Of Martians and Venusians: The Gender Gap in ACS?

Recent epidemiological studies have once again highlighted the gender-specific difference in mortality in acute myocardial infarction (AMI).1,2 Women tend to do worse than men with AMI. Even more concerning is that younger women (<55 years) admitted with AMI have higher in-hospital mortality than older women, and for men of all ages. Although admission rates for AMI were lower for women than men, as only 26% of AMI admissions were women, comorbidities such as hypertension, diabetes, congestive heart failure and renal disease were more prevalent among women than men in all age groups, especially among younger women. Importantly, women had higher in hospital mortality across all age groups, especially among younger (<55 years) women. Of note, in this study it was seen that there was a trend towards lower AMI rates in younger men (40-54 years) over a 10 year period; however, the opposite was seen in women in the same age group, who had a trend towards increasing AMI rates.

Similarly, a recent meta analysis, examining gender based mortality differences in patients undergoing primary percutaneous coronary intervention (PCI), found that women had higher mortality than men presenting with ST elevation MI (STEMI).2 Of concern, this study showed that in-hospital all-cause mortality for women was close to double (7.5 percent vs. 3.9 percent) that of men. Moreover, women also had a higher 1-year all cause mortality. These studies highlight once again that in the AMI population, women do worse in comparison to men, and young women actually fare even worse.

What part does the difference in pathophysiology of AMI play between the genders? It is well known that there are differences in angiogenesis and patterns of collateralization in women. This does put women at greater risk of sudden cardiac death and other complications associated with STEMI.3,4 Differences also exist in the plaque composition associated with the culprit lesion. Although the textbook description of AMI from plaque rupture is the most common pathology, it is less frequently seen in women, 5,6 in whom plaque erosion is fairly common.7 Hormonal differences are an important factor, estrogen can affect the presentation, which in case of women can be atypical.8 Some of the complications of percutaneous coronary intervention (PCI), such as bleeding, are also more common in women.9 Does this difference in the pathophysiology lead to differences in clinical outcome in women with AMI? It has long been believed that women, especially younger women, present with non-atherosclerotic mechanisms of AMI such as dissection, and thus may not have classical coronary artery disease. However, the finding of higher prevalence of traditional cardiovascular risk factors among young women in these studies certainly makes it appear that the paradigm of atypical disease in younger women with AMI is less relevant now than previously thought.1

Can this difference result from psychosocial factors? Limited access to health care, delay in access to health care, delay in transfer have all been identified as barriers in the care of females presenting with AMI 10,11. Part of this stems from the widespread notions regarding the late onset of coronary artery disease in women, leading to a delay in diagnosis and treatment of a young woman with AMI. Additionally, women tend to ignore their symptoms and delay seeking help due to concerns of disrupting care to their family.12 Women are now subjected to the same stress as men, due to similar jobs and careers. This is in addition to taking care of home, children and family. Not surprisingly, women present late in their disease, and most of the time, with an acute event.

As women cardiologists, it is important for us to realize that traditional coronary artery disease can present early and acutely in women. Unfortunately, in the future, we are likely to see younger women with AMI. Thus, at every opportunity we must educate our young female patients regarding the importance of primary and secondary prevention. That would be one way to close the gap between the two planets.


  1. Gupta A, Wang Y, Spertus JA, Geda M, Lorenze N, Nkonde-Price C, et al. Trends in Acute Myocardial Infarction in Young Patients and Differences by Sex and Race, 2001 to 2010. J Am Coll Cardiol. 2014 Jul 29;64(4):337–45.
  2. Pancholy S, Shantha G, Patel T, Cheskin LJ. Sex differences in short-term and long-term all-cause mortality among patients with st-segment elevation myocardial infarction treated by primary percutaneous intervention: A meta-analysis. JAMA Intern Med [Internet]. 2014 Sep 29 [cited 2014 Oct 2]; Available from: http://dx.doi.org/10.1001/jamainternmed.2014.4762
  3. Hochman JS, Tamis JE, Thompson TD, Weaver WD, White HD, Van de Werf F, et al. Sex, Clinical Presentation, and Outcome in Patients with Acute Coronary Syndromes. N Engl J Med. 1999 Jul 22;341(4):226–32.
  4. Nicholls SJ, Tuzcu EM, Crowe T, Sipahi I, Schoenhagen P, Kapadia S, et al. Relationship Between Cardiovascular Risk Factors and Atherosclerotic Disease Burden Measured by Intravascular Ultrasound. J Am Coll Cardiol. 2006 May 16;47(10):1967–75.
  5. Yahagi K, Davis HR, Arbustini E, Virmani R. Sex differences in coronary artery disease: Pathological observations. Atherosclerosis. 2015 Jan 20;239(1):260–7.
  6. Arbustini E, Bello BD, Morbini P, Burke AP, Bocciarelli M, Specchia G, et al. Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction. Heart. 1999 Sep 1;82(3):269–72.
  7. Burke AP, Farb A, Malcom GT, Liang Y, Smialek J, Virmani R. Effect of Risk Factors on the Mechanism of Acute Thrombosis and Sudden Coronary Death in Women. Circulation. 1998 Jun 2;97(21):2110–6.
  8. Khan NA, Daskalopoulou SS, Karp I, Eisenberg MJ, Pelletier R, Tsadok MA, et al. Sex differences in acute coronary syndrome symptom presentation in young patients. JAMA Intern Med. 2013 Nov 11;173(20):1863–71.
  9. Argulian E, Patel AD, Abramson JL, Kulkarni A, Champney K, Palmer S, et al. Gender Differences in Short-Term Cardiovascular Outcomes After Percutaneous Coronary Interventions. Am J Cardiol. 2006 Jul 1;98(1):48–53.
  10. Shaw LJ, Bairey Merz CN, Bittner V, Kip K, Johnson BD, Reis SE, et al. Importance of Socioeconomic Status as a Predictor of Cardiovascular Outcome and Costs of Care in Women with Suspected Myocardial Ischemia. Results from the National Institutes of Health, National Heart, Lung and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE). J Womens Health. 2008 Sep;17(7):1081–92.
  11. Kip KE, Marroquin OC, Shaw LJ, Arant CB, Wessel TR, Olson MB, et al. Global inflammation predicts cardiovascular risk in women: A report from the Women's Ischemia Syndrome Evaluation (WISE) study. Am Heart J. 2005 Nov;150(5):900–6.
  12. Lefler LL, Bondy KN. Women's delay in seeking treatment with myocardial infarction: a meta-synthesis. J Cardiovasc Nurs. 2004 Aug;19(4):251–68.

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, Atherosclerotic Disease (CAD/PAD), SCD/Ventricular Arrhythmias, Acute Heart Failure, Interventions and ACS, Interventions and Coronary Artery Disease, Hypertension

Keywords: Cardiovascular Diseases, Comorbidity, Coronary Artery Disease, Coronary Disease, Death, Sudden, Cardiac, Diabetes Mellitus, Epidemiologic Studies, Estrogens, Heart Failure, Hospital Mortality, Hypertension, Myocardial Infarction, Percutaneous Coronary Intervention, Prevalence, Risk Factors, Secondary Prevention, Acute Coronary Syndrome

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