Sex differences in myocardial infarction and rupture

Abstract

Although myocardial rupture occurs in a relatively low percentage (2-4%) of cases of acute myocardial infarction (MI), it is associated with an extremely high mortality rate due to cardiogenic shock (up to 90% in cases of free wall rupture and 50% of cases involving septal rupture), and it accounts for up to 25% of in-hospital death [1]. Understanding the molecular mechanisms leading to myocardial rupture therefore represents an important challenge for improving the short term prognosis of MI. In the present issue of the Journal, Fang and coauthors [2] investigate an intriguing aspect of the pathophysiology of this disease, which relates to the mechanisms underlying the gender differences in the rate of post-MI rupture.It is well documented that the incidence of acute MI varies according to both gender and age. The Framingham study, for example, has demonstrated that the incidence of acute MI is 2.5-fold higher in males than females before age 45, however, this gender difference disappears after 55 years of age [3]. Clinical studies indicate that the rate of acute mortality, including sudden death, in men is about twice that observed in women [4]. This poorer prognosis in men is also supported by the observation that myocardial rupture after MI is observed twice as often in men than in women [5]. The prognosis of MI is also usually worse in younger patients due to the absence of a history of chronic ischemia and secondary collateral development, and because an early MI is usually due to the accumulation of several risk factors, such as diabetes, smoking, metabolic syndrome and consumption of recreational drugs [6].These clinical observations of sex differences in the incidence and the prognosis of acute cardiovascular events correlate with several studies conducted in large mammals [7][8][9][10]. In a monkey model of aging, gender differences in gene and protein expression can explain several aspects of the characteristic protection of females against cardiovascular disease, including a better preservation with aging of the expression of enzymes of glycolytic and oxidative pathways [10], a better cardiovascular response to β-adrenergic stimulation [9], less apoptosis and myocyte hypertrophy in old female monkeys than in old male monkeys [11], as well as differences in the composition of the extracellular matrix of conductance vessels, such as elastin and collagen isoforms, which correlates with lower vascular stiffness in females compared to males [7,8]. Some of these differences between males and females are already present at a young age, especially for genes expressed on sex chromosomes, suggesting that gender differences in expression of genes and proteins in the cardiovascular system can already be programmed early in life [8]. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof be...

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