Canadian Journal of Cardiology
-
(2014) 1e8
Review
Time to Standardize and Broaden the Criteria of Acute Coronary Syndrome Symptom Presentations in Women John G. Canto, MD, MSPH,a Elizabeth A. Canto,b and Robert J. Goldberg, PhDc a b c
Watson Clinic, Lakeland, Florida, USA
All Saints’ Academy, Winter Haven, Florida, USA
University of Massachusetts Medical School, Worcester, Massachusetts, USA
ABSTRACT
RESUM E
Early recognition of the signs and symptoms of acute coronary syndromes (ACS) is essential to improving patient management and associated outcomes. It is widely reported that women might have a different ACS symptom presentation than men. Multiple review articles have examined sex differences in symptom presentation of ACS and these studies have yielded inconclusive results and/or inconsistent recommendations. This is largely because these studies have included diverse study populations, different methods of assessing the chief complaint and associated coronary symptoms, relatively small sample sizes of women and men, and lack of adequate adjustment for age or other potentially confounding differences between the sexes. There is a substantial overlap of ACS symptoms that are not mutually exclusive according to sex, and are generally found in women and men. However, there are apparent differences in the frequency and distribution of ACS symptoms among women and men. Women, on average, are also more likely to have a greater number of ACS-related symptoms contributing to the perception that women have more atypical symptoms than men. In this review, we address issues surrounding whether women should have a different ACS symptom presentation message than men, and provide general recommendations from a public policy
pistage pre coce des signes et des symptômes des syndromes Le de lioration de la prise en coronariens aigus (SCA) est essentiel à l’ame sultats associe s. On rapporte souvent que charge des patients et des re rente les symptômes les femmes pourraient manifester de façon diffe s au SCA par rapport aux hommes. De nombreux articles de revues ont lie les diffe rences entre les sexes dans la manifestation des examine s au SCA, et ces e tudes ont abouti à des re sultats peu symptômes lie concluants ou à des recommandations contradictoires, ou les deux. tudes ont inclus des populations C’est en grande partie parce que ces e thodes diffe rentes pour e valuer les principales plaintes diverses, des me s, des e chantillons relativement et les symptômes coronariens associe quat en petits de femmes et d’hommes, et le manque d’ajustement ade rences de facteurs potentiellement fonction de l’âge ou d’autres diffe confusionnels entre les sexes. Il existe un important chevauchement des s au SCA, qui ne s’excluent pas mutuellement selon le symptômes lie ne ralement observe s chez les femmes et les sexe, et qui sont ge rences e videntes dans la hommes. Cependant, il existe des diffe quence et la distribution des symptômes lie s au SCA entre les fre galement plus femmes et les hommes. En moyenne, les femmes sont e s au SCA, ce susceptibles d’avoir un plus grand nombre de symptômes lie
Coronary heart disease (CHD) is the leading cause of death among women and men in the industrialized world.1 Early recognition of the signs and symptoms of acute coronary syndromes (ACS) is essential to reducing the size of myocardial infarction (MI), receiving lifesaving reperfusion and medical therapies, and improving patient outcome. However, failure to recognize and/or acknowledge ACS and atypical symptoms of this condition might lead to greater delays in seeking medical care, receipt of fewer evidence-based therapies, and higher
mortality rates compared with MI patients with typical symptoms.2 It is widely reported by the media and general public that women might have an entirely different ACS symptom presentation than men.3 The MI symptom message currently promoted by health care agencies is sex-neutral.4,5 If women do, in fact, have a different symptom presentation, then perhaps women should receive a custom-tailored, sex-specific message that is different than men. Such a personalized recommendation, however, should be based on a review of the published scientific literature and not on myth or public perception. Canto et al., in a comprehensive review of the presenting symptoms of ACS in women, found that the absence of chest pain or discomfort was noted more commonly in women than in men in the cumulative summary from large cohort studies (37% vs 27%) and in single-centre investigations and small
Received for publication August 2, 2013. Accepted October 20, 2013. Corresponding author: Dr John G. Canto, Watson Clinic, 1600 Lakeland Hill Blvd, Lakeland, Florida 33805, USA. Tel.: þ1-863-680-7341; fax: þ1863-904-3208. E-mail: [email protected] See page 7 for disclosure information.
0828-282X/$ - see front matter Ó 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cjca.2013.10.015
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Canadian Journal of Cardiology Volume - 2014
perspective. In the future, our goal should be to standardize ACS symptom presentation and to elucidate the full range of ACS and myocardial infarction symptoms considering the substantial overlap of symptoms among women and men rather than use conventional terms such as “typical” and “atypical” angina.
qui contribue à la perception que les femmes ont plus de symptômes atypiques que les hommes. Dans cette revue, nous abordons les questions à savoir si les femmes devraient recevoir un message rent au sujet de la manifestation des symptômes lie s au SCA par diffe rapport à celui des hommes, et fournissons des recommandations ne rales du point de vue des politiques publiques. Dans le futur, notre ge s but devrait être de standardiser la manifestation des symptômes lie lucider l’e tendue complète des symptômes lie s au SCA et au SCA et d’e à l’infarctus du myocarde en tenant compte du chevauchement important des symptômes des femmes et des hommes plutôt que d’utiliser les expressions conventionnelles comme angine « typique » et angine « atypique ».
reports (30% vs 17%) (Fig. 1).3,6 However, multiple review articles on the topic of sex differences in symptom presentation in patients presenting with ACS over the past 15 years have yielded inconclusive results and/or inconsistent recommendations.3,7-12 This is largely because these studies were heterogeneous in nature including diverse study populations, different methods of assessing the chief complaint and associated coronary symptoms, relatively small sample sizes of women and men, and lack of adequate adjustment for age and other meaningful differences between the sexes that might explain differences in symptom presentation.3 Three major reasons might explain potential or perceived sex differences in symptom presentation in the setting of ACS:
known to have more atypical symptoms compared with those without diabetes.15 To date, significant gaps in our description of ACS symptoms in diabetic patients and women remain.15 3. Sex-related (cultural) factors in the expression and interpretation of symptoms by patients16,17 and even health care providers.18 A woman’s perception of pain/discomfort might be greatly influenced by her past experiences and culture. For example, a woman who experiences natural childbirth, arguably one of the most severe forms of pain, might later have a higher threshold when experiencing pain/discomfort during ACS and thus might go undetected or even ignored. Also, women, as caretakers of the family, might place other people’s needs before their own, which might influence their interpretation of their own symptoms and subsequent action.
1. Sex-based biological, anatomical, and physiological factors such as differences in sex hormones, autonomic nervous system, cardiac output, microvascular disease, collateral circulation, coronary lumen size, and functional status.13 2. Sociodemographic and comorbidity related factors such as age, race, socioeconomic status, education, income, CHD risk factors, especially diabetes, and possibly other medical conditions, such as heart failure, renal failure, stroke, and depression. Women are, on average, typically much older than men at the time of their MI,2,14 and perhaps (older) age, and not necessarily sex-specific factors, might account for perceived differences in symptom presentation. In addition, among MI patients with diabetes, a condition more prevalent in women, these individuals are widely
The terms “sex” and “gender” are often used interchangeably. According to the World Health Organization, “sex refers to the biological and physiological traits that define women and men,” and “gender refers to the cultural, behavioural, or social attributes among women and men.”19 Yet others view the terms as a “complex interweaving of both nature and nurture.”20 In this report, we use the term “sex” to highlight this relationship of biology and environment. In this review, we address issues surrounding whether women should have a different ACS symptom presentation message than men and provide general recommendations
Summary of Studies Large Cohorts
40
60
N = 9 Studies; N = 471,730
31.6%
37.5% 27.4%
20 0
Percent
Percent
60
Summary of Studies Small Reports or Interviews N = 20 Studies; N = 5324
40
30.3% 25.0% 17.0%
20 0
Overall
Women
Men
Overall
Women Men
Figure 1. Acute coronary syndromes presentation without chest pain/discomfort according to sex: summary of studies from large cohorts and small reports. P < 0.001 for all comparisons. Reprinted from Canto et al.6 with permission from Female Patient.
