Background: Lipoprotein (a) [Lp(a)] is a molecule that induces inflammation of the blood vessels, atherogenesis, valvular calcification, and thrombosis. Methods: We review the available evidence that suggests that high Lp(a) levels are associated with a persisting risk for atherosclerotic cardiovascular diseases despite optimization of established risk factors, including low-density lipoprotein cholesterol (LDL-C) levels Observations: Approximately a quarter of the world population have Lp(a) levels of >50 mg/dL (125 nmol/L), a level associated with elevated cardiovascular risk. Lifestyle modification, statins, and ezetimibe do not effectively lower Lp(a) levels, while proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors and niacin only lower Lp(a) levels modestly. We describe clinical studies suggesting that gene silencing therapeutics, such as small interfering RNA (siRNA) and antisense oligonucleotide targeting Lp(a), offer a targeted approach with the potential for safe and robust Lp(a)- lowering with only a few doses (3-4) per year. Prospective randomized phase 3 studies are ongoing to validate safety, effectiveness in improving hard clinical outcomes, and tolerability to assess these therapies. Conclusion: Several emerging treatments with robust Lp(a)-lowering effects may significantly lower atherosclerotic cardiovascular risk.

中文翻译：

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脂蛋白 (a) 作为心血管疾病的生物标志物和降低风险的潜在新疗法

背景：脂蛋白 (a) [Lp(a)] 是一种诱导血管炎症、动脉粥样硬化、瓣膜钙化和血栓形成的分子。方法：我们回顾了现有的证据，这些证据表明，尽管优化了包括低密度脂蛋白胆固醇 (LDL-C) 水平在内的既定危险因素，但高 Lp(a) 水平与动脉粥样硬化性心血管疾病的持续风险相关。 观察结果：大约四分之一世界人口的 Lp(a) 水平>50 mg/dL (125 nmol/L)，该水平与心血管风险升高相关。生活方式改变、他汀类药物和依折麦布不能有效降低 Lp(a) 水平，而前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型 (PCSK-9) 抑制剂和烟酸只能适度降低 Lp(a) 水平。我们描述的临床研究表明，基因沉默疗法，例如针对 Lp(a) 的小干扰 RNA (siRNA) 和反义寡核苷酸，提供了一种靶向方法，只需少量剂量即可安全、稳健地降低 Lp(a)。 3-4) 每年。前瞻性随机 3 期研究正在进行中，以验证安全性、改善硬临床结果的有效性以及评估这些疗法的耐受性。结论：几种具有强大降低 Lp(a) 作用的新兴治疗方法可能会显着降低动脉粥样硬化性心血管风险。