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Gender differences in symptom predictors associated with acute coronary syndrome: A prospective observational study
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Gender differences in symptom predictors associated with acute coronary syndrome: A prospective observational study Hossein Asgar Pour BSc, RN, MSN, PhD (Assistant Professor) a,*, Reza Norouzzadeh BSc, RN, MSN (Lecturer) b, Mohammad Reza Heidari BSc, RN, MSN, PhD (Assistant Professor) b a b
Department of Surgical Nursing, Aydın Health School, Adnan Menderes University, Aydın, Turkey Faculty of Midwifery and Nursing, Shahed University, Tehran, Iran
A R T I C L E
I N F O
Article history: Received 25 August 2014 Received in revised form 26 June 2015 Accepted 28 June 2015 Keywords: Acute coronary syndrome Typical symptoms Symptom predictors
A B S T R A C T
Signs and symptoms (typical and atypical symptoms) of acute coronary syndromes (ACS) differ between men and women. Identification of gender differences has implications for both health care providers and the general public. The aim of this study was to determine the symptom predictors of the acute coronary syndromes in men and women. In this prospective study, nurse data collectors directly observed 256 men and 182 women (N = 438) with symptoms suggestive of ACS in the Emergency Departments of eight hospitals in Tehran. ACS was eventually diagnosed in 183 (57.2%) men and 137 (42.8%) women on the basis of standard electrocardiogram and cardiac enzyme (CPK-MB) level. In men, chest symptoms (OR = 3.22, CI = 0.137–0.756, P = 0.009), dyspnea (OR = 2.65, CI = 1.78–4.123 P = 0.001) and diaphoresis (OR = 2.175, CI = 1.020–4.639, P = 0.044) were significantly associated with the diagnosis of ACS 3.78, 2.72 and 1.87 times more than in women having these symptoms, respectively. These results indicated that chest symptoms, diaphoresis and dyspnea were the more pronounced typical symptoms of ACS in men compared to women. Additionally, the numbers of typical symptoms can be considered as more predictive of ACS in men (OR = 1.673, CI = 1.211–2.224, P < 0.001) than women (OR = 1.271, CI = 1.157–2.331, P = 0.212). Therefore, clinicians need to take men showing typical symptoms into consideration carefully. © 2015 Elsevier Ltd. All rights reserved.
1. Introduction Cardiovascular diseases mainly related to coronary artery disease (CAD) and its acute complications are one of the major causes of death in developing countries (Pankert et al., 2012). CAD remains the leading cause of morbidity and mortality in both men and women worldwide (Pelter et al., 2012). Acute coronary syndromes (ACS) are the most common causes of hospitalization for men and women in the United States (Biranvand and Asadpourpiranfar, 2006, Biranvand et al., 2008; McCaig and Nawar, 2006). ACS encompass a spectrum of coronary artery diseases, including unstable angina, ST-elevation myocardial infarction and non-ST elevation myocardial infarction with initial presentation and early management (Achar et al., 2005). Symptoms are often the initial clinical feature of ACS (Pelter et al., 2012). The accurate labeling of the symptoms of ACS as being cardiac in nature may reduce the time for treatment and expedite a timely
diagnosis (Hwang et al., 2009; McCaig and Nawar, 2006; Thygesen et al, 2007). Previous research studies suggest that the presentation of ACS and ACS symptoms may differ in both men and women (Arslanian-Engoren et al., 2006; Milner et al., 1999). Gender differences in the cardiovascular physiologic factors may further contribute to the differences between the men and women in the symptoms of ACS. Identification of the gender differences has implications for health care providers and the general public (DeVon and Zerwic, 2002; Patel et al., 2004). There are not enough studies regarding the differences of typical and atypical symptoms of ACS in both men and women (Milner et al., 1999). Therefore, the aim of this study was to determine the differences of typical and atypical symptom predictors of ACS in men and women. 2. Methods 2.1. Design, sample and setting
* Corresponding author. Department of Surgical Nursing, Aydın Health School, University of Adnan Menderes, P.O. Box: 09100, Aydın, Turkey. Tel.: +90 256 213 88 66; fax: +90 256 212 42 19. E-mail address: [email protected] (H. Asgar Pour).
