Premature atherosclerosis in pediatric systemic lupus erythematosus: risk factors for increased carotid intima-media thickness in the atherosclerosis prevention in pediatric lupus erythematosus cohort.
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.
Schanberg
Laura E
LE
Duke University Medical Center, Durham, North Carolina 27710, USA. schan001@mc.duke.edu
Sandborg
Christy
C
Barnhart
Huiman X
HX
Ardoin
Stacy P
SP
Yow
Eric
E
Evans
Gregory W
GW
Mieszkalski
Kelly L
KL
Ilowite
Norman T
NT
Eberhard
Anne
A
Levy
Deborah M
DM
Kimura
Yukiko
Y
von Scheven
Emily
E
Silverman
Earl
E
Bowyer
Suzanne L
SL
Punaro
Lynn
L
Singer
Nora G
NG
Sherry
David D
DD
McCurdy
Deborah
D
Klein-Gitelman
Marissa
M
Wallace
Carol
C
Silver
Richard
R
Wagner-Weiner
Linda
L
Higgins
Gloria C
GC
Brunner
Hermine I
HI
Jung
Lawrence
L
Soep
Jennifer B
JB
Reed
Ann
A
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
D008074:Lipoproteins; D003404:Creatinine; D001379:Azathioprine; D011241:Prednisone