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

Angela Byun Robinson, Vin Tangpricha, Eric Yow, Reut Gurion, Laura E Schanberg, Grace A McComsey, 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, Laura E Schanberg, Grace A McComsey, 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 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.

Keywords: Cardiovascular Disease; Childhood/paediatric lupus; Inflammation; Systemic Lupus Erythematosus.

Figures

Figure 1
Figure 1
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.

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Source: PubMed

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