Women and heart disease, the underrecognized burden: sex differences, biases, and unmet clinical and research challenges

Abstract

For many years the significance of heart disease in women was vastly underappreciated, and women were significantly underrepresented in cardiovascular clinical research. We now know that cardiovascular disease is the leading cause of death for women. Women and men share many similarities in the pathophysiology and manifestations of heart disease. However, as research advances with the continued inclusion of more women, knowledge about gender differences between the female and male heart, both on a physiological and pathophysiological basis, grows. These differences can be found in all domains of cardiovascular health and disease, including heart rhythm, heart failure, coronary disease and valvular disease. Further understanding of gender differences in the heart is crucial for advancing our ability to maintain a healthy population and identify and treat heart disease in both women and men. Specific examples within the spectrum of heart disease will be discussed in this review paper, and areas for further research will be proposed.

Taking cardiology clinical trials to the next level: A call to action

“…Thus, it is not surprising that reactivity of the coronary microvasculature plays an important role in the IHD pathophysiology of women . Moreover, plaque erosion (vs plaque rupture) is more common in women (vs men) and is the most common cause of acute coronary thrombosis leading to SCD in women age < 50 years …”

“…The 2 forms of HF are nearly equally common, and both are associated with a high degree of morbidity and mortality . Heart failure with preserved ejection fraction (HFpEF) is significantly more prevalent in women . When age and other risk factors are adjusted for, however, the risk of HFpEF appears similar in men and women, whereas the adjusted risk of HF with reduced ejection fraction remains greater in men …”

“…Extensive research has been done on the pathophysiology of HF with reduced ejection fraction, and numerous effective therapies have been developed for this male‐prevalent form of HF . In contrast, few treatments have been shown to be beneficial for HFpEF based on randomized clinical trials . In large part, those treatment failures resulted from a lack of consensus on criteria for diagnosing HFpEF and enrolling participants in HFpEF clinical trials, as well as underenrollment of women in clinical research on HF, in general .…”

“…Pregnancy increases the overall demand placed on the maternal CV system, which is accompanied by increased blood volume and cardiac output, systemic vasodilation, decreased arterial pressure, and remodeling of the heart and vasculature . Women have higher risks of cardiac arrhythmias and are at sex‐specific risk for MI due to spontaneous coronary‐artery dissection during pregnancy or peripartum . Pregnancy complications such as gestational diabetes substantially increase a woman's risk of later developing diabetes mellitus, which is a strong risk factor for CVD, and preeclampsia doubles a woman's risk of IHD later in life …”

“…With heart disease, women and men exhibit many similarities in risk factors, pathophysiology, manifestations, and outcomes. However, the recent inclusion of more women in CV clinical research reveals an expanding horizon of sex/gender differences across all domains of CV health and disease, including heart rhythm, valvular disease, ischemic heart disease (IHD), and heart failure (HF) . Within those domains, research has started to show substantial sex differences in risk factors, epidemiology, disease manifestations, and/or clinical outcomes.…”