Cardiovascular disease in Autoimmune Rheumatic

SLE and Rheumatoid Arthritis both carry an early and increased risk of cardiovascular diseases (CVD). I explored the following linked areas that may contribute to the increased risk; Immunological markers- Apolipoprotein A1 (ApoA1) is the main constituent of high density lipoproteins (HDL), which have an atheroprotective role. Using ELISA, there were no differences in serum levels of IgG anti-apoA-1 antibodies in SLE CVD patients compared to SLE controls. I studied invariant natural killer cells (iNKT) responses from serum samples of RA CVD, matched RA controls and healthy PBMCs using flow cytometry. iNKT cells are known to play a role in both autoimmunity and atherosclerosis. No differences in the RA cohort were found. Carotid vascular ultrasound studies -Using a cohort of previously scanned 100 patients with no history of CVD, I re-scanned 69% of this cohort on average 5 years later and found that 9% developed new plaque, 26% had plaque progression (increase in plaque number) and almost all patients who developed CVD events had plaque at baseline (6/7). Age >52 years and a systolic BP>133 mmol/ mg were independent predictors of plaque progression. Novel ultrasound measures such as total plaque area and plaque echolucency may be better predictors of CVD risk in SLE, but further studies are required. Metabolomics- I found that various subclasses and sizes of very low density lipoprotein (VLDL) concentrations were significantly higher in SLE vs HC. I have identified five individual VLDL metabolites whose levels could be measured to distinguish SLE-P from SLE-NP. Significantly, higher concentrations in of HDL particles was found in HC vs RA. Traditional CVD risk factors- I explored the feasibility of assessing traditional risk factors, by designing a simple one-page protocol. Using this protocol in the SLE population at UCLH at the time, 77% (309/400) of patients in the total cohort were captured over a 9-month period.