Coronary heart disease (CHD) mortality rates in the United States have declined by up to two thirds in recent decades. Closer examination of these trends reveals substantial inequities in the distribution of mortality benefits. It is worrying that the uneven distribution of CHD that exists from lowest to highest social class—the social gradient—has become more pronounced in the United States since 1990 and is most pronounced for women. Here we consider ways in which this trend disproportionately affects premenopausal women aged 35 to 54 years. We apply a social determinants of health framework focusing on intersecting axes of inequalities—notably gender, class, ethnicity, geographical location, access to wealth, and class—among other power relations to which young and middle-aged women are especially vulnerable, and we argue that increasing inequalities may be driving these unprecedented deteriorations. We conclude by discussing interventions and policies to target and alleviate inequality axes that have potential to promote greater equity in the distribution of CHD mortality and morbidity gains. The application of this framework in the context of women’s cardiovascular health can help shed light regarding why we are seeing persistently poorer outcomes for premenopausal US women.