Determining the Relationship Between Inflammation, Therapeutic Exposure and Cardiovascular Risk in Patients with Systemic Lupus Erythematosus
Introduction SLE is associated with pro-atherogenic metabolic derangement and an elevated cardiovascular risk. The vascular endothelium may be a key interface between active SLE and premature atherosclerosis. Improved understanding of the contribution of inflammation and its management to cardiovasc...
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| Format: | Dissertation |
| Language: | English |
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ProQuest Dissertations & Theses
01-01-2013
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| Online Access: | Get full text |
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| Summary: | Introduction SLE is associated with pro-atherogenic metabolic derangement and an elevated cardiovascular risk. The vascular endothelium may be a key interface between active SLE and premature atherosclerosis. Improved understanding of the contribution of inflammation and its management to cardiovascular risk in SLE will inform personalised treatment decisions in SLE patients. Methods: Data from an international inception cohort was used to investigate the relationship between inflammatory disease activity, lupus phenotype and corticosteroid exposure and the metabolic syndrome (MetS) over 2 years in SLE patients. The relationship between disease activity (BILAG-2004) and markers of endothelial function (flow-mediated dilatation (FMD) of the brachial artery) and endothelial damage (endothelial microparticles (EMPs)) following a change in anti-inflammatory therapy was investigated in a longitudinal cohort of patients with active SLE. Results: MetS was common in young SLE patients (12.6-16.0%) over the initial 2 years of disease. Factors independently associated with developing MetS over the 2-year study period were (odds ratio (95% CI)) Hispanic ethnicity (3.47 (1.76, 6.86)), higher initial peak corticosteroid dose (1.02 (1.01,1.03)), and elevated anti-dsDNA antibodies at study entry (1.86(1.19,2.81)). MetS was often persistent and preceding MetS strongly predicted future MetS (4.83 (2.93, 7.87)). Patients with active SLE had reduced FMD (median (IQR) FMD 1.63% (-1.22, 5.32) vs. 5.40% (3.02, 8.57); p = 0.05) and elevated EMPs (157,548/ml (59,906, 272,643) vs. 41,025 (30,179, 98,082); p = 0.003) compared to age-matched controls. Both improved following a change in anti-inflammatory therapy, and correlated moderately with change in disease activity over time. Conclusions: Inflammatory disease activity and higher doses of corticosteroids in very early disease influence the development of MetS in SLE, which can become persistent. Endothelial dysfunction is common in patients with active SLE but can be improved with better disease control. Therefore even from disease onset, therapeutic regimes should be individually tailored to achieve good disease control whilst minimising corticosteroid doses, to improve cardiovascular risk surrogates in SLE. |
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| ISBN: | 9781073909254 1073909255 |