Searching for Explanations for Cryptogenic Stroke in the Young

Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design

Jukka Putaala, Nicolas Martinez-Majander, Sahrai Saeed, Nilufer Yesilot, Pekka Jäkälä, Ossi Nerg, Georgios Tsivgoulis, Heikki Numminen, Daniel Gordin, Bettina von Sarnowski, Ulrike Waje-Andreassen, Pauli Ylikotila, Risto O. Roine, Marialuisa Zedde, Juha Huhtakangas, Catarina Fonseca, Petra Redfors, Frank Erik de Leeuw, Alessandro Pezzini, Janika Kõrv & 21 others Siim Schneider, Christian Tanislav, Christian Enzinger, Dalius Jatuzis, Bob Siegerink, Patricia Martínez-Sánchez, Armin J. Grau, Frederick Palm, Per Henrik Groop, Sylvain Lanthier, Hugo Ten Cate, Pirkko Pussinen, Susanna Paju, Juha Sinisalo, Mika Lehto, Arne Lindgren, José Ferro, Steven Kittner, Franz Fazekas, Eva Gerdts, Turgut Tatlisumak

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. Key hypotheses/aims: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient–control pairs enrolled by the end of 2018. Summary: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.

Original languageEnglish (US)
Pages (from-to)116-125
Number of pages10
JournalEuropean Stroke Journal
Volume2
Issue number2
DOIs
StatePublished - Jun 1 2017

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Stroke
Hemostasis
Thrombosis
RNA Sequence Analysis
Gene Expression
Patent Foramen Ovale
Systems Analysis
Embolism
Causality
Echocardiography
Reading
Electrocardiography
Biomarkers
Therapeutics

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Searching for Explanations for Cryptogenic Stroke in the Young : Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design. / Putaala, Jukka; Martinez-Majander, Nicolas; Saeed, Sahrai; Yesilot, Nilufer; Jäkälä, Pekka; Nerg, Ossi; Tsivgoulis, Georgios; Numminen, Heikki; Gordin, Daniel; von Sarnowski, Bettina; Waje-Andreassen, Ulrike; Ylikotila, Pauli; Roine, Risto O.; Zedde, Marialuisa; Huhtakangas, Juha; Fonseca, Catarina; Redfors, Petra; de Leeuw, Frank Erik; Pezzini, Alessandro; Kõrv, Janika; Schneider, Siim; Tanislav, Christian; Enzinger, Christian; Jatuzis, Dalius; Siegerink, Bob; Martínez-Sánchez, Patricia; Grau, Armin J.; Palm, Frederick; Groop, Per Henrik; Lanthier, Sylvain; Ten Cate, Hugo; Pussinen, Pirkko; Paju, Susanna; Sinisalo, Juha; Lehto, Mika; Lindgren, Arne; Ferro, José; Kittner, Steven; Fazekas, Franz; Gerdts, Eva; Tatlisumak, Turgut.

In: European Stroke Journal, Vol. 2, No. 2, 01.06.2017, p. 116-125.

