Redesigning cardiovascular medicine around sex differences

Cardiovascular disease remains the leading cause of death in women and a major contributor to disability, yet the evidence guiding diagnosis and treatment is still largely derived from studies in which men and male-pattern disease phenotypes have predominated. Women exhibit distinct cardiovascular physiology that contributes to sex differences in cardiovascular health and disease across the life course. However, these biological differences rarely inform clinical decision-making and remain incompletely understood, owing to a research ecosystem that inadequately addresses sex-specific biology. Conditions such as spontaneous coronary artery dissection, Takotsubo syndrome and coronary vasomotor disorders disproportionately affect women but were historically under-recognized as distinct clinical entities. Consequently, they remain understudied, with limited mechanistic insight and few evidence-based therapeutic strategies. In this Perspective, we advocate strengthening the translational understanding of sex-biased mechanisms and integrating these insights into diagnostics and therapeutics, with a focus on female-predominant conditions. We outline a roadmap for translational research that embeds sex as a biological variable and illustrates how advances in emerging technologies can accelerate the development of an evidence base that improves cardiovascular care for women.