Atrial Fibrillation and Cause-Specific Risks of Pulmonary Embolism and Ischemic Stroke

Background: Atrial fibrillation (AF) is a well-established risk factor for ischemic stroke (IS). Emerging evidence also indicates an association between AF and pulmonary embolism (PE). Because IS may potentially mediate the observed risk of PE in AF, we aimed to assess the impact of AF on the cause-specific risks of PE and IS in a large cohort recruited from the general population. Methods and Results-We observed 29 842 participants from 3 surveys of the Tromsø study (inclusion in 1994-1995, 2001- 2002, and 2007-2008) to the end of 2012. Incident events of AF, IS, and PE during follow-up were recorded, and information on potential confounders was obtained at baseline. Cox regression models, with AF as a time-dependent variable, were used to calculate cause-specific hazard ratios (HRs) with 95% confidence intervals (CIs) for PE and IS. There were 2067 participants diagnosed as having AF, 296 with PE and 1164 with IS, during a median of 17.6 years of follow-up. The risks of PE (HR, 10.88; 95% CI, 6.23-18.89) and IS (HR, 6.16; 95% CI, 4.47-8.48) were substantially increased during the first 6 months after AF diagnosis, with crude incidence rates of 18.5 per 1000 person-years for PE and 52.8 per 1000 person-years for IS. The risk estimates remained elevated for both PE (HR, 1.72; 95% CI, 1.10-2.71) and IS (HR, 2.45; 95% CI, 2.05-2.92) throughout the study period. Conclusions-AF was associated with increased cause-specific risks of both PE and IS. Our findings infer that the risk of PE in AF is not explained by intermediate IS.