Vitamin D deficiency is common and associated with increased C-reactive protein in children and young adults with lupus: an Atherosclerosis Prevention in Pediatric Lupus Erythematosus substudy

Angela Byun Robinson, Vin Tangpricha, Eric Yow, Reut Gurion, Grace A McComsey, Laura E Schanberg, APPLE Investigators, Stacy Ardoin, Esi Morgan Dewitt, C Egla Rabinovich, Janet Ellis, Kelly Mieszkalski, Janet Wootton, Peter Chira, Joyce Hsu, Tzielan Lee, Christy Sandborg, Jan Perea, Beth Gottlieb, Patricia Irigoyen, Jennifer Luftig, Shaz Siddiqi, Zhen Ni, Marilynn Orlando, Eileen Pagano, Andrew Eichenfield, Lisa Imundo, Deborah Levy, Philip Kahn, Candido Batres, Digna Cabral, Kathleen A Haines, Yukiko Kimura, Suzanne C Li, Jennifer Weiss, Mary Ellen Riordan, Beena Vaidya, Emily von Scheven, Michelle Mietus-Snyder, Earl Silverman, Lawrence Ng, Suzanne Bowyer, Susan Ballinger, Thomas Klausmeier, Debra Hinchman, Andrea Hudgins, Marilynn Punaro, Shirley Henry, Shuzen Zhang, Nora G Singer, Elizabeth B Brooks, Stacy Miner, Nancy Szabo, Lisabeth Scalzi, David Sherry, Libby Dorfeld, Sarajane Wilson, Jenna Tress, Deborah McCurdy, Tatiana Hernandez, Jyotsna Vitale, Marisa Klein-Gitelman, Angela Kress, Nicole Lowe, Falguni Patel, Carol Wallace, Stephanie Hamilton, Richard Silver, Katie Caldwell, Diane Kamen, Linda Wagner-Weiner, Becky Puplava, Atanas Lonchev, Gloria Higgins, Monica Bacani, Hermine Brunner, Cynthia Rutherford, Jamie Meyers-Eaton, Shannen Nelson, Alexei Grom, Larry Jung, Teresa Conway, Lacey Frank, Lori Kuss, Jenny Soep, Hazel Senz, Ann Reed, Thomas Mason, Jane Jaquith, Diana E Paepke-Tollefsrud, Angela Byun Robinson, Vin Tangpricha, Eric Yow, Reut Gurion, Grace A McComsey, Laura E Schanberg, APPLE Investigators, Stacy Ardoin, Esi Morgan Dewitt, C Egla Rabinovich, Janet Ellis, Kelly Mieszkalski, Janet Wootton, Peter Chira, Joyce Hsu, Tzielan Lee, Christy Sandborg, Jan Perea, Beth Gottlieb, Patricia Irigoyen, Jennifer Luftig, Shaz Siddiqi, Zhen Ni, Marilynn Orlando, Eileen Pagano, Andrew Eichenfield, Lisa Imundo, Deborah Levy, Philip Kahn, Candido Batres, Digna Cabral, Kathleen A Haines, Yukiko Kimura, Suzanne C Li, Jennifer Weiss, Mary Ellen Riordan, Beena Vaidya, Emily von Scheven, Michelle Mietus-Snyder, Earl Silverman, Lawrence Ng, Suzanne Bowyer, Susan Ballinger, Thomas Klausmeier, Debra Hinchman, Andrea Hudgins, Marilynn Punaro, Shirley Henry, Shuzen Zhang, Nora G Singer, Elizabeth B Brooks, Stacy Miner, Nancy Szabo, Lisabeth Scalzi, David Sherry, Libby Dorfeld, Sarajane Wilson, Jenna Tress, Deborah McCurdy, Tatiana Hernandez, Jyotsna Vitale, Marisa Klein-Gitelman, Angela Kress, Nicole Lowe, Falguni Patel, Carol Wallace, Stephanie Hamilton, Richard Silver, Katie Caldwell, Diane Kamen, Linda Wagner-Weiner, Becky Puplava, Atanas Lonchev, Gloria Higgins, Monica Bacani, Hermine Brunner, Cynthia Rutherford, Jamie Meyers-Eaton, Shannen Nelson, Alexei Grom, Larry Jung, Teresa Conway, Lacey Frank, Lori Kuss, Jenny Soep, Hazel Senz, Ann Reed, Thomas Mason, Jane Jaquith, Diana E Paepke-Tollefsrud

Abstract

Objective: Epidemiological associations suggest vitamin D may play a role in inflammation and atherosclerosis. Using frozen serum and 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: Baseline APPLE serum samples were used to measure 25(OH)D levels. Logistic regression models for vitamin D deficiency [25(OH)D levels <20 ng/mL] were constructed using baseline variables collected as part of the trial, including race, season, latitude, disease duration, disease activity, high-sensitivity C-reactive protein (hsCRP), proteinuria, fasting lipids and carotid intima medial thickness (CIMT).

Results: Samples were available from 201 of 221 APPLE subjects; 61/201 (30%) had vitamin D deficiency at baseline. In univariable analysis, baseline vitamin 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 CIMT (p=0.01), LDL-cholesterol (p=0.03) and timed urine protein (p=0.03). In multivariable modelling, vitamin D deficiency was associated with age, latitude, season, minority status, proteinuria and hsCRP.

Conclusions: Vitamin D deficiency is common in paediatric lupus and is independently associated with elevated hsCRP, a marker of inflammation that predicts cardiovascular disease risk. Although association is not proof of causation, this association is novel in the paediatric SLE population and suggests that vitamin D deficiency may contribute to heightened inflammation and cardiovascular risk in this population.

Trial register number: NCT00065806.

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Source: PubMed

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