Lipid Associated Biomarkers in Patients withSystemic Lupus Erythematosus andRheumatoid Arthritis

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Abstract

Patients with chronic inflammatory conditions such as systemic lupus erythematosus(SLE) and rheumatoid arthritis (RA) experience premature cardiovascularmortality and morbidity compared with the general population. Theincreased risk of cardiovascular disease (CVD) may in part, result from an interactionbetween traditional and non-traditional risk factors, modulated by chronicinflammation. The aim of this project was to look at lipid associated biomarkersin patients with SLE/RA and the association between these markers and cardiovasculardisease outcomes. We also aimed to study the effect of inflammationreduction 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 controlsmedian 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 andpremature atherosclerosis as measured by carotid intima media thickness (cIMT)and plaque. In addition to age and systolic blood pressure, oxidised-LDL andurinary 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 significantnegative association between CRP and lipid profile namely TC, LDL, TG andApoA-1. During a median (IQR) follow up=5.5 (3.7-7.7) years 100 (7%) patientsdied (all causes) of which 33% (33) deaths were attributed to CVD. Forwardstepwise regression analysis demonstrated that a low total cholesterol was independentlyassociated with all cause mortality HR (95%CI) 0.75 (0.61, 0.91) andCVD mortality HR (95%CI) 0.49 (0.29, 0.85).In a small cohort 27 SLE patients and 15 healthy controls. We measuredendothelial function using flow mediated dilatation of the brachial artery. Atbaseline 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 functionin 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 reduce TG level andimproved endothelial function. Oxidised-LDL did not change significantly.In conclusion, oxidant stress is increased in SLE patients and relates to somemeasures of subclinical atherosclerosis. Control of inflammation may not be sufficientto completely control this in routine practice. In early RA, active inflammationmay mask any tendency to hyperlipidemia in this population. Low totalcholesterol may be the best biomarker of the overall metabolic and inflammatorystatus of the patients as well as indicating a group with increased risk of futuremortality.

Keyword(s)

systemic lupus erythematosus, rheumatoid arthritis, inflammatory polyarthritis, cardiovascular disease, risk factors, oxidant stress, lipid, endothelial dysfunction, FMD, EndoPAT, mortality, sub-clinical atherosclerosis.

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