Trial reportArthritis & rheumatology (Hoboken, N.J.)2024
Atherosclerosis Progression in the APPLE Trial Can Be Predicted in Young People With Juvenile-Onset Systemic Lupus Erythematosus Using a Novel Lipid Metabolomic Signature.
Trial report in Arthritis & rheumatology (Hoboken, N.J.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Insights into the pathogenesis of childhood-onset SLE in the past decade.Nature reviews. Rheumatology · 2026Review
- Systemic lupus erythematosus-driven accelerated atherosclerosis: the immune-metabolic-vascular axis and therapeutic implications.Frontiers in immunology · 2026Review
- Machine learning and multi-omics technologies for precision cardiovascular medicine: advancing diagnosis, risk prediction, and therapeutic guidance.Frontiers in cardiovascular medicine · 2026Review
- Gut microbiota and metabolism in systemic lupus erythematosus: from dysbiosis to targeted interventions.European journal of medical research · 2025Review
- Serum untargeted metabolomics alterations in systemic lupus erythematosus patients with elevated serum ferritin.Scientific reports · 2025Article
- Subclinical Atherosclerosis Risk Can Be Predicted in Female Patients With Systemic Lupus Erythematosus Using Metabolomic Signatures: An Observational Study.Journal of the American Heart Association · 2025Observational
- Dyslipidemia and metabolic syndrome in childhood-onset systemic lupus erythematosus: is it time to screen?Lipids in health and disease · 2024Article
- Active implementation of low disease activity state as a treatment endpoint in childhood-onset systemic lupus erythematosus in routine practice is both feasible and associated with better outcomes.Clinical rheumatology · 2024Article
- Learning from serum markers reflecting endothelial activation: longitudinal data in childhood-onset systemic lupus erythematosus.Lupus science & medicine · 2024Article
- The past 25 years in paediatric rheumatology: insights from monogenic diseases.Nature reviews. Rheumatology · 2024Review
- Investigation of the performance of validated cardiovascular risk scores in a global (UK/US) cohort of young people with childhood-onset systemic lupus erythematosus.Lupus science & medicine · 2024Article
- Systemic lupus in the era of machine learning medicine.Lupus science & medicine · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
objectivePatients with juvenile-onset systemic lupus erythematosus (JSLE) have increased atherosclerosis risk. This study investigated novel atherosclerosis progression biomarkers in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, the largest investigator-led randomized control trial of atorvastatin versus placebo for atherosclerosis progression in JSLE, using carotid intima-media thickness (CIMT) as the primary outcome.
methodsUnsupervised clustering of baseline CIMT and CIMT progression over 36 months was used to stratify patients with JSLE. Disease characteristics, cardiovascular risk scores, and baseline serum metabolome were investigated in CIMT-stratified patients. Machine learning techniques were used to identify and validate a serum metabolomic signature of CIMT progression.
resultsBaseline CIMT stratified patients with JSLE (N = 151) into three groups with distinct high, intermediate, and low CIMT trajectories irrespective of treatment allocation, despite most patients having low cardiovascular disease risk based on recommended assessment criteria. In the placebo group (n = 60), patients with high versus low CIMT progression had higher total (P = 0.001) and low-density lipoprotein (LDL) (P = 0.002) cholesterol levels, although within the reference range. Furthermore, a robust baseline metabolomic signature predictive of high CIMT progression was identified in the placebo arm (area under the curve, 80.7%). Patients treated with atorvastatin (n = 61) had reduced LDL cholesterol levels after 36 months, as expected; however, despite this, 36% still had high atherosclerosis progression, which was not predicted by metabolomic biomarkers, suggesting nonlipid drivers of atherosclerosis in JSLE with management implications for this subset of patients.
conclusionSignificant baseline heterogeneity and distinct subclinical atherosclerosis progression trajectories exist in JSLE. Metabolomic signatures can predict atherosclerosis progression in some patients with JSLE with relevance for clinical trial stratification.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.