Research output: Contribution to journalArticle

Putaala, J, Martinez-Majander, N, Saeed, S, Yesilot, N, Jäkälä, P, Nerg, O, Tsivgoulis, G, Numminen, H, Gordin, D, von Sarnowski, B, Waje-Andreassen, U, Ylikotila, P, Roine, RO, Zedde, M, Huhtakangas, J, Fonseca, C, Redfors, P, de Leeuw, FE, Pezzini, A, Kõrv, J, Schneider, S, Tanislav, C, Enzinger, C, Jatuzis, D, Siegerink, B, Martínez-Sánchez, P, Grau, AJ, Palm, F, Groop, PH, Lanthier, S, Ten Cate, H, Pussinen, P, Paju, S, Sinisalo, J, Lehto, M, Lindgren, A, Ferro, J, Kittner, S, Fazekas, F, Gerdts, E & Tatlisumak, T 2017, 'Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design', European Stroke Journal, vol. 2, no. 2, pp. 116-125. https://doi.org/10.1177/2396987317703210
Putaala, Jukka ; Martinez-Majander, Nicolas ; Saeed, Sahrai ; Yesilot, Nilufer ; Jäkälä, Pekka ; Nerg, Ossi ; Tsivgoulis, Georgios ; Numminen, Heikki ; Gordin, Daniel ; von Sarnowski, Bettina ; Waje-Andreassen, Ulrike ; Ylikotila, Pauli ; Roine, Risto O. ; Zedde, Marialuisa ; Huhtakangas, Juha ; Fonseca, Catarina ; Redfors, Petra ; de Leeuw, Frank Erik ; Pezzini, Alessandro ; Kõrv, Janika ; Schneider, Siim ; Tanislav, Christian ; Enzinger, Christian ; Jatuzis, Dalius ; Siegerink, Bob ; Martínez-Sánchez, Patricia ; Grau, Armin J. ; Palm, Frederick ; Groop, Per Henrik ; Lanthier, Sylvain ; Ten Cate, Hugo ; Pussinen, Pirkko ; Paju, Susanna ; Sinisalo, Juha ; Lehto, Mika ; Lindgren, Arne ; Ferro, José ; Kittner, Steven ; Fazekas, Franz ; Gerdts, Eva ; Tatlisumak, Turgut. / Searching for Explanations for Cryptogenic Stroke in the Young : Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design. In: European Stroke Journal. 2017 ; Vol. 2, No. 2. pp. 116-125.
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abstract = "Background: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50{\%} can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. Key hypotheses/aims: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient–control pairs enrolled by the end of 2018. Summary: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.",
author = "Jukka Putaala and Nicolas Martinez-Majander and Sahrai Saeed and Nilufer Yesilot and Pekka J{\"a}k{\"a}l{\"a} and Ossi Nerg and Georgios Tsivgoulis and Heikki Numminen and Daniel Gordin and {von Sarnowski}, Bettina and Ulrike Waje-Andreassen and Pauli Ylikotila and Roine, {Risto O.} and Marialuisa Zedde and Juha Huhtakangas and Catarina Fonseca and Petra Redfors and {de Leeuw}, {Frank Erik} and Alessandro Pezzini and Janika K{\~o}rv and Siim Schneider and Christian Tanislav and Christian Enzinger and Dalius Jatuzis and Bob Siegerink and Patricia Mart{\'i}nez-S{\'a}nchez and Grau, {Armin J.} and Frederick Palm and Groop, {Per Henrik} and Sylvain Lanthier and {Ten Cate}, Hugo and Pirkko Pussinen and Susanna Paju and Juha Sinisalo and Mika Lehto and Arne Lindgren and Jos{\'e} Ferro and Steven Kittner and Franz Fazekas and Eva Gerdts and Turgut Tatlisumak",
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TY - JOUR

T1 - Searching for Explanations for Cryptogenic Stroke in the Young

T2 - Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design

AU - Putaala, Jukka

AU - Martinez-Majander, Nicolas

AU - Saeed, Sahrai

AU - Yesilot, Nilufer

AU - Jäkälä, Pekka

AU - Nerg, Ossi

AU - Tsivgoulis, Georgios

AU - Numminen, Heikki

AU - Gordin, Daniel

AU - von Sarnowski, Bettina

AU - Waje-Andreassen, Ulrike

AU - Ylikotila, Pauli

AU - Roine, Risto O.

AU - Zedde, Marialuisa

AU - Huhtakangas, Juha

AU - Fonseca, Catarina

AU - Redfors, Petra

AU - de Leeuw, Frank Erik

AU - Pezzini, Alessandro

AU - Kõrv, Janika

AU - Schneider, Siim

AU - Tanislav, Christian

AU - Enzinger, Christian

AU - Jatuzis, Dalius

AU - Siegerink, Bob

AU - Martínez-Sánchez, Patricia

AU - Grau, Armin J.

AU - Palm, Frederick

AU - Groop, Per Henrik

AU - Lanthier, Sylvain

AU - Ten Cate, Hugo

AU - Pussinen, Pirkko

AU - Paju, Susanna

AU - Sinisalo, Juha

AU - Lehto, Mika

AU - Lindgren, Arne

AU - Ferro, José

AU - Kittner, Steven

AU - Fazekas, Franz

AU - Gerdts, Eva

AU - Tatlisumak, Turgut

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Background: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. Key hypotheses/aims: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient–control pairs enrolled by the end of 2018. Summary: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.

AB - Background: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. Key hypotheses/aims: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient–control pairs enrolled by the end of 2018. Summary: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.

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