Female-specific risk factors are associated with increased risk of acute myocardial infarction in young women

Background The incidence of acute myocardial infarction (AMI) is increasing among young women, and as female-specific risk factors present early in life, improved knowledge on these may allow for early detection of women at high risk of future cardiovascular disease (CVD). Purpose To examine the prevalence of female-specific risk factors among young women presenting with AMI compared with matched controls from the background population. Methods Using Danish nationwide registries, all women aged 18–50 years with a first-time diagnosis of AMI between 1977 and 2024 were identified and matched 1:4 with women from the background population based on year of birth and index. The prevalence of traditional (i.e., hypertension, diabetes, use of statins, and obesity) and female-specific (i.e., adverse pregnancy outcomes (APOs), endometriosis, polycystic ovarian syndrome, premature menopause, secondary amenorrhea and use of combined oral contraception) risk factors was examined and compared between women with and without AMI. Logistic regression was used to evaluate the association between traditional and female-specific risk factors and AMI, including interaction analyses. Results The study included 9,505 women aged 18–50 years with AMI and 38,013 matched controls (median age 45.1 years). Overall, women with AMI had a higher prevalence of traditional as well as female-specific risk factors compared to controls. Traditional risk factors were associated with the greatest risk of AMI. However, all female-specific risk factors also demonstrated an increased associated risk of AMI (Figure 1). Among APOs, the variables associated with statistically significant increased risk of AMI were: preeclampsia (OR 1.40, 95% CI 1.24–1.59), small for gestational age (OR 1.64, 95% CI 1.42–1.89), placental abruption (OR 1.84, 95% CI 1.43–2.36) and preterm delivery (OR 1.37, 95% CI 1.21–1.55). Interaction analysis between traditional and female-specific risk factors was statistically significant (p< 0.0001). An additive effect of both traditional and female-specific risk factors on the risk of AMI was observed (Figure 2). In the absence of traditional risk factors, an additive effect of female-specific risk factors was statistically significant with progressively increasing ORs by increasing number of risk factors. In the presence of traditional risk factors, the effect was less pronounced; however, if three or more female-specific risk factors, an additive effect remained, although insignificant. Conclusion Young women with AMI had a higher prevalence of both traditional and female-specific risk factors compared with controls. Even after adjustment for traditional risk factors, female-specific risk factors were independently associated with an increased risk of AMI and demonstrated an additive effect, especially in the absence of traditional risk factors. These findings suggest considering female-specific risk factors in CVD risk assessment.