Premature atherosclerosis in pediatric systemic lupus erythematosus: risk factors for increased carotid intima-media thickness in the atherosclerosis prevention in pediatric lupus erythematosus cohort
Laura E Schanberg, Christy Sandborg, Huiman X Barnhart, Stacy P Ardoin, Eric Yow, Gregory W Evans, Kelly L Mieszkalski, Norman T Ilowite, Anne Eberhard, Deborah M Levy, Yukiko Kimura, Emily von Scheven, Earl Silverman, Suzanne L Bowyer, Lynn Punaro, Nora G Singer, David D Sherry, Deborah McCurdy, Marissa Klein-Gitelman, Carol Wallace, Richard Silver, Linda Wagner-Weiner, Gloria C Higgins, Hermine I Brunner, Lawrence Jung, Jennifer B Soep, Ann Reed, Atherosclerosis Prevention in Pediatric Lupus Erythematosus Investigators, Esi Morgan Dewitt, C Egla Rabinovich, Janet Ellis, Janet Wootton, Peter Chira, Joyce Hsu, Tzielan Lee, Jan Perea, Beth Gottlieb, Patricia Irigoyen, Jennifer Luftig, Shaz Siddiqi, Zhen Ni, Marilynn Orlando, Eileen Pagano, Andrew Eichenfield, Lisa F Imundo, Philip Kahn, Candido Batres, Digna Cabral, Kathleen Haines, Suzanne C Li, Jennifer Weiss, Mary Ellen Riordan, Beena Vaidya, Michelle Mietus-Snyder, Lawrence Ng, Susan Ballinger, Thomas Klausmeier, Debra Hinchman, Andrea Hudgins, Shirley Henry, Shuzen Zhang, Elizabeth B Brooks, Stacy Miner, Nancy Szabo, Libby Dorfeld, Sarajane Wilson, Tatiana Hernandez, Jyotsna Vitale, Angela Kress, Nicole Lowe, Falguni Patel, Stephanie Hamilton, Katie Caldwell, Diane Kamen, Becky Puplava, Atanas Lonchev, Monica Bacani, Cynthia Rutherford, Jamie Meyers-Eaton, Teresa Conway, Lacey Frank, Lori Kuss, Hazel Senz, Thomas Mason, Jane Jaquith, Diana Paepke-Tollefsrud, Laura E Schanberg, Christy Sandborg, Huiman X Barnhart, Stacy P Ardoin, Eric Yow, Gregory W Evans, Kelly L Mieszkalski, Norman T Ilowite, Anne Eberhard, Deborah M Levy, Yukiko Kimura, Emily von Scheven, Earl Silverman, Suzanne L Bowyer, Lynn Punaro, Nora G Singer, David D Sherry, Deborah McCurdy, Marissa Klein-Gitelman, Carol Wallace, Richard Silver, Linda Wagner-Weiner, Gloria C Higgins, Hermine I Brunner, Lawrence Jung, Jennifer B Soep, Ann Reed, Atherosclerosis Prevention in Pediatric Lupus Erythematosus Investigators, Esi Morgan Dewitt, C Egla Rabinovich, Janet Ellis, Janet Wootton, Peter Chira, Joyce Hsu, Tzielan Lee, Jan Perea, Beth Gottlieb, Patricia Irigoyen, Jennifer Luftig, Shaz Siddiqi, Zhen Ni, Marilynn Orlando, Eileen Pagano, Andrew Eichenfield, Lisa F Imundo, Philip Kahn, Candido Batres, Digna Cabral, Kathleen Haines, Suzanne C Li, Jennifer Weiss, Mary Ellen Riordan, Beena Vaidya, Michelle Mietus-Snyder, Lawrence Ng, Susan Ballinger, Thomas Klausmeier, Debra Hinchman, Andrea Hudgins, Shirley Henry, Shuzen Zhang, Elizabeth B Brooks, Stacy Miner, Nancy Szabo, Libby Dorfeld, Sarajane Wilson, Tatiana Hernandez, Jyotsna Vitale, Angela Kress, Nicole Lowe, Falguni Patel, Stephanie Hamilton, Katie Caldwell, Diane Kamen, Becky Puplava, Atanas Lonchev, Monica Bacani, Cynthia Rutherford, Jamie Meyers-Eaton, Teresa Conway, Lacey Frank, Lori Kuss, Hazel Senz, Thomas Mason, Jane Jaquith, Diana Paepke-Tollefsrud
Abstract
Objective: To evaluate risk factors for subclinical atherosclerosis in a population of patients with pediatric systemic lupus erythematosus (SLE).
Methods: In a prospective multicenter study, a cohort of 221 patients underwent baseline measurements of carotid intima-media thickness (CIMT) as part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial. SLE disease measures, medications, and traditional risk factors for atherosclerosis were assessed. A standardized protocol was used to assess the thickness of the bilateral common carotid arteries and the mean maximal IMT of 12 segments. Univariable analysis identified potential associations with CIMT, which were examined in multivariable linear regression modeling.
Results: Based on the mean-mean common or the mean-max CIMT as the dependent variable, univariable analysis showed significant associations of the following variables with increased CIMT: increasing age, longer SLE duration, minority status, higher body mass index (BMI), male sex, increased creatinine clearance, higher lipoprotein(a) level, proteinuria, azathioprine treatment, and prednisone dose. In multivariable modeling, both azathioprine use (P=0.005 for the mean-mean model and P=0.102 for the mean-max model) and male sex (P<0.001) were associated with increases in the mean-max CIMT. A moderate dosage of prednisone (0.15-0.4 mg/kg/day) was associated with decreases in the mean-max CIMT (P=0.024), while high-dose and low-dose prednisone were associated with increases in the mean-mean common CIMT (P=0.021) and the mean-max CIMT (P=0.064), respectively. BMI (P<0.001) and creatinine clearance (P=0.031) remained associated with increased mean-mean common CIMT, while increasing age (P<0.001) and increasing lipoprotein(a) level (P=0.005) were associated with increased mean-max CIMT.
Conclusion: Traditional as well as nontraditional risk factors were associated with increased CIMT in this cohort of patients in the APPLE trial. Azathioprine treatment was associated with increased CIMT. The relationship between CIMT and prednisone dose may not be linear.
Trial registration: ClinicalTrials.gov NCT00065806.
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Source: PubMed