A normotriglyceridemic, low HDL-cholesterol phenotype is characterised by elevated oxidative stress and HDL particles with attenuated antioxidative activity

Objective: Low levels of high density lipoprotein-cholesterol (HDL-C) are highly prevalent in subjects presenting premature atherosclerosis. It is indeterminate as to whether high cardiovascular risk in low HDL-C subjects occurs concomitantly with elevated oxidative stress and/or with biologically dysfunctional HDL particles. Methods and results: Systemic oxidative stress (as plasma 8-isoprostanes) was 2.3-fold elevated (p < 0.05) in normocholesterolemic, normotriglyceridemic, normoglycernic low HDL-C subjects (plasma HDL-C, <40 mg/dL; n = 8) as compared to nonnolipidemic controls (n = 15). HDL subfractions (HDL2b, 2a, 3a, 3b and 3c) isolated by density gradient ultracentrifugation from low HDL-C subjects displayed significantly lower (-21 to -43%, p < 0.05) specific antioxidative activity (sAA; capacity to protect LDL from oxidation on a unit particle mass or on a particle number basis) as compared to controls. Altered chemical composition (core triglyceride enrichment, cholesteryl ester depletion) paralleled antioxidative dysfunction of HDL subfractions. Plasma 8-isoprostane levels negatively correlated with sAA of HDL subfractions and positively correlated with the total cholesterol/HDL-C ratio, which was significantly elevated in the low HDL-C phenotype. Conclusions: Low HDL-C subjects display elevated oxidative stress and possess HDL particle subspecies with attenuated intrinsic antioxidative activity which is intimately related to their altered chemical composition. (c) 2005 Elsevier Ireland Ltd. All rights reserved.