Schanberg, L. E. et al. 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 Rheum. 60, 1496-1507

Duke University Medical Center, Durham, North Carolina 27710, USA.
Arthritis & Rheumatology (Impact Factor: 7.76). 05/2009; 60(5):1496-507. DOI: 10.1002/art.24469
Source: PubMed


To evaluate risk factors for subclinical atherosclerosis in a population of patients with pediatric systemic lupus erythematosus (SLE).
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.
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.
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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    • "A 3-year randomized, double-blind, placebo-controlled clinical trial of atorvastatin in cSLE suggests male gender (P <0.001), higher body mass index (P <0.001), decreased creatinine clearance (P = 0.031), older age (P <0.001), and azathioprine use (P = 0.005 to 0.0102) all to be positively associated with an increased burden of sub-clinical coronary artery disease as measured by carotid intima-media thickening [39]. Notably, moderate prednisone doses (0.15 to 0.4 mg/kg/day) were associated with fewer abnormal carotid intima-media thickening measurements (P = 0.024), and there was a trend towards slowed progression of subclinical atherosclerosis over time [40]. "
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