Why Is a Woman Different from a Man, at Least as Far as Stroke Risk?

Abstract & Commentary

By Dara Jamieson, MD, Associate Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Jamieson reports she is a retained consultant for Boehringer Ingelheim, Merck, and Ortho-McNeil, and is on the speaker's bureau for Boehringer Ingelheim and Merck.

Synopsis: An increased prevalence of atrial fibrillation leads to an increase in arterial territorial strokes in women. Hormonal risk factors are responsible for the increased risk of cerebral venous thrombosis in women, as compared to men.

Sources: Förster A, Gass A, Kern R, et al. Gender differences in acute ischemic stroke: Etiology, stroke patterns and response to thrombolysis. Stroke 2009;40:2428-2432; Coutinho JM, Ferro JM, Canhão P, et al. Cerebral venous and sinus thrombosis in women. Stroke 2009;40:2356-2361.

Men and women have different predilections for stroke types and clinical outcomes, for reasons that are incompletely understood. Förster and colleagues compared baseline characteristics, etiology, CT/MRI stroke patterns, clinical outcome, and complications of 237 women (46.8%) and men (53.2%) with acute ischemic stroke (AIS) who were treated in a stroke unit, from 2004 to 2007, with recombinant tissue plasminogen activator (rtPA) within three hours after onset of symptoms. Women were older (P=0.001), but a history of hyperlipidemia (P=0.03), smoking (P=0.03), and coronary heart disease (CHD) (P<0.001) was less frequent than in men. The definite or probable cause of the AIS could be identified in only 65.4% of patients, with internal carotid artery disease more often in men (P=0.02) and atrial fibrillation more often in women (P=0.002). On MRI evaluation, borderzone/small embolic and lacunar stroke was found more frequently (39.7 versus 27.2%) in men, whereas women were more likely to have a large territorial stroke (72.8 versus 60.3%, P=0.09). Baseline and discharge National Institute of Health Stroke Scale scores, three-month-outcome modified Rankin Scale score, thrombolysis-related or independent complications, and mortality after three months were similar. Rates of rtPA-related and independent complications, as well as clinical outcomes, were not different between women and men with AIS. Persistent vessel occlusion after thrombolysis was found more often in large vessel disease compared to cardioembolic infarct, but was not independently gender-dependent.

Coutinho and colleagues used data from the International Study on Cerebral Vein and Dural Sinus Thrombosis, a multicenter prospective observational study, to analyze gender-specific differences in clinical presentation, etiology, and outcome of cerebral venous thrombosis (CVT), a female-predominant cause of venous infarction with secondary intracerebral hemorrhage. The women in the study (465 / 624) were significantly younger and were more likely to have headache at presentation, with more rapid onset of symptoms. A gender-specific risk factor (oral contraceptives, pregnancy, puerperium, and hormonal replacement therapy) was present in 65% of women with CVT. No risk factor (including thrombophilia, infection, or malignancy) was identified in 8% of women and 25% of men, although only about 80% of both genders had a complete evaluation. Women had a better prognosis than men (complete recovery 81% versus 71%; P=0.01) due to a better outcome in female patients with gender-specific risk factors. Women without gender-specific risk factors were similar to men in clinical presentation, risk factor profile, and outcome. Logistic regression analysis confirmed that the absence of gender-specific risk factors was a strong and independent predictor of poor outcome in women with sinus thrombosis (OR, 3.7; CI, 1.9 to 7.4), whereas women with a gender-specific risk factor for CVT had a much better prognosis.

Commentary

Women are different from men in both arterial and venous stroke risk. Gender differences in arterial stroke may be related to increased age (increased prevalence of atrial fibrillation and increased disability) as well as fewer risk factors (decreased prevalence of CHD, smoking and hyperlipidemia) in women at the time of stroke. Gender differences in venous stroke are related to female hormonal changes, both exogenous and pregnancy-related. Despite gender-specific risk for stroke, outcome after stroke treatment of both types is not specifically gender- dependent in the studies cited. However, older studies have indicated worse functional outcome in women after an ischemic stroke, perhaps related to their increased age and more tenuous social support at the time of stroke.

Recognition of the gender differences in stroke types can identify individuals at increased risk, with the goal of stroke prevention and individualized treatment. However, men and women have similar treatment outcomes, indicating that aggressive, appropriately gender-blind therapy is indicated for both ischemic and venous stroke.