Canto et al. ACS Symptom Presentations in Women
from a public policy perspective. For purposes of this commentary, the term “MI” will be preferentially used when the population studied involved only MI patients or the message is targeted for this specific group. The term “ACS” will be used to refer to the broader spectrum of acute presentations of unstable angina, non-ST segment elevation MI, and ST segment elevation MI. Definition of ACS Symptoms Symptoms of “typical” chest pain or discomfort Typical symptoms of ACS primarily involve the presence of pain or discomfort localized to the chest or precordial region. The chest pain or discomfort is often described as a fullness pressure, tightness, squeezing sensation, or as if an elephant is sitting on one’s chest. The symptom might radiate to other areas of the upper body such as the jaw, neck, shoulders, right or left arm, back, and epigastric region. It is often associated with any combination of symptoms such as shortness of breath, nausea, vomiting, diaphoresis, or lightheadedness. The symptoms might be exacerbated by exertion though they generally occur at rest. The symptoms of ACS can vary in intensity, severity, duration, and might crescendo in nature. The symptoms of ACS might develop suddenly or slowly over a period of several days, weeks, or months. Symptoms of “atypical” chest pain or discomfort The symptoms of chest pain or discomfort, which are “atypical” in nature, include descriptors such as sharp, pleuritic, burning, or reproducible by chest wall palpation. The pain/discomfort can oftentimes be localized in a small area on the chest (the size of a half-dollar coin or 2 fingerbreadths). ACS symptoms in the absence of chest pain or discomfort Additional symptoms in the literature have been described and include pain or discomfort which is localized in the upper areas of the thorax such as the jaw, neck, shoulders, right or left arm, back, and epigastric region in the absence of chest pain/discomfort. The other significant category of ACS presentation in the absence of chest pain/discomfort involves unexplained shortness of breath. A number of patients describe indigestion-like symptoms or even flu-like symptoms. Principal symptoms, associated symptoms, and prodromal symptoms Principal and associated symptoms by sex. Identifying the chief complaint from associated ACS symptoms is important in forming a differential diagnosis. Although the symptom complex of ACS has been identified, we are not aware of any comparative studies that have specifically examined sex differences in the principal symptoms of acute coronary disease vs other accompanying symptoms. Future studies should attempt to discriminate primary vs secondary symptoms in ACS by sex. Prodromal symptoms by sex. Prodromal symptoms can be defined as those experienced before an acute coronary event
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and might serve as an early MI warning sign. In a study of 515 women with MI, 95% of subjects experienced prodromal MI symptoms which included fatigue (71%), sleep disturbance (48%), shortness of breath (42%), and chest discomfort (30%), although sex comparisons were not possible because of the lack of men in the study.21 Few studies have examined the differences in the early warning or prodromal symptoms between women and men.22-24 Among 914 Swedish patients admitted to a coronary care unit for suspected MI, slightly more than half (57%) with confirmed MI reported chest pain within 48 hours and 61% reported other prodromal symptoms; although women reported more prodromal symptoms than men (70% vs 58%; P < 0.01).22 However, in a multicentre, cross-sectional study of 533 Norwegian patients with MI, nearly half of the patients experienced prodromal chest symptoms (45%), fatigue (62%), shoulder and back pain (51%), arm pain (38%), and dyspnea (33%) within the year before their first MI; no statistically significant differences were observed in prodromal symptoms between sexes.23 These prodromal symptoms were eventually associated with symptoms that occurred during the acute stage of MI in both sexes, but these associations were more pronounced in women than in men.23 Lastly, in a large population-based study of 14,230 patients who presented to emergency departments in the Province of Alberta with a diagnosis of ACS, only a small proportion of patients (16%) actually sought medical attention for prodromal symptoms in the 90 days before their ACS, which was associated with improved 1-year survival in women but not in men.24 Early recognition of the signs and symptoms of ACS before the acute event (prodromal symptoms) might enhance earlier detection of CHD and potentially improve patient outcomes. Differences in Symptom Presentation Among Women and Men: Overlap of ACS Symptoms Chest pain/discomfort is generally regarded as the hallmark symptom of ACS in women and men.3,7-12 There are, however, a considerable number of ACS patients who will not have this cardinal symptom,3,7-12 and the absence of chest pain/discomfort is generally seen in a higher proportion of women than in men.3,7-9,12 The symptoms of ACS are not mutually exclusive by sex and are generally found in women and men. However, there appear to be differences in the frequency of symptoms in ACS among women and men. In general, women are more likely to experience back pain,3,7-9,12 neck pain,3,7-9,12 jaw pain,3,7-9,12 arm pain,7 shortness of breath,3,9-10,12 paroxysmal nocturnal dyspnea,3 nausea or vomiting,3,7-10,12 indigestion,3,10,12 loss of appetite,3,8,10 weakness or fatigue,3,7,9-10,12 cough,3,9 dizziness,3,7,10 syncope,7,10 and palpitations3,8,10 compared with men. Men generally experience more chest pain3,7-10,12 and diaphoresis3,8-10,12 compared with women. Canto et al. examined sex differences in MI symptom presentation and subsequent hospital mortality, after adjusting for age, among 1.1 million patients enroled in the National Registry of Myocardial Infarction between 1994 and 2004. In this large observational study, chest pain/discomfort was a common symptom of MI seen in more than two-thirds of the overall study population.14 However, the absence of chest
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Canadian Journal of Cardiology Volume - 2014
Adjusted Odds Ratio*
Percent N = 1,143,513
40
38.1%
1.40
35.4% 35
%
30.7%
30
25 0
Odds Ratio (Women vs Men)
45
1.30 1.26
1.30
1.13
1.20 1.10
1.03
1.00 OR > 1.0 women have higher odds of MI presentation without CP than men
0.90 All
Women
1.24
Men
< 45
45-54
55-64
65-74
75-84
Years Figure 2. MI presentation without chest pain/discomfort, adjusted data stratified by age: Women vs men. CP, chest pain; MI, myocardial infarction; OR, odds ratio. Reprinted from Canto et al.14 with permission from the American Medical Association.
pain/discomfort was more commonly noted in women than men (42% vs 30%; P < 0.001).14 Younger women were more likely to present without chest pain/discomfort and had higher hospital death rates than similarly aged younger men (< 55 years of age); in contrast, sex differences in presentation and mortality were markedly attenuated and nearly disappeared with increasing age (Fig. 2).14 Although younger women were more likely to present without chest pain/discomfort than similarly aged men in this study, this effect was relatively modest and not absolute, because it was also observed among men and older patients.14 In comparing the symptom profile of the younger women to older women, older women were significantly more likely to present with atypical symptoms of MI than younger aged women (Fig. 3).14 This highlights the problem of making general and mutually exclusive statements by sex considering the substantial overlap of symptom presentation in women and men.
Novel approaches have been attempted to portray potential differences, and similarities, in symptom presentation according to sex.16,17 Shin et al. compared sex differences in retrospective reports of MI symptoms that resulted from 2 different assessment methods: (1) an open-ended inquiry alone; and (2) a combined assessment approach that consisted of an open-ended inquiry followed by a series of closed-ended questions.16 Women reported more atypical symptoms of ACS in their responses to the open-ended inquiry and a greater number of typical and atypical symptoms, and total symptoms in the combined assessment approach, compared with men.16 Thus, the manner in which patients were interviewed might explain potential differences in how MI symptoms are expressed and interpreted. Kreatsoulas et al. examined sex differences in cardiac symptoms among 237 patients with suspected CHD who underwent their first coronary angiogram using a novel construct of angina by
Women
Men
N = 481,581 (42%)
60
60
P value for trend < 0.001
50.4%
50
20 18.5%
21.6%
10
32.7%
30
20
21.8% 13.0%
15.7%
10
0 Years:
46.6%
40
Percent
28.9%
30
P value for trend < 0.001
50
37.9%
40
Percent
N = 661,932 (58%)
0
< 45
45-54
55-64
65-74 75-84
N: 15,236
31,899
61,164 107,877 265,405
Years:
< 45
45-54
55-64
65-74 75-84
N: 51,304 100,878 139,855 159,603 210,292
Figure 3. MI presentation without chest pain/discomfort according to age and sex. CP, chest pain; MI, myocardial infarction. Data obtained from Canto et al.14
Canto et al. ACS Symptom Presentations in Women
scaling symptom expression along a continuum.17 The authors demonstrated “substantial overlap of shared symptoms between women and men with obstructive coronary artery disease,” and “a predominance of similar symptoms between women and men.”17 The investigators reported that “the descriptors more commonly expressed by women were not unique to women,” and concluded that “the choice of terms used to describe a symptom might be a function of ‘gendered language’ rather than of conventionally portrayed biological sex differences.”17 Last, many studies capture symptom presentation through a retrospective review of the medical record, which might be distorted by several filters to provide effective communication in the chart.18 The patient must provide a verbal description of their presenting symptoms which is then modified by the well-intended health care providers who provide a written summary portraying the patient’s actual words to convey a clear diagnostic picture.18 However, if health care providers have an index of suspicion of ACS, which might be lower in women than men, it is conceivable that an atypical presentation might be recorded in the medical chart to reflect this bias. In summary, it appears that women and men experience similar ACS symptoms although the distribution and magnitude of these symptoms between women and men is subject to debate. Our goal should be to elucidate the full range of ACS and MI symptoms considering the substantial overlap of symptoms among women and men rather than use conventional terms such as “typical” and “atypical” angina. Number of Associated ACS Symptoms A number of investigators have reported that women have a greater number of associated symptoms in ACS presentation compared with men.16,25-27 This might significantly contribute to the perception that women have atypical presentations compared with men. In 2 population-based MI registries from Germany and Sweden respectively, women were twice as likely to report > 4 symptoms as men (odds ratio, 2.14)26 and more than 3 times as likely to report > 3 symptoms as men (odds ratio, 3.26).27 Although 1 study found no differences in the number of acute coronary symptoms according to sex, this study might have considerably been underpowered to examine such an association (N ¼ 60).28 McSweeney and colleagues conducted interviews of 515 women with MI using a standardized patient questionnaire and reported that women had more acute (mean, 7.3; range, 0-29) than prodromal (mean, 5.71; range, 0-25) symptoms although no comparative data were available in men.21 Despite this shortcoming, the average number of acute or prodromal symptoms reported in women was dramatic. In summary, women are more likely to report more symptoms as part of their ACS presentation compared with men, which might contribute to challenges in the interpretation of symptom presentation in women and the perception that women have more atypical symptoms. Limitations of the Current Literature and Need to Standardize ACS Symptom Presentation The published literature is not standardized for ACS symptom presentation, making it difficult to provide any conclusive statements on symptom presentation in women. In
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addition, a distinct majority of studies lack adequate adjustment for differences in age, race, and ACS classification (such as MI type).29 Also, many of the studies in the literature have excluded ACS patients who do not have the presence of chest pain/discomfort, thus potentially biasing their results. In addition, many of the studies lumped pain/discomfort localized in other areas of the body with chest pain/discomfort. Many observational studies and randomized trials in ACS have used a simplistic classification of patients’ symptoms, such as the presence or absence of chest pain/discomfort (yes/ no), rather than elucidating the entire ACS symptom complex.29 A recent meta-analysis by Shin et al. clearly differentiated between studies reporting on chest pain (N ¼ 19) and chest discomfort (N ¼ 9) and found women to be significantly less likely to have chest pain, but not necessarily chest discomfort, than men.16 When women experienced chest pain/discomfort, they commonly used descriptors such as pressure, aching, or tightness, not pain.21 This confusion might be attributed in part to a lack of standardization in the collection of ACS symptom presentation and its timing making comparative analyses difficult between published reports. In a recent editorial by Canto et al.,29 the investigators proposed collecting several key data elements using common definitions to help standardize the recording and analysis of information about symptoms experienced in the wide spectrum of CHD (Supplemental Table S1). These elements included: “Important demographic features including age, sex, race, and socioeconomic status; presence/absence of CHD risk factors and comorbidities; specifying ACS classification vs chronic CHD/angina using standard terminology; clearly specifying which are principal symptoms vs associated symptoms vs prodromal symptoms; duration and frequency of these symptoms; description of pain/discomfort (if present) to include the intensity, location, radiation, and relief of symptoms; other pertinent factors which are not directly related to symptom presentation, but their inclusion may help ascertain the association of ACS symptoms with duration of patient delay in seeking medical care, processes of care received in hospital, and subsequent short and longterm outcomes whenever possible.”
