Heart of the Matter

Abstract

Stroke is the leading neurological cause of death and disability, but, despite awareness of many modifiable vascular risk factors for stroke, the United States continues to record 800 000 events each year. Identifying circulating biomarkers associated with a disease outcome, such as stroke or coronary heart disease, has been a time-honored method to improve our understanding of disease pathophysiology and improve risk prediction, but it has proven challenging to identify such markers associated with stroke risk.1 In a recent attempt to identify circulating biomarkers associated with stroke, higher levels of B-type natriuretic peptide (BNP) were found, along with an elevated urinary albumin/creatinine ratio, to be associated with a 30% to 40% greater risk of stroke and transient ischemic attack.2 Natriuretic peptides are biologically plausible biomarkers for stroke risk because of their role in regulation of intravascular volume and blood pressure, and their relationship with cardiac structure and function. The prohormone of BNP, proBNP, is stored within granules in cardiac myocytes and is released when the cardiac myocytes are stretched; this happens with ventricular volume expansion or pressure overload. ProBNP is cleaved by a previously unknown enzyme into 2 fragments: the inactive N-terminal proBNP and the bioactive peptide BNP. The transmembrane serine protease responsible for this cleavage has recently been characterized in vitro and in animal models and named corin because of its abundant presence in the heart. 3,4 In this issue of Stroke, Peng et al 5 describe the results of a case-control study investigating the association of serum levels of corin with first-ever ischemic or hemorrhagic stroke. Consecutive stroke cases (481 ischemic and 116 hemorrhagic) were recruited from 3 Chinese hospitals during 5 months in 2014. Cases were compared with healthy community participants (2498 controls) randomly recruited in 2010 from the district of Suzhou, outside of Shanghai. Overall, women had lower median levels of serum soluble corin than men. In sexstratified analyses, persons with an ischemic or hemorrhagic stroke had lower levels than stroke-free controls. Both women and men were significantly more likely to have either type of stroke if their circulating corin levels were in the lowest quartile. In men, risk of ischemic stroke was 5-fold higher and risk of hemorrhagic stroke was 17.5-fold higher among persons with corin levels in the lowest quartile compared with persons with corin levels in the top quartile. In women, the risks were 3-and 8.5-fold higher, respectively, and risks persisted in multivariable analyses adjusting for conventional stroke risk factors. This is the first study of serum corin levels in stroke patients, and the results should be considered hypothesis generating. Further caution is warranted because the study was restricted to relatively young, Chinese patients with less severe strokes (median NIHSS score was 4).Corin is found in the heart and the kidneys. What are the potential pathoph...

Role of corin in the regulation of blood pressure

“…Low levels of serum corin were also associated with a high risk for major disability within 3 months after stroke [73]. Given the role of corin in regulating blood pressure, these new findings should encourage further investigations to understand the potential role of corin in stroke [74]. …”