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.
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.


BACKGROUND
NCT00065806.
Department of Pediatrics , Rainbow Babies and Children's Hospital/Case Medical Center , Cleveland, Ohio , USA.
Angela Byun
AB
Robinson
Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine and Atlanta VA Medical Center, Atlanta, Georgia, USA.
Vin
0000-0002-4021-5853
V
Tangpricha
Duke Clinical Research Institute , Durham, North Carolina , USA.
Eric
E
Yow
Department of Pediatrics , Rainbow Babies and Children's Hospital/Case Medical Center , Cleveland, Ohio , USA.
Reut
R
Gurion
Department of Pediatrics , Duke University Medical Center , Durham, North Carolina , USA.
Laura E
LE
Schanberg
Department of Medicine and Pediatrics , Case Medical Center , Cleveland, Ohio , USA.
Grace A
GA
McComsey
Cardiovascular Disease; Childhood/paediatric lupus; Inflammation; Systemic Lupus Erythematosus