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

作者：Anastasios P. Makris, Fotios Barkas, Petros Paul Sfikakis, Evangelos N. Liberopoulos, Theodosios D. Filippatos, Kausik Kumar Ray, Aris P. Agouridis · 发表于：Atherosclerosis Plus · 年份：2023 · DOI：10.1016/j.athplu.2023.09.001 · 被引用次数：39 · 研究领域：Lipoproteins and Cardiovascular Health、Atherosclerosis and Cardiovascular Diseases、Adipokines, Inflammation, and Metabolic Diseases

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 L...