This prospective observational study was conducted in the Emergency Departments of eight affiliated teaching hospitals in Tehran, Iran between March 2011 and June 2012. These departments were selected by a cluster sampling method. The voluntary patients having
http://dx.doi.org/10.1016/j.ienj.2015.06.008 1755-599X/© 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hossein Asgar Pour, Reza Norouzzadeh, Mohammad Reza Heidari, Gender differences in symptom predictors associated with acute coronary syndrome: A prospective observational study, International Emergency Nursing (2015), doi: 10.1016/j.ienj.2015.06.008
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at least one of the typical or atypical symptoms of ACS were considered for participation in the study. The typical symptoms of ACS were chest symptoms not related to trauma (chest pressure, heaviness, tightness/squeezing, or center or left chest pain), diaphoresis, shortness of breath (dyspnea) not related to pulmonary disorders, arm pain, and jaw/neck pain not related to trauma. Atypical symptoms were numbness, tingling, pricking, or stabbing in the chest (mid-back pain and chest pain in another location), palpitation, nausea/vomiting (not related to gastrointestinal diseases), dizziness or syncope, fatigue and indigestion (Milner et al., 2001). Patients with the history of stroke, neurologic disorders, trauma, chronic obstructive pulmonary diseases, pneumonia or pulmonary embolism were excluded. According to the results of a pilot study with p = 0.3 and d = 0.04 a selection of 530 patients was sufficient for the sample. Therefore, a total of 530 patients meeting study criteria were approached for the participation in the study. Of these, 438 patients agreed to participate and enrolled in this study. 2.2. Ethical approval The study was approved by the Institutional Ethics Committee of the Shahed University in Tehran. Written approvals were obtained from the Shahed University Institute of Health Sciences (March 2010), Ethics Board of the Shahed University Midwifery and Nursing Faculty (May 2010), and the affiliated teaching hospitals (June 2010). Written and verbal informed consents were obtained from all patients after explaining the aims and protocol of the study.
by electrocardiography changes (ST-segment and T-wave changes) and cardiac enzyme (creatine kinase-MB). For the more unified data collection, the investigators interviewed and trained the nurses before beginning the study. The data about symptoms were obtained by observing the patient–nurse interview, and the related symptoms of ACS expressed by the patients were documented in the ACS symptoms check list. The demographics data (sex, age, education) and the risk factors (history of hypertension, hypercholesterolemia, diabetes, smoking, and obesity) were collected from the medical records and by interviews with patients. Obesity was considered as body mass index (BMI) ≥ 30. 2.4. Data analysis The statistical analysis of data was performed by using the SPSS windows program (version 16.0). To examine the associations between the ACS and baseline characteristics and also presenting symptoms in women and men, the chi-squared test was used. The symptoms reported by at least 5% were included in the bivariate analyses. To determine symptom predictors in the men and women patients, the method of multiple logistic regressions with stepwise was performed. Logistic regression methods were used to identify the best model and the cutoff to stay in the model was P < 0.20 (Milner et al., 1999). Adjusted Odd ratios were estimated for each symptom predictor. The statistical significance was set at P < 0.05. 3. Results
2.3. Data collection, instruments and procedures 3.1. Risk factors and symptom predictors of ACS in men Data collecting instruments were developed based on a review of literature and from the specialists’ comments. The specialists were one ED physician, one ED nurse specialist, two ED staff nurses, one cardiologist, and a cardiac clinical nurse specialist. The checklist included the typical and atypical symptoms of ACS. To determine the validity of the checklist, each of the specialists was asked to note each symptom relevant or not relevant to the ACS. This process was done several times until the specialists were in 100% agreement. To determine the inter rater reliability two independent emergency nurse observers assessed twenty patients by using the checklist. The reliability of each item was calculated by using the percent agreement and the Kappa coefficient. The total percent agreement ranged from 86% to 100%, and the Kappa statistics ranged from 0.24 to 1. Therefore, providing the symptoms checklist was a reliable tool for identifying the symptoms of ACS. The data were collected by eight nurses who observed all the patients and met the study criteria as they were admitted to the ED during 6 hour shift intervals in a day for 7 days. ACS was defined as either unstable angina or acute myocardial infarction, confirmed
Out of 438 patients, 73.05% (N = 320) of them had ACS diagnosis. For the diagnosed patients with ACS, 57.2% (n = 183) were male and their mean age was 60.92 ± 1.24 years. Regarding the risk factors, the men with ACS usually had diabetes and hypercholesterolemia compared with men without ACS (P < 0.05). Additionally, men with ACS reported a higher number of typical and atypical symptoms (2.75 ± 1.36) compared to the men without ACS (1.78 ± 0.58) (P = 0.006) (Table 1). The most reported typical symptoms in the male patients with ACS were chest symptoms, diaphoresis and dyspnea (P < 0.05). The men with typical symptoms such as chest symptoms (P < 0.001), arm pain (P = 0.012), diaphoresis (P < 0.001) and dyspnea (P < 0.001) were significantly more likely to be diagnosed with ACS compared to the men who did not report these symptoms (Table 2). According to the atypical symptoms, there was a trend for more indigestion and dizziness/syncope in the men with non-ACS compared to the men with ACS, and the difference was statistically significant (P < 0.05) (Table 3).
