Although it is well documented that, prior to menopause, women develop heart disease less frequently than men of similar age, evidence is accumulating that women are at a greater risk when it does develop. For example, women suffer greater complications and have a higher mortality risk from heart attack and when they undergo procedures such as coronary artery bypass surgery. The reasons for this increased risk in women is unexplained. As well, in response to long-term increases in blood pressure ("hypertension"), women appear to suffer from a greater degree of heart enlargement than men, which puts women at a greater risk for sudden death and heart failure. Using an animal model (rats), we have verified that females develop larger hearts than males in response to elevations in blood pressure, and that this increase is modulated by the hormone estrogen. Specifically, when estrogen is present, the degree of enlargement is greater than when it is absent. Surprisingly, this greater amount of heart enlargement in females occurred even under normal blood pressure conditions. This suggests that females have an inherent property that leads to a larger heart than males under similar conditions, which may be related to estrogen. When blood flow to the heart is reduced or stopped, as in heart attack or during bypass surgery, the energy producing mechanisms of the heart switch to pathways that are less efficient and that ultimately lead to the production of harmful by-products. We have shown in an animal model, that the molecules that control these alternate pathways ("enzymes") are more active in female versus male hearts both in the presence and absence of hypertension. If this occurs in humans, it may help to explain the increased risk for women experiencing reduced blood flow to the heart, since the increased use of alternative energy pathways would increase the production of harmful by-products. The activity of these enzymes also appears to be modulated by hormones.
Together, these findings may begin to explain the clinical findings of increased heart enlargement and risk from heart attack in women. This may lead to the development of gender-specific treatment and improve outcome for women suffering from heart disease.