Congruence of Symptoms and Relationship with Hospital-Associated Delay Patients’ misinterpretation of the symptoms of ACS is a major cause for prolonged prehospital delay. Symptom congruence is defined as “the extent to which one’s ACS symptom experience matches those expected,”30 and has been associated with a greater likelihood of seeking timely medical care.28,31-35 “Patients, bystanders, and those at higher risk expected MI symptoms to present as often portrayed in the movies with crushing chest pain rather than the more common onset of initially ambiguous but gradually increasing discomfort.”36 In a study of 559 women and 1684 men with MI from a populationbased registry, symptom incongruence did not significantly differ
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between women and men.37 “Although the location and quality of discomfort were important components of symptom congruence, symptom severity by far outweighed their importance.”30 In fact, severe chest pain/discomfort was the strongest predictor of symptom congruence (along with a previous MI); conversely, nonsevere symptoms were more likely to be associated with symptom incongruence. There were no observed differences in the quality of the symptoms experienced and expected by women and men.30 These investigators concluded that education remains needed to dispel the common perception that chest pain/discomfort must be of severe intensity to be considered a symptom of MI for women and men.30 Current National Institute of Health MI Symptom Message and Calling 9-1-1 The most common signs and symptoms of an MI for women and men include4: 1. “Chest pain or discomfort. Most MIs involve discomfort in the centre or left side of the chest. The discomfort usually lasts for more than a few minutes or goes away and comes back. It can feel like pressure, squeezing, fullness, or pain. It also can feel like heartburn or indigestion. The feeling can be mild or severe. 2. Upper body pain or discomfort: one or both arms, back, shoulders, neck, jaw, or upper part of the stomach (above the belly button). 3. Shortness of breath. This may be the patient’s major symptom, or it may occur before or along with chest pain or discomfort. It can occur when one is resting or performing limited physical activity.” Other possible signs and symptoms of an MI include the following4: 1. “Breaking out in a cold sweat; 2. Feeling unusually tired for no reason, sometimes for days” (especially for women); 3. Nausea (feeling sick to the stomach) and vomiting; 4. Light-headedness or sudden dizziness; 5. Any sudden, new symptoms or a change in the pattern of symptoms” (for example, if one’s symptoms become stronger or last longer than usual); 6. If one has already had an MI, the symptoms may not be the same for another one. However, some may have a similar pattern of symptoms that recur.” Another potential concern is the substantial overlap of symptoms consistent with ACS and those of noncardiac diagnoses. In fact, most women experiencing the symptoms as outlined by the National Institutes of Health will not be having an ACS or MI.38,39 Based on a systematic review that examined the accuracy of 10 important signs and symptoms in patients with and without ACS,40 there were no definitive symptoms that might confirm the diagnosis of ACS or MI, though “chestwall tenderness on palpation largely ruled out MI or ACS in low-prevalence settings.”40 Furthermore, even if women were to be fully knowledgeable of the signs and symptoms of an MI, they must also be aware they are at risk for an MI, otherwise, they might not take their symptoms seriously. A number of women at higher risk of MI unrealistically judge their personal risk as low and “describe heart attack as a ‘male problem,’ an
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important aspect of their underestimation of personal risk.”36 In addition, a significant number of women still do not correctly recognize that heart disease is the leading cause of death in women, a disparity most apparent among Hispanic and AfricanAmerican women.41 Women who were the most likely to be at risk for developing CHD based on their Framingham risk score were also the least likely to know the correct symptoms of MI.42 Clearly, more education is needed linking one’s risk of CHD and personal risk of experiencing an MI. It has been continuously recommended by a number of voluntary health agencies and organizations that patients who suspect they have ACS should activate emergency medical services (EMS) for a number of reasons. These include having the availability of life-saving automated external defibrillators in case of cardiac arrest, using a prehospital electrocardiogram to make the diagnosis of MI in the field, and receiving lifesaving treatments early such as oxygen, nitroglycerin, and aspirin before hospital arrival. EMS use has also been shown to improve the speed by which primary percutaneous coronary intervention and fibrinolytic therapy are implemented.43 In addition, paramedics are more likely to triage a suspected MI patient to referral centres more likely to administer these life-saving acute reperfusion therapies.43 Despite the many benefits associated with early activation of EMS, many high-risk women understand little about the benefits of rapid action and are generally unaware of the benefits of calling 9-1-1.36 The reasons why women might not call for an ambulance include the following36: Symptoms are ambiguous or not perceived as life threatening Patient denial that they are having an MI Personal assessment of CHD risk was low Think driving might be faster than calling for an ambulance Fear Lack of control Embarrassment Permission from health care provider, spouse, relatives, or friends to take action No plan of action Cost Nevertheless, aggressive national public health campaigns educating the public about the signs and symptoms of MI have increased the use of EMS, but not necessarily reduced delay in seeking treatment.44 Thus, novel strategies are needed if delay time from symptom onset to hospital presentation is to be further decreased in women with suspected MI.44 Because most patients with ACS or MI have at least 1 CHD risk factor present,45-47 perhaps a public health message should be that if you are a woman at risk for an acute coronary event with at least 1 CHD risk factor and are experiencing suspected MI symptoms, seek medical evaluation as soon as possible. The ACS symptom complex is subjective and the diagnosis of MI relies on clear-cut objective tests such as a 12-lead electrocardiogram and cardiac biomarkers of cell necrosis such as troponin. However, without a heightened suspicion of an acute coronary event based on symptom presentation, this might lead to an incorrect diagnosis and lack of receipt of appropriate lifesaving therapies.
