trial number: Not applicable.