Female sex as a biological variable: A review on younger patients with acute coronary syndrome

Although acute coronary syndrome (ACS) mainly occurs in individuals >60 years, younger adults can be affected as well. Women continue to be at higher risk of 30-day mortality after ST-segment elevation myocardial infarction (STEMI) even in the current era of percutaneous coronary intervention (PCI). Importantly, the excess mortality among women is only significant at younger ages. Previous work has suggested that the reason for the differences in outcome is likely multifactorial and may partially be explained by some of the following factors: atypical presentation, delayed presentation, under-recognition of STEMI at initial medical contact, and underuse of medications because of concern regarding increased risk of bleeding. While these hypotheses may be true in some occasions, recent studies pointed out that the proportion of women presenting within 2 h after symptom onset was greater in the younger than in older cohorts. In addition, sex differences in administration of adjunctive medical therapies were greater in the older than in the younger cohort. Thus, there is not any one of the abovementioned factors able to explain the increase in mortality in the young women. Disparities alone could not account for the gap in mortality across sexes. Unless the effects of sex are studied, we will continue to have gaps in the knowledge of potential different mechanisms leading young women and men to die after ACS, which may result in missed opportunities for implementing a better health in our community. Randomizing or balancing the sexes as well as powering studies to detect sex differences is warranted in future research.