The exact mecha- nism whereby metabolic syndrome affects cardiovascular risk is unknown; it is thought that components of the syndrome synergistically increase vascular risk through mechanisms that include insulin resistance, hypercoagulability, endothelial dysfunction, and inflammation. Studies suggest that meta- bolic syndrome confers a higher stroke risk on women than and metabolic syndrome accounts for a larger percentage of stroke events in women than in men (30% ver- The mechanisms for this difference are not completely understood. Pathophysiologic Mechanisms of Obesity, Abdominal Adiposity, and Metabolic Syndrome That Affect Stroke Risk The pathophysiological mechanisms by which general obesity increases stroke risk remain unclear. One proposed mecha- nism is that obesity is associated with a prothrombotic and BMI is directly associated with fibrinogen, factor VII, plasminogen activator inhibitor, and tis- sue-type plasminogen activator antigen levels in both men and Similar associations are present between abdomi- nal obesity and hemostatic factors. These associations persist after controlling for age, smoking, total and high- density lipo- protein cholesterol, triglycerides, glucose level, BP, and use of In addition, higher levels of acute phase reactants such as C-reactive protein may decrease endothelial cell production of nitric oxide, which may in turn instigate a cascade of events leading to vasoconstriction, leu- kocyte adherence, platelet activation, oxidation, and thrombo- Attenuation of the protective effect of high-density attributable to general obesity may also play a role. The biological pathways by which abdomi- nal adiposity increases stroke risk are also not yet understood, but platelet activation, inflammation, endothelial dysfunction, or an overactive endocannabinoid system335 may all serve key roles in the process. In addition, increased very low-density lipoprotein production caused by the high lipolytic activity of abdominal adipose tissue304,312 may increase stroke risk. 