Canto et al. ACS Symptom Presentations in Women
Conclusions The evaluation of acute and/or prodromal symptoms in women and men with suspected ACS is a challenging task. There is a substantial overlap of ACS symptoms that are not mutually exclusive according to sex, and are generally found to a certain extent in women and men. However, there are apparent differences in the frequency and distribution of ACS symptoms in women and men. Women are also more likely to have a greater number of symptoms after ACS than men that might lead to the misperception that women have more atypical symptoms. The literature is not standardized for ACS symptom presentation and often lacks adequate adjustment for differences in age, race, socioeconomic status, additional comorbidities, ACS classification (such as MI type), and methods of symptom assessment that make it challenging to formulate any definitive statements about sex differences in acute symptom presentation. In fact, the magnitude of the differences in symptom presentation according to age appears to be much greater than the magnitude of the differences in symptom presentation between the 2 sexes. In the future, our goal should be to standardize ACS symptom presentation and to elucidate the full range of ACS and MI symptoms considering the substantial overlap of symptoms among women and men rather than use conventional terms such as “typical” and “atypical” angina. Disclosures The authors have no conflicts of interest to disclose. References 1. World Health Organization. The 10 leading causes of death in the world, 2000 and 2011. Available at: http://who.int/mediacentre/factsheets/ fs310/en/index.html. Accessed January 10, 2014. 2. Canto JG, Shlipak MG, Rogers WJ, et al. Prevalence, clinical characteristics and mortality among patients with myocardial infarction presenting without chest pain. JAMA 2000;283:3223-9. 3. Canto JG, Goldberg RJ, Hand MH, et al. Symptom presentation of women with acute coronary syndromes: myth versus reality. Arch Intern Med 2007;167:2405-13. 4. U.S. Department of Health & Human Services. National Institutes of Health. National Heart, Lung, and Blood Institute. What are the symptoms of a heart attack? Available at: http://www.nhlbi.nih.gov/ health/health-topics/topics/heartattack/signs.html. Accessed January 10, 2014.
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9. Chen W, Woods SL, Puntillo KA. Gender differences in symptoms associated with acute myocardial infarction: a review of the research. Heart Lung 2005;34:240-7. 10. DeVon HA, Zerwic JJ. Symptoms of acute coronary syndromes: are there gender differences? A review of the literature. Heart Lung 2002;31: 235-45. 11. Kyker KA, Limacher MC. Gender differences in the presentation and symptoms of coronary artery disease. Curr Womens Health Rep 2002;2: 115-9. 12. Herlitz J, Bang A, Karlson BW, Hartford M. Is there a gender difference in aetiology of chest pain and symptoms associated with acute myocardial infarction? Eur J Emerg Med 1999;6:311-5. 13. Devon HA, Ryan CJ, Ochs AL. Symptoms across the continuum of acute coronary syndromes: differences between women and men. Am J Crit Care 2008;17:14-25. 14. Canto JG, Rogers WJ, Goldberg RJ, et al. Association of age and sex differences in myocardial infarction symptom presentation and mortality. JAMA 2012;307:813-22. 15. Stephen SA, Darney BG, Rosenfield AG. Symptoms of acute coronary syndrome in women with diabetes: an integrative review of the literature. Heart Lung 2008;37:179-89. 16. Shin JY, Martin R, Howren MB. Influence of assessment methods on reports of gender differences in AMI symptoms. West J Nurs Res 2009;31:553-68. 17. Kreatsoulas C, Shannon HS, Giacomini M, et al. Reconstructing angina: cardiac symptoms are the same in women and men. JAMA Intern Med 2013;173:829-31. 18. Peterson ED, Alexander KP. Learning to suspect the unexpected: evaluating women with cardiac syndromes. Am Heart J 1998;136:186-8. 19. World Health Organization. Gender, women and health. Available at: http://www.who.int/gender/whatisgender/en. Accessed January 10, 2014. 20. Mills ME. Sex difference vs. gender difference? Oh, I’m so confused! Psychol Today 2011. Available at: http://www.psychologytoday.com/ blog/the-how-and-why-sex-differences/201110/sex-difference-vs-genderdifference-oh-im-so-confused. Accessed January 10, 2014. 21. McSweeney JC, Cody M, O’Sullivan P, et al. Women’s early warning symptoms of acute myocardial infarction. Circulation 2003;108: 2619-23. 22. Hofgren C, Karlson BW, Herlitz J. Prodromal symptoms in subsets of patients hospitalized for suspected acute myocardial infarction. Heart Lung 1995;24:3-10. 23. Lovlien M, Johansson I, Hole T, Schei B. Early warning signs of an acute myocardial infarction and their influence on symptoms during the acute phase, with comparisons by gender. Gender Med 2009;6:444-53.
5. American Heart Association. Symptoms of a heart attack and stroke. Available at: https://www.goredforwomen.org/home/about-heart-diseasein-women/symptoms-of-heart-disease. Accessed January 10, 2014.
24. Graham MM, Westerhout CM, Kaul P, Norris CM, Armstrong PW. Sex differences in patients seeking medical attention for prodromal symptoms before an acute coronary event. Am Heart J 2008;156:1210-6.
6. Canto JG, Canto AJ, Goldberg RJ, Hand MH. Symptom presentation of women with acute coronary syndromes. Female Patient 2009;34:26-8.
25. Milner KA, Funk M, Richards S, et al. Gender differences in symptom presentation associated with coronary heart disease. Am J Cardiol 1999;84:396-9.
7. Coventry LL, Finn J, Bremner AP. Sex differences in symptom presentation in acute myocardial infarction: a systematic review and metaanalysis. Heart Lung 2011;40:477-91. 8. Shin JY, Martin R, Suls J. Meta-analytic evaluation of gender differences and symptom measurement strategies in acute coronary syndromes. Heart Lung 2010;39:283-95.
26. Kirchberger I, Heier M, Kuch B, et al. Sex differences in patient-reported symptoms associated with myocardial infarction (from the populationbased MONICA/KORA Myocardial Infarction Registry). Am J Cardiol 2011;107:1585-9. 27. Berg J, Björck L, Dudas K, et al. Symptoms of a first acute myocardial infarction in women and men. Gender Med 2009;6:454-62.
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28. King KB, McGuire MA. Symptom presentation and time to seek care in women and men with acute myocardial infarction. Heart Lung 2007;36: 235-43. 29. Canto JG, Goldberg RJ, Sopko G. A call to standardize symptom presentation in acute coronary syndromes. Am Heart J 2012;164:801-6. 30. Fox-Wasylyshyn S. Predictors of symptom congruence among patients with acute myocardial infarction. J Cardiovasc Nurs 2012;12:325-33. 31. Nymark C, Mattiasson A, Henriksson P, et al. The turning point: from self-regulative illness behavior to care-seeking in patients with an acute myocardial infarction. J Clin Nurs 2009;23:3358-65. 32. Fox-Wasylyshyn S, El-Masri M, Artinian NT. Testing a model of delayed care-seeking for acute myocardial infarction. Clin Nurs Res 2010;1: 38-54. 33. Perry K, Petrie KJ, Ellis CJ, et al. Symptom expectation and delay in acute myocardial infarction patients. Heart 2001;1:91-3. 34. Horne R, James D, Petrie K, Weinman J, Vincent R. Patients’ interpretation of symptoms as a cause of delay in reaching hospital during acute myocardial infarction. Heart 2000;83:388-93. 35. Zerwic JJ. Symptoms of acute myocardial infarction: expectations of a community sample. Heart Lung 2007;2:75-81.
Canadian Journal of Cardiology Volume - 2014 40. Bruyninckx R, Aertgeerts B, Bruyninckx P, Buntinx F. Signs and symptoms in diagnosing acute myocardial infarction and acute coronary syndrome: a diagnostic meta-analysis. Br J Gen Pract 2008;58:105-11. 41. Mochari-Greenberger H, Miller KL, Mosca L. Racial/ethnic and age differences in women’s awareness of heart disease. J Womens Health (Larchmt) 2012;21:476-80. 42. Flink LE, Sciacca RR, Bier ML, et al. Women at risk for cardiovascular disease lack knowledge of MI symptoms. Clin Cardiol 2013;36:133-8. 43. Canto JG, Zalenski R, Ornato JP, et al. Prevalence, predictors, and consequences of the use of emergency medical services in acute myocardial infarction: observations from the National Registry of Myocardial Infarction 2. Circulation 2002;106:3018-23. 44. Luepker RV, Raczynski JM, Osganian S, et al. Effect of a community intervention on patient delay and emergency medical service use in acute coronary heart disease: the Rapid Early Action for Coronary Treatment (REACT) trial. JAMA 2000;284:60-7. 45. Canto JG, Kiefe CI, Rogers WJ, et al. Number of coronary heart disease risk factors and mortality in patients with first myocardial infarction. JAMA 2011;306:2120-7.
36. Finnegan JR Jr, Meischke H, Zapka JG, et al. Patient delay in seeking care for heart attack symptoms: findings from focus groups conducted in five US regions. Prev Med 2000;31:205-13.
46. Khot UN, Khot MB, Bajzer CT, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA 2003;290:898-904.
37. Kirchberger I, Heier M, Wende R. The patient’s interpretation of myocardial infarction symptoms and its role in the decision process to seek treatment: the MONICA/KORA Myocardial Infarction Registry. Clin Res Cardiol 2012;101:909-16.
47. Yusuf S, Hawken S, Ôunpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004;364:937-52.
38. Pope JH, Aufderheide TP, Ruthazer R, et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med 2000;342: 1163-70. 39. Weaver WD, Cerqueira M, Hallstrom AP, et al. Prehospital-initiated vs hospital-initiated thrombolytic therapy. The myocardial infarction triage and intervention trial. JAMA 1993;270:1211-6.
Supplementary Material To access the supplementary material accompanying this article, visit the online version of the Canadian Journal of Cardiology at www.onlinecjc.ca and at http://dx.doi.org/10. 1016/j.cjca.2013.10.015.
