Background Rheumatoid Arthritis (RA) is associated with accelerated atherosclerosis and inflammation associated with RA may increase the propensity to develop dyslipidaemia and insulin resistance. In established RA, HDL-C (HDL) and ApoA-1 are negatively correlated with disease activity and insulin resistance is increased in RA patients. A few studies have suggested that lipid and glucose handling may be impaired prior to the onset of RA with Apo-B and triglyceride levels being found to be higher and HDL levels lower in those individuals who later develop inflammatory polyarthritis (IP).
Objectives To investigate the association between lipid levels, diabetes and glycated haemoglobin on future risk of IP.
Methods In the European Prospective Investigation of Cancer in Norfolk (EPIC-Norfolk) cohort, all participants completed a questionnaire at baseline and provided a non-fasting blood sample for routine lipid analysis. In subsets, additional biomarkers were measured including HbA1c, Apo-A1 and ApoB. Individuals with incident IP were identified by linkage with the Norfolk Arthritis Register (NOAR), a primary-care based disease register with an overlapping catchment area. We assessed the association of HDL, Apo-A1, ApoB and HbA1c with future risk of IP using Cox proportional hazard models. Confounders included age, gender, smoking status, smoking intensity, self-reported diabetes (DM) and Body Mass Index (BMI) and were controlled for in the final analyses.
Results 25,455 EPIC participants aged 40-79 years were followed for a median (IQR) of 14.2 (12.9, 15.3) years (342,916 person-years of follow-up). 184 developed incident IP (69.6% women). Univariately, HbA1c [HR=1.3 (95% CI: 1.09, 1.55) per 1% increase] was associated with an increased risk of IP, remaining significant after further adjustment for confounders [HR=1.24 (95% CI: 1.05, 1.47) per 1% increase]. Univariately, neither Apo-A1, Apo-B nor HDL levels predicted IP onset. When multiple biomarkers were included in a single multivariable model, both HDL and HbA1c were significantly associated with incident IP [HR 0.76 (95%CI: 0.57, 1.00) per 0.4mmol/l and 1.24 (95% CI: 1.05, 1.47) per 1% respectively].
Conclusions In a prospective population-based cohort study low HDL and high HbA1c were identified as being associated with subsequent IP development. Several anti-inflammatory properties of HDL may be of relevance to its potential protective role. Glycated haemoglobin reflects insulin resistance which can promote a pro-inflammatory state in an at-risk population.
Disclosure of Interest None Declared
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