TY - JOUR
T1 - Temporal relations between atrial fibrillation and ischaemic stroke and their prognostic impact on mortality
AU - Camen, Stephan
AU - Ojeda, Francisco M.
AU - Niiranen, Teemu
AU - Gianfagna, Francesco
AU - Vishram-Nielsen, Julie K.
AU - Costanzo, Simona
AU - Söderberg, Stefan
AU - Vartiainen, Erkki
AU - Donati, Maria Benedetta
AU - Løchen, Maja Lisa
AU - Pasterkamp, Gerard
AU - Magnussen, Christina
AU - Kee, Frank
AU - Jousilahti, Pekka
AU - Hughes, Maria
AU - Kontto, Jukka
AU - Mathiesen, Ellisiv B.
AU - Koenig, Wolfgang
AU - Palosaari, Tarja
AU - Blankenberg, Stefan
AU - De Gaetano, Giovanni
AU - Jørgensen, Torben
AU - Zeller, Tanja
AU - Kuulasmaa, Kari
AU - Linneberg, Allan
AU - Salomaa, Veikko
AU - Iacoviello, Licia
AU - Schnabel, Renate B.
N1 - Funding Information:
Conflict of interest: S.Sö. has received lecture honoraria and advisory board fees from Actelion Pharmaceuticals Ltd outside the scope of the submitted work. V.S. has participated in a conference trip sponsored by Novo Nordisk and received a honorarium from the same source for participating in an advisory board meeting. He also has on-going research collaboration with Bayer Ltd (unrelated to the present study). W.K. reports personal fees from AstraZeneca, Novartis, DalCor, Kowa, Amgen, and Sanofi, grants and non-financial support from Roche Diagnostics, Beckmann, Singulex, and Abbott, all outside the scope of the submitted work. S.B. reports investigator-initiated grants from SIEMENS, Abbott Diagnostics, and Thermofisher, all outside the scope of the submitted work. R.B.S. has received lecture honoraria and advisory board fees from BMS/Pfizer outside the scope of the submitted work. V.S. has consulted for Novo Nordisk and Sanofi and received honoraria from these companies. He also has ongoing research collaboration with Bayer AG. St.C., F.M.O., T.N., F.F., J.K.V.-N., Si.C., E.K., M.B.D., M.-J.L., G.P., C.M., F.K., P.J., M.H., J.K., E.B.M., G.d.G., T.J., T.Z., K.K., A.L., and L.I. all declare no conflict of interest.
Funding Information:
The BiomarCaRE Project is funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement No. HEALTH-F2-2011-278913. The activities of the MORGAM Data Center have been sustained by recent funding from European Union FP 7 project CHANCES (HEALTH-F3-2010-242244). The FINRISK surveys were mainly supported by budgetary funds of THL. Additional funding has been obtained from numerous non-profit foundations. V.S. (PI) has been supported by the Finnish Foundation for Cardiovascular Research and the Academy of Finland (139635). T.N. has been supported by the Finnish Medical Foundation, the Emil Aaltonen Foundation, the Paavo Nurmi Foundation, and the Academy of Finland (321351). The DanMONICA cohorts at the Research Center for Prevention and Health were established over a period of 10 years and have been funded by numerous sources which have been acknowledged, where appropriate, in the original articles. The Moli-sani Project was partially supported by research grants from Pfizer Foundation (Rome, Italy), the Italian Ministry of University and Research (MIUR, Rome, Italy)'Programma Triennale di Ricerca, Decreto n.1588 and Instrumentation Laboratory, Milan, Italy. The Northern Sweden MONICA project was supported by Norrbotten and Vasterbotten County Councils. S.S. has been supported by the Swedish Heart'Lung Foundation (20140799, 20120631, 20100635), the County Council of Va'sterbotten (ALF, VLL-548791) and Umea University. The Troms' Study was supported by the UiT Arctic University of Norway, the municipality of Tromso, the Norwegian Research Council and the National Health Screening Service. T.Z. is supported by the German Center of Cardiovascular Reseasrch (Grant 81Z1710101, Partner site Project). We thank the participants and the staff of the cohorts for their continuing dedication and efforts. Conflict of interest: S.So. has received lecture honoraria and advisory board fees from Actelion Pharmaceuticals Ltd outside the scope of the submitted work. V.S. has participated in a conference trip sponsored by Novo Nordisk and received a honorarium from the same source for participating in an advisory board meeting. He also has ongoing research collaboration with Bayer Ltd (unrelated to the present study). W.K. reports personal fees from AstraZeneca, Novartis, DalCor, Kowa, Amgen, and Sanofi, grants and non-financial support from Roche Diagnostics, Beckmann, Singulex, and Abbott, all outside the scope of the submitted work. S.B. reports investigator-initiated grants from SIEMENS, Abbott Diagnostics, and Thermofisher, all outside the scope of the submitted work. R.B.S. has received lecture honoraria and advisory board fees from BMS/Pfizer outside the scope of the submitted work. V.S. has consulted for Novo Nordisk and Sanofi and received honoraria from these companies. He also has ongoing research collaboration with Bayer AG. St.C., F.M.O., T.N., F.F., J.K.V.-N., Si.C., E.K., M.B.D., M.-J.L., G.P., C.M., F.K., P.J., M.H., J.K., E.B.M., G.d.G., T.J., T.Z., K.K., A.L., and L.I. all declare no conflict of interest.
Funding Information:
The BiomarCaRE Project is funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement No. HEALTH-F2-2011-278913. The activities of the MORGAM Data Center have been sustained by recent funding from European Union FP 7 project CHANCES (HEALTH-F3-2010-242244). The FINRISK surveys were mainly supported by budgetary funds of THL. Additional funding has been obtained from numerous non-profit foundations. V.S. (PI) has been supported by the Finnish Foundation for Cardiovascular Research and the Academy of Finland (139635). T.N. has been supported by the Finnish Medical Foundation, the Emil Aaltonen Foundation, the Paavo Nurmi Foundation, and the Academy of Finland (321351). The DanMONICA cohorts at the Research Center for Prevention and Health were established over a period of 10 years and have been funded by numerous sources which have been acknowledged, where appropriate, in the original articles. The Moli-sani Project was partially supported by research grants from Pfizer Foundation (Rome, Italy), the Italian Ministry of University and Research (MIUR, Rome, Italy)–Programma Triennale di Ricerca, Decreto n.1588 and Instrumentation Laboratory, Milan, Italy. The Northern Sweden MONICA project was supported by Norrbotten and Västerbotten County Councils. S.S. has been supported by the Swedish Heart–Lung Foundation (20140799, 20120631, 20100635), the County Council of Västerbotten (ALF, VLL-548791) and Umeå University. The Tromsø Study was supported by the UiT Arctic University of Norway, the municipality of Tromsø, the Norwegian Research Council and the National Health Screening Service. T.Z. is supported by the German Center of Cardiovascular Reseasrch (Grant 81Z1710101, Partner site Project).
Publisher Copyright:
© 2019 Published on behalf of the European Society of Cardiology. All rights reserved.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
KW - Atrial fibrillation
KW - Cohort study
KW - Ischaemic stroke
KW - Temporal relationship
UR - http://www.scopus.com/inward/record.url?scp=85083042692&partnerID=8YFLogxK
U2 - 10.1093/europace/euz312
DO - 10.1093/europace/euz312
M3 - Article
C2 - 31740944
AN - SCOPUS:85083042692
SN - 1099-5129
VL - 22
SP - 522
EP - 529
JO - Europace
JF - Europace
IS - 4
ER -