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(2014) 1e8
Review
Time to Standardize and Broaden the Criteria of Acute Coronary Syndrome Symptom Presentations in Women John G. Canto, MD, MSPH,a Elizabeth A. Canto,b and Robert J. Goldberg, PhDc a b c
Watson Clinic, Lakeland, Florida, USA
All Saints’ Academy, Winter Haven, Florida, USA
University of Massachusetts Medical School, Worcester, Massachusetts, USA
ABSTRACT
RESUM E
Early recognition of the signs and symptoms of acute coronary syndromes (ACS) is essential to improving patient management and associated outcomes. It is widely reported that women might have a different ACS symptom presentation than men. Multiple review articles have examined sex differences in symptom presentation of ACS and these studies have yielded inconclusive results and/or inconsistent recommendations. This is largely because these studies have included diverse study populations, different methods of assessing the chief complaint and associated coronary symptoms, relatively small sample sizes of women and men, and lack of adequate adjustment for age or other potentially confounding differences between the sexes. There is a substantial overlap of ACS symptoms that are not mutually exclusive according to sex, and are generally found in women and men. However, there are apparent differences in the frequency and distribution of ACS symptoms among women and men. Women, on average, are also more likely to have a greater number of ACS-related symptoms contributing to the perception that women have more atypical symptoms than men. In this review, we address issues surrounding whether women should have a different ACS symptom presentation message than men, and provide general recommendations from a public policy
pistage pre coce des signes et des symptômes des syndromes Le de lioration de la prise en coronariens aigus (SCA) est essentiel à l’ame sultats associe s. On rapporte souvent que charge des patients et des re rente les symptômes les femmes pourraient manifester de façon diffe s au SCA par rapport aux hommes. De nombreux articles de revues ont lie les diffe rences entre les sexes dans la manifestation des examine s au SCA, et ces e tudes ont abouti à des re sultats peu symptômes lie concluants ou à des recommandations contradictoires, ou les deux. tudes ont inclus des populations C’est en grande partie parce que ces e thodes diffe rentes pour e valuer les principales plaintes diverses, des me s, des e chantillons relativement et les symptômes coronariens associe quat en petits de femmes et d’hommes, et le manque d’ajustement ade rences de facteurs potentiellement fonction de l’âge ou d’autres diffe confusionnels entre les sexes. Il existe un important chevauchement des s au SCA, qui ne s’excluent pas mutuellement selon le symptômes lie ne ralement observe s chez les femmes et les sexe, et qui sont ge rences e videntes dans la hommes. Cependant, il existe des diffe quence et la distribution des symptômes lie s au SCA entre les fre galement plus femmes et les hommes. En moyenne, les femmes sont e s au SCA, ce susceptibles d’avoir un plus grand nombre de symptômes lie
Coronary heart disease (CHD) is the leading cause of death among women and men in the industrialized world.1 Early recognition of the signs and symptoms of acute coronary syndromes (ACS) is essential to reducing the size of myocardial infarction (MI), receiving lifesaving reperfusion and medical therapies, and improving patient outcome. However, failure to recognize and/or acknowledge ACS and atypical symptoms of this condition might lead to greater delays in seeking medical care, receipt of fewer evidence-based therapies, and higher
mortality rates compared with MI patients with typical symptoms.2 It is widely reported by the media and general public that women might have an entirely different ACS symptom presentation than men.3 The MI symptom message currently promoted by health care agencies is sex-neutral.4,5 If women do, in fact, have a different symptom presentation, then perhaps women should receive a custom-tailored, sex-specific message that is different than men. Such a personalized recommendation, however, should be based on a review of the published scientific literature and not on myth or public perception. Canto et al., in a comprehensive review of the presenting symptoms of ACS in women, found that the absence of chest pain or discomfort was noted more commonly in women than in men in the cumulative summary from large cohort studies (37% vs 27%) and in single-centre investigations and small
Received for publication August 2, 2013. Accepted October 20, 2013. Corresponding author: Dr John G. Canto, Watson Clinic, 1600 Lakeland Hill Blvd, Lakeland, Florida 33805, USA. Tel.: þ1-863-680-7341; fax: þ1863-904-3208. E-mail: [email protected] See page 7 for disclosure information.
0828-282X/$ - see front matter Ó 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cjca.2013.10.015
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perspective. In the future, our goal should be to standardize ACS symptom presentation and to elucidate the full range of ACS and myocardial infarction symptoms considering the substantial overlap of symptoms among women and men rather than use conventional terms such as “typical” and “atypical” angina.
qui contribue à la perception que les femmes ont plus de symptômes atypiques que les hommes. Dans cette revue, nous abordons les questions à savoir si les femmes devraient recevoir un message rent au sujet de la manifestation des symptômes lie s au SCA par diffe rapport à celui des hommes, et fournissons des recommandations ne rales du point de vue des politiques publiques. Dans le futur, notre ge s but devrait être de standardiser la manifestation des symptômes lie lucider l’e tendue complète des symptômes lie s au SCA et au SCA et d’e à l’infarctus du myocarde en tenant compte du chevauchement important des symptômes des femmes et des hommes plutôt que d’utiliser les expressions conventionnelles comme angine « typique » et angine « atypique ».
reports (30% vs 17%) (Fig. 1).3,6 However, multiple review articles on the topic of sex differences in symptom presentation in patients presenting with ACS over the past 15 years have yielded inconclusive results and/or inconsistent recommendations.3,7-12 This is largely because these studies were heterogeneous in nature including diverse study populations, different methods of assessing the chief complaint and associated coronary symptoms, relatively small sample sizes of women and men, and lack of adequate adjustment for age and other meaningful differences between the sexes that might explain differences in symptom presentation.3 Three major reasons might explain potential or perceived sex differences in symptom presentation in the setting of ACS:
known to have more atypical symptoms compared with those without diabetes.15 To date, significant gaps in our description of ACS symptoms in diabetic patients and women remain.15 3. Sex-related (cultural) factors in the expression and interpretation of symptoms by patients16,17 and even health care providers.18 A woman’s perception of pain/discomfort might be greatly influenced by her past experiences and culture. For example, a woman who experiences natural childbirth, arguably one of the most severe forms of pain, might later have a higher threshold when experiencing pain/discomfort during ACS and thus might go undetected or even ignored. Also, women, as caretakers of the family, might place other people’s needs before their own, which might influence their interpretation of their own symptoms and subsequent action.
1. Sex-based biological, anatomical, and physiological factors such as differences in sex hormones, autonomic nervous system, cardiac output, microvascular disease, collateral circulation, coronary lumen size, and functional status.13 2. Sociodemographic and comorbidity related factors such as age, race, socioeconomic status, education, income, CHD risk factors, especially diabetes, and possibly other medical conditions, such as heart failure, renal failure, stroke, and depression. Women are, on average, typically much older than men at the time of their MI,2,14 and perhaps (older) age, and not necessarily sex-specific factors, might account for perceived differences in symptom presentation. In addition, among MI patients with diabetes, a condition more prevalent in women, these individuals are widely
The terms “sex” and “gender” are often used interchangeably. According to the World Health Organization, “sex refers to the biological and physiological traits that define women and men,” and “gender refers to the cultural, behavioural, or social attributes among women and men.”19 Yet others view the terms as a “complex interweaving of both nature and nurture.”20 In this report, we use the term “sex” to highlight this relationship of biology and environment. In this review, we address issues surrounding whether women should have a different ACS symptom presentation message than men and provide general recommendations
Summary of Studies Large Cohorts
40
60
N = 9 Studies; N = 471,730
31.6%
37.5% 27.4%
20 0
Percent
Percent
60
Summary of Studies Small Reports or Interviews N = 20 Studies; N = 5324
40
30.3% 25.0% 17.0%
20 0
Overall
Women
Men
Overall
Women Men
Figure 1. Acute coronary syndromes presentation without chest pain/discomfort according to sex: summary of studies from large cohorts and small reports. P < 0.001 for all comparisons. Reprinted from Canto et al.6 with permission from Female Patient.
