Inflammation
Interleukin-6 receptor inhibitors lower Lp(a) by 16-41%, less than dedicated Lp(a) drugs but with an added anti-inflammatory effect, a review (Atheroscler Plus 2023)
Original title: Lipoprotein(a), Interleukin-6 inhibitors, and atherosclerotic cardiovascular disease: Is there an association?
This review examines the relationship between Lp(a), the most common inherited lipid disorder, and interleukin-6 (IL-6), a key driver of residual atherosclerotic cardiovascular disease (ASCVD) risk alongside inflammation. Although Lp(a) levels are largely determined by the LPA gene locus, acute stress and chronic inflammatory disease can alter them. IL-6 receptor inhibitors lower Lp(a) by 16-41%, an effect attributed to inhibition of IL-6 response elements in the LPA gene promoter, though this is smaller than the reductions of over 90% achieved by dedicated Lp(a)-lowering therapies now in development. The authors argue that the dual anti-inflammatory and Lp(a)-lowering effect of IL-6 receptor inhibitors could prove equally or more clinically significant for ASCVD outcomes, warranting further trials to establish their role in prevention.
Original 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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.