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Abstract 18720: HDL Particle Subclasses, Rosuvastatin Therapy, and Risk of Vascular Events: An Analysis From the JUPITER Trial


 Background:
 In the JUPITER trial, total HDL particle concentration (HDL-P) performed better that HDL-cholesterol (HDL-C) in predicting residual vascular risk. It is uncertain whether biological heterogeneity of HDL particle subclasses relates to differential vascular risk in the setting of statin therapy.
 
 
 Methods:
 We analyzed data from JUPITER (NCT00239681) in which participants with LDL-C <130 mg/dL and hsCRP ≥2 mg/L were randomized to 20mg/day of rosuvastatin vs placebo. HDL subclass concentrations were measured and categorized into 5 groups (very large, large, medium, small, and very small) by NMR spectroscopy (LipoScience, NC [now LapCorp]) in 12,487 participants before and 1 year after randomization.
 
 
 Results:
 A total of 308 first vascular events (MI, stroke, revascularization, unstable angina, CVD death) occurred during maximum follow-up of 5.0 (median, 1.9) years. For baseline risk, multivariable adjusted Cox regression models demonstrated that the baseline concentrations of all HDL subclasses were inversely associated with incident vascular events (Table), with statistically significant associations for large HDL (adjusted HR per SD: 0.85, 95% CI, 0.76-0.95) and medium HDL (HR 0.89, 95% CI 0.80-0.98) even after mutually adjusting for the other HDL subclasses. By contrast, among rosuvastatin-allocated participants, on-treatment concentrations of very large HDL subclasses were associated with an increased risk of residual risk of vascular events (adjusted HR per SD: 1.65, 95% CI, 1.02-2.66).
 
 
 Conclusion:
 In JUPITER participants, baseline levels of HDL subclasses were inversely associated with the risk of incident vascular events with significant associations for the large and medium particles. However, on-statin levels of very large HDL particles were significantly associated with an increased risk of vascular events.
 
 
 
