Abstract

BackgroundRheumatoid arthritis (RA) patients have a reduced life expectancy, with cardiovascular disease (CVD) being the most frequent cause of death. The mechanisms behind the increased CVD morbidity and mortality in RA are not fully understood. Systemic inflammation is an important contributor to the accelerated arteriosclerosis in RA, and traditional risk factors for CVD are usually more prevalent in RA patients than in the general population. How much the current state of RA disease control impacts the short-term risk of CVD events remains unclear.ObjectivesTo estimate the short-term risks and relative risks of acute coronary syndrome (ACS) in patients with RA as a function of RA disease activity, with particular focus on remission.MethodsWe identified patients with RA from the clinical rheumatology registers (CRR) in Sweden (SE) and Norway (NO), and for these patients we retrieved all registered clinical rheumatology visits from January 1st, 2012 to December 31st, 2020. At each visit, we assessed whether the patient was in remission or not according to multiple definitions including DAS28, ACR criteria, and SDAI. We also categorised the disease activity at each visit into categories (remission, low, moderate and high) using DAS28-ESR. Patients had to be free of any history of ACS in a five-year look back window (assessed at the visit date), and were followed for 6 months from each visit date until ACS event (defined as hospitalization due to ACS or death due to either ACS or sudden death) or censoring (death due to other causes, migration, end of the study). We compared the risk of ACS between patients who were (vs. were not) in remission using Cox regression with robust standard errors (accounting for the correlated data structure), adjusted for covariates (including age at the visit, sex, number of previous treatment courses, use of prednisolone, the expanded risk score in RA (ERS-RA), and defined co-morbidities: diabetes, malignancy, respiratory failure, liver failure and kidney disease) and stratified by country.ResultsWe included 43,338 RA patients and their 223,197 visits (211,158 (SE), 12,039 (NO)). 74% of the visits were from women, with a mean age (SD) at visit of 62 (14) years. Several clinical characteristics including treatments and comorbidity history varied with disease activity (Table 1). By contrast, age, number of previous DMARDs, disease duration and smoking habits were relatively similar across categories of disease activity (Table 1).Table 1.Median [Q1-Q3] or percentage for clinical characteristics in remission (DAS28-ESR<=2.6) and high disease activity (DAS28-ESR>5.1) categoriesVariableRemissionHigh disease activityN (visits)91,49725,364Age, years65[53-72]63[53-72]Disease duration10[4-18]8[2-17]N treatment courses0[0-0]0[0-1]Prednisolon28%58%Tender joint count, 28-joints (TJC)0[0-0]10[6-14]Swollen joint count, 28-joints (SJC)0[0-0]7[4-10]Erythrocyte sedimentation rate, ESR10[6-18]28[15-47]C-reactive protein (CRP)3[1-4]14[5-32]Patient global assessment, PGA13[4-27]70[55-82]Pain12[4-27]70[55-82]ERS-RA8[3-16]12[5-23]Ischemic heart disease6%7%Diabetes9%13%Hypertension39%42%Hyperlipidemia23%25%Ever smoking45%50%We observed 598 ACS events (in 554 patients) during the 6-month follow-up window. Comparing patients not in remission to patients in remission, adjusting for the covariates described above, indicated that not being in remission increased the risk of ACS occurrence (Figure 1). Similarly, there was an association between DAS28-ESR at the visit and the risk of ACS during the coming six months.Figure 1.Hazard ratio (95% confidence interval) comparing patients not in remission to patients in remission, using several remission definitions. Percentage of visits with an ACS event within 6 months (bottom panel).ConclusionBeing in RA remission at any visit is associated with a noticeably lower risk of ACS during the following months, suggesting that RA disease activity not only affects CVD risk in the longer term but also in the short term.AcknowledgementsNordForsk and Foreum partially funded this research project.Disclosure of InterestsBénédicte Delcoigne: None declared, Sella Aarrestad Provan: None declared, Eirik kristianslund: None declared, Johan Askling Grant/research support from: AbbVie, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Janssen, Merck, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB, Lotta Ljung: None declared.

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