Gender differences Abbate

Symposium: Gender (dis)advantages in cardiac remodeling – lessons from mice and men. 934001

 Vienna, Austria, 4 September 2007: The topic of gender-related differences in cardiac care is an extremely complex one. Unfortunately women have been neglected in several fields of medicine for too long. I think that cardiology is only one of the many fields in the past where the male predominance was obvious. As most of the original studies tended to include more men, this generated the idea that women were less likely to be affected and because they presented differently from men were labeled as ‘atypical presentation’. In reality we never had enough data to define what ‘typical’ angina in women really is.

The differences between men and women are therefore not only biological but also social. Moreover the biology of heart disease is extremely complex as it involves differences in epidemiology and prevalence in risk factors, incidence of the inciting event, differences in the response to the insult, and differences in outcome, making therefore even more complex to appreciate true gender-dependent differences.

Many studies have shown that women with MI are usually diagnosed late during the course, are often misdiagnosed at first, are less likely to receive optimal medical care, and in many series their crude mortality is higher than men. This has lead to the idea that women are disadvantaged. Indeed they are disadvantaged if they are diagnosed late and if they are treated less aggressively (social disadvantage). The question whether they are biologically disadvantaged on the other hand is still debated. It is indeed plausible that female gender is protective toward adverse remodeling after MI.

After an insult (i.e. ischemia, infarct, pressure overload) the heart attempts to compensate by remodeling which usually entails hypertrophy of the walls and enlargement of cavity. This process although initially beneficial in maintaining an adequate cardiac output eventually leads to unfavorable outcome. It has been described that females (humans and animals) tend to have a prevalent hypertrophic response rather than dilatation of the cavity and this associated with preserved contractile function and overall better outcome. There may indeed be a gender-dependent difference in the pathway dominating the remodeling process. Several candidate molecules have been proposed but no definite data are available. An increased resistance to apoptosis in females is suggested.

The role of estrogens in gender-related differences in cardiac care is also complex. Estrogens play a major role in the difference in incidence of ischemic heart disease. As a general rule, premenopausal women have a more favorable lipid profile and are relatively protected from atherosclerosis which is however lost as time goes by after menopause. Estrogens however do not explain other differences in the outcome. The differences in remodeling seem to persist even when the role of circulating estrogens is limited (post-menopausal). The plot thickens as it has been shown that estrogens are not only produced in the ovaries which undergo failure at menopause but also in other organs such as the heart. Myocardial synthesis of estrogens has been demonstrated, and it remains not completely clear how it is affected by menopause. It is indeed possible that although the circulating levels of estrogens are low, the tissue levels may still be higher than men and mediate the beneficial effects. The data on this topic is scattered and inconclusive, and further studies are necessary.