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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 and von Sarnowski, Bettina, et al. (2017) In European Stroke Journal 2(2). p.116-125
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... (More)

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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keywords
Brain infarction, echocardiography, electrocardiography, embolism, middle aged, paradoxical embolism, patent foramen ovale, prognosis, risk factors, stroke, thrombosis, young adult
in
European Stroke Journal
volume
2
issue
2
pages
10 pages
publisher
SAGE Publications Inc.
external identifiers
  • scopus:85060508142
ISSN
2396-9873
DOI
10.1177/2396987317703210
language
English
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yes
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fce74cee-9719-46fa-9df6-ccf15e744f68
date added to LUP
2019-02-11 09:08:48
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2019-10-15 06:58:23
@article{fce74cee-9719-46fa-9df6-ccf15e744f68,
  abstract     = {<p>Background: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged &lt;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.</p>},
  author       = {Putaala, Jukka and Martinez-Majander, Nicolas and Saeed, Sahrai and Yesilot, Nilufer and Jäkälä, Pekka and Nerg, Ossi and Tsivgoulis, Georgios and Numminen, Heikki and Gordin, Daniel and von Sarnowski, Bettina and Waje-Andreassen, Ulrike and Ylikotila, Pauli and Roine, Risto O. and Zedde, Marialuisa and Huhtakangas, Juha and Fonseca, Catarina and Redfors, Petra and de Leeuw, Frank Erik and Pezzini, Alessandro and Kõrv, Janika and Schneider, Siim and Tanislav, Christian and Enzinger, Christian and Jatuzis, Dalius and Siegerink, Bob and Martínez-Sánchez, Patricia and Grau, Armin J. and Palm, Frederick and Groop, Per Henrik and Lanthier, Sylvain and Ten Cate, Hugo and Pussinen, Pirkko and Paju, Susanna and Sinisalo, Juha and Lehto, Mika and Lindgren, Arne and Ferro, José and Kittner, Steven and Fazekas, Franz and Gerdts, Eva and Tatlisumak, Turgut},
  issn         = {2396-9873},
  keyword      = {Brain infarction,echocardiography,electrocardiography,embolism,middle aged,paradoxical embolism,patent foramen ovale,prognosis,risk factors,stroke,thrombosis,young adult},
  language     = {eng},
  month        = {06},
  number       = {2},
  pages        = {116--125},
  publisher    = {SAGE Publications Inc.},
  series       = {European Stroke Journal},
  title        = {Searching for Explanations for Cryptogenic Stroke in the Young : Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design},
  url          = {http://dx.doi.org/10.1177/2396987317703210},
  volume       = {2},
  year         = {2017},
}