Temporal relations between atrial fibrillation and ischaemic stroke and their prognostic impact on mortality

Stephan Camen, Francisco M Ojeda, Teemu Niiranen, Francesco Gianfagna, Julie K Vishram-Nielsen, Simona Costanzo, Stefan Söderberg, Erkki Vartiainen, Maria Benedetta Donati, Maja-Lisa Løchen, Gerard Pasterkamp, Christina Magnussen, Frank Kee, Pekka Jousilahti, Maria Hughes, Jukka Kontto, Ellisiv B Mathiesen, Wolfgang Koenig, Tarja Palosaari, Stefan BlankenbergGiovanni de Gaetano, Torben Jørgensen, Tanja Zeller, Kari Kuulasmaa, Allan Linneberg, Veikko Salomaa, Licia Iacoviello, Renate B Schnabel

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Abstract

AIMS: Limited evidence is available on the temporal relationship between atrial fibrillation (AF) and ischaemic stroke and their impact on mortality in the community. We sought to understand the temporal relationship of AF and ischaemic stroke and to determine the sequence of disease onset in relation to mortality.

METHODS AND RESULTS: Across five prospective community cohorts of the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project we assessed baseline cardiovascular risk factors in 100 132 individuals, median age 46.1 (25th-75th percentile 35.8-57.5) years, 48.4% men. We followed them for incident ischaemic stroke and AF and determined the relation of subsequent disease diagnosis with overall mortality. Over a median follow-up of 16.1 years, N = 4555 individuals were diagnosed solely with AF, N = 2269 had an ischaemic stroke but no AF diagnosed, and N = 898 developed both, ischaemic stroke and AF. Temporal relationships showed a clustering of diagnosis of both diseases within the years around the diagnosis of the other disease. In multivariable-adjusted Cox regression analyses with time-dependent covariates subsequent diagnosis of AF after ischaemic stroke was associated with increased mortality [hazard ratio (HR) 4.05, 95% confidence interval (CI) 2.17-7.54; P < 0.001] which was also apparent when ischaemic stroke followed after the diagnosis of AF (HR 3.08, 95% CI 1.90-5.00; P < 0.001).

CONCLUSION: The temporal relations of ischaemic stroke and AF appear to be bidirectional. Ischaemic stroke may precede detection of AF by years. The subsequent diagnosis of both diseases significantly increases mortality risk. Future research needs to investigate the common underlying systemic disease processes.

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Camen, S., Ojeda, F. M., Niiranen, T., Gianfagna, F., Vishram-Nielsen, J. K., Costanzo, S., Söderberg, S., Vartiainen, E., Donati, M. B., Løchen, M-L., Pasterkamp, G., Magnussen, C., Kee, F., Jousilahti, P., Hughes, M., Kontto, J., Mathiesen, E. B., Koenig, W., Palosaari, T., ... Schnabel, R. B. (2019). Temporal relations between atrial fibrillation and ischaemic stroke and their prognostic impact on mortality. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. https://doi.org/10.1093/europace/euz312