Canto et al. ACS Symptom Presentations in Women
from a public policy perspective. For purposes of this commentary, the term “MI” will be preferentially used when the population studied involved only MI patients or the message is targeted for this specific group. The term “ACS” will be used to refer to the broader spectrum of acute presentations of unstable angina, non-ST segment elevation MI, and ST segment elevation MI. Definition of ACS Symptoms Symptoms of “typical” chest pain or discomfort Typical symptoms of ACS primarily involve the presence of pain or discomfort localized to the chest or precordial region. The chest pain or discomfort is often described as a fullness pressure, tightness, squeezing sensation, or as if an elephant is sitting on one’s chest. The symptom might radiate to other areas of the upper body such as the jaw, neck, shoulders, right or left arm, back, and epigastric region. It is often associated with any combination of symptoms such as shortness of breath, nausea, vomiting, diaphoresis, or lightheadedness. The symptoms might be exacerbated by exertion though they generally occur at rest. The symptoms of ACS can vary in intensity, severity, duration, and might crescendo in nature. The symptoms of ACS might develop suddenly or slowly over a period of several days, weeks, or months. Symptoms of “atypical” chest pain or discomfort The symptoms of chest pain or discomfort, which are “atypical” in nature, include descriptors such as sharp, pleuritic, burning, or reproducible by chest wall palpation. The pain/discomfort can oftentimes be localized in a small area on the chest (the size of a half-dollar coin or 2 fingerbreadths). ACS symptoms in the absence of chest pain or discomfort Additional symptoms in the literature have been described and include pain or discomfort which is localized in the upper areas of the thorax such as the jaw, neck, shoulders, right or left arm, back, and epigastric region in the absence of chest pain/discomfort. The other significant category of ACS presentation in the absence of chest pain/discomfort involves unexplained shortness of breath. A number of patients describe indigestion-like symptoms or even flu-like symptoms. Principal symptoms, associated symptoms, and prodromal symptoms Principal and associated symptoms by sex. Identifying the chief complaint from associated ACS symptoms is important in forming a differential diagnosis. Although the symptom complex of ACS has been identified, we are not aware of any comparative studies that have specifically examined sex differences in the principal symptoms of acute coronary disease vs other accompanying symptoms. Future studies should attempt to discriminate primary vs secondary symptoms in ACS by sex. Prodromal symptoms by sex. Prodromal symptoms can be defined as those experienced before an acute coronary event
3
and might serve as an early MI warning sign. In a study of 515 women with MI, 95% of subjects experienced prodromal MI symptoms which included fatigue (71%), sleep disturbance (48%), shortness of breath (42%), and chest discomfort (30%), although sex comparisons were not possible because of the lack of men in the study.21 Few studies have examined the differences in the early warning or prodromal symptoms between women and men.22-24 Among 914 Swedish patients admitted to a coronary care unit for suspected MI, slightly more than half (57%) with confirmed MI reported chest pain within 48 hours and 61% reported other prodromal symptoms; although women reported more prodromal symptoms than men (70% vs 58%; P < 0.01).22 However, in a multicentre, cross-sectional study of 533 Norwegian patients with MI, nearly half of the patients experienced prodromal chest symptoms (45%), fatigue (62%), shoulder and back pain (51%), arm pain (38%), and dyspnea (33%) within the year before their first MI; no statistically significant differences were observed in prodromal symptoms between sexes.23 These prodromal symptoms were eventually associated with symptoms that occurred during the acute stage of MI in both sexes, but these associations were more pronounced in women than in men.23 Lastly, in a large population-based study of 14,230 patients who presented to emergency departments in the Province of Alberta with a diagnosis of ACS, only a small proportion of patients (16%) actually sought medical attention for prodromal symptoms in the 90 days before their ACS, which was associated with improved 1-year survival in women but not in men.24 Early recognition of the signs and symptoms of ACS before the acute event (prodromal symptoms) might enhance earlier detection of CHD and potentially improve patient outcomes. Differences in Symptom Presentation Among Women and Men: Overlap of ACS Symptoms Chest pain/discomfort is generally regarded as the hallmark symptom of ACS in women and men.3,7-12 There are, however, a considerable number of ACS patients who will not have this cardinal symptom,3,7-12 and the absence of chest pain/discomfort is generally seen in a higher proportion of women than in men.3,7-9,12 The symptoms of ACS are not mutually exclusive by sex and are generally found in women and men. However, there appear to be differences in the frequency of symptoms in ACS among women and men. In general, women are more likely to experience back pain,3,7-9,12 neck pain,3,7-9,12 jaw pain,3,7-9,12 arm pain,7 shortness of breath,3,9-10,12 paroxysmal nocturnal dyspnea,3 nausea or vomiting,3,7-10,12 indigestion,3,10,12 loss of appetite,3,8,10 weakness or fatigue,3,7,9-10,12 cough,3,9 dizziness,3,7,10 syncope,7,10 and palpitations3,8,10 compared with men. Men generally experience more chest pain3,7-10,12 and diaphoresis3,8-10,12 compared with women. Canto et al. examined sex differences in MI symptom presentation and subsequent hospital mortality, after adjusting for age, among 1.1 million patients enroled in the National Registry of Myocardial Infarction between 1994 and 2004. In this large observational study, chest pain/discomfort was a common symptom of MI seen in more than two-thirds of the overall study population.14 However, the absence of chest
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Adjusted Odds Ratio*
Percent N = 1,143,513
40
38.1%
1.40
35.4% 35
%
30.7%
30
25 0
Odds Ratio (Women vs Men)
45
1.30 1.26
1.30
1.13
1.20 1.10
1.03
1.00 OR > 1.0 women have higher odds of MI presentation without CP than men
0.90 All
Women
1.24
Men
< 45
45-54
55-64
65-74
75-84
Years Figure 2. MI presentation without chest pain/discomfort, adjusted data stratified by age: Women vs men. CP, chest pain; MI, myocardial infarction; OR, odds ratio. Reprinted from Canto et al.14 with permission from the American Medical Association.
pain/discomfort was more commonly noted in women than men (42% vs 30%; P < 0.001).14 Younger women were more likely to present without chest pain/discomfort and had higher hospital death rates than similarly aged younger men (< 55 years of age); in contrast, sex differences in presentation and mortality were markedly attenuated and nearly disappeared with increasing age (Fig. 2).14 Although younger women were more likely to present without chest pain/discomfort than similarly aged men in this study, this effect was relatively modest and not absolute, because it was also observed among men and older patients.14 In comparing the symptom profile of the younger women to older women, older women were significantly more likely to present with atypical symptoms of MI than younger aged women (Fig. 3).14 This highlights the problem of making general and mutually exclusive statements by sex considering the substantial overlap of symptom presentation in women and men.
Novel approaches have been attempted to portray potential differences, and similarities, in symptom presentation according to sex.16,17 Shin et al. compared sex differences in retrospective reports of MI symptoms that resulted from 2 different assessment methods: (1) an open-ended inquiry alone; and (2) a combined assessment approach that consisted of an open-ended inquiry followed by a series of closed-ended questions.16 Women reported more atypical symptoms of ACS in their responses to the open-ended inquiry and a greater number of typical and atypical symptoms, and total symptoms in the combined assessment approach, compared with men.16 Thus, the manner in which patients were interviewed might explain potential differences in how MI symptoms are expressed and interpreted. Kreatsoulas et al. examined sex differences in cardiac symptoms among 237 patients with suspected CHD who underwent their first coronary angiogram using a novel construct of angina by
Women
Men
N = 481,581 (42%)
60
60
P value for trend < 0.001
50.4%
50
20 18.5%
21.6%
10
32.7%
30
20
21.8% 13.0%
15.7%
10
0 Years:
46.6%
40
Percent
28.9%
30
P value for trend < 0.001
50
37.9%
40
Percent
N = 661,932 (58%)
0
< 45
45-54
55-64
65-74 75-84
N: 15,236
31,899
61,164 107,877 265,405
Years:
< 45
45-54
55-64
65-74 75-84
N: 51,304 100,878 139,855 159,603 210,292
Figure 3. MI presentation without chest pain/discomfort according to age and sex. CP, chest pain; MI, myocardial infarction. Data obtained from Canto et al.14
Canto et al. ACS Symptom Presentations in Women
scaling symptom expression along a continuum.17 The authors demonstrated “substantial overlap of shared symptoms between women and men with obstructive coronary artery disease,” and “a predominance of similar symptoms between women and men.”17 The investigators reported that “the descriptors more commonly expressed by women were not unique to women,” and concluded that “the choice of terms used to describe a symptom might be a function of ‘gendered language’ rather than of conventionally portrayed biological sex differences.”17 Last, many studies capture symptom presentation through a retrospective review of the medical record, which might be distorted by several filters to provide effective communication in the chart.18 The patient must provide a verbal description of their presenting symptoms which is then modified by the well-intended health care providers who provide a written summary portraying the patient’s actual words to convey a clear diagnostic picture.18 However, if health care providers have an index of suspicion of ACS, which might be lower in women than men, it is conceivable that an atypical presentation might be recorded in the medical chart to reflect this bias. In summary, it appears that women and men experience similar ACS symptoms although the distribution and magnitude of these symptoms between women and men is subject to debate. Our goal should be to elucidate the full range of ACS and MI symptoms considering the substantial overlap of symptoms among women and men rather than use conventional terms such as “typical” and “atypical” angina. Number of Associated ACS Symptoms A number of investigators have reported that women have a greater number of associated symptoms in ACS presentation compared with men.16,25-27 This might significantly contribute to the perception that women have atypical presentations compared with men. In 2 population-based MI registries from Germany and Sweden respectively, women were twice as likely to report > 4 symptoms as men (odds ratio, 2.14)26 and more than 3 times as likely to report > 3 symptoms as men (odds ratio, 3.26).27 Although 1 study found no differences in the number of acute coronary symptoms according to sex, this study might have considerably been underpowered to examine such an association (N ¼ 60).28 McSweeney and colleagues conducted interviews of 515 women with MI using a standardized patient questionnaire and reported that women had more acute (mean, 7.3; range, 0-29) than prodromal (mean, 5.71; range, 0-25) symptoms although no comparative data were available in men.21 Despite this shortcoming, the average number of acute or prodromal symptoms reported in women was dramatic. In summary, women are more likely to report more symptoms as part of their ACS presentation compared with men, which might contribute to challenges in the interpretation of symptom presentation in women and the perception that women have more atypical symptoms. Limitations of the Current Literature and Need to Standardize ACS Symptom Presentation The published literature is not standardized for ACS symptom presentation, making it difficult to provide any conclusive statements on symptom presentation in women. In
5
addition, a distinct majority of studies lack adequate adjustment for differences in age, race, and ACS classification (such as MI type).29 Also, many of the studies in the literature have excluded ACS patients who do not have the presence of chest pain/discomfort, thus potentially biasing their results. In addition, many of the studies lumped pain/discomfort localized in other areas of the body with chest pain/discomfort. Many observational studies and randomized trials in ACS have used a simplistic classification of patients’ symptoms, such as the presence or absence of chest pain/discomfort (yes/ no), rather than elucidating the entire ACS symptom complex.29 A recent meta-analysis by Shin et al. clearly differentiated between studies reporting on chest pain (N ¼ 19) and chest discomfort (N ¼ 9) and found women to be significantly less likely to have chest pain, but not necessarily chest discomfort, than men.16 When women experienced chest pain/discomfort, they commonly used descriptors such as pressure, aching, or tightness, not pain.21 This confusion might be attributed in part to a lack of standardization in the collection of ACS symptom presentation and its timing making comparative analyses difficult between published reports. In a recent editorial by Canto et al.,29 the investigators proposed collecting several key data elements using common definitions to help standardize the recording and analysis of information about symptoms experienced in the wide spectrum of CHD (Supplemental Table S1). These elements included: “Important demographic features including age, sex, race, and socioeconomic status; presence/absence of CHD risk factors and comorbidities; specifying ACS classification vs chronic CHD/angina using standard terminology; clearly specifying which are principal symptoms vs associated symptoms vs prodromal symptoms; duration and frequency of these symptoms; description of pain/discomfort (if present) to include the intensity, location, radiation, and relief of symptoms; other pertinent factors which are not directly related to symptom presentation, but their inclusion may help ascertain the association of ACS symptoms with duration of patient delay in seeking medical care, processes of care received in hospital, and subsequent short and longterm outcomes whenever possible.”
