Report of the National Heart, Lung, and Blood Institute Working Group on Sex Differences Research in Cardiovascular Disease: Scientific Questions and Challenges.

Abstract

Although cardiovascular disease (CVD) is a leading cause of death in both women and men,1 accumulating evidence suggests that biological sex is a major determinant for the development and progression of CVD, which adversely affects >1 million people per year in the United States alone.2,3 However, many of the basic mechanisms underlying sex differences in CVD remain unknown. Thus, the National Heart, Lung, and Blood Institute convened a Working Group meeting on September 22, 2014 in Bethesda, MD, to explore the issues relevant to sex differences in CVD, particularly basic research. The goals of the Working Group were to (1) discuss the importance of and challenges in conducting basic research on sex differences in CVD and (2) advise on specific research priorities that will improve our understanding of sex differences in basic cardiovascular biology. The Working Group consisted of extramural experts involved in sex differences research related to hypertension, myocardial ischemia/reperfusion injury, sex hormones and their receptors, cardiac and vascular cell–based therapy, genetics, and the evolution and function of the sex chromosomes. Representatives from the National Institutes of Health Office of Research on Women’s Health, Office of Extramural Research, Center for Scientific Review, and the Food and Drug Administration were also engaged in the Working Group’s discussions. This article represents the Working Group’s recommendations on major challenges and research gaps associated with sex differences in CVD and the opportunities they create for research moving forward. ### Assumptions About the Difficulty of Studying Both Sexes Recent assessments of published literature in biomedical sciences indicate that in preclinical research on animals, males are studied more than females,4 which may obscure key sex differences that could guide clinical studies.5 One common reason for this preference to use male animals is that females are viewed as being inherently more variable than males because of their estrous cycles. …