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Prof. Dr. med. MSc Mira Katan

Department of Clinical Research
Profiles & Affiliations

Stroke

Early Risk Stratification After Stroke

After identifying copeptin as a novel hypothalamic stress marker in 2007 she could demonstrate that it improved currently used risk stratification algorithms of stroke patients. To externally validate the incremental value of copeptin she performed an independent international multi-center cohort study. With her team they further aimed at assessing copeptin’s reliability for risk stratification in patients with transient ischemic attacks (TIAs) and they were able to validate these results again in an independent international multicenter cohort study. Thus routine copeptin measurement is an additional tool for risk stratification and targeted resource allocation after stroke and TIA. A new prognostic score based on copeptin levels has been developed and is available to the community to use in clinical practice.


Novel Risk Factor Identification For Primary Prevention

Based on epidemiological data chronic infections and neuroendocrine dysfunction may play a role in the development of incident ischemic stroke. She identified procalcitonin (PCT) as a marker of chronic infection, as well as mid-regional pro atrial natriuretic peptide (MR-proANP) as a marker of underlying cardiopathy and hemodynamic stress. Both were highly associated with ischemic stroke risk during a median follow up time of 11 years in the Northern Manhattan Stroke cohort (one of the largest population base stroke studies). PCT was specifically associated with small vessel and MRproANP with cardioembolic stroke risk.


Identification Of Underlying Stroke Etiology For Secondary Prevention

She also identified mid-regional pro atrial natriuretic peptide (MR-proANP) as new independent and reliable diagnostic marker for cardioembolic etiology in acute stroke patients. Together with her team they were able to further validate MR-proANP as a surrogate cardio-embolic (CE) stroke marker in a multicenter study (CoRisk study n=788).In a next step they were able to validate the pre-specified MR-proANP cut off for the identification of CE stroke. Finally, MR-proANP predicted the future detection of AF during the one-year follow-up period of the BIOSIGNAL study (n=1800). Based on these results, demonstrating that MRproANP is a validated marker of underlying cardioembolic stroke mechanism, she is currently conducting the first blood biomarker guided secondary preventive acute stroke RCT (The MOSES-trial) mainly funded by the SNF.

Moreover, her group was able to show in a multicenter cohort study of 1733 stroke patients that lipoprotein (a), a lipoprotein composed of apolipoprotein B-100 and apolipoprotein(a) is an novel independent and reliable diagnostic marker for large artery atherosclerotic (LAA) stroke. In this study age was found to be a potent effect modifier resulting in an even stronger relationship of Lp(a) with LAA stroke among patients age < 60 years an often understudied patient group. Among these younger stroke patients Lp(a) levels ≥100 nmol/l were also associated with an increased risk for recurrent events, with an adjusted hazard ratio (HR) of 2.40, (95% CI 1.05-5.47).

In conclusion, in the last years she has built up large acute stroke cohort studies (with a biobank including more than 2500 samples).

Selected Publications

Schweizer J, Arnold M, König IR, Bicvic A, Westphal LP, Schütz V, Inauen C, Scherrer N, Luft A, Galovic M, Ferreira Atuesta C, Pokorny T, Arnold M, Fischer U, Bonati LH, De Marchis GM, Kahles T, Nedeltchev K, Cereda CW, et al. (2022). Measurement of Midregional Pro-Atrial Natriuretic Peptide to Discover Atrial Fibrillation in Patients With Ischemic Stroke. Journal of the American College of Cardiology, 79(14), 1369–1381. https://doi.org/10.1016/j.jacc.2022.01.042

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Arnold M, Schweizer J, Nakas CT, Schütz V, Westphal LP, Inauen C, Pokorny T, Luft A, Leichtle A, Arnold M, Bicvic A, Fischer U, De Marchis GM, Bonati LH, Müller MD, Kahles T, Nedeltchev K, Cereda CW, Kägi G, et al. (2021). Lipoprotein(a) is associated with large artery atherosclerosis stroke aetiology and stroke recurrence among patients below the age of 60 years: Results from the BIOSIGNAL study. European Heart Journal, 42(22), 2186–2196. https://doi.org/10.1093/eurheartj/ehab081

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De Marchis, Gian Marco, Dankowski, Theresa, König, Inke R., Fladt, Joachim, Fluri, Felix, Gensicke, Henrik, Foerch, Christian, Findling, Oliver, Kurmann, Rebekka, Fischer, Urs, Luft, Andreas, Buhl, Daniela, Engelter, Stefan T., Lyrer, Philippe A., Christ-Crain, Mirjam, Christ-Crain, Mirjam, Arnold, Marcel, & Katan, Mira. (2019). A novel biomarker-based prognostic score in acute ischemic stroke: The CoRisk score. Neurology, 92(13), e1517–e1525. https://doi.org/10.1212/wnl.0000000000007177

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De Marchis, Gian Marco, Schneider, Juliane, Weck, Anja, Fluri, Felix, Fladt, Joachim, Foerch, Christian, Mueller, Beat, Luft, Andreas, Christ-Crain, Mirjam, Arnold, Marcel, & Katan, Mira. (2018). Midregional proatrial natriuretic peptide improves risk stratification after ischemic stroke. Neurology, 90, e455–e465. https://doi.org/10.1212/wnl.0000000000004922

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Katan M., Moon Y., Von Eckardstein A., Spanaus K., Derosa J., Gutierrez J., Decarli C., Wright C., Sacco R., & Elkind M. (2017). Procalcitonin and Midregional Proatrial Natriuretic Peptide as Biomarkers of Subclinical Cerebrovascular Damage: The Northern Manhattan Study. Stroke, 48(3), 604–610. https://doi.org/10.1161/strokeaha.116.014945

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Selected Projects & Collaborations

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CiRculating mEdiators of Stroke reCurrENce anD aetiOlogies: the CRESCENDO Consortium

Research Project  | 1 Project Members

Patients who suffered ischaemic stroke are at high risk for a recurrent cerebrovascular event. Despite all efforts in secondary prevention, stroke is still among the top causes for invalidity and death. Traditionally, risks for stroke recurrence are thought to be based on categorized stroke aetiologies and the amount of vascular risk factors. This concept however does not sufficiently reflect the complex pathophysiology and thus comes along with substantial issues. Rather, it appears probable that circulating mediators related to the extent of acute and chronic brain damage in concert with aetiological mechanisms and underlying comorbidities influence the risk for recurrent cerebrovascular events. With the CiRculating mEdiators of Stroke reCurrENce anD aetiOlogies (CRESCENDO) consortium, we aim to address this hypothesis. CRESCENDO will utilize existing biosample collections from a total of over 5,000 thoroughly evaluated patients at the three study sites in Hannover, Seville and Basel/Zurich. We on the one hand will investigate well-characterized biomarkers of cerebral damage, inflammation, immunothrombosis and stress in a hypothesis-driven approach and on the other hand explore predictive targets via a data-driven approach applying proteomics. The objective of this collaboration is to initiate a paradigm shift towards an integrated pathophysiology-based evaluation of individual cerebrovascular risks and to identify innovative approaches for secondary stroke prevention.