Genetic and Hemostatic Risk Factors for Stroke Herik, E.G. van den 2011-12-06 Doctoral Thesis

Cardiovascular disorders are the main causes of death worldwide, with stroke accounting for 9-10% of all deaths1,2. Moreover, stroke is the most frequent cause of disability in the western world3. In the Netherlands alone, over 39,000 persons are admitted to hospitals with stroke each year4. There are two main types of stroke; ischemic stroke (occurring in about 80% of cases) and hemorrhagic stroke (20%). Hemorrhagic strokes can be further subdivided into intracerebral hemorrhage (15%) and subarachnoid hemorrhage (5%). In ischemic stroke, an artery or arteriole is blocked by thrombosis or an embolus, impeding blood flow to a part of the brain and causing tissue damage in the supplied territory. Intracerebral hemorrhage, on the other hand, results from rupture of a blood vessel, leading to the formation of a hematoma in the brain parenchyma. Although ischemic stroke and intracerebral hemorrhage are in a way opposite, they share several risk factors such as coagulation abnormalities, atherosclerosis and cardiac disorders. It is known that individuals with a positive family history for cardiovascular diseases have a higher risk of stroke. This may be explained by shared environmental risk factors and socioeconomic status, similar dietary habits (e.g. high cholesterol intake), but most obviously by common genetic material. The observation of increased risk of cerebrovascular disease in first degree relatives of stroke patients has fostered the notion of a genetic component of stroke. Until a few years ago, knowledge of the genetic background of stroke risk was limited, and mostly derived from small, family-based linkage studies5. Since the beginning of this millennium, however, advances in genomics have skyrocketed, paving the way for very large genetic studies6. New genetic risk factors are discovered continuously, rapidly increasing our knowledge on the genetics of complex diseases. Also in stroke, these studies are being undertaken to gain more insight in the role of genetic factors in stroke etiology.

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