Abstract

Introduction: While high-density lipoprotein (HDL) cholesterol is a component of metabolic syndrome, an ASCVD risk factor, other markers of HDL metabolism better associate with ASCVD. However, it is unclear whether these markers better discriminate between metabolic health and obese groups. Hypothesis: We hypothesized that higher cholesterol efflux capacity (CEC) and a favorable HDL profile would be associated with metabolically healthy profiles within each weight category. Methods: Data from the second phase of the Dallas Heart Study were used to classify participants (n=2156) into four groups based on a harmonized definition of metabolic health and obesity status: Metabolically Healthy, Normal Weight (MHNW); Metabolically Unhealthy, Normal Weight (MUNW); Metabolically Healthy, Obese (MHO); Metabolically Unhealthy, Obese (MUO). MU was classified as having one or more of the following: elevated blood pressure (SBP/DBP ≥130/85 mmHg), fasting glucose (≥100 mg/dL), or fasting triglycerides (≥150 mg/dL); a history of CVD or diabetes; or any medications for these conditions. Obesity was defined as BMI ≥ 30kg/m 2 . CEC was measured using J774 macrophages, BODIPY- and radio-labeled cholesterol, and apoB-precipitated plasma. HDL particle (HDL-P) subfractions were quantified by NMR spectroscopy. Generalized linear models were used to compare paired means of CEC and HDL traits between groups controlling for age, sex, race, and smoking. Results: Small HDL-P concentration was higher in MU groups regardless of weight status. Total and medium HDL-P concentrations and radio-labeled CEC were higher in NW groups, regardless of metabolic health status. Mean HDL-P size and large HDL-P concentrations were different across all groups, with the rank order being MHNW, MUNW, MHO, MUO (Table 1). Conclusions: In conclusion, associations between HDL subfractions, CEC and metabolic/weight status are heterogeneous, highlighting the complexity of HDL physiology as it pertains to body weight and metabolic disease.

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