Dr Stefano Savonitto, Director of Cardiology at Manzoni Hospital sheds light on the risk of heart disease in women
When thinking about their health, women are especially concerned about cancer. However, the most frequent cause of death among women is heart disease and especially coronary artery disease. The number of women dying of heart disease has surpassed the number of men in Europe. What is still a negative peculiarity of male destiny is the higher risk of premature cardiac death (that is before the age of 65), since women are probably protected by oestrogen before the age of menopause. After that age, the risk of cardiac events, especially myocardial infarction, but also stroke, among women gradually equalises men’s risk to become more prevalent after the age of 75. A single, but important, an epidemiological study carried out in the Netherlands involving more than 12 thousand post-menopausal women, followed for up to 20 years in a breast cancer program, showed that each year’s delay in menopause is associated with a 2% reduction in cardiovascular mortality. This reduction in risk with later menopause seems to be particularly important in the early post-menopausal years, to disappear after the age of 80.
Therefore, understanding the development of heart disease after the natural cessation of oestrogen protection might disclose potential means of protecting women from their first debilitating disease. Particularly considering that, as shown by the United States heart and stroke statistics, life expectancy is 30 years for postmenopausal women, and 20 years after the age of 65.
The protecting role of oestrogen against heart attacks is incompletely known but seems to be multifactorial. A first piece of the puzzle might be that oestrogen causes a reduction in serum lipid concentration, a well-known risk factor for atherosclerosis which, however, may be efficiently reduced by the currently available cholesterol-lowering drugs, such as the statins and the even more powerful agents under development. A more recent observation is the association of early menopause with a higher risk of developing diabetes mellitus, another powerful atherogenetic risk factor. Oestrogen also has direct effects on the vasculature, by promoting vasodilatation and regulating the growth of vascular cells.
However, the evidence that oestrogen replacement therapy may affect the progression of coronary disease after menopause is incomplete, and most studies have used a combination of oestrogen and progestin, more generally referred to as hormone replacement therapy (HRT). Observational studies consistently indicate that HRT is associated with a lower risk of coronary heart disease. Initial and large randomised trials have shown a null effect although most women in these trials were older than 60 and more than 10 years postmenopausal. Subsequent studies and meta-analyses indicate that cardiovascular and total mortality are reduced when HRT is initiated in women aged less than 60 or within 10 years of menopause. In a recent large randomised study from Denmark, more than 1000 women with recent menopause were treated using HRT (or left untreated in the control group) for up to 10 years and followed up for up to 16 years: HRT has significantly reduced the risk of mortality, myocardial infarction, or heart failure, as compared to a control group left without HRT. In this study, there was no excess risk of cancer or stroke, a potential “side effect” of HRT.
Besides these trials on potential preventive treatments, knowledge of the evolution of coronary disease after menopause is scanty. Whereas at a younger age women have the less coronary obstructive disease as compared to men, even in the cases with acute myocardial infarction, the prevalence of obstructive disease increases with age and as time passes after menopause. In Lecco, a multicenter study is being coordinated, involving 800 patients with acute myocardial infarction at 8 Italian centres, in order to assess by quantitative angiographic methods whether the age of menopause has any impact on the severity of coronary artery disease in the postmenopausal years. Prior data on this same issue seems to suggest that the impact of menopausal age, if any, is limited to the early postmenopausal years of women with very early menopause (before the age of 45). Should the data suggest that early menopause is associated with more severe and diffuse coronary disease, an impulse to either prolong the effect of oestrogen after menopause or, alternatively to treat more aggressively the concurrent atherosclerotic risk factors in women with early menopause would be warranted. Besides the atherosclerotic mechanisms, the recent OCTAVIA multicenter study using optical computerised tomography (OCT) in age and sex-matched myocardial infarction patients showed that the final mechanisms of infarction are very similar in women and men. This data find correspondence in clinical practice.
Dr Stefano Savonitto
Director of Cardiology
Tel: +39 034 148 9490