title: Premature atherosclerosis in pediatric systemic lupus erythematosus: risk factors for increased carotid intima-media thickness in the atherosclerosis prevention in pediatric lupus erythematosus cohort.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Duke University Medical Center, Durham, North Carolina 27710, USA. schan001@mc.duke.edu
authors.forename: Laura E
authors.initials: LE
authors.lastname: Schanberg
authors.forename: Christy
authors.initials: C
authors.lastname: Sandborg
authors.forename: Huiman X
authors.initials: HX
authors.lastname: Barnhart
authors.forename: Stacy P
authors.initials: SP
authors.lastname: Ardoin
authors.forename: Eric
authors.initials: E
authors.lastname: Yow
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Evans
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Mieszkalski
authors.forename: Norman T
authors.initials: NT
authors.lastname: Ilowite
authors.forename: Anne
authors.initials: A
authors.lastname: Eberhard
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Levy
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kimura
authors.forename: Emily
authors.initials: E
authors.lastname: von Scheven
authors.forename: Earl
authors.initials: E
authors.lastname: Silverman
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Bowyer
authors.forename: Lynn
authors.initials: L
authors.lastname: Punaro
authors.forename: Nora G
authors.initials: NG
authors.lastname: Singer
authors.forename: David D
authors.initials: DD
authors.lastname: Sherry
authors.forename: Deborah
authors.initials: D
authors.lastname: McCurdy
authors.forename: Marissa
authors.initials: M
authors.lastname: Klein-Gitelman
authors.forename: Carol
authors.initials: C
authors.lastname: Wallace
authors.forename: Richard
authors.initials: R
authors.lastname: Silver
authors.forename: Linda
authors.initials: L
authors.lastname: Wagner-Weiner
authors.forename: Gloria C
authors.initials: GC
authors.lastname: Higgins
authors.forename: Hermine I
authors.initials: HI
authors.lastname: Brunner
authors.forename: Lawrence
authors.initials: L
authors.lastname: Jung
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Soep
authors.forename: Ann
authors.initials: A
authors.lastname: Reed
mesh_terms: D000293:Adolescent; D050197:Atherosclerosis / Q000209:etiology / Q000517:prevention & control*; D001379:Azathioprine / Q000009:adverse effects; D015992:Body Mass Index; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging*; D002648:Child; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000188:drug therapy; D008297:Male; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging*; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D008074:Lipoproteins; D003404:Creatinine; D001379:Azathioprine; D011241:Prednisone