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Identifying and Attaining LDL-C Goals: Mission Accomplished? Next Target: New Therapeutic Options to Raise HDL-C Levels

机译:确定并实现LDL-C目标:任务完成了吗?下一个目标:提高HDL-C水平的新治疗选择

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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.nnThis 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.nnHDL-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.
机译:当前,低密度脂蛋白胆固醇(LDL-C)水平是主要的(即使不是唯一的)脂质靶标,可降低心血管疾病(CVD)的发病率和死亡率。使用他汀类药物进行的几项初级和次级CVD预防试验形成了当前的指南,并提供了一系列CVD风险类别的详细目标。这些目标可以使用有效的他汀类药物或联合疗法达到。但是,如果我们解决其他脂质风险因素,则可以提高降低CVD风险的净收益。流行病学研究提出了高密度脂蛋白胆固醇(HDL-C)作为最有希望的靶标。该评价将HDL-C水平的提高与“旧”(例如持续释放烟酸)和新疗法的临床获益联系起来。静脉内施用的合成产生的重组载脂蛋白A-I Milano似乎在减轻动脉粥样硬化负担方面具有显著作用。抗胆固醇酯转移蛋白(CETP)疫苗(CETi-1)产生针对CETP的自身抗体,因此增加了HDL颗粒中胆固醇酯的含量。 CETP抑制剂(例如JTT-705和torcetrapib)似乎是增加HDL-C水平的最有希望的方案。 Torcetrapib(已经在IIIa期研究中)单独或与阿托伐他汀联合使用可显着提高HDL-C水平(最高106%)。nnHDL-C策略与有效他汀类药物结合是旨在进一步降低的新药物靶标与他汀类单一疗法相比,CVD发病率和死亡率更高。

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