Clinical-Metabolic Risk Phenotypes and Carotid Plaque Burden Among Community-Dwelling Individuals at High Cardiovascular Risk: An Exploratory Cross-Sectional Study

Background: Community-dwelling individuals at high cardiovascular risk are clinically heterogeneous, but whether distinct clinical-metabolic phenotypes differ in carotid plaque burden remains unclear. Methods: From 4191 participants in a community-based screening project conducted in two communities in Guangzhou, 1015 individuals in the high-cardiovascular-risk stage with nonmissing high-plaque-burden status were included. All 1015 participants underwent exploratory clustering using 17 clinical, metabolic, lifestyle-related, and disease-history variables. High plaque burden was defined as bilateral carotid plaques, multiple plaques, or maximum plaque thickness at or above the 75th percentile among plaque-positive participants. Logistic regression examined associations between phenotypes and high plaque burden. Results: Among the 1015 participants included in the clustering analysis, 329 (32.4%) met the definition of high plaque burden. Four phenotypes were identified: relatively low metabolic burden, older age–ASCVD burden, smoking–low HDL-C, and blood pressure-loaded phenotypes. The corresponding prevalences of high plaque burden were 15.9%, 44.4%, 49.7%, and 33.2%. After adjustment for age and sex, all three non-reference phenotypes showed higher odds of high plaque burden. In sensitivity analysis excluding age and prior ASCVD from clustering, the blood pressure-loaded phenotype remained associated with high plaque burden. Conclusions: Four exploratory clinical-metabolic phenotypes showed different levels of carotid plaque burden among community-dwelling individuals at high cardiovascular risk. The blood pressure-loaded and smoking–low HDL-C phenotypes were associated with greater plaque burden and may provide an exploratory framework for describing heterogeneity within high-risk populations.