Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


CD146 Endothelial Progenitor Cell Number Increases Following 36 Months of Atorvastatin Therapy in Children and Adolescents with SLE: The Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Cohort.

Ardoin1,  Stacy P., Povsic2,  Thomas, Schanberg3,  Laura E., Sandborg4,  Christy I., Barnhart5,  Huiman, Yow5,  Eric, Evans6,  Greg

Ohio State University, Columbus, OH
Childrens Hospital of New York, Columbia University Medical Center, New York, NY
Pediatrics, Hackensack, NJ
Hospital for Sick Children, Toronto, ON
James Whitcomb Riley Hospital, Indianapolis, IN
Texas Scottish Rite Hospital, Dallas, TX
Director, Division of Rheumatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH
Children's Hospital of Philadelphia, Philadelphia, PA
Mattel Children's Hospital, University of California, Los Angeles, Los Angeles, CA
Children's Memorial Hospital, Chicago, IL
Childrens Hosp & Regional Med, Seattle, WA
Duke University, Durham, NC
MUSC, Charleston, SC
University of Chicago Hospital, Chicago, IL
Nationwide Childrens Hosp, Columbus, OH
Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Duke University Medical Center, Durham, NC
Stanford University, Palo Alto, CA
Duke Clinical Research Institute, Durham, NC
Winston-Salem, NC
Children's Hospital Montefiore, Bronx, NY
UC San Francisco, San Francisco, CA
Cohen Children's Hospital Medical Center, New Hyde Park, NY

Background/Purpose:

Endothelial progenitor cells (EPCs) promote endothelial repair, and their number and function are reduced in adult SLE. In the general population, statins decrease cardiovascular (CV) mortality, reduce EPC apoptosis and increase circulating EPCs. The impact of statins on EPCs has not been studied in SLE. We hypothesized that 36 months of statin therapy increase circulating EPC number in pediatric SLE (pSLE).

Methods:

In the APPLE trial, 221 pSLE patients were randomized to receive atorvastatin or placebo. Carotid intima medial thickening (CIMT) was measured by b-mode ultrasonography using standard protocol. Lipids, high sensitivity c-reactive protein were measured after a 12 hour fast in a central laboratory. Samples were selected from subjects with CIMT and stored cell samples at 0, 12, 36 months (n=107).

Peripheral blood mononuclear cells (MNCs) were assayed using fluorescent antibodies against CD34, CD 133 and CD 146. Samples containing < 20,000 MNCs were excluded from analysis (n=35). EPC number was calculated as % of total MNC number.

Baseline characteristics were summarized using descriptive statistics. Differences between treatment groups were assessed with chi-square test, Fisher's exact test, or the nonparametric Wilcoxon test. Univariable relationships between CD 146+ cell subset and clinical variables were assessed, followed by multivariable linear regression modeling. All statistical analyses were 2-sided, and the level of significance was 0.05.

Results:

At baseline, atorvastatin- (n=35) and placebo- (n=37) treated subjects had similar proportions of CD133+ CD34+, CD133+/34+ and CD146+ cells and did not differ according to age, gender, sociodemographics, BMI, renal status, disease duration or activity, or medications. In the placebo group, the proportion of CD133+, CD34+, CD133+/34+, and CD146+ cells did not change significantly over time. In the atorvastatin group, there were no significant changes from baseline in the CD133+, CD34+, CD133/34+ groups. The mean increase in proportion of CD146+ cells from baseline to 36 months was +1.48% (SD 1.0) in the atorvastatin group and +0.06% (SD 0.9) in the placebo group (p 0.011). In multivariable analysis, after covariate adjustment for age, gender, LDL, hscrp, prednisone dose, mean-mean CIMT, disease activity and damage, atorvastatin remained significantly associated with increase in CD 146+ cells (p 0.025; 95% CI 0.07, 1.04).

Conclusion:

After 36 months of atorvastatin therapy, the proportion of CD146+ MNCs increased in the atorvastatin group but not in the placebo group. CD34+, 133+, 133+/34+ MNCs did not change significantly from baseline in either treatment group. Atorvastatin was independently associated with CD 146+ MNC increase in multivariable analysis. The CD146 marker is specific for EPCs but limitations include the following: EPC measurement is not widely standardized, normal values for adults and children are not defined, and clinically relevant magnitude of change in EPCs remains unknown. Despite these limitations, these exploratory analyses suggest that statin therapy may increase circulating EPCs, potentially enhancing capacity for CV repair in pSLE.

To cite this abstract, please use the following information:
Ardoin, Stacy P., Povsic, Thomas, Schanberg, Laura E., Sandborg, Christy I., Barnhart, Huiman, Yow, Eric, et al; CD146 Endothelial Progenitor Cell Number Increases Following 36 Months of Atorvastatin Therapy in Children and Adolescents with SLE: The Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Cohort. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2047
DOI:

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