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 & 7 others Richard Silver, Linda Wagner-Weiner, Gloria C. Higgins, Hermine I. Brunner, Lawrence Jung, Jennifer B. Soep, Ann Reed

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1496-1507
Number of pages12
JournalArthritis and Rheumatism
Volume60
Issue number5
DOIs
StatePublished - May 2009

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Carotid Intima-Media Thickness
Systemic Lupus Erythematosus
Atherosclerosis
Pediatrics
Prednisone
Azathioprine
Lipoprotein(a)
Creatinine
Body Mass Index
Common Carotid Artery
Proteinuria
Multicenter Studies
Linear Models

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Premature atherosclerosis in pediatric systemic lupus erythematosus : Risk factors for increased carotid intima-media thickness in the atherosclerosis prevention in pediatric lupus erythematosus cohort. / Schanberg, Laura E.; Sandborg, Christy; Barnhart, Huiman X.; Ardoin, Stacy P.; Yow, Eric; Evans, Gregory W.; Mieszkalski, Kelly L.; Ilowite, Norman T.; Eberhard, Anne; Levy, Deborah M.; Kimura, Yukiko; Von Scheven, Emily; Silverman, Earl; Bowyer, Suzanne L.; Punaro, Lynn; Singer, Nora G.; Sherry, David D.; McCurdy, Deborah; Klein-Gitelman, Marissa; Wallace, Carol; Silver, Richard; Wagner-Weiner, Linda; Higgins, Gloria C.; Brunner, Hermine I.; Jung, Lawrence; Soep, Jennifer B.; Reed, Ann.

In: Arthritis and Rheumatism, Vol. 60, No. 5, 05.2009, p. 1496-1507.

Research output: Contribution to journalArticle

Schanberg, LE, Sandborg, C, Barnhart, HX, Ardoin, SP, Yow, E, Evans, GW, Mieszkalski, KL, Ilowite, NT, Eberhard, A, Levy, DM, Kimura, Y, Von Scheven, E, Silverman, E, Bowyer, SL, Punaro, L, Singer, NG, Sherry, DD, McCurdy, D, Klein-Gitelman, M, Wallace, C, Silver, R, Wagner-Weiner, L, Higgins, GC, Brunner, HI, Jung, L, Soep, JB & Reed, A 2009, 'Premature atherosclerosis in pediatric systemic lupus erythematosus: Risk factors for increased carotid intima-media thickness in the atherosclerosis prevention in pediatric lupus erythematosus cohort', Arthritis and Rheumatism, vol. 60, no. 5, pp. 1496-1507. https://doi.org/10.1002/art.24469
Schanberg, Laura E. ; Sandborg, Christy ; Barnhart, Huiman X. ; Ardoin, Stacy P. ; Yow, Eric ; Evans, Gregory W. ; Mieszkalski, Kelly L. ; Ilowite, Norman T. ; Eberhard, Anne ; Levy, Deborah M. ; Kimura, Yukiko ; Von Scheven, Emily ; Silverman, Earl ; Bowyer, Suzanne L. ; Punaro, Lynn ; Singer, Nora G. ; Sherry, David D. ; McCurdy, Deborah ; Klein-Gitelman, Marissa ; Wallace, Carol ; Silver, Richard ; Wagner-Weiner, Linda ; Higgins, Gloria C. ; Brunner, Hermine I. ; Jung, Lawrence ; Soep, Jennifer B. ; Reed, Ann. / Premature atherosclerosis in pediatric systemic lupus erythematosus : Risk factors for increased carotid intima-media thickness in the atherosclerosis prevention in pediatric lupus erythematosus cohort. In: Arthritis and Rheumatism. 2009 ; Vol. 60, No. 5. pp. 1496-1507.
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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.",
author = "Schanberg, {Laura E.} and Christy Sandborg and Barnhart, {Huiman X.} and Ardoin, {Stacy P.} and Eric Yow and Evans, {Gregory W.} and Mieszkalski, {Kelly L.} and Ilowite, {Norman T.} and Anne Eberhard and Levy, {Deborah M.} and Yukiko Kimura and {Von Scheven}, Emily and Earl Silverman and Bowyer, {Suzanne L.} and Lynn Punaro and Singer, {Nora G.} and Sherry, {David D.} and Deborah McCurdy and Marissa Klein-Gitelman and Carol Wallace and Richard Silver and Linda Wagner-Weiner and Higgins, {Gloria C.} and Brunner, {Hermine I.} and Lawrence Jung and Soep, {Jennifer B.} and Ann Reed",
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TY - JOUR

T1 - Premature atherosclerosis in pediatric systemic lupus erythematosus

T2 - Risk factors for increased carotid intima-media thickness in the atherosclerosis prevention in pediatric lupus erythematosus cohort

AU - Schanberg, Laura E.

AU - Sandborg, Christy

AU - Barnhart, Huiman X.

AU - Ardoin, Stacy P.

AU - Yow, Eric

AU - Evans, Gregory W.

AU - Mieszkalski, Kelly L.

AU - Ilowite, Norman T.

AU - Eberhard, Anne

AU - Levy, Deborah M.

AU - Kimura, Yukiko

AU - Von Scheven, Emily

AU - Silverman, Earl

AU - Bowyer, Suzanne L.

AU - Punaro, Lynn

AU - Singer, Nora G.

AU - Sherry, David D.

AU - McCurdy, Deborah

AU - Klein-Gitelman, Marissa

AU - Wallace, Carol

AU - Silver, Richard

AU - Wagner-Weiner, Linda

AU - Higgins, Gloria C.

AU - Brunner, Hermine I.

AU - Jung, Lawrence

AU - Soep, Jennifer B.

AU - Reed, Ann

PY - 2009/5

Y1 - 2009/5

N2 - 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.

AB - 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.

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