Congruence of Symptoms and Relationship with Hospital-Associated Delay Patients’ misinterpretation of the symptoms of ACS is a major cause for prolonged prehospital delay. Symptom congruence is defined as “the extent to which one’s ACS symptom experience matches those expected,”30 and has been associated with a greater likelihood of seeking timely medical care.28,31-35 “Patients, bystanders, and those at higher risk expected MI symptoms to present as often portrayed in the movies with crushing chest pain rather than the more common onset of initially ambiguous but gradually increasing discomfort.”36 In a study of 559 women and 1684 men with MI from a populationbased registry, symptom incongruence did not significantly differ
6
between women and men.37 “Although the location and quality of discomfort were important components of symptom congruence, symptom severity by far outweighed their importance.”30 In fact, severe chest pain/discomfort was the strongest predictor of symptom congruence (along with a previous MI); conversely, nonsevere symptoms were more likely to be associated with symptom incongruence. There were no observed differences in the quality of the symptoms experienced and expected by women and men.30 These investigators concluded that education remains needed to dispel the common perception that chest pain/discomfort must be of severe intensity to be considered a symptom of MI for women and men.30 Current National Institute of Health MI Symptom Message and Calling 9-1-1 The most common signs and symptoms of an MI for women and men include4: 1. “Chest pain or discomfort. Most MIs involve discomfort in the centre or left side of the chest. The discomfort usually lasts for more than a few minutes or goes away and comes back. It can feel like pressure, squeezing, fullness, or pain. It also can feel like heartburn or indigestion. The feeling can be mild or severe. 2. Upper body pain or discomfort: one or both arms, back, shoulders, neck, jaw, or upper part of the stomach (above the belly button). 3. Shortness of breath. This may be the patient’s major symptom, or it may occur before or along with chest pain or discomfort. It can occur when one is resting or performing limited physical activity.” Other possible signs and symptoms of an MI include the following4: 1. “Breaking out in a cold sweat; 2. Feeling unusually tired for no reason, sometimes for days” (especially for women); 3. Nausea (feeling sick to the stomach) and vomiting; 4. Light-headedness or sudden dizziness; 5. Any sudden, new symptoms or a change in the pattern of symptoms” (for example, if one’s symptoms become stronger or last longer than usual); 6. If one has already had an MI, the symptoms may not be the same for another one. However, some may have a similar pattern of symptoms that recur.” Another potential concern is the substantial overlap of symptoms consistent with ACS and those of noncardiac diagnoses. In fact, most women experiencing the symptoms as outlined by the National Institutes of Health will not be having an ACS or MI.38,39 Based on a systematic review that examined the accuracy of 10 important signs and symptoms in patients with and without ACS,40 there were no definitive symptoms that might confirm the diagnosis of ACS or MI, though “chestwall tenderness on palpation largely ruled out MI or ACS in low-prevalence settings.”40 Furthermore, even if women were to be fully knowledgeable of the signs and symptoms of an MI, they must also be aware they are at risk for an MI, otherwise, they might not take their symptoms seriously. A number of women at higher risk of MI unrealistically judge their personal risk as low and “describe heart attack as a ‘male problem,’ an
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important aspect of their underestimation of personal risk.”36 In addition, a significant number of women still do not correctly recognize that heart disease is the leading cause of death in women, a disparity most apparent among Hispanic and AfricanAmerican women.41 Women who were the most likely to be at risk for developing CHD based on their Framingham risk score were also the least likely to know the correct symptoms of MI.42 Clearly, more education is needed linking one’s risk of CHD and personal risk of experiencing an MI. It has been continuously recommended by a number of voluntary health agencies and organizations that patients who suspect they have ACS should activate emergency medical services (EMS) for a number of reasons. These include having the availability of life-saving automated external defibrillators in case of cardiac arrest, using a prehospital electrocardiogram to make the diagnosis of MI in the field, and receiving lifesaving treatments early such as oxygen, nitroglycerin, and aspirin before hospital arrival. EMS use has also been shown to improve the speed by which primary percutaneous coronary intervention and fibrinolytic therapy are implemented.43 In addition, paramedics are more likely to triage a suspected MI patient to referral centres more likely to administer these life-saving acute reperfusion therapies.43 Despite the many benefits associated with early activation of EMS, many high-risk women understand little about the benefits of rapid action and are generally unaware of the benefits of calling 9-1-1.36 The reasons why women might not call for an ambulance include the following36: Symptoms are ambiguous or not perceived as life threatening Patient denial that they are having an MI Personal assessment of CHD risk was low Think driving might be faster than calling for an ambulance Fear Lack of control Embarrassment Permission from health care provider, spouse, relatives, or friends to take action No plan of action Cost Nevertheless, aggressive national public health campaigns educating the public about the signs and symptoms of MI have increased the use of EMS, but not necessarily reduced delay in seeking treatment.44 Thus, novel strategies are needed if delay time from symptom onset to hospital presentation is to be further decreased in women with suspected MI.44 Because most patients with ACS or MI have at least 1 CHD risk factor present,45-47 perhaps a public health message should be that if you are a woman at risk for an acute coronary event with at least 1 CHD risk factor and are experiencing suspected MI symptoms, seek medical evaluation as soon as possible. The ACS symptom complex is subjective and the diagnosis of MI relies on clear-cut objective tests such as a 12-lead electrocardiogram and cardiac biomarkers of cell necrosis such as troponin. However, without a heightened suspicion of an acute coronary event based on symptom presentation, this might lead to an incorrect diagnosis and lack of receipt of appropriate lifesaving therapies.
