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Abstract Number: 1709

Biomarkers of Atherosclerosis Are Associated with Progression of Non-Cardiovascular Damage in Patients with SLE

Sarah J. Kim1, Jennifer M. Grossman2, Brian Skaggs3, Elaine Lourenco3, Lori Sahakian4, John FitzGerald5, Nagesh Ragavendra6, Christina Charles-Schoeman7, Alan H. Gorn8, Bevra H. Hahn8 and Maureen A. McMahon9, 1UCLA David Geffen School of Medicine, Los Angeles, CA, 2Div of Rheumatology, UCLA David Geffen School of Medicine, Los Angeles, CA, 3Medicine/Rheumatology, UCLA David Geffen School of Medicine, Los Angeles, CA, 4Division of Rheumatology, Department of Medicine,, UCLA David Geffen School of Medicine, Los Angeles, CA, 5Medicine-Rheumatology, UCLA David Geffen School of Medicine, Los Angeles, CA, 6Radiology, UCLA David Geffen School of Medicine, Los Angeles, CA, 7University of California, Los Angeles, CA, 8Rheumatology, UCLA David Geffen School of Medicine, Los Angeles, CA, 9Division of Rheumatology, UCLA David Geffen School of Medicine, Los Angeles, CA

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Atherosclerosis and systemic lupus erythematosus (SLE)

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Session Information

Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment III: Cardiovascular

Session Type: Abstract Submissions (ACR)

Background/Purpose: Studies have shown that even after taking traditional cardiac risk factors into account, SLE patients have up to 50-fold higher risk of developing atherosclerotic (ATH) cardiovascular disease.  We previously identified several biomarkers associated with the progression of atherosclerosis in SLE, including pro-inflammatory high-density lipoprotein (piHDL), leptin, sTWEAK, and homocysteine.  These 4 biomarkers plus increased age combined into a “high oxidative stress” variable was also highly associated with progression of ATH in SLE.  The goal of this study was to investigate the association between biomarkers of ATH and overall progression of non-ATH, lupus-related damage. 

Methods: Systemic Lupus International Collaborating Clinics / ACR damage index (SDI) was used to score damage progression in 159 SLE patients enrolled in the longitudinal “Biomarkers of Atherosclerosis in SLE” cohort study between January 2004 and September 2008.  Lupus-related damage scores were determined using the SDI at baseline and at the time of the 2-3 year follow-up carotid ultrasound excluding scores in cardiovascular domains. The associations between accumulation of any lupus-related non-ATH damage and biomarkers of atherosclerosis were examined using the chi-square test for dichotomous variables and Student’s t-test for continuous variables (SPSS Inc, Chicago, IL).

Results: After excluding cardiovascular and cerebrovascular events from the SDI score, new carotid plaque at 2 year follow-up was present in 34% of patients with non-ATH SDI score increase as opposed to 18% in patients without SDI change (p=0.01).    In patients with SDI increase, mean homocysteine (p=0.037), sTWEAK (p=0.043) and leptin  (p=0.02) levels were significantly higher than in those without SDI change..  The combination high-oxidative stress variable was found in a higher proportion of patients with SDI increase (50% vs 28.9%, p=0.02), and was associated with a higher mean SDI increase (0.52±0.94 vs 0.19±0.47, p=0.02).  In multivariate analysis controlling for lupus medications, baseline SDI, and other potential confounders, high-oxidative stress was associated with a 2.9-fold increased odds for progression of non-atherosclerotic damage (p=0.02), and lifetime cumulative prednisone use >20g was associated with 2.6-fold increased odds (p=0.046). 

Conclusion: Non-atherosclerotic lupus-related damage as measured by SDI scoring is associated with presence of carotid plaque, high-oxidative stress and elevated levels of homocysteine, sTWEAK, and leptin.  Patients with baseline biomarkers for atherosclerosis progression have higher incidence of overall progression of non-ATH disease damage which may serve as important predictors for lupus disease course.


Disclosure:

S. J. Kim,
None;

J. M. Grossman,

medimmune, UCB, Pfizer, TEVA, Cephalon, American College of Rheumatology, Eli Lilly, ,

2;

B. Skaggs,
None;

E. Lourenco,
None;

L. Sahakian,
None;

J. FitzGerald,
None;

N. Ragavendra,
None;

C. Charles-Schoeman,
None;

A. H. Gorn,
None;

B. H. Hahn,

Teva Pharmaceuticals,

2,

Aspreva Pharmaceutical,

2,

Anthera,

5,

Abbott,

5,

Eli Lilly,

5;

M. A. McMahon,

Human Genome Sciences, Inc.,

8,

Glaxo Smith Klein,

8.

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