This thesis focuses on cardiovascular (CV) disease (CVD) risk in rheumatoid arthritis (RA). Inflammation and CV risk factors are increased in RA patients. This population has a higher carotid intima-media thickness and more CV events than the general population and kynurenine (KYN) concentration levels are higher in RA patients compared to healthy controls. Therefore, in this thesis inflammation and CVD risk factors are investigated for increased risk of future RA development. RA and type2 diabetes (T2D) carotid intima-media thickness (CIMT) are compared and measurements of serum KYN for CVD, cancer and mortality are studied. First I tested the hypothesis that inflammation, CVD and CV risk factors are associated with increased risk of future RA development. Data from the Norwegian HUNT population health survey were obtained to compare groups with RA at baseline and follow-up (HUNT2 and HUNT3, n = 429) or follow up alone (HUNT3, n = 786), or without RA at both times (n = 33,567). Results showed female gender, age, smoking, body mass index (BMI), and history of previous CVD were associated with self-reported incident RA (previous CVD: odds ratio 1.52 (95% confidence interval 1.11-2.07). The findings regarding previous CVD were confirmed in sensitivity analyses excluding participants with psoriasis (odds ratio (OR) 1.70 (1.232.36)) or restricting the analysis to cases with hospital diagnosis of RA (OR 1.90 (1.10-3.27)) or carriers of the shared epitope (OR 1.76 (1.134-2.74)). History of previous CVD was not associated with increased risk of osteoarthritis (OR 1.04 (0.86-1.27)). I then compared the characteristics of CV risk and progression of CIMT in 78 RA patients from an outpatient Rheumatology Clinic and 212 patients with T2D who attended a community or hospital diabetes clinic in Brisbane. We found that the burden of risk varied between the 2 cohorts. RA patients were older, had a higher proportion of smokers, females and previous CVD. T2D patients had a higher body mass index (BMI), diastolic blood pressure, triglycerides, lower high density lipoprotein and a higher statin use. At baseline, CIMT measurements were similar in the RA and T2D cohorts. In an adjusted linear regression model, RA was significantly associated with lower CIMT at follow-up. Despite a shorter follow-up, 91 % of the T2D cohort had increased CIMT at follow-up compared to 54 % of the RA cohort. In the RA cohort, disease modifying anti-rheumatic drug (DMARD) use at baseline was associated with significantly lower CIMT values at follow-up.
Finally we hypothesized that increased KYN in RA patients may predispose to CVD, infections and cancer. We measured KYN in 129 RA patients followed for 10 years for development of CVD, cancer and death. Median KYN concentrations were significantly higher in RA patients than in controls, but there was large overlap between groups. There were no variables in our data set that could explain the differences in KYN concentrations among the RA patients and KYN concentrations did not predict development of CVD, new malignancies or death. The number of pack-years of smoking was the only variable associated with death in logistic or Cox regression analysis. In summary, CVD risk factors are associated with increased risk of future RA development. The burden of risk varies in RA and T2D, and CIMT progression is slower for RA than for T2D. Although serum KYN concentrations are significantly higher in RA than in controls, they were not associated with CVD, new malignancies or death.