Across an ample body of research, findings consistently show that women fare worse than men in a range of outcomes associated with cardiovascular disease (CVD). Among patients with myocardial infarction (MI), diagnosis and treatment are often delayed in women, who also experience higher rates of in-hospital mortality and complications associated with MI compared with men.1 These delays in care may be partly related to a lack of awareness regarding unique aspects of MI presentation in women.
MI Symptoms in Women vs Men
“In general, when experiencing acute coronary syndrome (ACS) or MI, the majority of women present with the same symptoms as men, such as chest pain described as pain, pressure, tightness, or discomfort,” said Lena Mathews, MD, MHS, medical director of cardiac rehabilitation and assistant professor of medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland. “However, women often have unique presentations of MI with additional symptoms such as palpitations, jaw or neck pain, shortness of breath, fatigue, or epigastric symptoms including indigestion.”2
In a 2022 meta-analysis, Cardeillac et al examined 15 prospective studies (N=10,730) and found that the following symptoms were more common among women vs men with suspected ACS: dyspnea (relative risk [RR], 1.13; 95% CI, 1.10-1.17), arm pain (1.30; 95% CI, 1.05-1.59], nausea and vomiting (1.40; 95% CI, 1.26-1.50), fatigue (1.08; 95% CI, 1.01-1.16), palpitations (1.67; 95% CI, 1.49-1.86), and pain in the shoulder (1.78; 95% CI, 1.02-3.13). Consistent results were observed in a subgroup of patients with confirmed acute coronary syndrome.3
These findings align with a 2018 study by Lichtman et al, in which similar rates of young women (87.0%) and young men (89.5%) with acute MI presented with chest pain; however, women were more likely to present with 3 or more additional non-chest symptoms compared to men (61.9% vs 54.8%; P <.001).2 Adjusted analyses of data from patients with ST-segment-elevation AMI revealed that women were 1.5 times more likely than men to present without chest pain (95% CI, 1.03–2.22).2
According to Dr Mathews, differences in pathophysiology may represent 1 of the mechanisms driving these differences, “Men are more likely to have obstructive disease of epicardial vessels with plaque rupture while women are more likely to have MI with non-obstructive disease (MINOCA), spontaneous coronary artery dissection, stress cardiomyopathy, and plaque erosion as opposed to plaque rupture.”4,5
She pointed to sex differences in pain perception as another potential factor driving MI disparities in women vs men, as “evidence shows that nervous system pain processing of visceral pain can be different in women.”1
MI in Women Often Overlooked
Despite these findings, physician and public awareness of these differences remains subpar, resulting in diagnostic and treatment delays, and ultimately worse outcomes, for women experiencing MI.
“Women are less likely to attribute their symptoms to coronary artery disease or MI and instead attribute them to anxiety or stress, and thus may seek care only when their symptoms are severe and hard to ignore,” Dr Mathews explained. In addition, clinicians are more likely to categorize women as having a lower cardiovascular risk even in the presence of traditional risk factors, and they often fail to account for sex-specific risk factors that increase the risk for developing CVD, including premature menopause and pregnancy complications such as pre-eclampsia and gestational diabetes.6
In the study by Lichtman et al, women were more likely than men to perceive their AMI symptoms as stress or anxiety (20.9% vs 11.8%; P <.001), and providers viewed prodromal symptoms as non-heart-related in 53% of women vs 37% of men (P <.001).2
“Women who are having a heart attack tend to show up to ER later than men and, because they have atypical symptoms, clinicians are testing and treating them for MI later than their male counterparts,”7 said Leslie Cho, MD, director of the Women’s Cardiovascular Center at Cleveland Clinic in Cleveland, Ohio, and chair of the American College of Cardiology’s Cardiovascular Diseases in Women Council. “This has an enormous impact because time is muscle.”
