Prediction of Atherosclerosis Development and Modification of Its Risk Factors in Patients With Systemic Lupus Erythematosus

Abstract

Objective: Early-onset atherosclerosis with cardiovascular (CV) sequelae is the major cause of death in systemic lupus erythematosus (SLE); that cannot be explained only by traditional Framingham risk factors as SLE-related factors may also have an impact. The present study aimed to analyze the determinants of atherosclerosis development and risk factors modification by statin therapy in SLE patients. Design and method: This prospective randomized study included 100 SLE patients aged 40.9±1.4 years (90 females, 10 males) and 32 age-, sex-matched healthy controls. Brachial artery flow-mediated dilation (FMD), ultrasound of extracranial and peripheral arteries, and cardiac calcium scoring were used for the identification of atherosclerosis. 52 SLE patients with dyslipidemia were randomized to receive simvastatin 40 mg/day (n = 27) or placebo (n = 25). Lipid panel, FMD, and inflammatory markers were assessed at baseline and after 6 months. Results: The mean duration of SLE was 9.9±0.88 years. The disease activity index (SLEDAI) and SLE damage score (SLICC) were 11.8±0.6 and 1.85±0.13 points, respectively. In 66% of SLE patients, atherosclerosis was present in at least one vascular area which was 3.5 times more frequently compared with controls. Atherosclerosis of carotid arteries was detected in 41% of SLE patients, lower limb arteries, and coronary arteries in 58% and 39% of patients, respectively. FMD was significantly decreased in SLE patients compared to controls (7.95±0.49% vs 11.6±0.3%, p<0.001). In multiple linear regression, age (p<0.001), nephritis (p = 0.001), polyarthritis (p = 0.019), and Raynaud's syndrome (p = 0.045) were associated with low FMD. In binary logistic regression, independent determinants of the atherosclerosis development in SLE were age (p<0.001), body mass index (BMI) (p = 0.001), anti-dsDNA (p = 0.023), FMD (p = 0.017) and malar rash (p = 0.02). After simvastatin treatment, the level of LDL-Cholesterol reduced by 42%, erythrocyte sedimentation rate, C-reactive protein, and interleukin-6 decreased by 34.7%, 51.1%, and 47.7% respectively, while FMD increased by 26.0% (p<0.05); in the placebo group, there were no significant changes. Conclusions: The independent determinants of atherosclerosis in SLE patients were both traditional CV risk factors (age, BMI) and SLE-specific factors (anti-dsDNA, malar rash, FMD). In SLE patients with dyslipidemia, simvastatin may have not only lipid-lowering but also potentially anti-inflammatory benefits.