Female sex is important ... in relation to thromboembolism in atrial fibrillation

Atrial fibrillation is the commonest heart rhythm condition.  Women with atrial fibrillation have a much higher risk for thromboembolic stroke than men suffering from the same condition. Despite being at higher risk, however, women are less likely than their male counterparts to receive appropriate stroke prevention treatments, that is, oral anticoagulation. Thus, female patients with atrial fibrillation should be aware of the elevated risk of stroke associated with their sex, get involved in decision making concerning anticoagulant therapy and see to it that at least their treatable stroke risk factors are reduced.

Atrial fibrillation is the commonest heart rhythm condition, and female sex is an independent risk factor for thromboembolism (especially stroke) in this condition.  The underlying reasons, i.e. the pathophysiological mechanisms, responsible for this increased risk of thromboembolism in women are not well understood. Thus Christina L. Cove, MD, vascular medicine specialist and current fellow in cardiology at Boston University Medical Center, MA, U.S.A., and her team published a ‘state of the art’ review  to explore potential underlying mechanisms for sex differences and to alert the public about the necessity of anticoagulant therapy in women. They noted that observational data suggest that these sex-based differences in stroke severity are not only related to differences in stroke risk factor profile and management, but also to underutilization of anticoagulant therapy in women.

Based on Virchow’s triad, thrombosis formation - eventually leading to thromboembolism (especially stroke) in patients suffering from atrial fibrillation - is based on three co-existing phenomena, i.e. structural abnormalities, blood stasis and a hypercoagulable state. In other words, clot formation occurs under conditions of altered blood flow, blood vessel abnormalities and hypercoaguability. Scientific evidence  in trying to explain the higher risk of thromboembolism among women with atrial fibrillation compared to men suggests that sex-related differences exist in the vasculature and structure of the heart muscle. These differences may predispose to alterations in blood flow, shear stress, and altered endothelial function. There may also be a potential sex-based increase, especially in the post-menopausal state, in systemic inflammatory and procoagulant markers, thrombogenic particles and platelet aggregation, all of which contribute to a prothrombotic milieu.

There are obvious deleterious changes following menopause, highlighting the need to specifically address the aging female population 65 years and older. Protective effects of endogenous estrogens may be lost after menopause, even if women are on hormone replacement therapy. The combined consequence of these changes in cardiac and vasculature structure along with loss of natural hormonal protection might explain the increased risk of thromboembolism in women with atrial fibrillation.

Therefore, the authors urged that it become imperative that healthcare providers aggressively treat modifiable risk factors for thromboembolism and stroke, such as diabetes and hypertension in this higher-risk patient population. Female sex is particularly important, especially in association with one or more such risk factors.

"Now that we know female patients carry an innately higher risk for thromboembolism especially stroke, oral anticoagulant therapy should be considered in these patients by health care providers, taking into account risks and benefits of various treatment options," Cove said. Future challenges in research might help to identify strategic targets amenable to intervention. In the meantime, however, there is an increased need for stroke prevention therapy and risk-factor reduction in women with atrial fibrillation.
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References

Cove CL, Albert CM, Andreotii F, et al.  Opens external link in new windowFemale Sex as an Independent Risk Factor for Stroke in Atrial Fibrillation: Possible Mechanisms. Thromb  Haemost 2014; 111: 385-391.

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