摘要
脂蛋白(a)[Lp(a)]是与载脂蛋白B连接的另外的载脂蛋白载脂蛋白(a),[apo(a)]的低密度脂蛋白(LDL)样颗粒。最近流行病学和孟德尔随机化研究 提供了证据表明Lp(a)与动脉粥样硬化和心血管疾病(CVD)的发病机制有因果关系。 Lp(a)浓度和CVD之间的风险关联仍然是有争议的,但似乎是连续的,且没有明显的阈值Lp(a)水平。Lp(a)的循环浓度是遗传决定的; 理想水平<50mg / dl。 血浆浓度为60 mg / dl与其他心血管危险因素调整后的冠状动脉心脏病的优势比约为1.5。 延长释放烟酸是降低Lp(a)水平升高(约20-30%)的一种选择,但通常耐受性差。膳食措施,运动和降脂药物如他汀类药物和依泽替米贝没有显着疗效。在严重性CVD和非常高的Lp(a)水平的患者中,脂蛋白单采血液成分可以降低Lp(a)浓度。该方法对于大多数患者而言是昂贵的和不切实际的,其可行性主要取决于医疗保险系统。由于没有确定的治疗方法可以降低Lp(a)而不影响其他脂蛋白,所以没有任何试验评估是否可以减少Lp(a)浓度提高为临床益处。最近,针对apo(a),IONIS-APO(a)Rx的反义寡核苷酸已经显示出选择性地将Lp(a)降低了近80%。 这项药物的第二阶段研究已于2015年底完成,预期结果将很快公布。
关键词: 反义寡核苷酸,载脂蛋白(a),心血管疾病,脂蛋白(a),脂蛋白单采血浆。
Current Medicinal Chemistry
Title:Lipoprotein(a) Management: Pharmacological and Apheretic Treatment
Volume: 24 Issue: 10
关键词: 反义寡核苷酸,载脂蛋白(a),心血管疾病,脂蛋白(a),脂蛋白单采血浆。
摘要: Lipoprotein (a) [Lp(a)] is a low-density lipoprotein (LDL)-like particle with an additional apolipoprotein, apolipoprotein (a), [apo(a)] attached to apolipoprotein B. Recent epidemiologic and Mendelian randomization studies have provided evidence that Lp(a) is causally related to the pathogenesis of atherosclerosis and cardiovascular disease (CVD). The risk association between Lp(a) concentrations and CVD is still controversial but seems to be continuous and without an obvious threshold Lp(a) level. Circulating concentrations of Lp(a) are genetically determined; desirable levels are < 50 mg/dl. A plasma concentration of 60 mg/dl is associated with an odds ratio for coronary heart disease of about 1.5 after adjustment for other cardiovascular risk factors. Extended-release niacin is an option for decreasing elevated Lp(a) levels (by ~20-30%) but it is often poorly tolerated. Dietary measures, exercise and lipid-lowering drugs such as statins and ezetimibe are without significant effect. In patients with severe progressive CVD and very high Lp(a) levels, lipoprotein apheresis can decrease Lp(a) concentrations. The method is expensive and impractical for most patients and its feasibility depends mainly on the healthcare reimbursement system. Since no established treatment reduces Lp(a) without influencing other lipoproteins, there has been no trial that evaluated whether decreasing Lp(a) concentrations translates to clinical benefits. Recently, an antisense oligonucleotide against apo(a), IONIS-APO(a)Rx, has been shown to selectively decrease Lp(a) by almost 80%. A phase 2 study with this drug has been completed in late 2015 and results are expected to be published soon.
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Cite this article as:
Lipoprotein(a) Management: Pharmacological and Apheretic Treatment, Current Medicinal Chemistry 2017; 24 (10) . https://dx.doi.org/10.2174/0929867324666170112110928
DOI https://dx.doi.org/10.2174/0929867324666170112110928 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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