Abstract 4142745: Lipoprotein(a) distribution across autoimmune inflammatory diseases: a pooled analysis from 28 Phase III clinical trials

Background: Lipoprotein(a) [Lp(a)] is largely determined by genetic factors and is associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). Real-world evidence is limited due to low rates of Lp(a) testing, and little is known regarding the Lp(a) distributions in diseases beyond ASCVD, including autoimmune inflammatory diseases. Methods: This cross-sectional study identified adult patients with available Lp(a) levels at baseline (before randomization) from 28 Phase III randomized clinical trials across autoimmune inflammatory diseases: rheumatoid arthritis (RA), psoriasis, psoriatic arthritis (PA), and ankylosing spondylitis (AS). Individuals from clinical trials for ASCVD were used as the reference group. Multivariable logistic regression analysis was performed to assess whether patients with certain autoimmune diseases were more likely to have Lp(a) ≥30mg/dL (≥75nmol/L) compared with ASCVD. Results: We identified 12,799 adults from RA (1287, 10%), psoriasis (5578, 44%), PA (1928, 15%), AS (1146, 9%), and ASCVD (2860, 22%) trials. Overall, the mean age (SD) was 50.4 (14.6) years, 41% female, 2.7% Black individuals, 15.2% Asian individuals, 37.7% history of ever smoking, and 77.8% with diabetes. Lp(a)>=30mg/dL was most common among those with RA (57%), followed by PA (46%), ASCVD (43%), AS (42%) and psoriasis (39%). A consistent Lp(a) distribution across diseases was seen for Lp(a)≥50mg/dL (Figure). Adjusting for age, sex, race, BMI, diabetes, total cholesterol, lipid lowering therapies and C-reactive protein (CRP), patients with RA and PA were 72% and 39% more likely to have Lp(a)>=30mg/dL compared with ASCVD (p<0.05). CRP was also significantly associated with Lp(a)>=30mg/dL: Odds Ratio (OR) = 1.07 (1.05 – 1.10), p<0.0002). Conclusion: In this pooled analysis of Phase III trials, increased levels of Lp(a) were observed among patients with RA, psoriasis, PA and AS with patients with RA and PA more likely to have Lp(a)≥30mg/dL than patients with ASCVD. Future research with longitudinal Lp(a) levels is important to clarify the interplay between inflammation, Lp(a), and ASCVD risk, especially in autoimmune diseases associated with increased Lp(a) levels.