Myocardial ischemia in women when genetic susceptibility matters

Ischemic heart disease is the most common cause of death in both female and male genders. Though coronary artery disease is the most common determinant of ischemia in males, women present more often chest pain associated with normal epicardial coronary arteries. In females, coronary microvascular dysfunction plays a key role in developing symptoms and imbalance between delivery and request of coronary blood flow. Coronary ion channels play a major role in the regulation of coronary blood flow. According to the epidemiological, pathophysiological and clinical differences between male and female genders in ischemic heart diseases, it is legitimate to suspect the possible impact of gender on modulating the effect of cardiovascular risk factors. Whereas it is well known the role of estrogens in cardiovascular system, the role of genetics it has never been extensively addressed. Considering the high prevalence of coronary microvascular dysfunction in females and the regulatory function of coronary ion channels, we speculate that genetic differences in genes encoding the ion channels could be a major determinant of the difference in ischemic phenotypic expression among genders. Our previous study clearly shows that the single nucleotide polymorphism rs5215_GG of KCNJ11 gene encoding for coronary KATP channel is more prevalent in women and reduces the susceptibility to ischemic heart disease regardless the presence of other cardiovascular risk factors. This finding suggests a major role of genetics in the development of ischemic heart diseases and warrants further studies to evaluate the usefulness of genetic screening in clinical daily practice.