Vitamin D status is a determinant of atorvastatin effect on carotid intima medial thickening progression rate in children with lupus: An Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) substudy

• Type of Material: Article
• Authors: Angela Byun Robinson, Rainbow Babies and Children's Hospital; Vin Tangpricha, Emory University; Eric Yow, Duke Clinical Research Institute; Reut Gurion, Rainbow Babies and Children's Hospital; Laura E. Schanberg, Duke University; Grace A. McComsey, Case Medical Center
• Language: English
• Date: 2014-06-01
• Publisher: BMJ Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © 2014 BMJ Publishing Group Ltd & Lupus Foundation of America.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/lupus-2014-000037
• Title of Journal or Parent Work: Lupus Science & Medicine
• ISSN: 2053-8790
• Volume: 1
• Issue: 1
• Start Page: e000037
• End Page: e000037
• Grant/Funding Information: This publication was made possible by the Clinical and Translational Science Collaborative of Cleveland, UL1TR000439 from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research.; APPLE is supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases contract N01-AR-2-2265), the Edna and Fred L. Mandel Jr. Center for Hypertension and Atherosclerosis and Pfizer, which provided atorvastatin and matching placebo.; Secondary analysis was supported by the Rainbow Babies and Children's Hospital Pediatrics Pilot Award and the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases contract 5P30-AR-047363-12).
• Keywords: Cardiovascular Disease; Childhood/paediatric lupus; Inflammation; Systemic Lupus Erythematosus; Pediatrics

Abstract

Objective: Epidemiological associations suggest that vitamin D status may play a role in inflammation and progression of atherosclerosis. Using frozen serum, carotid intima medial thickness (CIMT) measurements and other existing data from the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we assessed interactions between serum 25-hydroxyvitamin D (25(OH)D), atorvastatin randomisation and CIMT progression rate. Methods: Participants in the 3-year APPLE trial were randomised to placebo or atorvastatin and CIMT progression rate was measured. Baseline frozen serum was used to measure 25(OH)D concentrations. Mixed effect longitudinal models for CIMT progression at 3 years were used to evaluate interaction between vitamin D deficiency (serum 25(OH)D <20 ng/mL) at baseline and atorvastatin or placebo treatment, adjusting for key systemic lupus erythematosus disease variables and cardiovascular risk factors. Results: 201/221 APPLE participants had available samples and were included in this analysis; 61/201 (30%) had vitamin D deficiency at baseline. In adjusted longitudinal modelling, there was significant interaction between baseline vitamin D deficiency and atorvastatin randomisation in 3-year progression of mean-max CIMT. In four out of six carotid segments, there was a greater decrease in mean-max CIMT progression rate in subjects who were treated with atorvastatin compared with placebo if they had baseline serum 25(OH)D levels ≥20 ng/mL. Conclusions: Subjects with serum 25(OH)D ≥20 ng/mL had less mean-max CIMT progression following 3 years of atorvastatin treatment. Results from secondary analyses must be interpreted cautiously, but findings suggest that underlying vitamin D deficiency may be involved in response to atorvastatin in atherosclerosis prevention.