Canto et al. ACS Symptom Presentations in Women
Conclusions The evaluation of acute and/or prodromal symptoms in women and men with suspected ACS is a challenging task. There is a substantial overlap of ACS symptoms that are not mutually exclusive according to sex, and are generally found to a certain extent in women and men. However, there are apparent differences in the frequency and distribution of ACS symptoms in women and men. Women are also more likely to have a greater number of symptoms after ACS than men that might lead to the misperception that women have more atypical symptoms. The literature is not standardized for ACS symptom presentation and often lacks adequate adjustment for differences in age, race, socioeconomic status, additional comorbidities, ACS classification (such as MI type), and methods of symptom assessment that make it challenging to formulate any definitive statements about sex differences in acute symptom presentation. In fact, the magnitude of the differences in symptom presentation according to age appears to be much greater than the magnitude of the differences in symptom presentation between the 2 sexes. In the future, our goal should be to standardize ACS symptom presentation and to elucidate the full range of ACS and MI symptoms considering the substantial overlap of symptoms among women and men rather than use conventional terms such as “typical” and “atypical” angina. Disclosures The authors have no conflicts of interest to disclose. References 1. World Health Organization. The 10 leading causes of death in the world, 2000 and 2011. Available at: http://who.int/mediacentre/factsheets/ fs310/en/index.html. Accessed January 10, 2014. 2. Canto JG, Shlipak MG, Rogers WJ, et al. Prevalence, clinical characteristics and mortality among patients with myocardial infarction presenting without chest pain. JAMA 2000;283:3223-9. 3. Canto JG, Goldberg RJ, Hand MH, et al. Symptom presentation of women with acute coronary syndromes: myth versus reality. Arch Intern Med 2007;167:2405-13. 4. U.S. Department of Health & Human Services. National Institutes of Health. National Heart, Lung, and Blood Institute. What are the symptoms of a heart attack? Available at: http://www.nhlbi.nih.gov/ health/health-topics/topics/heartattack/signs.html. Accessed January 10, 2014.
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9. Chen W, Woods SL, Puntillo KA. Gender differences in symptoms associated with acute myocardial infarction: a review of the research. Heart Lung 2005;34:240-7. 10. DeVon HA, Zerwic JJ. Symptoms of acute coronary syndromes: are there gender differences? A review of the literature. Heart Lung 2002;31: 235-45. 11. Kyker KA, Limacher MC. Gender differences in the presentation and symptoms of coronary artery disease. Curr Womens Health Rep 2002;2: 115-9. 12. Herlitz J, Bang A, Karlson BW, Hartford M. Is there a gender difference in aetiology of chest pain and symptoms associated with acute myocardial infarction? Eur J Emerg Med 1999;6:311-5. 13. Devon HA, Ryan CJ, Ochs AL. Symptoms across the continuum of acute coronary syndromes: differences between women and men. Am J Crit Care 2008;17:14-25. 14. Canto JG, Rogers WJ, Goldberg RJ, et al. Association of age and sex differences in myocardial infarction symptom presentation and mortality. JAMA 2012;307:813-22. 15. Stephen SA, Darney BG, Rosenfield AG. Symptoms of acute coronary syndrome in women with diabetes: an integrative review of the literature. Heart Lung 2008;37:179-89. 16. Shin JY, Martin R, Howren MB. Influence of assessment methods on reports of gender differences in AMI symptoms. West J Nurs Res 2009;31:553-68. 17. Kreatsoulas C, Shannon HS, Giacomini M, et al. Reconstructing angina: cardiac symptoms are the same in women and men. JAMA Intern Med 2013;173:829-31. 18. Peterson ED, Alexander KP. Learning to suspect the unexpected: evaluating women with cardiac syndromes. Am Heart J 1998;136:186-8. 19. World Health Organization. Gender, women and health. Available at: http://www.who.int/gender/whatisgender/en. Accessed January 10, 2014. 20. Mills ME. Sex difference vs. gender difference? Oh, I’m so confused! Psychol Today 2011. Available at: http://www.psychologytoday.com/ blog/the-how-and-why-sex-differences/201110/sex-difference-vs-genderdifference-oh-im-so-confused. Accessed January 10, 2014. 21. McSweeney JC, Cody M, O’Sullivan P, et al. Women’s early warning symptoms of acute myocardial infarction. Circulation 2003;108: 2619-23. 22. Hofgren C, Karlson BW, Herlitz J. Prodromal symptoms in subsets of patients hospitalized for suspected acute myocardial infarction. Heart Lung 1995;24:3-10. 23. Lovlien M, Johansson I, Hole T, Schei B. Early warning signs of an acute myocardial infarction and their influence on symptoms during the acute phase, with comparisons by gender. Gender Med 2009;6:444-53.
5. American Heart Association. Symptoms of a heart attack and stroke. Available at: https://www.goredforwomen.org/home/about-heart-diseasein-women/symptoms-of-heart-disease. Accessed January 10, 2014.
24. Graham MM, Westerhout CM, Kaul P, Norris CM, Armstrong PW. Sex differences in patients seeking medical attention for prodromal symptoms before an acute coronary event. Am Heart J 2008;156:1210-6.
6. Canto JG, Canto AJ, Goldberg RJ, Hand MH. Symptom presentation of women with acute coronary syndromes. Female Patient 2009;34:26-8.
25. Milner KA, Funk M, Richards S, et al. Gender differences in symptom presentation associated with coronary heart disease. Am J Cardiol 1999;84:396-9.
7. Coventry LL, Finn J, Bremner AP. Sex differences in symptom presentation in acute myocardial infarction: a systematic review and metaanalysis. Heart Lung 2011;40:477-91. 8. Shin JY, Martin R, Suls J. Meta-analytic evaluation of gender differences and symptom measurement strategies in acute coronary syndromes. Heart Lung 2010;39:283-95.
26. Kirchberger I, Heier M, Kuch B, et al. Sex differences in patient-reported symptoms associated with myocardial infarction (from the populationbased MONICA/KORA Myocardial Infarction Registry). Am J Cardiol 2011;107:1585-9. 27. Berg J, Björck L, Dudas K, et al. Symptoms of a first acute myocardial infarction in women and men. Gender Med 2009;6:454-62.
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28. King KB, McGuire MA. Symptom presentation and time to seek care in women and men with acute myocardial infarction. Heart Lung 2007;36: 235-43. 29. Canto JG, Goldberg RJ, Sopko G. A call to standardize symptom presentation in acute coronary syndromes. Am Heart J 2012;164:801-6. 30. Fox-Wasylyshyn S. Predictors of symptom congruence among patients with acute myocardial infarction. J Cardiovasc Nurs 2012;12:325-33. 31. Nymark C, Mattiasson A, Henriksson P, et al. The turning point: from self-regulative illness behavior to care-seeking in patients with an acute myocardial infarction. J Clin Nurs 2009;23:3358-65. 32. Fox-Wasylyshyn S, El-Masri M, Artinian NT. Testing a model of delayed care-seeking for acute myocardial infarction. Clin Nurs Res 2010;1: 38-54. 33. Perry K, Petrie KJ, Ellis CJ, et al. Symptom expectation and delay in acute myocardial infarction patients. Heart 2001;1:91-3. 34. Horne R, James D, Petrie K, Weinman J, Vincent R. Patients’ interpretation of symptoms as a cause of delay in reaching hospital during acute myocardial infarction. Heart 2000;83:388-93. 35. Zerwic JJ. Symptoms of acute myocardial infarction: expectations of a community sample. Heart Lung 2007;2:75-81.
Canadian Journal of Cardiology Volume - 2014 40. Bruyninckx R, Aertgeerts B, Bruyninckx P, Buntinx F. Signs and symptoms in diagnosing acute myocardial infarction and acute coronary syndrome: a diagnostic meta-analysis. Br J Gen Pract 2008;58:105-11. 41. Mochari-Greenberger H, Miller KL, Mosca L. Racial/ethnic and age differences in women’s awareness of heart disease. J Womens Health (Larchmt) 2012;21:476-80. 42. Flink LE, Sciacca RR, Bier ML, et al. Women at risk for cardiovascular disease lack knowledge of MI symptoms. Clin Cardiol 2013;36:133-8. 43. Canto JG, Zalenski R, Ornato JP, et al. Prevalence, predictors, and consequences of the use of emergency medical services in acute myocardial infarction: observations from the National Registry of Myocardial Infarction 2. Circulation 2002;106:3018-23. 44. Luepker RV, Raczynski JM, Osganian S, et al. Effect of a community intervention on patient delay and emergency medical service use in acute coronary heart disease: the Rapid Early Action for Coronary Treatment (REACT) trial. JAMA 2000;284:60-7. 45. Canto JG, Kiefe CI, Rogers WJ, et al. Number of coronary heart disease risk factors and mortality in patients with first myocardial infarction. JAMA 2011;306:2120-7.
36. Finnegan JR Jr, Meischke H, Zapka JG, et al. Patient delay in seeking care for heart attack symptoms: findings from focus groups conducted in five US regions. Prev Med 2000;31:205-13.
46. Khot UN, Khot MB, Bajzer CT, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA 2003;290:898-904.
37. Kirchberger I, Heier M, Wende R. The patient’s interpretation of myocardial infarction symptoms and its role in the decision process to seek treatment: the MONICA/KORA Myocardial Infarction Registry. Clin Res Cardiol 2012;101:909-16.
47. Yusuf S, Hawken S, Ôunpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004;364:937-52.
38. Pope JH, Aufderheide TP, Ruthazer R, et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med 2000;342: 1163-70. 39. Weaver WD, Cerqueira M, Hallstrom AP, et al. Prehospital-initiated vs hospital-initiated thrombolytic therapy. The myocardial infarction triage and intervention trial. JAMA 1993;270:1211-6.
Supplementary Material To access the supplementary material accompanying this article, visit the online version of the Canadian Journal of Cardiology at www.onlinecjc.ca and at http://dx.doi.org/10. 1016/j.cjca.2013.10.015.
