Metabolically Abnormal Obesity and Carotid Plaque Vulnerability: A Vessel Wall MRI Study Linking Obesity Phenotypes to Atherosclerotic Instability.

Background: Carotid plaque vulnerability, driven by metabolic dysfunction and obesity, is a critical determinant of ischemic stroke risk. However, the heterogeneity of obesity phenotypes-defined by metabolic health-remains underexplored in cardiovascular risk stratification. Therefore, this study employs high-resolution magnetic resonance vessel wall imaging to assess differences in high-risk carotid plaque features among obesity subtypes stratified by metabolic dysfunction and body mass index.

Methods: This multicenter, cross-sectional study of 1037 Chinese adults with symptomatic carotid atherosclerosis utilized magnetic resonance vessel wall imaging to assess differences in high-risk carotid plaque features-intraplaque hemorrhage (IPH), lipid-rich necrotic core, and fibrous cap rupture-across 4 obesity phenotype subgroups: metabolically healthy normal weight (MHNW), metabolically abnormal normal weight, metabolically healthy obese (MHO), and metabolically abnormal obese (MAO).

Results: Of 1037 eligible patients, the proportion of patients in MHNW, metabolically abnormal normal weight, MHO, and MAO groups was 51.6% (n=535), 6.9% (n=72), 16.7% (n=173), and 24.8% (n=257), respectively. Both prevalences of high-risk carotid plaque (22.5% versus 16.6% in MHNW; P=0.002) and IPH (17.1% versus 10.1% in MHNW; P<0.001) in the MAO group were higher than those in the MHNW and MHO groups (all P<0.05). The MHO group exhibited plaque stability similar to MHNW, whereas metabolically abnormal normal weight had greater maximum wall thickness (P=0.004) than MHO and higher IPH prevalence than MHNW (P=0.054). Several carotid plaque morphological variables significantly differed among the 4 groups (all P<0.05). In further adjusted logistic regression models, MAO was independently associated with IPH (P=0.015), alongside male sex, advanced age, and antihypertensive agent use.

Conclusions: This study redefines the role of obesity in atherosclerosis by prioritizing metabolic health over body mass index, demonstrating that MAO is independently associated with IPH and exhibits elevated high-risk carotid plaque/IPH prevalence versus MHNW/MHO. The robustness of IPH as a metabolic instability indicator warrants particular attention.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02017756.