Serum osteoprotegrin (OPG) in subclinical atherosclerosis in systemic lupus erythematosus.

Introduction Osteoprotegerin (OPG) is a member of the tumor necrosis factor (TNF) receptor family. It has recently been demonstrated that OPG is produced by a variety of tissues, including the cardiovascular system (heart, arteries, veins), lung, kidney, immune tissues, and bone. The OPG-RANKL signaling pathway is strongly related to vascular calcification. We determined the association of this biomarker with subclinical atherosclerosis in systemic lupus erythematous (SLE). Methods We measured OPG and markers of subclinical atherosclerosis (coronary artery calcium (CAC), carotid intima-media thickness (cIMT) carotid plaque) in 166 SLE patients (91% female, 64% Caucasian, 31% African American, 5% others, mean age 45 years). Subgroups of patients with different levels of OPG level were compared with respect to average levels of CAC, cIMT, and with respect to presence of carotid plaque. Age was adjusted for using multiple regression. Results OPG was highly correlated with age ( p < 0.0001). Individuals with higher levels of OPG tended to have higher measures of CAC, cIMT, and more carotid plaque. However, after adjustment for age, these associations, while still positive, were no longer statistically significant. Conclusion In our study much of the association observed was due to confounding by age, and after adjusting for age, our findings do not rule out the possibility of a null association.

Lupus Atherosclerosis Prevention Study (LAPS).

BACKGROUND: Cardiovascular disease is one of the major causes of death in systemic lupus erythematosus (SLE). A study was undertaken to investigate whether treatment with statins would reduce subclinical measures of atherosclerosis over a 2-year period. METHODS: 200 patients with SLE without clinical cardiovascular disease were randomised to receive atorvastatin 40 mg daily or an identical placebo. At baseline and after 2 years of follow-up, helical CT scanning (for coronary artery calcium) and carotid duplex (for intima media thickness/plaque) were performed. Patients were seen for measures of disease activity at 1 month, 3 months and quarterly thereafter. The primary outcome variable was change in coronary artery calcium. RESULTS: At baseline, 43% had coronary artery calcium. At 2 years there was no significant difference between the groups in progression of coronary artery calcium, carotid intima media thickness or carotid plaque. There was no significant difference between the groups in disease activity, measures of inflammation or endothelial cell activation. CONCLUSION: This study provides no evidence that atorvastatin reduces subclinical measures of atherosclerosis or disease activity over 2 years in patients with SLE. In fact, it does not appear to reduce biochemical measures of inflammation. The anti-inflammatory effects of statins observed in the general population were not replicated in this SLE clinical trial. Clinicaltrials.gov (NCT 00120887).

Aortic valve calcification in systemic lupus erythematosus.

Aortic valve calcification is associated with atherosclerosis in the general population. We investigated the prevalence of and associates of aortic valve calcification in systemic lupus erythematosus (SLE). One-hundred and ninety-nine SLE patients enrolled in a clinical trial had aortic valve calcification assessed by helical CT. The patients had a mean age of 44.3 +/- 11.4 years and were 92% female, 61% Caucasian, 34% African-American, 2% Asian and 2% Hispanic. Aortic valve calcification was present in 1.5%, whereas coronary calcium was found in 43% and carotid plaque in 17%. Among cardiovascular risk factors, hs-CRP (P = 0.0592), fibrinogen (P = 0.0507), and lipoprotein(a) (P = 0.0250), were associated with aortic valve calcification. Prednisone use (P = 0.049) and use of methotrexate (P = 0.0174) were also associated with aortic valve calcification. Aortic valve calcification was associated with antiphospholipid antibody positivity (0.0287) (lupus anticoagulant, by dilute Russell viper venom time). It was not associated with coronary calcium or carotid plaque. Aortic valve calcification, although rare in SLE, was associated with some novel cardiovascular risk factors and with a marker of hypercoagulability (lupus anticoagulant). In contrast to the general population, aortic valve calcification in SLE is not associated with subclinical measures of atherosclerosis, such as coronary calcium or carotid plaque.