Risk of ischemic stroke in patients with atrial fibrillation and concomitant hyperthyroidism: a nationwide cohort study

Abstract Background Hyperthyroidism is strongly associated with atrial fibrillation (AF) and the latter confers a significant risk for stroke and mortality (1). However, there is conflicting evidence on the association between the hyperthyroidism and stroke in patients with AF (2–4). Purpose We aimed to investigate the incidence of stroke and bleeding, as well as the predictive accuracy of CHA2DS2VASc and HAS-BLED scores in the AF patients with hyperthyroidism. Methods Anonymised and coded information of patients who were admitted to French hospitals with AF between January 2010 and December 2019 were retrospectively collected from the French National Hospital Discharge Database. Incidence rates of ischaemic stroke and bleeding were calculated and compared in AF patients with and without concomitant hyperthyroidism. The associations of risk factors with ischaemic stroke were assessed by univariate and multivariate Cox regression analysis. The predictive value of CHA2DS2VASc and HAS-BLED scores in AF patients with and without hyperthyroidism were assessed using the receiver operating characteristic (ROC) curves and Harrell C indexes compared with the DeLong test. Results Concomitant hyperthyroidism was identified in 32,400 (1.3%) patients among the 2,421,087 AF patients included in this study. The yearly incidence of ischaemic stroke was 2.6 (95% confidence interval CI: 2.5–2.8) in hyperthyroid AF patients, and 2.3 (95% CI: 2.3–2.4) in non-thyroid AF patients over a mean follow-up of 2.0 (SD2.2) years. The incidence of ischemic stroke was higher in the first year after AF diagnosis (3.24%/year, 95% CI 3.21–3.26) than in the subsequent follow-up (1.95%/year, 95% CI 1.93–1.96) and this phenomenon was more marked in patients with hyperthyroidism. There was a stepwise increase in the incidence of stroke with increasing CHA2DS2VASc score, irrespective of sex groups and hyperthyroidism status. Hyperthyroidism was an independent risk factor for ischaemic stroke (adjusted hazard ratio HR: 1.133, 95% CI: 1.080–1.189, p<0.001) overall, particularly within the first year of hyperthyroidism diagnosis (HR 1.203, 95% CI 1.120–1.291), with a nonsignificant association beyond 1 year (HR 1.047, 95% CI 0.980–1.118). Major bleeding incidence was lower in hyperthyroid AF group (incidence ratio IR: 5.1%/year) as compared to non-thyroid AF group (IR: 5.4%/year, p<0.001). The predictive value of CHA2DS2VASc and HAS-BLED scores for ischaemic stroke and bleeding events respectively did not significantly differ between AF patients with or without hyperthyroidism diagnosis. Conclusions Hyperthyroidism was independent risk factor of ischaemic stroke among AF patients, within the first year of hyperthyroidism diagnosis. Beyond 1 year, there was no independent contribution of hyperthyroidism to ischaemic stroke in AF. Funding Acknowledgement Type of funding sources: None. Flow chart of the cohort studyCumulative incidence for ischemic stroke