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Title: Lipid associated biomarkers in patients with systemic lupus erythematosus and rheumatoid arthritis
Author: Almohmedhusain, Awal
ISNI:       0000 0004 2737 458X
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2013
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Patients with chronic inflammatory conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) experience premature cardiovascular mortality and morbidity compared with the general population. The increased risk of cardiovascular disease (CVD) may in part, result from an interaction between traditional and non-traditional risk factors, modulated by chronic inflammation. The aim of this project was to look at lipid associated biomarkers in patients with SLE/RA and the association between these markers and cardiovascular disease outcomes. We also aimed to study the effect of inflammation reduction on vascular biomarkers. In the first study we examined 168 SLE patients median (IQR) age was 53 (46-61) years and median disease duration 13 (7, 23) years and 56 healthy controls median age 50 (39-60) years. We demonstrated elevated level of oxidised-LDLin SLE patients compared with healthy controls (76 (57, 99) U/l vs 56 (42, 88)U/l P= 0.02). We further explored the association between oxidant stress and premature atherosclerosis as measured by carotid intima media thickness (cIMT) and plaque. In addition to age and systolic blood pressure, oxidised-LDL and urinary 8-isoprostane were significantly and independently associated with cIMTin SLE patients _ coefficient 95%CI [0.00007 (5.29−6, 0.0001) and 0.003 (0.0008,0.004)], respectively. In healthy controls, age was the only independent variable. In the Norfolk Arthritis Register, 1266 patients with early inflammatory polyarthritis (IP) were studied. A linear regression analysis revealed a significant negative association between CRP and lipid profile namely TC, LDL, TG and ApoA-1. During a median (IQR) follow up = 5.5 (3.7-7.7) years 100 (7%) patients died (all causes) of which 33% (33) deaths were attributed to CVD. Forward stepwise regression analysis demonstrated that a low total cholesterol was independently associated with all cause mortality HR (95%CI) 0.75 (0.61, 0.91) and CVD mortality HR (95%CI) 0.49 (0.29, 0.85). In a small cohort 27 SLE patients and 15 healthy controls. We measured endothelial function using flow mediated dilatation of the brachial artery. At baseline we found a significant increase in TG level [1.36 (0.9, 1.87) mmol/l vs0.88 (0.64, 1) mmol/l P= 0.009] and a significant impaired endothelial function in SLE patients compared to the healthy controls [2.86 (0.6, 5.3) vs 6.81 (3.46,8.57), P= 0.03]. After treatment, there was a trend towards reduced TG level and improved endothelial function. Oxidised-LDL did not change significantly. In conclusion, oxidant stress is increased in SLE patients and relates to some measures of subclinical atherosclerosis. Control of inflammation may not be sufficient to completely control this in routine practice. In early RA, active inflammationmay mask any tendency to hyperlipidemia in this population. Low total cholesterol may be the best biomarker of the overall metabolic and inflammatory status of the patients as well as indicating a group with increased risk of future mortality.
Supervisor: Durrington, Paul; Bruce, Ian Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: systemic lupus erythematosus ; rheumatoid arthritis ; inflammatory polyarthritis ; cardiovascular disease ; risk factors ; oxidant stress ; lipid ; endothelial dysfunction ; FMD ; EndoPAT ; mortality ; sub-clinical atherosclerosis.