Dysfunctional high-density lipoprotein in chronic inflammatory rheumatic diseases

BACKGROUND: The mechanism explaining low cholesterol concentrations in chronic inflammatory rheumatic disease (CIRD) is incompletely understood. We hypothesized that chronic inflammation impairs the functionality of high-density lipoprotein (HDL), for example, by oxidative processes. OBJECTIVES: Assessment of oxidized HDL (HDL(ox)), a marker of dysfunctional HDL, in newly diagnosed patients with CIRD before and after initiation of immunosuppressive therapy and comparison of HDL(ox) values of patients with CIRD to non-CIRD controls. DESIGN: Prospective observational trial. METHODS: The study was conducted on 44 newly diagnosed CIRD patients, who were initiated on immunosuppressive therapy (baseline). A total of 136 patients without CIRD served as control. Lipid profiles including HDL(ox) levels and C-reactive protein (CRP) were measured in both groups at baseline. In CIRD patients, measurements were repeated 12 weeks after baseline. Validated outcome tools for disease activity and function were assessed at baseline and 12 weeks. RESULTS: A total of 33 (75%) patients with rheumatoid arthritis, 7(16%) with axial spondyloarthritis, and 4 (9%) with systemic lupus erythematosus were included. Groups were comparable for age and BMI. CIRD patients had higher HDL(ox) concentrations (1.57 versus 0.78, p = 0.02) and tended to have lower low-density lipoprotein cholesterol, HDL cholesterol, and cholesterol concentrations compared to controls. HDL(ox) (1.57 versus 1.4, p = 0.26) and CRP levels (2.1 versus 0.7 mg/dl, p < 0.01) decreased in CIRD patients from baseline to follow-up. CONCLUSION: CIRD is associated with an impairment of the anti-inflammatory properties of HDL as reflected by an increase in HDL(ox) concentrations. This effect may contribute to the increased cardiovascular risk in chronic inflammatory diseases.