Schettler V J J, Ringel J, Jacob S, Julius U, Klingel R, Heigl F, Roeseler E, Grützmacher P
Center of Nephrology Göttingen GbR, Göttingen, Germany.
Center for Dialysis Potsdam, Potsdam, Germany.
Atheroscler Suppl. 2017 Nov;30:44-49. doi: 10.1016/j.atherosclerosissup.2017.05.005. Epub 2017 Jun 1.
According to current European guidelines, lipid lowering therapy for progressive cardiovascular disease including cardiovascular events has to be focused on a target level for LDL-C. In contrast for Lp(a) a threshold has to be defined with respect to the method of measurement. However, due to new lipid lowering drug developments like PCSK9-inhibitors (PCSK-9-I) a therapeutic algorithm for patients with severe hypercholesterolemia or isolated Lipoprotein(a)-hyperlipoproteinemia with progressive cardiovascular disease may be necessary to manage the use of PCSK9-I, lipoprotein apheresis (LA) or both. The therapeutic approach for patients with homozygous familial hypercholesterolemia is unambiguous: In addition to LA, in order to improve LDL-C reduction, PCSK9-I could be applied. In patients with heterozygous familial hypercholesterolemia, PCSK9-I is to be applied first. If in addition to a pronounced LDL-C elevation, cardiovascular complications exist or if imaging techniques documented atherosclerotic changes pre-disposing for a cardiovascular event while LDL-C reduction is insufficiently reduced (LDL-C > 100 mg/dl (2.6 mmol/l)), LA treatment should then be applied as last resort. In patients with elevated Lp(a) concentrations (Lp(a) > 60 mg/dl (>120 nmol/l)) and established cardiovascular disease, therapy should rely primarily on LA methods. If in addition to high Lp(a) levels insufficiently treated LDL-C concentrations (LDL-C > 100 mg/dl (2.6 mmol/l)) exist, in rare cases PCSK9-I can supplement the lipid lowering concept.
根据当前欧洲指南,针对包括心血管事件在内的进展性心血管疾病的降脂治疗必须聚焦于低密度脂蛋白胆固醇(LDL-C)的目标水平。相比之下,对于脂蛋白(a)[Lp(a)],必须根据测量方法定义一个阈值。然而,由于新型降脂药物的研发,如前蛋白转化酶枯草溶菌素9抑制剂(PCSK9-I),对于患有严重高胆固醇血症或伴有进展性心血管疾病的孤立性脂蛋白(a)-高脂蛋白血症患者,可能需要一种治疗算法来管理PCSK9-I、脂蛋白分离术(LA)或两者的使用。纯合子家族性高胆固醇血症患者的治疗方法是明确的:除了LA之外,为了提高LDL-C的降低幅度,可应用PCSK9-I。对于杂合子家族性高胆固醇血症患者,应首先应用PCSK9-I。如果除了明显的LDL-C升高外还存在心血管并发症,或者如果成像技术记录了易引发心血管事件的动脉粥样硬化改变,而LDL-C降低不充分(LDL-C>100mg/dl(2.6mmol/l)),则LA治疗应作为最后手段应用。对于Lp(a)浓度升高(Lp(a)>60mg/dl(>120nmol/l))且已确诊心血管疾病的患者,治疗应主要依靠LA方法。如果除了高Lp(a)水平外还存在未得到充分治疗的LDL-C浓度(LDL-C>100mg/dl(2.6mmol/l)),在极少数情况下,PCSK9-I可补充降脂方案。