Lipoprotein(a), Interleukin-6 inhibitors, and atherosclerotic cardiovascular disease: Is there an association?

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE Atherosclerosis plus Pub Date : 2023-09-09 DOI:10.1016/j.athplu.2023.09.001
Anastasios Makris , Fotios Barkas , Petros P. Sfikakis , Evangelos Liberopoulos , Theodosios D. Filippatos , Kausik K. Ray , Aris P. Agouridis
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引用次数: 1

Abstract

Background and aims

Lipoprotein(a) [Lp(a)] and interleuking-6 (IL-6), an inflammation biomarker, have been established as distinct targets of the residual atherosclerotic cardiovascular disease (ASCVD) risk. We aimed to investigate the association between them, and the potential clinical implications in ASCVD prevention.

Methods

A literature search was conducted in PubMed until December 31st, 2022, using relevant keywords.

Results

Elevated lipoprotein(a) [Lp(a)] levels constitute the most common inherited lipid disorder associated with ASCVD. Although Lp(a) levels are mostly determined genetically by the LPA gene locus, they may be altered by acute conditions of stress and chronic inflammatory diseases. Considering its resemblance with low-density lipoproteins, Lp(a) is involved in atherosclerosis, but it also exerts oxidative, thrombotic, antifibrinolytic and inflammatory properties. The cardiovascular efficacy of therapies lowering Lp(a) by >90% is currently investigated. On the other hand, interleukin (IL)-1b/IL-6 pathway also plays a pivotal role in atherosclerosis and residual ASCVD risk. IL-6 receptor inhibitors [IL-6(R)i] lower Lp(a) by 16–41%, whereas ongoing trials are investigating their potential anti-atherosclerotic effect. The Lp(a)-lowering effect of IL-6(R)i might be attributed to the inhibition of the IL-6 response elements in the promoter region of the LPA gene.

Conclusions

Although the effect of IL-6(R)i on Lp(a) levels is inferior to that of available Lp(a)-lowering therapies, the dual effect of the former on both inflammation and apolipoprotein (a) synthesis may prove of equal or even greater significance when it comes ASCVD outcomes. More trials are required to establish IL-6(R)i in ASCVD prevention and elucidate their interplay with Lp(a) as well as its clinical significance.

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脂蛋白(a)、白细胞介素-6抑制剂与动脉粥样硬化性心血管疾病:是否存在关联?
背景和目的脂蛋白(a)[Lp(a)]和白细胞介素-6(IL-6),一种炎症生物标志物,已被确定为残余动脉粥样硬化性心血管疾病(ASCVD)风险的不同靶点。我们旨在研究它们之间的关系,以及在ASCVD预防中的潜在临床意义。方法在PubMed检索相关文献,检索期至2022年12月31日。结果脂蛋白(a)[Lp(a)]水平升高是ASCVD最常见的遗传性脂质紊乱。尽管Lp(a)水平主要由LPA基因座决定,但它们可能会因急性应激和慢性炎症性疾病而改变。考虑到其与低密度脂蛋白的相似性,Lp(a)参与动脉粥样硬化,但它也具有氧化、血栓形成、抗纤溶和炎症特性。将Lp(a)降低>;90%目前正在调查中。另一方面,白细胞介素-1b/IL-6通路在动脉粥样硬化和残余ASCVD风险中也起着关键作用。IL-6受体抑制剂IL-6(R)i]可将Lp(a)降低16-41%,而正在进行的试验正在研究其潜在的抗动脉粥样硬化作用。IL-6(R)i的Lp(a)-降低作用可能归因于LPA基因启动子区中IL-6应答元件的抑制。结论尽管IL-6(R)i对Lp(a)水平的影响不如现有的Lp(a)降低疗法,但前者对炎症和载脂蛋白(a)合成的双重作用可能在ASCVD结果中具有同等甚至更大的意义。需要更多的试验来确定IL-6(R)i在ASCVD预防中的作用,并阐明它们与Lp(a)的相互作用及其临床意义。
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来源期刊
Atherosclerosis plus
Atherosclerosis plus Cardiology and Cardiovascular Medicine
CiteScore
2.60
自引率
0.00%
发文量
0
审稿时长
66 days
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