Abstract 14630: Elevated CETP Activity is Associated With Low, Dysfunctional HDL in High Cardiovascular Risk South Asians
Background and Rationale: Low HDL in South Asians (SA) contribute greatly to their high coronary heart disease (CHD) risk relative to European Caucasians (EC), however, the cause of low HDL in SA is unknown. Here we investigated whether cholesteryl-ester transfer protein (CETP) plays a role in mediating low HDL in SA.
Methods: Serum was obtained from metabolically well characterized individuals of SA and EC descent (N=244 and 238, respectively) and measured for CETP activity. HDL lipid and protein contents were quantified and HDL size and particle number were measured via NMR. The capacity of HDL to mediate cholesterol efflux was assessed in J774 macrophages with apoB-depleted patient serum.
Results: CETP activity was elevated in SA compared with EC (26.5±0.45 vs. 18.5±0.45 pmol/uL/hr, P< 0.0001). HDL from SA was pro-atherogenic - that is, triglyceride-enriched, cholesteryl ester-depleted, reduced in apoAI and smaller in size than in EC (P< 0.05 for all). SA HDL, moreover, showed a reduced capacity to mediate macrophage cholesterol efflux (by 20%, P< 0.0001), even in a subset of younger SA (<40 years, P<0.01). Composition and size changes in HDL were independent predictors of carotid artery intima-media thickness (IMT) in SA (P< 0.05).
Conclusions: We have identified for the first time a mechanism to account for low HDL in SA. Elevated CETP in SA was associated with triglyceride-enriched, cholesteryl ester-depleted HDL, smaller in size and reduced in apoA-I content, producing HDL that is less stable in the circulation and less atheroprotective. This was confirmed with the lower relative capacity of HDL from SA to mediate cellular cholesterol efflux and independent correlation of their HDL compositional changes with carotid IMT.
Author Disclosures: M. Melone: None. S. Rashid: None.
- © 2015 by American Heart Association, Inc.