Risk of atrial fibrillation and stroke in rheumatoid arthritis: Danish nationwide cohort study OPEN ACCESS

Objectives To determine if patients with rheumatoid arthritis have increased risk of atrial fibrillation and stroke. Design Longitudinal nationwide register based cohort study. Setting Inpatient and outpatient hospital care in Denmark from 1997 to 2009. Participants Entire Danish population aged over 15 years without rheumatoid arthritis, atrial fibrillation, or stroke before 1997. Participants with rheumatoid arthritis were identified by individual level linkage of diagnoses and rheumatoid arthritis treatment. Main outcome measures Rates of atrial fibrillation and stroke. Results Of 4 182 335 participants included in the cohort, 18 247 were identified as having rheumatoid arthritis during follow-up, with a mean age at disease onset of 59.2 years and a median follow-up of 4.8 years. A total of 156 484 people, including 774 with rheumatoid arthritis, were diagnosed as having atrial fibrillation (age and sex matched event rates of 8.2 per 1000 person years in rheumatoid arthritis patients and 6.0 per 1000 person years in the general population), with an adjusted incidence rate ratio of 1.41 (95% confidence interval 1.31 to 1.51). In addition, 165 343 people, including 718 with rheumatoid arthritis, had a stroke (7.6 per 1000 person years in rheumatoid arthritis and 5.7 per 1000 person years in the general population), with a resultant rate ratio of 1.32 (1.22 to 1.42). For both atrial fibrillation and stroke, relative risks were increased in all strata based on thirds of sex and age, with higher relative risks in younger patients but higher absolute risk differences in older patients. Conclusions Rheumatoid arthritis was associated with an increased incidence of atrial fibrillation and stroke. The novel finding of increased risk of atrial fibrillation in rheumatoid arthritis suggests that this arrhythmia is relevant in cardiovascular risk assessment of these patients. Introduction Rheumatoid arthritis has been shown to be associated with substantial cardiovascular comorbidity, but most of the available evidence originates from studies on the risk of myocardial infarction and cardiovascular mortality. In contrast to the risk of myocardial infarction related to rheumatoid arthritis, the results from studies on risk of stroke have been inconsistent, which may reflect the diverse causes of stroke, including atherothrombosis, thromboembolism, and haemorrhage, but also differences in study designs and characteristics of rheumatoid arthritis populations examined. Atrial fibrillation is an important and modifiable risk factor for stroke. To our knowledge, however, studies on the incidence of atrial fibrillation, and its effect on the risk of stroke, in patients with rheumatoid arthritis have not been reported, even though the incidence of atrial fibrillation is known to be increased by several factors that are more prevalent in people with rheumatoid arthritis, such as heart failure, ischaemic heart disease, and smoking. 12-14 Furthermore, studies have suggested that inflammation plays a role in the development of atrial fibrillation. In this study, therefore, we examined the risk of atrial fibrillation and stroke associated with rheumatoid arthritis in a Danish nationwide register based cohort study from 1997 to 2009. Methods Study cohort and data sources Our study cohort consisted of all Danish inhabitants aged over 15 years on 1 January 1997, as identified through the Danish Correspondence to: J Lindhardsen [email protected] Extra material supplied by the author (see http://www.bmj.com/content/344/bmj.e1257?tab=related#webextra) No commercial reuse: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe BMJ 2012;344:e1257 doi: 10.1136/bmj.e1257 (Published 8 March 2012) Page 1 of 12