Department of Pharmacological and Biomolecular Sciences "Rodolfo Paoletti", Università Degli Studi di Milano, Milan, Italy.
Section of Diabetes and Metabolism, Pederzoli Hospital, Peschiera Del Garda, Verona, Italy.
Nutr Metab Cardiovasc Dis. 2023 Oct;33(10):1866-1877. doi: 10.1016/j.numecd.2023.07.019. Epub 2023 Jul 19.
In view of the consolidating evidence on the causal role of Lp(a) in cardiovascular disease, the Italian Society for the Study of Atherosclerosis (SISA) has assembled a consensus on Lp(a) genetics and epidemiology, together with recommendations for its measurement and current and emerging therapeutic approaches to reduce its plasma levels. Data on the Italian population are also provided.
Lp(a) is constituted by one apo(a) molecule and a lipoprotein closely resembling to a low-density lipoprotein (LDL). Its similarity with an LDL, together with its ability to carry oxidized phospholipids are considered the two main features making Lp(a) harmful for cardiovascular health. Plasma Lp(a) concentrations vary over about 1000 folds in humans and are genetically determined, thus they are quite stable in any individual. Mendelian Randomization studies have suggested a causal role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis and observational studies indicate a linear direct correlation between cardiovascular disease and Lp(a) plasma levels. Lp(a) measurement is strongly recommended once in a patient's lifetime, particularly in FH subjects, but also as part of the initial lipid screening to assess cardiovascular risk. The apo(a) size polymorphism represents a challenge for Lp(a) measurement in plasma, but new strategies are overcoming these difficulties. A reduction of Lp(a) levels can be currently attained only by plasma apheresis and, moderately, with PCSK9 inhibitor treatment.
Awaiting the approval of selective Lp(a)-lowering drugs, an intensive management of the other risk factors for individuals with elevated Lp(a) levels is strongly recommended.
鉴于脂蛋白(a)(Lp(a))在心血管疾病中具有因果作用的证据不断增多,意大利动脉粥样硬化研究学会(SISA)就 Lp(a)遗传学和流行病学达成了共识,同时提出了 Lp(a)测量的建议以及目前和新兴的降低其血浆水平的治疗方法。本文还提供了意大利人群的数据。
Lp(a)由一个载脂蛋白(a)(apo(a))分子和一个类似于低密度脂蛋白(LDL)的脂蛋白组成。其与 LDL 的相似性以及携带氧化磷脂的能力被认为是使 Lp(a)对心血管健康有害的两个主要特征。人类血浆 Lp(a)浓度差异约为 1000 倍,且由遗传决定,因此在任何个体中都相当稳定。孟德尔随机化研究表明 Lp(a)与动脉粥样硬化性心血管疾病(ASCVD)和主动脉瓣狭窄之间存在因果关系,观察性研究表明心血管疾病与 Lp(a)血浆水平之间存在线性直接相关性。建议在患者的一生中,特别是在 FH 患者中,对 Lp(a)进行一次测量,但也作为初始血脂筛查的一部分,以评估心血管风险。apo(a)大小多态性是血浆中 Lp(a)测量的一个挑战,但新的策略正在克服这些困难。目前只能通过血浆清除术,以及中等程度地通过 PCSK9 抑制剂治疗来降低 Lp(a)水平。
在等待批准选择性 Lp(a)降低药物的同时,强烈建议对 Lp(a)水平升高的个体进行其他危险因素的强化管理。