Cardiovascular disease in rheumatoid arthritis : risk factors, clinical presentation, treatment and prognosis

Sammanfattning: It is well known that patients with rheumatoid arthritis (RA) are at increased risk of developing or dying from cardiovascular disease (CVD). There are several important questions remaining regarding the association between RA and specific CVDs. In this work, we have identified gaps in the existing knowledge and translated them into the objectives of the four sub-studies included in this thesis, which all focus on clinical aspects of CVD in RA. Several studies have assessed potential risk factors for CVD overall in RA, whereas no previous study has investigated the impact of RA-related factors on the risk of clinically significant acute coronary syndrome (ACS) in contemporary RA-patients. Existing results are thereby difficult to extrapolate into clinical praxis. Using a nested case-control design, we therefore aimed in Study I to investigate risk factors for ACS in new-onset RA. We found that laboratory measures of high inflammatory activity, clinical markers of high disease activity as well as poorer perceived health and a high number of sick days already during the first year following RA-onset were associated with an increased risk of ACS in RA. Seropositivity for the autoantibody rheumatoid factor (RF) was not associated with ACS, whereas antibodies towards citrullinated peptides (ACPAs) and in particular high positive levels of ACPAs was associated with an increased risk of ACS. Thus, the increased risk of ACS in patients with RA seems to be, at least partly, driven by inflammatory activity. Inflammation is known to affect the extent and composition of atherosclerosis, why the clinical phenotype of ACS in RA might differ compared with non-RA patients. However, little is known about the actual clinical phenotype, its treatment, follow-up care and outcomes of ACS in RA. For this reason, we investigated clinical ACS characteristics, short- and long-term outcomes and the usage of gold standard secondary preventive drugs in 1,135 RA-patients with ACS compared to 3,184 non-RA patients with ACS in Studies II and III. Our results indicated that patients with RA suffer from more severe ACS compared with non-RA patients. Furthermore, patients with RA also suffer from an increased risk of developing recurrent events or dying after the ACS. Usage of secondary preventive drugs was not substantially different in patients with RA compared with non-RA patients, and did not seem to explain the impaired prognosis following ACS. In the fourth and final study, we focused on assessing the relative risk (RR) of heart failure (HF) in RA, which, despite the known involvement of inflammation in the pathogenesis of HF, has only been assessed in a few studies. In Study IV, we estimated the relative risk (RR) of HF in RA both in the presence and absence of ischemic heart disease (IHD) in patients with new-onset RA and patients with established RA compared with non-RA patients. We also investigated the impact of RA-related inflammation on the risk of HF in patients with new-onset RA. We found that the risk of both ischemic and nonischemic HF was increased in RA. The risk increase, in particular for nonischemic HF, developed early after RA-onset and was associated with high inflammatory activity. The results of the four studies emphasize the importance of early disease control in RA, suggest that RA comorbidity should be acknowledged when risk stratifying ACS patients and also point out the importance of observing and investigating clinical signs of HF in patients with RA.