Inflammation
Lp(a) may be the mechanistic bridge between inflammation and excess cardiovascular risk in rheumatoid arthritis, review argues, with IL-6 blockade as a lever (J Clin Lipidol 2025)
Original title: Lipoprotein(a) at the crossroads of inflammation and atherosclerosis in rheumatoid arthritis: A narrative review
This narrative review synthesises observational, mechanistic, genetic and treatment-trial evidence on lipoprotein(a) in rheumatoid arthritis (RA), a disease whose markedly elevated cardiovascular risk is not fully explained by traditional risk factors. RA patients frequently show elevated Lp(a), particularly during active systemic inflammation, and Lp(a) is linked to subclinical atherosclerosis, arterial stiffness and cardiovascular events in RA independent of conventional lipids, acting through arterial wall retention, oxidised phospholipid carriage, endothelial activation and impaired fibrinolysis. The review highlights interleukin-6 as a driver of Lp(a) metabolism in RA, providing a biological rationale for the Lp(a)-lowering effect seen with IL-6 receptor blockade, and notes that standardised assays, LPA genetic insights and emerging RNA-based therapies are renewing interest in Lp(a) as both biomarker and treatment target in this population.
Original abstract
Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with a markedly increased risk of cardiovascular disease (CVD) that is not fully explained by traditional risk factors. Lipoprotein(a) [Lp(a)], a genetically determined lipoprotein with proatherogenic, prothrombotic, and proinflammatory properties, has emerged as a potential contributor to this excess cardiovascular burden. Growing evidence suggests that Lp(a) may represent a mechanistic link between chronic inflammation, immune dysregulation, and accelerated atherosclerosis in RA.
Sources Of Material: This narrative review synthesizes evidence from observational studies, mechanistic research, genetic analyses, biomarker investigations, and emerging therapeutic trials examining Lp(a) in RA. Relevant literature was identified through comprehensive searches of major biomedical databases, with emphasis on studies addressing pathophysiology, cardiovascular outcomes, disease activity, and treatment effects on Lp(a).
Abstract Of Findings: RA patients frequently exhibit elevated Lp(a) levels, particularly in the presence of active systemic inflammation. Lp(a) contributes to vascular injury through enhanced arterial wall retention, carriage of oxidized phospholipids, endothelial activation, and impaired fibrinolysis. Clinical studies associate elevated Lp(a) with subclinical atherosclerosis, arterial stiffness, and increased cardiovascular events in RA, independent of conventional lipid parameters. Inflammatory cytokines, particularly interleukin-6 (IL-6), appear to modulate Lp(a) metabolism, providing a biological rationale for the Lp(a)-lowering effects observed with IL-6 receptor blockade. Advances in standardized assays, genetic insights into LPA polymorphisms, and novel RNA-based therapies have revitalized interest in Lp(a) as both a biomarker and therapeutic target in RA.
Conclusion: Lp(a) occupies a critical intersection between inflammation and atherosclerosis in RA. Incorporating Lp(a) into cardiovascular risk stratification and exploring targeted therapies may enable more precise, integrated management of cardiovascular risk in RA patients, warranting dedicated prospective studies.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.