The Conundrum of Sex Differences in Outcomes of Young Patients with Acute Myocardial Infarction: The YOUNG-MI Registry

Merna Hussien, MD; Roger S. Blumenthal, MD, FACC; Martha Gulati, MD, MS, FACC; Garima Sharma, MBBS, FACC



Cardiovascular disease (CVD) remains the leading cause of deaths in women of all ages in the United States. For adult women under the age of 65, about one out of every eight deaths is caused by CVD.[1] Differences between presentation, underlying pathophysiology, treatments, and outcomes between men and women with CVD have been clearly demonstrated.[2]

Whether these differences persist when investigating younger patients is what the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study,[3] and the more recent analysis of the YOUNG-MI registry[4] attempted to identify. There has been an increasing trend in hospitalizations for acute myocardial infarction (AMI) in women younger than 50 years old, compared to men of the same age, and both sexes of older age.[5] This, coupled with the decline in awareness of heart disease symptoms particularly among younger women, underscores the need to further understand how differently CVD affects younger women.[6]

Study design and results

The YOUNG-MI registry included patients ≤50 years-old who presented to the Brigham and Women's Hospital and Massachusetts General Hospital with a type 1 MI from 2000 to 2016. Patients with known coronary artery disease (CAD) or previous MI were excluded. The cohort was followed for a median of 11.2 years. Out of the 2097 patients, 404 (19%) were women with a median age of 45.

Women, similar to men, were mostly White, but they had a significantly lower median income and were more likely to have public health insurance.

Figure 1

Women were more likely to have diabetes, in particular that depended on insulin therapy, rheumatological diseases, and depression. However, when comparing a composite risk factor score, there was no significant difference between women and men.

Women, like men, usually presented with chest pain, but were more likely to have additional symptoms, such as dyspnea, fatigue, and palpitations. They were less likely to present with ST-segment elevation myocardial infarction (STEMI) than men, and less likely to undergo angiography if they have presented with non-STEMI.

Women who underwent coronary angiography were more likely to have non-obstructive CAD, lower plaque disruption, and single-vessel disease. Women also had a higher rate of spontaneous coronary artery dissection.

Women, regardless of type of MI and even with obstructive CAD, were also less likely to undergo revascularization. While this may be related to the different underlying pattern of coronary disease or technical limitations, there remains a contribution from referral bias, as less women with MI were taken to angiography initially.

Women also had longer hospitalizations and were less likely to be discharged on aspirin, beta-blockers, ACE or ARBs, and statins. While CV-mortality did not differ significantly between men and women, women had significantly higher all-cause mortality, even after adjusting for underlying risk factors and treatments. Most of the non-CV deaths were from cancer and sepsis.

What did YOUNG-MI add to VIRGO?

VIRGO was a prospective observational study that included patients ≤55 years-old admitted with AMI. Similar to YOUNG-MI, the majority of young women and men presented with chest pain, but women were more likely to present with additional associated symptoms and perceive symptoms as stress or anxiety.

Women were again less likely to receive revascularization procedures. VIRGO did not report significant mortality difference between men and women, but participants were only followed for one year post-MI, compared to more than 10 years in YOUNG-MI. Also, potentially sicker patients who were not able to provide informed consent were not involved in VIRGO, while YOUNG-MI retrospectively included all patients who presented with an MI and met inclusion criteria. VIRGO, on the other hand, only involved STEMI patients.

In summary, YOUNG-MI not only confirms the underlying risk factors, presentation, and management differences between young men and women with AMI shown in VIRGO, but also adds important information about overall long-term differences in outcome.

The conundrum: why do women have overall worse long-term mortality despite having comparable risk factors?

The difference in overall long-term mortality, but not CV-mortality, between women and men in YOUNG-MI is difficult to explain. It may have been related to the smaller proportion of women with MI included in the study, which limits the power to assess for CV mortality. Moreover, despite including various underlying factors, unmeasured confounders that particularly affect women, such as pregnancy-related CVD, were unaccounted for.

Traditional risk factors may have a greater influence on women than men. For instance, the risk associated with smoking, after adjusting for tobacco exposure, is reported to be higher in women.[7] Regardless of reported underlying risks, presentation, or management, there seems to be an excessive inherent risk for young women post-MI.

Data from the YOUNG-MI registry adds to the continuously reported sex disparity in the management of CVD. A case in point is the recent retrospective study about sex disparity in treatment of cardiogenic shock complicating AMI in young patients. Women were less likely to undergo early angiography, percutaneous coronary intervention, and mechanical circulatory support. Additionally, they had a higher in-hospital mortality.[8]

The sex disparity also extends to differences in bystander cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrests, guideline-directed therapies for heart failure with reduced ejection fraction, and in anticoagulation for atrial fibrillation.[9,10,11]

What more can be done?

Despite growing efforts in studying cardiovascular disease in women and improving educational and public awareness, sex disparity in cardiovascular care persists. As discussed in the commentary, "A Decade of Lost Ground in the Awareness of Heart Disease Symptoms in Women: A Call to Action", the key to tackling this complex problem is continuing to re-examine the multiple factors in place.[12] These include lower awareness of women-specific CVD risks among physicians, as well as gaps in understanding the different pathophysiology of CVD in women.

Our clinical practice should always include discussions about cardiovascular prevention with a focus on standardized clinical guidelines and improving awareness about CVD symptoms, particularly among young women. Empowering our young patients to learn more about CVD and advocating for competent care that is sensitive to sex disparities and other social determinants of health are crucial to improving long-term outcomes for all of our patients.


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