Metabolically unhealthy normal weight is associated with subclinical carotid atherosclerosis: cross-sectional and longitudinal evidence from a Chinese health examination cohort

Background and aims Whether metabolically unhealthy normal weight (MUNW) is associated with subclinical carotid atherosclerosis (SCAS) and how its risk compares with that of metabolically unhealthy overweight/obesity (MUO) remain uncertain, particularly in longitudinal analyses and across age groups. Methods A cross-sectional sample (n = 26,202) and a longitudinal subcohort (n = 4,938) were derived from a health examination database; all participants in the longitudinal subcohort were free of SCAS at baseline. Participants were classified into four metabolic-obesity phenotypes based on body mass index and metabolic health status: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obesity (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obesity (MUO). SCAS was defined as carotid intima-media thickness ≥1.0 mm and/or carotid plaque. Results Compared with metabolically healthy normal weight (MHNW), MUNW was associated with increased odds of prevalent SCAS (OR 1.55, 95% CI 1.30–1.84) and increased risk of incident SCAS (HR 1.69, 95% CI 1.12–2.56). Compared with MUO, MUNW showed a numerically higher risk estimate for prevalent SCAS, although the difference was not statistically significant (OR 1.11, 95% CI 0.93–1.32, P = 0.247); a similar pattern was observed for incident SCAS (HR 1.25, 95% CI 0.83–1.91, P = 0.290). Metabolically healthy overweight/obesity (MHO) was associated with prevalent but not incident SCAS (OR 1.10, 95% CI 1.02–1.20; HR 1.14, 95% CI 0.94–1.38). A significant phenotype-by-age interaction was observed ( P = 0.029); among adults aged <50 years, MUNW was associated with more than twofold higher odds of prevalent SCAS (OR 2.33, 95% CI 1.39–3.76). Findings were consistent in sensitivity analyses excluding covariates overlapping with phenotype definitions and in plaque-restricted analyses. Conclusions MUNW was associated with increased odds of prevalent SCAS and a higher hazard of incident SCAS after multivariable adjustment, with numerically higher risk estimates than MUO, although direct comparisons did not reach statistical significance.