Improving Awareness of MI in Women
To improve MI detection and outcomes in women, clinicians should remain aware that “women can have MI despite having no traditional risk factors such as coronary artery dissection,” and they should “investigate symptoms that indicate ischemia or MI in women and not dismiss them as non-cardiac symptoms,” Dr Mathews advised. Clinicians should also educate their patients—especially those with risk factors for MI—about symptoms of MI and increase awareness that women can have atypical symptoms.
Recent study results underscore the importance of efforts to spread awareness of CVD risk and symptoms in women. “Despite aggressive campaigns by the American Heart Association (AHA) and other organizations like the American College of Cardiology, only 44% of women surveyed in 2019 listed CVD as the leading cause of death for women,” Dr Cho said.8 “This is a stark decrease from 2009, when 65% of women identified CVD as the leading cause of death for women. The decline in awareness of CVD risk is alarming.”
Awareness of CVD risk is especially low among underrepresented minority women, particularly Black and Hispanic women, although CVD risk is higher among these groups compared to age-matched White women.8
Dr Cho further noted that if women are unaware of their heart disease risk, they are less likely to address hypertension, high cholesterol, and other morbidities that contribute to the development of CVD. “We need to keep educating our patients and physicians. We cannot be complacent,” she emphasized.
Remaining Research Gaps
Along with the critical need to educate physicians and increase public awareness about MI differences in women, there are numerous research questions that require ongoing investigation in this area.
For example, “Are gender differences in presentation of MI due to the underlying pathophysiology of coronary artery disease, due to the nervous system perception of pain, or due to differences in recognition of symptoms?” Dr Mathews asked. As women have been underrepresented in clinical trials investigating MI-specific treatments, there is also a need to examine whether these therapies work the same in women compared with men, and evidence-based management strategies are needed for management of unique presentations of MI in women vs men, such as MINOCA and coronary artery dissection.
“There is so much work that needs to be done in regards to gender differences in CVD – from the most basic fundamental things like understanding platelet differences, plaque and atherosclerosis differences, all the way to drug and device response differences between men and women, more research is warranted,” Dr Cho stated.
- Mehta PK, Wei J, Shufelt C, Quesada O, Shaw L, Bairey Merz CN. Gender-related differences in chest pain syndromes in the Frontiers in CV Medicine Special Issue: Sex & Gender in CV Medicine. Front Cardiovasc Med. Published online November 17, 2021. doi:10.3389/fcvm.2021.744788
- Lichtman JH, Leifheit EC, Safdar B, et al. Sex differences in the presentation and perception of symptoms among young patients with myocardial infarction: evidence from the VIRGO Study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients). Circulation. Published online February 20, 2018. doi:10.1161/CIRCULATIONAHA.117.031650
- Cardeillac M, Lefebvre F, Baicry F, et al. Symptoms of infarction in women: Is there a real difference compared to men? a systematic review of the literature with meta-analysis. J Clin Med. Published online February 27, 2022. doi:10.3390/jcm11051319
- Lansky A, Baron SJ, Grines CL, et al. SCAI expert consensus statement on sex-specific considerations in myocardial revascularization. Published online February 4, 2022. doi:10.1016/j.jscai.2021.100016
- Solola Nussbaum S, Henry S, Yong CM, Daugherty SL, Mehran R, Poppas A. Sex-specific considerations in the presentation, diagnosis, and management of ischemic heart disease: JACC Focus Seminar 2/7. J Am Coll Cardiol. Published online April 4, 2022. doi:10.1016/j.jacc.2021.11.065
- O’Kelly AC, Michos ED, Shufelt CL, et al. Pregnancy and reproductive risk factors for cardiovascular disease in women. Circ Res. Published online February 17, 2022. doi:10.1161/CIRCRESAHA.121.319895
- Schulte KJ, Mayrovitz HN. Myocardial infarction signs and symptoms: Females vs. males. Cureus. Published online April 13, 2023. doi:10.7759/cureus.37522
- Cushman M, Shay CM, Howard VJ, et al; on behalf of the American Heart Association. 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. Published online September 21, 2021. doi:10.1161/CIR.0000000000000907