title: Identifying and attaining LDL-C goals: mission accomplished? Next target: new therapeutic options to raise HDL-C levels.
abstract: Currently, low density lipoprotein cholesterol (LDL-C) levels are the main, if not the only, lipid target in the effort to reduce cardiovascular disease (CVD) morbidity and mortality. Several primary and secondary CVD prevention trials with statins shaped current guidelines and provided detailed targets across a range of CVD risk categories. These targets can be attained using effective statins or combination therapy. However, the net benefit in CVD risk reduction may be improved if we address other lipid risk factors. High density lipoprotein cholesterol (HDL-C) emerges from epidemiological studies as the most promising target. This review links the increase in HDL-C levels with clinical benefit from "old" (e.g. sustained release niacin) and new treatment options. Synthetically produced recombined apolipoprotein A-I Milano administered intravenously seems to have a marked effect in reducing the atheroma burden. The anti-cholesterol ester transfer protein (CETP) vaccine (CETi-1) produces auto-antibodies against CETP thus increasing the cholesterol ester content in HDL particles. CETP inhibitors (e.g. JTT-705 and torcetrapib) seem to be the most promising regimen to increase HDL-C levels. Torcetrapib (already in phase IIIa studies) can substantially increase HDL-C levels (up to 106%), alone or in combination with atorvastatin. HDL-C strategies, in combination with effective statins, are a new drug target aimed at a further reduction in CVD morbidity and mortality compared with statin monotherapy.
authors.affiliation: Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.
authors.forename: Vasilios G
authors.initials: VG
authors.lastname: Athyros
authors.forename: Dimitri P
authors.initials: DP
authors.lastname: Mikhailidis
authors.forename: Anna I
authors.initials: AI
authors.lastname: Kakafika
authors.forename: Asterios
authors.initials: A
authors.lastname: Karagiannis
authors.forename: Apostolos
authors.initials: A
authors.lastname: Hatzitolios
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tziomalos
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Ganotakis
authors.forename: Evangelos N
authors.initials: EN
authors.lastname: Liberopoulos
authors.forename: Moses
authors.initials: M
authors.lastname: Elisaf
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000378:metabolism; D008076:Cholesterol, HDL / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL