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Background: 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].
Objectives: This is the first global (UK/US) cSLE study investigating the comparative performance of four validated CVD-risk scores.
Methods: 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 ( A therosclerosis P revention in P ediatric L upus E 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.
Results: 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<0.001). CYP with cSLE in both cohorts have been stratified based on individual CVD-risk score validated cut-offs (Table 1).
| cSLE patient cohorts stratified based on cross-validated metabolomic signatures of CIMT progression | The UCL cohort
| The APPLE cohort
|
|---|---|---|
| QRISK-3 score (N ) | 109 | 144 |
| Very low QRISK-3 risk <5% | 92 (84.4%) | 120 (83%) |
| Low QRISK-3 risk = 5-9.9% | 8 (7.3%) | 19 (13%) |
| Moderate QRISK-3 risk = 10-19.9% | 2 (1.8%) | 3 (2%) |
| High QRISK-3 risk >20% | 7 (6.4%) | 2 (1%) |
| FRS score (N ) | 80 | 144 |
| Very low FRS <5% | 80 (100%) | 144 (100%) |
| Low FRS = 5-9.9% | 0 | 0 |
| Moderate FRS =10-19.9% | 0 | 0 |
| High FRS >20% | 0 | 0 |
| ASCVD score (N ) | 62 | 99 |
| Low ASCVD risk <5% | 60 (96.8%) | 92 (93%) |
| Moderate ASCVD risk = 5-7.4% | 1 (1.6%) | 3 (3%) |
| High ASCVD risk = 7.5-20% | 1 (1.6%) | 4 (4%) |
| PDAY score (N ) | 78 | 138 |
| Very low PDAY score <2 points | 8 (7.3%) | 98 (71%) |
| Low PDAY score = 2-5 points | 29 (26.6%) | 22 (16%) |
| Moderate PDAY score = 6-10 points | 17 (21.8%) | 14 (10%) |
| High PDAY score>10 points | 34 (43.5%) | 4 (3%) |
All scores had very low performance against CVD-risk robust stratification. The PDAY-score performed best, with 67% specificity but only 50% sensitivity 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<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).
Conclusion: 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].
REFERENCES: [1] Ambrose N et al., Lupus . 2016;25:1542-1550.
[2] Groot N et al., Arthritis Rheumatol . 2019;71:290-301.
[3] Robinson GA et al., EBioMedicine. 2021 Mar;65:103243. doi: 10.1016/j.ebiom.2021.103243.
[4] Ciurtin C et al., Front Med (Lausanne ). 2022;9:814905.
[5] Schanberg LE et al., Arthritis Rheum . 2009;60:1496-507.
Acknowledgements: NIL.
Disclosure of Interests: 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.