脂蛋白(a)治疗现状及最新研究方向

丽敏 赵(内蒙古医科大学研究生院，中国)
兴胜 赵(内蒙古自治区人民医院，中国)

摘要

脂蛋白（a）是心血管疾病的独立危险因素，是低密度脂蛋白胆固醇优化后，残余心血管风险的重要原因。传统的治疗方法，如生活方式的改变没有达到预期的疗效；他汀类药物治疗不仅不会降低脂蛋白（a）水平，甚至还会使其升高；烟酸虽可降低脂蛋白（a）水平，但无降低心血管风险的作用。新型的治疗方式，如前蛋白转化酶枯草溶菌素9抑制剂、反义寡核苷酸、靶向脂蛋白（a）的小干扰核苷酸，不仅可降低脂蛋白（a）水平，还在降低心血管风险方面具有重要意义。论文主要针对脂蛋白（a）升高的治疗研究进展进行阐述。

关键词

脂蛋白（a）；前蛋白转化酶枯草溶菌素9抑制剂；脂蛋白分离术；反义寡核苷酸；小干扰核苷酸

参考

Tsimikas S, Moriarty PM, Stroes ES. Emerging RNA therapeutics to lower blood levels of Lp (a): JACC Focus Seminar 2/4[J]. Journal of the American College of Cardiology, 2021, 77(12): 1576-1589.

Jawi MM, Frohlich J, Chan SY. Lipoprotein(a) the Insurgent: A New Insight into the Structure, Function, Metabolism, Pathogenicity, and Medications Affecting Lipoprotein(a) Molecule[J]. Journal of lipids, 2020(2020): 3491764-3491790.

Chemello K, Chan D C, Lambert G, et al. Recent advances in demystifying the metabolism of lipoprotein (a)[J]. Atherosclerosis, 2022(349): 82-91.

McCormick SPA, Schneider WJ. Lipoprotein (a) catabolism: a case of multiple receptors[J]. Pathology, 2019, 51(2): 155-164.

李建军.脂蛋白(a)与心血管疾病风险关系及临床管理的专家科学建议[J].中国循环杂志,2021,36(12):1158-1167.

Welsh P, Welsh C, Celis-Morales CA, et al. Lipoprotein(a) and cardiovascular disease: prediction, attributable risk fraction, and estimating benefits from novel interventions[J]. European journal of preventive cardiology, 2020, 28(18): 1991-2000.

Littmann K, Hagström E, Häbel H, et al. Plasma lipoprotein(a) measured in the routine clinical care is associated to atherosclerotic cardiovascular disease during a 14-year follow-up[J]. European journal of preventive cardiology, 2021, 28(18): 2038-2047.

Pottle A, Thompson G, Barbir M, et al. Corrigendum to “Lipoprotein apheresis efficacy, challenges and outcomes: A descriptive analysis from the UK Lipoprotein Apheresis Registry, 1989–2017”[J]. Atherosclerosis, 2019(290): 44-51.

Zhao L, Gao Y, Liu G, et al. Lipoprotein apheresis in patients with familial hypercholesterolemia: a single center research[J]. Zhonghua xin xue guan bing za zhi, 2022, 50(6): 585-590.

Sahebkar A, Reiner Ž, Simental-Mendía LE, et al. Effect of extended-release niacin on plasma lipoprotein(a) levels: A systematic review and meta-analysis of randomized placebo-controlled trials[J]. Metabolism, 2016, 65(11): 1664-1678.

Parish S, Hopewell JC, Hill MR, et al. Impact of Apolipoprotein(a) Isoform Size on Lipoprotein(a) Lowering in the HPS2-THRIVE Study[J]. Circulation. Genomic and precision medicine, 2018, 11(2): e001696-e001705.

Cegla J, Neely RDG, France M, et al. Corrigendum to “HEART UK consensus statement on Lipoprotein(a): A call to action”[J]. Atherosclerosis, 2019, 291: 62-70.

Tsimikas S, Gordts PLSM, Nora C, et al. Statin therapy increases lipoprotein(a) levels[J]. European heart journal, 2020, 41(24): 2275-2284.

De Boer LM, Oorthuys AOJ, Wiegman A, et al. Statin therapy and lipoprotein(a) levels: A systematic review and meta-analysis[J].Eur J Prev Cardiol, 2022, 29(5): 779-792.

O'Donoghue ML, Fazio S, Giugliano RP, et al. Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk[J]. Circulation, 2019, 139(12): 1483-1492.

Bittner VA, Szarek M, Aylward PE, et al. Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome[J]. Journal of the American College of Cardiology, 2020, 75(2): 133-144.

Watts GF, Chan DC, Pang J, et al. PCSK9 Inhibition with alirocumab increases the catabolism of lipoprotein(a) particles in statin-treated patients with elevated lipoprotein(a)[J]. Metabolism, 2020, 107(prepublish): 154221-154229.

Fitzgerald K, Kallend D, Simon A. A Highly Durable RNAi Therapeutic Inhibitor of PCSK9[J]. The New England journal of medicine, 2017, 376(18): e38-e48.

Ray KK, Landmesser U, Leiter LA, et al. Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol[J]. The New England journal of medicine, 2017, 376(15): 1430-1440.

Reeskamp LF, Kastelein JJP, Moriarty PM, et al. Safety and efficacy of mipomersen in patients with heterozygous familial hypercholesterolemia[J]. Atherosclerosis, 2018, 280: 109-117.

DOI: http://dx.doi.org/10.12345/yzlcyxzz.v6i7.13348