The three-year cumulative risk of a recurrent stroke, dependent on aetiology, is up to 25 per cent. At present, preventing recurrence relies on a broad approach to reduce risk factors associated with atherosclerosis, heart disease and metabolic disorders. However, more specific interventions, such as anticoagulation and surgery or stenting, need aetiologic information. BIOSIGNAL aims to determine where the most promising biomarkers can help identify stroke aetiology and also predict recurrent stroke. In addition, the insights gained into the processes underlying different stroke subtypes may lead to more targeted diagnostic tools.
Objectives and specific aims:
The investigators propose to prospectively evaluate the predictive value of the most promising blood biomarkers to identify treatable stroke etiologies on admission and risk of recurrence in 3000 consecutive ischemic stroke patients enrolled by 10 centers in Europe and the US.
The clinical endpoints of the study are 1) recurrent stroke within one year, 2) all types of atrial fibrillation (AF) detected on admission or by prolonged ambulatory cardiac rhythm monitors, 3) presence of cerebrovascular atherosclerosis detected by ultrasound investigations and 4) new silent ischemic brain lesions and progression of chronic cerebral ischemic lesion volume detected by repeated magnetic resonance imaging (MRI and MRA) and (i.e. on admission and after 12 months).
Aim 1: To determine whether the proposed biomarkers independently predict recurrent stroke among all patients. Hypothesis 1: Elevated levels of one or more of the proposed biomarkers will independently predict recurrent strokes during trial follow-up, assessed by structured interviews, as well as chart reviews 90 days and 1 year after the index stroke.
Aim 2: To determine whether cardioembolic (CE) biomarkers are associated with atrial fibrillation among all patients. Hypothesis 2: Baseline values of one or more of the proposed CE biomarkers will be independently associated with AF, including history of AF, AF detection at baseline, or AF detected during the follow up period by prolonged ambulatory cardiac rhythm monitors and structured interviews as well as chart reviews 90 days and 1 year after the index stroke.
Aim 3: To determine whether large artery atherosclerosis (LAA) biomarkers are associated with a) the presence of cerebrovascular atherosclerosis among all patients. Hypothesis 3: Baseline values of one or more of the proposed LAA biomarkers will be independently associated with the presence of extra and intracranial atherosclerosis among patients with ischemic stroke, assessed by duplex sonography.
Exploratory Aim 4: To determine whether the proposed biomarkers will predict b) new silent strokes and c) progression of chronic cerebral ischemic lesion (white matter hyper-intensity) volume (WMHV) among cryptogenic stroke patients. Hypothesis 4: Baseline values of one or more of the proposed biomarkers will independently predict a) silent stroke b) progression of WMHV, during study follow-up, assessed by repeated magnetic resonance imaging (MRI) (on admission, and 1 year after the index stroke).
This study will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, and Good Clinical Practice (GCP) guidelines as well as all national legal and regulatory requirements.
- Observation: Cohort
- Perspective: Prospective
- Sampling: Probability Sample
The BIOSIGNAL study will be a prospective observational multicenter cohort study to evaluate selected CE and LAA blood biomarkers in patients with incident ischemic stroke. We will consecutively recruit at least 300 patients per center (i.e. 10 centers, thus totally 3000 patients) over a time period of two years. All participants will be followed for 1 year.
|Type||Measure||Time Frame||Safety Issue|
|Primary||Recurrent stroke, including fatal stroke.||Within 1 year after the index event.||No|
|Secondary||Atrial Fibrillation (AF)||Within 3 month after the index stroke||No|
|Secondary||Cerebrovascular atherosclerosis||participants will be followed for the duration of hospital stay, an expected average of 5 days.||No|
|Secondary||Silent stroke||One year after the index stroke||No|
|Secondary||Progression of WMHV||Within one year after the index stroke||No|
Biospecimen Retention:Samples With DNA - Blood