Association of Lipoprotein(a) with cardiovascular events among individuals with autoimmune conditions

Abstract

Background: Autoimmune conditions are associated with systemic inflammation, which elevates the risk of major adverse cardiovascular events (MACE). Systemic inflammation can increase plasma lipoprotein(a) [Lp(a)] levels by activating the interleukin-6 response element within the LPA gene promoter region. However, the association between elevated plasma Lp(a) and MACE risk in individuals with autoimmune conditions remains unclear.

Methods: We analyzed data from 353,035 UK Biobank participants without cardiovascular disease, including 11,229 individuals with autoimmune conditions such as systemic lupus erythematosus, rheumatoid arthritis, psoriasis, multiple sclerosis, and others. Cox proportional hazards regression models and Kaplan-Meier survival curves assessed the association between elevated Lp(a) (≥125 nmol/L), autoimmune status, and time to MACE (myocardial infarction, stroke, cardiovascular death).

Results: Over a median follow-up of 14 years, 19,091 MACEs occurred. Autoimmune conditions (HR, 1.30; 95 % CI, 1.20-1.41; P < 0.001) and elevated Lp(a) (HR, 1.24; 95 % CI, 1.18-1.30; P < 0.001) were independently associated with increased MACE risk. The interaction between autoimmune conditions and elevated Lp(a) was not significant (p = 0.40). Compared to participants with neither risk factor, those with both autoimmune conditions and elevated Lp(a) had the highest MACE risk (HR, 1.77; 95 % CI, 1.46-2.15; P < 0.001). Elevated MACE risk was also observed in individuals with only elevated Lp(a) (HR, 1.23; 95 % CI, 1.17-1.29; P < 0.001) or only autoimmune conditions (HR, 1.28; 95 % CI, 1.18-1.40; P < 0.001).

Conclusion: Autoimmune disease status and elevated Lp(a) level have an independent and additive joint association with MACE risk. This may have implications for Lp(a) lowering therapy use in high-risk primary prevention populations.

Keywords: Autoimmunity; Cardiovascular events; Lipoprotein(a).