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Healthcare Professionals

Ischemia Care Overview for Healthcare Professionals

Ischemia Care is built around the vision that being able to effectively diagnose stroke cause will lead to better outcomes for stroke victims.

Ischemia Care has conducted a major clinical trial, BASE  , recruiting over 1700 subjects, based upon significant peer reviewed published research, leading to the development and analytical validation of a blood test for cause of stroke based upon RNA expression using whole blood called ISCDX.

Ischemia Care created a laboratory division called “Ischemic Stroke Lab” to clinically offer ISCDX.

Future development will include point of care testing to triage patients (such as stroke y/n), additional etiology testing (lacunar stroke, atrial fibrillation, ESUS and other known causes), as well as developing personalized medicine strategies for interventional techniques, therapeutics, and devices.

Ischemia Care provides information on stroke mechanisms based upon blood

Ischemic stroke, in most cases, is a disease of the vasculature and blood, involving platelets, red blood cells, clotting factors, inflammatory cells, and endothelium. In simple terms, blood can provide a window into the mechanisms that cause stroke  .

Ischemic stroke and secondary prevention

Acute ischemic stroke (AIS) remains a leading cause of mortality and morbidity in the United States, affecting over 800,000 adults annually, leaving many with permanent disability. Furthermore, hundreds of thousands of Americans experience a transient ischemic attack (TIA) which often precedes a major stroke and serves as a warning for future ischemic events. Despite symptoms resolving, experiencing a TIA increases the risk of stroke by 20% within 90 days. Collectively, previous stroke and TIA confer an annual recurrent stroke risk of 3-4%.3 Emergent evaluation, prompt acute treatment, and identification of stroke or TIA etiology for secondary prevention are necessary to decreasing the morbidity and mortality of cerebrovascular disease    .

Cryptogenic stroke is a stroke of unknown cause

The most common causes of ischemic stroke are large-artery atherosclerosis, cardioembolism, small-vessel disease, other known causes, and cryptogenic. Cryptogenic strokes, or due to unknown cause, account for 10 to 40% of all ischemic strokes. Roughly 30-40% of first time strokes are cryptogenic. It is necessary to establish the cause of stroke to select appropriate preventative care.

Secondary prevention differs by cause

Key to treatment and prevention is the identification of stroke etiology, since secondary prevention measures differ based on stroke subtype. Typically, antithrombotic therapy is initiated for cardioembolic stroke, while antiplatelet agents are used for to prevent non-cardioembolic stroke, in addition to risk factor modification for all patients with stroke and TIA.  The diagnosis of ischemic stroke subtype stems from a combination of patient history, clinical assessment, and cerebrovascular and cardiovascular evaluation. However, even with extensive testing, identifying the cause of cerebrovascular ischemia is challenging. This represents danger for the patient because when a definitive cause is not identified the stroke is defined as cryptogenic in origin and definitive prevention measures are unclear.  Therefore, there is a great need to understand the pathogenesis of acute ischemic stroke in order to develop more effective preventative measures. Recent studies have suggested whole blood RNA expression may differentiate major ischemic stroke types        .

BASE clinical trial (NCT02014896)

The Biomarkers of Acute Stroke Etiology (BASE) study (NCT02014896) is a multicenter observational study utilizing RNA gene expression in to identify the etiology of acute ischemic stroke. When a stroke or TIA occurs, the immune system reacts by changes in gene expression in multiple cell lines, related to activation of innate and adaptive immune systems.  The Ischemia Care platform consists of whole blood biomarker tests determining the etiology of ischemic stroke (ISCDX) by measuring gene expression changes caused by acute ischemic stroke  .

Significant peer reviewed published research

Previous studies have suggested that differential gene expression is a function of stroke subtype      . Thus each test provides a “signature” of genes in which each is uniquely expressed from different stroke etiologies.   For example, the ISCDX test distinguishes between cardioembolic and large artery atherosclerotic stroke using a signature of 40 – 50 genes. A patient’s pattern of up or down gene regulation can determine if the etiology is that of a cardioembolic stroke or if it is the result of a large artery atherosclerotic stroke. Further, a separate 37 gene signature can differentiate whether cardioembolic strokes are caused by atrial fibrillation (AF) or not  .

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References:

  1. Biomarkers of Acute Stroke Etiology (BASE) Study Methodology, Jauch, E.C., Barreto, A.D., Broderick, J.P. et al. Transl. Stroke Res. (2017) 8: 424. https://doi.org/10.1007/s12975-017-0537-3.

  2. Sharp, et al. Molecular markers and mechanisms of stroke: RNA studies of blood in animals and humans, Journal of Cerebral Blood Flow & Metabolism (2011) 31, 1513–1531; doi:10.1038/jcbfm.2011.45;  

  3. Dhamoon MS, Sciacca RR, Rundek T, Sacco RL, Elkind MS. Recurrent stroke and cardiac risks after first ischemic stroke: the Northern Manhattan Study. Neurology 2006;66:641-6

  4. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke; a journal of cerebral circulation 2014;45:2160-236.

  5. Jickling GC, Xu H, Stamova B, et al. Signatures of cardioembolic and large-vessel ischemic stroke. Ann Neurol 2010;68:681-92.

  6. Stamova B, Jickling GC, Ander BP, et al. Gene expression in peripheral immune cells following cardioembolic stroke is sexually dimorphic. PloS one 2014;9:e102550.

  7. Stamova B, Xu H, Jickling G, et al. Gene expression profiling of blood for the prediction of ischemic stroke. Stroke; a journal of cerebral circulation 2010;41:2171-

  8. Tian Y, Stamova B, Jickling GC, et al. Effects of gender on gene expression in the blood of ischemic stroke patients. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 2012;32:780-91.

  9. Jickling GC, Stamova B, Ander BP, et al. Prediction of cardioembolic, arterial, and lacunar causes of cryptogenic stroke by gene expression and infarct location. Stroke; a journal of cerebral circulation 2012;43:2036-41.