Duality of statin action on lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome over time: Quantity versus quality

Abstract

Aim: Statins impact the metabolism, concentrations, composition and function of circulating lipoproteins. Time course relationships between statin-mediated reduction in atherogenic apoB-containing particles and dynamic intravascular remodelling of apoAI-containing lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome (MetS) were evaluated. Insulin-resistant, hypertriglyceridemic, hypercholesterolemic, obese males (n=12) were treated with pitavastatin (4mg/day) and response evaluated at 6, 42 and 180 days. Reduction in LDL-cholesterol, apoB and triglycerides (TG) was essentially complete at 42 days (-38, -32, and -35% respectively); rapid reduction equally occurred in remnant cholesterol, apoCII, CIII and E levels (day 6; -35, -50, -23 and -26% respectively). Small dense LDL predominated at baseline and was markedly reduced on treatment (-45% vs total LDL). CETP activity and mass decreased progressively (-18 and -16% respectively); concomitantly, TG depletion (up to -49%) and cholesteryl ester (CE) enrichment occurred in all HDL particle subpopulations with normalization of CE/TG mass ratio at 180 days. ApoAI was redistributed from LpAI to LpAIAII particles in HDL2a and HDL3a subpopulations; apoCIII was preferentially depleted from LpAIAII-rich particles on treatment. Overall, statin action exhibits duality in mixed dyslipidemia, as CETP-mediated normalization of the HDL CE/TG core lags markedly behind subacute reduction in elevated levels of atherogenic apoB-containing lipoproteins. Normalisation of the HDL neutral lipid core is consistent with enhanced atheroprotective function. The HDL CE/TG ratio constitutes a metabolomic marker of perturbed HDL metabolism in insulin-resistant states, equally allowing monitoring of statin impact on HDL metabolism, structure and function.