Table 1 Relationship between baseline characteristics and ACS in men and women. Characteristics
Hypertension Diabetes mellitus Currently smoking Hypercholesterolemia Obesity (BMI ≥ 30) Menopause Age (years) Number of presenting symptoms
Men
Women
With ACS (n = 183)
Without ACS (n = 73)
N
N
% 126 152 83 93 46
Mean ± SD 60.92 ± 1.24 2.75 ± 1.36
70 84.9 46.4 55.4 74.2
P
% 54 27 96 75 16
56.32 ± 1.11 1.78 ± 0.58
30 15.1 53.6 44.6 25.8
0.103 0.000 0.543 0.040 0.148
0.011 0.006
With ACS (n = 137)
Without ACS (n = 45)
N
%
N
50 88 123 64 63 103 Mean ± SD 63.29 ± 3.84 2.94 ± 1.78
39.4 65.2 90.4 50.4 80.8 74.1
77 47 13 63 15 36
P
% 60.6 34.8 9.6 49.6 19.2 25.9
0.722 0.033 0.764 0.860 0.034 0.660
59.13 ± 2.17 1.56 ± 0.69
0.020 0.018
Please cite this article in press as: Hossein Asgar Pour, Reza Norouzzadeh, Mohammad Reza Heidari, Gender differences in symptom predictors associated with acute coronary syndrome: A prospective observational study, International Emergency Nursing (2015), doi: 10.1016/j.ienj.2015.06.008
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Table 2 Relationship between presenting typical symptoms and ACS in men and women. Presentation symptoms
Men
Women
ACS (n = 183)
Chest symptoms Arm pain Diaphoresis Jaw/Neck pain Dyspnea
No ACS (n = 73)
p
N
%
N
%
169 108 158 34 141
92.3 59 86.3 18.6 77
14 75 25 149 42
7.7 41 13.7 81.4 23
ACS (n = 137)
0.000 0.012 0.000 0.129 0.000
No ACS (n = 45)
p
N
%
N
%
124 75 118 36 100
90.5 54.7 86.1 26.3 73
13 62 19 101 37
9.5 45.3 13.9 73.7 27
0.000 0.606 0.000 0.161 0.000
Table 3 Relationship between presenting atypical symptoms and ACS in men and women. Presentation symptoms
Men
Women
ACS (n = 183)
Nausea/Vomiting Palpitation Fatigue Indigestion Mid-back pain (between shoulder blades) Dizziness/Syncope Chest pain in other location
No ACS (n = 73)
p
ACS (n = 137)
No ACS (n = 45)
p
N
%
N
%
N
%
N
%
59 48 71 44 59
32.2 26.2 38.8 24 32.2
124 135 112 139 124
67.8 73.8 61.2 76 67.8
0.770 0.282 0.316 0.041 0.291
52 30 48 26 52
38 21.9 35 19 38
85 107 89 111 85
62 78.1 65 81 62
0.002 0.003 0.474 0.005 0.069
78 43
42.6 23.5
105 140
57.4 76.5
0.001 0.741
70 49
51.1 35.8
67 88
48.9 64.2
0.001 0.480
3.2. Risk factors and symptom predictors of ACS in women For the patients with ACS diagnosis, 42.8% (n = 137) were female and the mean age of women diagnosed with ACS was 63.29 ± 3.84 years. The women with ACS diagnosis were older than the men with ACS diagnosis (P < 0.05). Regarding the risk factors, the women with ACS diagnosis were more often diabetic and obese than the women without ACS (P < 0.05). Additionally, the number of reported symptoms in women with ACS (2.94 ± 1.78) was more than the women without ACS (1.56 ± 0.69) (P = 0.018) (Table 1). The most reported typical symptoms in the women patients with ACS diagnosis were chest symptoms, diaphoresis and dyspnea (P < 0.05). The women with typical symptoms such as chest symptoms (P < 0.001), diaphoresis (P < 0.001) and dyspnea (P < 0.001) were significantly more likely to be diagnosed with ACS compared to the women who did not report these symptoms (Table 2). According to the atypical symptoms, there was a trend for more nausea/vomiting, palpitation and indigestion in the women with non-ACS compared to the women with ACS, and the difference was statistically significant (P < 0.05). There was a trend for more dizziness/syncope in the women with ACS compared to the women
with non-ACS, and the difference was statistically significant (P < 0.001) (Table 3).
