J Clin Lipidol. 2026 Apr 9:S1933-2874(26)00104-2. doi: 10.1016/j.jacl.2026.04.005. Online ahead of print.
ABSTRACT
BACKGROUND: Autoimmune diseases are associated with increased atherosclerotic cardiovascular disease (ASCVD) risk driven by chronic systemic inflammation and prothrombotic mechanisms. Lipoprotein(a) [Lp(a)] is a causal ASCVD risk factor with proinflammatory and antifibrinolytic properties; however, its role in autoimmune diseases and the impact of immunomodulatory therapies remain unclear.
OBJECTIVE: To evaluate the consistency of Lp(a) elevation across autoimmune diseases and whether anti-inflammatory or immunomodulatory therapies modify circulating Lp(a) levels.
METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020-guided systematic review registered in International Prospective Register of Systematic Reviews (PROSPERO)(CRD420251121143) was conducted. MEDLINE and Cochrane were searched for English-language studies (1990-2025) assessing Lp(a) in adults with autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, psoriasis, Behçet's disease, and Takayasu arteritis. Two reviewers independently screened studies and assessed quality using the Newcastle-Ottawa Scale. Findings were synthesized descriptively.
RESULTS: Of 313 records, 13 studies met the inclusion criteria. Elevated Lp(a) was frequently observed, with variable outcome associations. In systemic lupus erythematosus, higher Lp(a) correlated with renal involvement and inflammatory activity, whereas cardiovascular associations were inconsistent. In rheumatoid arthritis, tumor necrosis factor inhibitor therapy did not significantly modify Lp(a). In psoriasis, Mendelian randomization supported a causal association between psoriasis and elevated Lp(a). In Takayasu arteritis and Behçet's disease, elevated Lp(a) was linked to vascular involvement. A population-based cohort demonstrated additive cardiovascular risk among individuals with autoimmune disease and elevated Lp(a).
CONCLUSION: Lp(a) elevation is common across autoimmune diseases and may contribute to excess ASCVD risk. Evidence for modification with immunomodulatory therapy is limited. Prospective studies are needed.
PMID:42067462 | DOI:10.1016/j.jacl.2026.04.005