Epidemiological and pathogenic aspects on cardiovascular disease in rheumatoid arthritis

Sammanfattning: Rheumatoid arthritis (RA) is a chronic disabling disease that is associated with a shortened life span. Cardiovascular disease (CVD) contributes to this increased mortality, and also to a great extent to the co-morbidity observed in patients with RA. This thesis aimed to investigate these issues further.The incidence of, and prognosis after an acute myocardial infarction (AMI) /or stroke in a cohort of RA patients was compared with that in the general population within the northern Sweden MONICA register. The standard incidence ratio (SIR) for AMI was 2.9 and for stroke 2.7 in RA patients compared with the general population (p<0.05 for both). During the first 10 years following an event, RA patients had a higher overall case fatality (CF) compared with controls (HR for AMI=1.67, 95%CI [1.02, 2.71], HR for stroke=1.65, 95%CI [1.03, 2.66]).An elevated level of homocysteine is regarded to be a risk marker for CVD. The effects of treatment with B vitamins on the homocysteine level in patients with RA were studied in a consecutive cohort of patients with RA. Sixty-two patients with RA having a homocysteine level of ?12 ?mol were randomized to receive either a placebo or a combination of the vitamins B6, B12 and folic acid. The patients were treated and evaluated in a double-blind manner over 12 months. The homocysteine level was found to be significantly decreased in the B-vitamin treated patients compared with the placebo group (p<0.0001).To evaluate the progression of sub-clinical atherosclerosis in patients with very early RA compared with controls, all patients from the three most northern counties of Sweden newly diagnosed with RA and aged ?60 years were consecutively recruited. Age and sex matched controls from the general population were also included. Intima media thickness (IMT) of the common carotid artery and endothelium dependent flow mediated dilation (ED-FMD) of the brachial artery were measured using ultrasonography. After 18 months the same measurements were undertaken in a sub-group of the patients with early RA and the relevant controls. There were no differences between patients with early RA and controls in terms of IMT or ED-FMD at inclusion into the study. However, after 18 months there was a significant increase in the IMT among the patients with early RA (p<0.05); no such increase occurred in the control group.Biomarkers of endothelial activation that may reflect the early atherosclerosis that occurs in RA were also evaluated. At inclusion, both IMT and ED-FMD among the patients with early RA related significantly to several of the biomarkers of endothelial activation. Furthermore, markers of inflammation (e.g., DAS28) were significantly related to biomarkers of endothelial activation.In conclusion, RA patients had a higher incidence of CVD and a higher CF after a CV event. The increased homocysteine level among patients with RA was as easy to decrease as in the general population. At the time of diagnosis of RA there were no differences in atherosclerosis between patients and controls, however the patients with RA had a more rapid progression of atherosclerosis than the control subjects. Moreover, there were implications of endothelial activation already in patients with very early RA. Taken together, these results emphasize the necessity of optimizing the preventive, diagnostic and caring strategies for CVD in patients with RA.