Abstract 13404: Novel Sized-Based HDL Subspecies Demonstrate Inverse Associations With Incident Vascular Events

Abstract

Recent studies suggest that total high-density lipoprotein particle concentration (HDL-P) outperforms HDL cholesterol (HDL-C) in predicting atherosclerotic cardiovascular disease (ASCVD). Whether specific size-based HDL subspecies contribute to the atheroprotective effects of HDL-P remains unknown. Our objective was to assess size-based HDL subspecies for association with both incident myocardial infarction (MI) and ischemic stroke in a large, diverse cohort, expecting heterogeneous associations regarding subspecies and vascular endpoints. Participants without prior ASCVD enrolled in the Dallas Heart Study, MESA, ARIC, and PREVEND were included as a single pooled cohort (N=15,371). Seven HDL size-based subspecies were quantified by NMR (LP4 algorithm; H1=smallest; H7=largest). The primary adjudicated outcomes over an average of 8-10 years of follow up were first MI and first ischemic stroke. Cox proportional hazards models included traditional ASCVD risk factors (except HDL-C) and all seven HDL subspecies. As continuous variables, higher H1, H2 and H4 concentrations were associated with lower risk of MI (Panel A), whereas higher H2 and H4 concentrations were associated with lower risk of ischemic stroke (Panel B). The top vs bottom quartiles of H2 and H4 had 27-32% lower incidence of MI (HR Q4 vs. Q1 [95% CI]: H1 0.73 [0.58-0.91]; H2 0.69 [0.54-0.89]; H4 0.68 [0.54-0.86]) and no significant associations with ischemic stroke. Serial adjustment for HDL-C attenuated all associations with ischemic stroke. However, H1 and H4 retained significant inverse associations with MI adjusted for HDL-C (HR/SD [95% CI]: H1 0.88 [0.81-0.94]; H4 0.89 [0.82-0.97]). H1 (small HDL) and H4 (medium HDL), but no large subspecies, demonstrated inverse associations with MI in a large multi-ethnic pooled cohort. Next steps include assessment of interactions by sex and race as well as incremental clinical utility of H1 and H4 compared to both HDL-C and total HDL-P in predicting MI.