While cardiovascular mortality rates in men have steadily declined since the 1980s, the disease is becoming more common in women, with cardiovascular deaths in women currently exceeding those in men. In fact, clinical outcomes from acute coronary syndrome and heart failure are consistently worse for women than men (Figure 1). However, the gender-specific environmental, molecular, and cellular variables that contribute to cardiovascular disease are largely unknown; patients are treated the same regardless of sex.
We recently observed significant sex- and age-specific differences in baseline left ventricular ejection fraction (LVEF), with a strong age-dependent increase in LVEF observed in healthy women but not in men (Figure 2). Given the prognostic importance of LVEF and its routine use in clinical decision making, understanding the variables that modulate myocardial contractility and vulnerability to cardiac injury in postmenopausal females and older males is of paramount importance for the development of personalized age- and gender-based therapies. In our current projects we therefore assess the impact of (patho)physiological factors contributing to sex- and age-related differences in cardiac function (Figure 3). More precisely, we are studying the extent to which these sex-differences can be attributed to sex hormones and their receptors, to differences in genetic predisposition, neurohumoral signalling, and gender-based lifestyle factors. For this purpose, we are using murine experimental models and a variety of in vivo imaging modalities including serial positron-emissions tomography, echocardiography and cardiovascular magnetic resonance imaging. Our ultimate goal is to improve and personalise gender-based therapeutic approaches in the aging population.