Posted 16 January 2008 - 05:49 AM
Here's my guess. Zetia lowers dense HDL too.
Curr Med Res Opin. 2007 May;23(5):1169-76.
Effect of ezetimibe monotherapy on the concentration of lipoprotein subfractions in patients with primary dyslipidaemia.
Kalogirou M, Tsimihodimos V, Gazi I, Filippatos T, Saougos V, Tselepis AD, Mikhailidis DP, Elisaf M.
Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.
BACKGROUND: Recent studies suggest that the distribution of lipoprotein subfractions is an independent predictor of vascular events. Therefore, we evaluated the effect of ezetimibe (a selective cholesterol transport inhibitor) on the concentrations of lipoprotein subfractions in patients with primary dyslipidaemia. MATERIALS AND METHODS: Patients (n = 50) with primary dyslipidaemias were recruited. The concentrations of the individual lipoprotein subfractions were measured using the Lipoprint system at baseline and after 16 weeks of treatment. RESULTS: Ezetimibe reduced total, low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (HDL-C) values as well as apolipoprotein B concentrations. Subfractionation of apolipoprotein B-containing lipoproteins showed that the reduction in LDL-C values was due to a fall in the concentrations of all LDL subfractions. However, a more pronounced trend towards a decrease in the concentrations of dense LDL subfractions was observed. Patients with triglyceride values >1.7 mmol/L had significantly greater reductions in the concentrations of small, dense LDL particles compared with those with normal triglyceride levels (49 vs. 19%, respectively; p < 0.05). Ezetimibe decreased the concentrations of HDL-C mainly due to a fall in the concentration of dense HDL subfractions. CONCLUSION: Ezetimibe can favourably affect the distribution of LDL subfractions, especially in patients with elevated triglyceride values. Further studies are needed to clarify the significance of the ezetimibe-induced reduction in the concentrations of dense HDL particles.
PMID: 17519084
Nat Clin Pract Cardiovasc Med. 2006 Mar;3(3):144-53.
Antiatherogenic small, dense HDL--guardian angel of the arterial wall?
Kontush A, Chapman MJ.
National Institute for Health and Medical Research (INSERM), Unité 551, Hôpital de la Pitié, Paris, France. kontush@chups.jussieu.fr
Our understanding of the relationship between the atheroprotective activities of HDL and heterogeneity of HDL particles has advanced greatly. HDL particles are highly heterogeneous in structure, intravascular metabolism and antiatherogenic activity. In this review, we discuss new findings on the antiatherogenic properties of HDL particles. Small, dense HDL possesses potent antioxidative activity but this is compromised under conditions of atherogenic dyslipidemia. HDL functional deficiency frequently coincides with reductions in HDL-cholesterol concentration and alterations in HDL metabolism and structure. Formation of small, dense HDL particles with attenuated antiatherogenic activity can be mechanistically related to HDL enrichment in triglycerides and in serum amyloid A, depletion of cholesteryl esters, covalent modification of HDL apolipoproteins and attenuated antiatherogenic function of apolipoprotein AI. Low circulating levels of HDL cholesterol might, therefore, be associated with the defective functionality of small HDL particles of abnormal structure and composition. In common metabolic diseases, such as type 2 diabetes and metabolic syndrome, deficiency of HDL particle number and function favor accelerated atherosclerosis. Therapeutic normalization of the quantity, quality and biological activities of HDL particles thus represents a novel approach to attenuating atherosclerosis in dyslipidemic individuals with metabolic disease. Cholesteryl ester transfer protein inhibitors, nicotinic acid, reconstituted HDL and other HDL-raising agents are being investigated. Induction of selective increase in the circulating concentrations of small, dense HDL3 particles with increased antiatherogenic activity seems especially promising, particularly for therapy of atherogenic dyslipidemia.
PMID: 16505860
