Editorial [Hot Topic: Gender Differences in Cardiovascular Diseases. A Need for Action (Executive Guest Editors: Giuseppe Barbaro and Giuseppe M.C. Rosano)]

In the past decades attention has been focused on gender differences in the access to health care resources and therapies but little emphasis has been put on the understanding of the basic mechanisms of gender differences and different action of cardiovascular drugs. The basic mechanisms underlying cell death and apoptosis which affect the way organs and systems respond to injury differ in the two sexes. It is known that estrogens improve endothelial repair after vascular injury but the gender differences in apoptosis and repair are not well understood. Malorni et al. discuss the basic mechanisms related to gender differences in apoptosis and cell death suggesting that these differences may explain, at least in part, those seen in physiology and in disease states. It is well known that men and women differ in the onset of cardiovascular diseases but that they level off later in life, it is also known that sex hormones have cardiovascular effect but little is known on their sex specific effect. In this issue Vitale et al detail the sex specific effect of sex hormones explaining why the same hormone may have different effect in the two sexes according to the underlying levels of the other sex hormones. Men and women have a different susceptibility to cardiovascular disease a different presentation and response to treatment and Banach, Anker, Kaski and Mercuro report on the gender differences in the treatment of cardiovascular diseases, heart failure and prevention. Most drugs have a different pharmacokinetic and pharmacodynamic properties in men, women. Furthermore, the effect of drugs may differ considerably between the two sexes and between adults and elderly. Several cardiovascular drugs have been approved for use in both sexes when there was evidence of effect only or predominantly in one of the two sexes. For example, statins have been approved for use in primary prevention of cardiovascular disease when the scientific evidence was gathered only in men (WOSCOPS), in some EU member states aspirin is approved for primary prevention of cardiovascular disease when its role in women is lacking, several anti-hypertensive drugs (especially first and second generation) have been approved and have indication for treatment of hypertension with similar dosages for the two sexes without a clear evidence of specific benefit in women. The Value study has shown that Valsartan is effective in men and much less in women and this evidence has also been reported for other cardiovascular drugs. Scientific guidelines only recently have started to highlight the differences between young and adults while only seldom take into account the gender differences or the lack of evidence for the effectiveness of some drugs in one of the two sexes. More recently the Regulatory Agencies have become more cautious on the possible gender difference in the effectiveness and safety of drugs. However, a gap still exists in recognizing the gender differences in the effectiveness and safety and in giving specific marketing authorizations according to the sex specific effect of the drugs. On ethical grounds drug companies should be more cautious in assessing the effectiveness of drugs according to age and sex. However, realistically this does not happen because of the interest to market the same drug for the wider range of users. It becomes evident that there is a need to develop gender specific guidelines for the scientific and regulatory evaluation of drugs and gender specific approvals when this is needed. Franconi et al. will discuss the issues related to the gender differences in cardiovascular pharmacology. There is still much needed to understand and solve the gender bias in cardiovascular medicine. However, this can be solved only using a scientifically correct and rigorous approach. Cardiovascular drugs should be developed according to their specific effect, the development should include patients of both sexes recruited according to the expected effect of the drugs in each sex. For most drugs unequal numbers of men and women will be required to show efficacy.