Limits...
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.

Robinson AB, Tangpricha V, Yow E, Gurion R, Schanberg LE, McComsey GA, APPLE Investigato - Lupus Sci Med (2014)

Bottom Line: 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.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.NCT00065806.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics , Rainbow Babies and Children's Hospital/Case Medical Center , Cleveland, Ohio , USA.

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.

Trial registration number: NCT00065806.

No MeSH data available.


Related in: MedlinePlus

Forest plot of CIMT progression rate for atorvastatin treatment versus placebo for 3 years by baseline serum 25-hydroxyvitamin D status. Multivariable mixed effects longitudinal modelling adjusted for lupus duration, female gender, systolic blood pressure, pubertal level, LDL cholesterol and hsCRP. VitD, serum 25-hydroxyvitamin D status, ng/mL; CIMT, carotid intima medial thickness, in mm; hsCRP, high-sensitivity C reactive protein; LDL, low-density lipoprotein. p Values for the interaction effect are listed in parentheses on the y-axis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4225736&req=5

LUPUS2014000037F1: Forest plot of CIMT progression rate for atorvastatin treatment versus placebo for 3 years by baseline serum 25-hydroxyvitamin D status. Multivariable mixed effects longitudinal modelling adjusted for lupus duration, female gender, systolic blood pressure, pubertal level, LDL cholesterol and hsCRP. VitD, serum 25-hydroxyvitamin D status, ng/mL; CIMT, carotid intima medial thickness, in mm; hsCRP, high-sensitivity C reactive protein; LDL, low-density lipoprotein. p Values for the interaction effect are listed in parentheses on the y-axis.

Mentions: In unadjusted longitudinal modelling, baseline vitamin D deficiency was associated with increased baseline mean-max CIMT (p=0.01). Other baseline associations between vitamin D deficiency and cardiovascular risk factors were detailed in a previous paper.23 In adjusted longitudinal modelling, there was a significant interaction effect between baseline vitamin D deficiency and atorvastatin treatment in 3-year progression of mean-max CIMT (see table 2 and figure 1). In four out of six carotid segments, there was a greater decrease in mean-max CIMT progression rate in subjects treated with atorvastatin compared with placebo if they had baseline 25(OH)D levels ≥20 ng/mL. In only one of six carotid segments, there was a greater decrease in mean-mean CIMT progression rate in those treated with atorvastatin with sufficient vitamin D levels. Of the subjects who changed in vitamin D status from deficient to either insufficient or sufficient at 1 year into the trial, there was a trend towards response to atorvastatin treatment in 3-year CIMT progression, but this did not reach statistical significance.


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.

Robinson AB, Tangpricha V, Yow E, Gurion R, Schanberg LE, McComsey GA, APPLE Investigato - Lupus Sci Med (2014)

Forest plot of CIMT progression rate for atorvastatin treatment versus placebo for 3 years by baseline serum 25-hydroxyvitamin D status. Multivariable mixed effects longitudinal modelling adjusted for lupus duration, female gender, systolic blood pressure, pubertal level, LDL cholesterol and hsCRP. VitD, serum 25-hydroxyvitamin D status, ng/mL; CIMT, carotid intima medial thickness, in mm; hsCRP, high-sensitivity C reactive protein; LDL, low-density lipoprotein. p Values for the interaction effect are listed in parentheses on the y-axis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4225736&req=5

LUPUS2014000037F1: Forest plot of CIMT progression rate for atorvastatin treatment versus placebo for 3 years by baseline serum 25-hydroxyvitamin D status. Multivariable mixed effects longitudinal modelling adjusted for lupus duration, female gender, systolic blood pressure, pubertal level, LDL cholesterol and hsCRP. VitD, serum 25-hydroxyvitamin D status, ng/mL; CIMT, carotid intima medial thickness, in mm; hsCRP, high-sensitivity C reactive protein; LDL, low-density lipoprotein. p Values for the interaction effect are listed in parentheses on the y-axis.
Mentions: In unadjusted longitudinal modelling, baseline vitamin D deficiency was associated with increased baseline mean-max CIMT (p=0.01). Other baseline associations between vitamin D deficiency and cardiovascular risk factors were detailed in a previous paper.23 In adjusted longitudinal modelling, there was a significant interaction effect between baseline vitamin D deficiency and atorvastatin treatment in 3-year progression of mean-max CIMT (see table 2 and figure 1). In four out of six carotid segments, there was a greater decrease in mean-max CIMT progression rate in subjects treated with atorvastatin compared with placebo if they had baseline 25(OH)D levels ≥20 ng/mL. In only one of six carotid segments, there was a greater decrease in mean-mean CIMT progression rate in those treated with atorvastatin with sufficient vitamin D levels. Of the subjects who changed in vitamin D status from deficient to either insufficient or sufficient at 1 year into the trial, there was a trend towards response to atorvastatin treatment in 3-year CIMT progression, but this did not reach statistical significance.

Bottom Line: 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.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.NCT00065806.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics , Rainbow Babies and Children's Hospital/Case Medical Center , Cleveland, Ohio , USA.

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.

Trial registration number: NCT00065806.

No MeSH data available.


Related in: MedlinePlus