Sex-Genetic Interaction in the Risk for Cerebrovascular Disease

Cerebrovascular disease (CeVD) is one of the major causes of death and a leading cause of disability worldwide. CeVD is a complex and multifactorial disease caused by the interaction of environment and genetic factors. Women have lower CeVD incidence than men until an advanced age, when the incidence of CeVD rises dramatically in women. Therefore, sex has been validated as an important risk factor in the etiology of CeVD, especially ischemic stroke. Although the importance of sex steroids have been heavily studied in the mechanism of neuronal injury, the experimental and clinical data suggest that hormones do not fully account for male versus female CeVD patterns. Sex-specific genetic processes have been implicated in the different rate of risk for atherosclerosis and CeVD. In this review, we discuss sex-specific CeVD processes, describe the hormonal impact on the risk for CeVD, the results from studies in transgenic animals, and from human genetic studies. Moreover, heritability of ischemic stroke in women and men as well as identification of possible sex-specific biomarkers for CeVD are discussed. Understanding the complex interactions between hormonal and genetic mechanisms in the CeVD risk will allow for new sex-specific approaches in disease treatment and prevention in clinical practice.