The Conundrum of Sex Differences in Outcomes of Young Patients with Acute Myocardial Infarction: The YOUNG-MI Registry
- Young women who present with acute MI are less likely than men to undergo coronary angiography and revascularization. They are also less likely to be discharged on guideline-directed medications.
- Young women have worse long-term outcomes after an acute MI, with higher overall mortality after more than 10 years.
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 registry4 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.
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.9-11
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.
- Underlying Cause of Death 1999-2018 (CDC website). 2020. Available at http://wonder.cdc.gov/ucd-icd10.html. Accessed 11/02/2020.
- Mehta LS, Beckie TM, DeVon HA, et al. Acute myocardial infarction in women: a scientific statement from the American Heart Association. Circulation 2016;133:916–947.
- Bucholz EM, Strait KM, Dreyer RP, et al. Editor's choice-sex differences in young patients with acute myocardial infarction: a VIRGO study analysis. Eur Heart J Acute Cardiovasc Care 2017;6:610-22.
- DeFilippis EM, Collins BL, Singh A, et al. Women who experience a myocardial infarction at a young age have worse outcomes compared with men: the Mass General Brigham YOUNG-MI registry. Eur Heart J 2020;41:4127-37.
- Gupta A, Wang Y, Spertus JA, et al. Trends in acute myocardial infarction in young patients and differences by sex and race, 2001 to 2010. J Am Coll Cardiol 2014;64:337–45.
- Cushman M, Shay CM, Howard VJ, et al. Ten-year differences in women's awareness related to coronary heart disease: results of the 2019 American Heart Association National Survey: a special report from the American Heart Association. Circulation 2020;Sep 21:[Epub ahead of print].
- Grundtvig M, Hagen TP, German M, Reikvam A. Sex-based differences in premature first myocardial infarction caused by smoking: twice as many years lost by women as by men. Eur J Cardiovasc Prev Rehabil 2009;16:174–79.
- Vallabhajosyula S, Ya'Qoub L, Singh M, et al. Sex disparities in the management and outcomes of cardiogenic shock complicating acute myocardial infarction in the young. Circ Heart Fail 2020;13:e007154.
- Blewer AL, McGovern SK, Schmicker RH, et al. Gender disparities among adult recipients of bystander cardiopulmonary resuscitation in the public. Circ Cardiovasc Qual Outcomes 2018;11:e004710.
- Dewan P, Rorth R, Jhund PS, et al. Differential impact of heart failure with reduced ejection fraction on men and women. J Am Coll Cardiol 2019;73:29-40.
- Thompson LE, Maddox TM, Lei L, et al. Sex differences in the use of oral anticoagulants for atrial fibrillation: a report from the National Cardiovascular Data Registry (NCDR®) PINNACLE Registry. J Am Heart Assoc 2017;6:e005801.
- Sharma G, Blumenthal RS, Mehta LS. A Decade of Lost Ground in the Awareness of Heart Disease Symptoms in Women: A Call to Action (American Heart Association website). 2020. Available at https://professional.heart.org/en/science-news/ten-year-differences-in-womens-awareness-related-to-coronary-heart-disease/Commentary. Accessed 11/02/2020.
Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Stable Ischemic Heart Disease, Atherosclerotic Disease (CAD/PAD), SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Nonstatins, Novel Agents, Statins, Acute Heart Failure, Interventions and Coronary Artery Disease, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging, Chronic Angina
Keywords: Dyslipidemias, Pregnancy, ST Elevation Myocardial Infarction, Female, Male, Retrospective Studies, Coronary Artery Disease, Prospective Studies, Coronary Angiography, Risk Factors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hospital Mortality, Shock, Cardiogenic, Out-of-Hospital Cardiac Arrest, Aspirin, Insulin, Patient Discharge, Atrial Fibrillation
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