Abstract
AIMS: Atherosclerosis is established as a chronic inflammatory disease, yet the potential mediating role of glucose and lipid metabolism in inflammation-driven atherogenesis has not been fully elucidated. Herein, we investigated the association between low-grade inflammation and atherosclerosis, with joint effects of the triglyceride–glucose (TyG) index. METHODS AND RESULTS: We included data from two cohorts: the UK Biobank (UKB), a prospective study, and the Huinan cohort in Shanghai, a cross-sectional study, both with complete data from duplex ultrasounds for carotid intima-media thickness and circulating blood cell counts We identified the function of TyG as an inflammatory index and compared the risk related to atherosclerosis among different TyG levels. In total, 33,123 UKB participants (mean [SD] age 55.24 [7.58] years; 51.42% women) and 3,440 Huinan participants (mean [SD] age 70.32 [6.63] years; 58.26% women) showed increased cIMT along with higher inflammation markers including INFLA-score 0.76 [8.65], and white blood cell (WBC) count (6.58 [1.76]), after adjusting for covariates. High TyG (over the median) was associated with a higher low-grade circulating inflammation-related estimate for cIMT compared to low TyG. In UKB cohort, mediation analysis revealed that the TyG index mediated 23.36%, 10.25%, 26.30%, and 12.19% of the effects exerted by the INFLA-score, CRP, WBC count, and lymphocyte count on cIMT, respectively. CONCLUSIONS: These findings suggested that circulating inflammation status can exacerbate both subclinical and clinical atherosclerosis, with joint effects from the TyG index. This highlights the role of a balance between metabolic and inflammatory factors in atherosclerosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-025-05199-1.