POS0133 POOR PERFORMANCE OF VALIDATED CARDIOVASCULAR RISK SCORES IN CHILDHOOD-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS - FIRST EVALUATION OF A GLOBAL US/UK COHORT
Authors: C. Ciurtin, J. Peng, Y. Gao, M. Niwa, S. Ardoin, L. Schanberg, L. Lewandowski, E. Jury, G. Robinson
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Childhood-onset systemic lupus erythematosus (cSLE) is associated with increased cardiovascular disease (CVD)-risk starting early in life. This led to 4% of children and young people (CYP) with cSLE experiencing CVD-events after 4 years[1] and 10.6% after 15 years[2] of follow-up. Carotid intima-media thickness (CIMT) is one of the best predictors of CVD-risk across the life span. CVD-risk assessment guidelines recommend the evaluation of various traditional CVD-risk factors and use of CVD-risk scores (rather than vascular scans) for stratified management approaches[3]. <h3>Objectives:</h3> This is the first global (UK/US) cSLE study investigating the comparative performance of four validated CVD-risk scores. <h3>Methods:</h3> Patient data, CVD-risk factors, cSLE characteristics were collected from two cSLE cohorts: a retrospective UCL (University College London) (N=109, UK) and a prospective APPLE (<b>A</b>therosclerosis <b>P</b>revention in <b>P</b>ediatric <b>L</b>upus <b>E</b>rythematosus) trial (N=121, US) cohort, stratified based on cross-validated metabolomic signatures of high CIMT progression, as previously published by our group[4,5]. QRISK-3, Framingham (FRS), Atherosclerotic Cardiovascular Disease (ASCVD) scores (validated for age 20-25) and the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) score (validated from age ≥ 14) were calculated and assessed for performance against robust CVD-risk stratification in both cohorts. We used descriptive statistics, area under the curve (AUC), correlation and linear regression analyses. <h3>Results:</h3> Mean patient age/disease duration for the UCL/APPLE cohorts were 26 ± 4.18 years/13.5± 4.71 years, and 15.60 ± 2.67 years/2.46± 2.44 years, respectively (P&lt;0.001). CYP with cSLE in both cohorts have been stratified based on individual CVD-risk score validated cut-offs (Table 1). All scores had very low performance against CVD-risk robust stratification. The PDAY-score performed best, with 67% <i>specificity</i> but only 50% <i>sensitivity</i> in correctly classifying CYP with high CVD-risk in the UCL cohort, and correlated with individuals' age, disease duration, median SLEDAI/SLICC scores (r=0.78, 0.48, 0.28 and 0.3, respectively, P&lt;0.05). Linear regression analysis found that age/disease activity were the strongest determinants of PDAY-score (one year increase in age/one point increase in median SLEDAI-2K score over the disease course were associated with 1.13/0.41 points increase in PDAY-score, respectively, when sex/disease duration/damage/lipid levels/steroids were accounted for). <h3>Conclusion:</h3> Overall disease activity and age were the strongest predictors of PDAY-score but only in the slightly older cSLE cohort. CVD-risk scores, even if validated for ages ≥14, do not adequately capture CVD-risk in cSLE. PDAY-score performed moderately well for young adults only, highlighting the need for better CVD-risk stratification tools in cSLE, especially for younger patients[3]. <h3>REFERENCES:</h3> [1] Ambrose N et al., <i>Lupus</i>. 2016;25:1542-1550. [2] Groot N et al., <i>Arthritis Rheumatol</i>. 2019;71:290-301. [3] Robinson GA et al., <i>EBioMedicine.</i> 2021 Mar;65:103243. doi: 10.1016/j.ebiom.2021.103243. [4] Ciurtin C et al., <i>Front Med (Lausanne</i>). 2022;9:814905. [5] Schanberg LE et al., <i>Arthritis Rheum</i>. 2009;60:1496-507. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Coziana Ciurtin Novartis, UCB, GSK, Junjie Peng: None declared, Yiming Gao: None declared, Misato Niwa: None declared, Stacy Ardoin: None declared, Laura Schanberg: None declared, Laura Lewandowski: None declared, Elizabeth Jury GSK, George Robinson: None declared.