Background/Purpose: Epidemiologic associations suggest vitamin D may play a role in inflammation and progression of atherosclerosis. Using frozen serum, carotid intima medial thickness (CIMT) measurements, and other data from the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we assessed associations between 25-hydroxyvitamin D [25(OH)D] and measures of systemic lupus erythematosus (SLE) disease activity and cardiovascular risk.

Methods: Participants in the 3-year APPLE trial were randomized to placebo or atorvastatin and CIMT progression was measured. Serum collected at baseline and 1 year was used to measure 25(OH)D levels. Logistic regression models for vitamin D deficiency [25(OH)D levels < 20 ng/mL] at baseline were constructed to evaluate univariable and multivariable associations with baseline variables. Variables collected as part of the APPLE trial included (1) known risk factors for vitamin D deficiency, (2) SLE-specific factors including duration of illness, disease activity, high sensitivity C-reactive protein (hsCRP), and proteinuria, and (3) traditional cardiovascular risk factors including fasting lipids and baseline CIMT.

Results: 201/221 APPLE subjects had available samples and were included in the analysis; 61/201 (30%) had vitamin D deficiency at baseline. There was no change in 25(OH)D levels after 1 year of atorvastatin or placebo. In univariable analysis, baseline 25(OH)D deficiency was associated with season (p < 0.01), minority status (p < 0.01), body mass index (p = 0.04), duration of SLE (p < 0.01), SLICC damage index (p = 0.04), hsCRP (p < 0.01), mean-max IMT (p = 0.01), LDL-cholesterol (p = 0.03), and timed urine protein (p = 0.03). In multivariable modeling, vitamin D deficiency was associated with age, latitude, season, minority status, proteinuria, and hsCRP (see Table).

Conclusion: Vitamin D deficiency is common in pediatric lupus and is independently associated with elevated hsCRP, a marker of inflammation which predicts higher general cardiovascular disease risk. Observed association differences between univariable and multivariable modeling may be related to confounding or loss of power and requires further study. The association between vitamin D deficiency and hsCRP is novel in the SLE population and suggests that vitamin D deficiency may independently contribute to heightened inflammation and cardiovascular risk in this population.

Grant support: ClinicalTrials.gov identifier: NCT00065806. APPLE supported by the NIH (NIAMS 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 supported by the Rainbow Babies and Children’s Hospital Pediatrics Pilot Award, and the NIH (NIAMS contract 5P30-AR-047363-12).

Table. Logistic modeling of vitamin D deficiency (25OHD < 20ng/mL)

	Odds ratio	95% CI	P-value
Age	1.28	1.09, 1.50	0.002
Latitude	0.87	0.76, 0.99	0.034
Season    1st quarter    2nd quarter    3rd quarter	2.83 1.23 0.57	0.87, 9.23 0.45, 3.36 0.19, 1.75	0.084 0.685 0.327
Minority status	17.47	5.22, 58.48	<0.001
Log timed urine proteinuria	2.47	0.96, 6.34	0.060
Log hsCRP	1.40	1.07, 1.83	0.015

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/vitamin-d-deficiency-is-common-and-associated-with-increased-c-reactive-protein-in-children-with-lupus-an-atherosclerosis-prevention-in-pediatric-lupus-erythematosus-substudy/