Background/Purpose:  Coronary atherosclerosis increases with age but is more prevalent in patients with systemic lupus erythematosus (SLE) independent of chronological age; this increased prevalence has been suggested to reflect accelerated biological aging in SLE. Telomeres protect chromosomal ends from shortening after replication, and telomere length is indicative of biological age. We examined the hypothesis that reduced telomere length, reflecting accelerated biological aging, is associated with inflammation, disease activity and damage, cardiometabolic risk factors, and coronary atherosclerosis in patients with SLE.

Methods: We performed a cross-sectional study in 126 patients with SLE. Telomere length was measured from whole blood DNA using real-time quantitative PCR as telomeric product to a single-copy gene product ratio (T/S ratio). Inflammation was assessed by high sensitivity C-reactive protein (CRP). SLE disease activity and damage were assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics Classification Criteria (SLICC), respectively. Homeostatic Model Assessment (HOMA) was used to assess degree of insulin resistance. Framingham Risk Score (FRS) was determined based on the American Heart Association criteria. Coronary artery calcium score was measured by electron beam computed tomography. Spearman correlation and linear or logistic regression models adjusting for age, race, and sex were used to determine the association between telomere length and clinical variables.  

Results:  Patients with SLE were predominantly female (91%) and Caucasian (65%) with median age 41 years. Telomere length was inversely associated with age (ρ =-0.43, P<0.001) and CRP (ρ=-0.31, P<0.001, Padj<0.001) but not with SLEDAI or SLICC scores (Table). Higher triglycerides (ρ=-0.21, P=0.02 Padj=0.007) and FRS (ρ=-0.43, P<0.001, Padj=0.03) were inversely associated with telomere length independent of age, race and sex. Systolic blood pressure and waist-hip ratio were inversely associated with telomere length, but the relationship was attenuated after adjustment. High-density and low density lipoproteins, diastolic blood pressure, HOMA, and coronary artery calcium score were not associated with telomere length (Table).

Conclusion: Telomere length was significantly inversely associated with chronological age in SLE; it was also inversely associated with some cardiometabolic risk factors such as triglycerides, FRS, and CRP independent of age, race, and sex.  However, coronary artery calcium score was not independently associated with telomere length, suggesting that factors other than accelerated biological aging are responsible for increased atherosclerosis in SLE.