ARTHRITIS & RHEUMATISM Vol. 54, No. ●, Month 2006, pp 000–000 DOI 10.1002/art.● © 2006, American College of Rheumatology ________________________________________________ Homocysteine Levels and Disease Duration Independently Correlate With Coronary Artery Calcification in Patients With Systemic Lupus Erythematosus Joan M. Von Feldt,1 Lisabeth V. Scalzi,2 Andrew J. Cucchiara,1 Suneetha Morthala,1 Carmel Kealey,1 Stephanie D. Flagg,3 Anna Genin,4 Alison L. Van Dyke,1 Eleni Nackos,1 Avantika Chander,1 Erika Gehrie,1 Randy Q. Cron,4 and Alexander S. Whitehead1 Objective. To compare the incidence and extent of coronary artery calcification (CAC) as measured by electron beam computed tomography (EBCT) in patients with systemic lupus erythematosus (SLE) and controls, and to identify variables associated with CAC in patients with SLE. Methods. Female patients with SLE and matched controls were recruited; EBCT of the coronary arteries was performed, and laboratory values (including the homocysteine concentration, the lipid level, the highsensitivity C-reactive protein [hsCRP] concentration, the glomerular filtration rate [GFR], and the level of soluble CD154 [sCD154]) were determined. For patients, Systemic Lupus International Collaborative Clinics Damage Index and the Systemic Lupus Erythematosus Disease Activity Index scores were recorded. Tests of association between the CAC score and the above-mentioned variables were performed. Results. The incidence of CAC was higher in patients with SLE than in controls (P _ 0.009), and patients had a higher mean raw CAC (rCAC) score (87.9 versus 9.6 in controls; P _ 0.02). In particular, more CAC-positive patients than CAC-positive controls had rCAC scores above the 75th percentile (P _ 0.003). Among both patients and controls, those with CAC were _10 years older than those without CAC. In addition to age, a significant determinant of positive CAC status in both groups was the number of cardiovascular risk factors. In patients with SLE, CAC was associated with a higher homocysteine concentration, a lower GFR, and longer disease duration. In controls, the total cholesterol level correlated positively with CAC. When multivariate logistic regression methods were applied to candidate explanatory variables, homocysteine concentration, age, and disease duration (but not the levels of sCD154 or hsCRP) contributed significantly to CAC status. The methylenetetrahydrofolate reductase C677T genotype did not predict hyperhomocysteinemia or CAC status. Conclusion. Among patients with SLE, the homocysteine concentration, the GFR, age, and disease duration were associated with CAC. CAC occurred more frequently and was more extensive in patients with SLE than in controls, suggesting that EBCT could be used to detect premature atherosclerosis in the former group. An elevated homocysteine concentration might identify patients with SLE who are likely to have premature atherosclerosis and who would benefit from evaluation of CAC by EBCT. Dr. Von Feldt’s work was supported by the Lupus Research Institute, the American Heart Association, the Lupus Foundation, and the General Clinical Research Center at the University of Pennsylvania. Dr. Scalzi’s work was supported by the American Heart Association and the General Clinical Research Center at the University of Pennsylvania. Dr. Cucchiara’s work was supported by the General Clinical Research Center at the University of Pennsylvania and the NIH (grant M01-RR-00040). Dr. Cron’s work was supported by the NIH (grant R01-AR-048257), the Arthritis Foundation, the Dorough Lupus Foundation, the Arthritis National Research Foundation, the General Clinical Research Center at The Children’s Hospital of Philadelphia, and the Kahn Foundation for Lupus Research. Dr. Whitehead’s work was supported by the NIH (grant R01-AR-47663). 1Joan M. Von Feldt, MD, Andrew J. Cucchiara, PhD, Suneetha Morthala, MD, Carmel Kealey, PhD, Alison L. Van Dyke, Eleni Nackos, Avantika Chander, Erika Gehrie, MD, Alexander S. Whitehead, DPhil: University of Pennsylvania, Philadelphia; 2Lisabeth V. Scalzi, MD: University Hospitals of Cleveland/Rainbow Babies and Children’s Hospital, Cleveland, Ohio; 3Stephanie D. Flagg, MD, PhD: Graduate Hospital of