3.3. Comparison of symptom predictors of ACS in men and women The results of the multiple logistic analyses of the symptom predictors of ACS in the men and women are shown in Table 4. Among the typical symptoms, chest symptoms were observed as a positive predictor of ACS in both men and women (P < 0.05), while diaphoresis and dyspnea were the positive predictors of ACS in the men (P < 0.05). Among the atypical symptoms, indigestion and dizziness/ syncope were the more predominant predictors of non-ACS in the men (P < 0.05). Comparison of the odd ratios (OR) showed that the men with typical symptoms such as chest symptoms (odds ratio [OR] = 3.22, confidence interval [CI] = 0.137–0.756, P = 0.009), diaphoresis (OR = 2.17, CI = 1.020–4.639, P = 0.044) and dyspnea (OR = 2.65, CI = 1.78–4.123, P = 0.001) were 3.78, 2.72 and 1.87 times more likely to have a diagnosis of ACS. This indicates that these symptoms might be helpful in the assessment during the triage process. The number of typical symptoms was an independent predictor of
Table 4 Symptom predictors of ACS in men and women by logistic regression analysis. Model and variable
Adjusted OR
Chest symptomsa Diaphoresis Dyspnea Indigestion Dizziness/Syncope Number of typical symptoms
3.222 2.175 2.654 2.545 2.191 1.673
95% (CI)
P
Adjusted OR
0.137–0.756 1.020–4.639 1.780–4.123 1.207–5.367 1.152–4.169 1.121–2.224
0.009 0.044 0.001 0.014 0.017 0.001
0.852 0.973 1.039 0.823 0.750 1.271
Men
a
95% (CI)
P
0.558–1.302 0.655–1.443 0.688–1.569 0.544–1.245 0.466–1.208 1.157–2.331
0.039 0.890 0.856 0.357 0.237 0.212
Women
Chest pressure, heaviness, tightness/squeezing, or center or left chest pain.
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ACS in the men (P < 0.05), while the number of typical symptoms was not an independent predictor of ACS in the women (P > 0.05). 4. Discussion The diagnosis of ACS symptoms in men and women is important. The inability of patients to detect the symptoms of ACS leads to a delay in treatment, infarct expansion and worse prognosis (Brieger et al., 2004). Identifying the symptoms of ACS and factors related to early symptoms is important for successful management and may help in the early detection and appropriate medical treatments (Calle et al., 1994; Nobahar and Vafaee, 2005; Paul et al., 1996). ACS is a major cause of mortality in the elderly (Dessotte et al., 2011; McCaig and Nawar, 2006; Thygesen et al., 2007). Sixty percent of all deaths reported are due to acute myocardial infarction in older patients and the mortality rate is about three times higher compared to younger patients (Biranvand and Asadpourpiranfar, 2006). Furthermore, the complication rates related to ACS have increased with age (Rittger et al., 2012). In our study, the men and women with ACS diagnosis were older than the men and women without ACS. In explanation, ageassociated changes in the arterial properties of individuals who are otherwise considered healthy may have relevance to the exponential increase in cardiovascular disease. Cross sectional studies in humans have found that wall thickening and dilatation are the prominent structural changes that occur within the large elastic arteries during aging (Wilbert and Aronow, 2005). The elderly constitute an increasing proportion of all patients with ACS and increased age has been identified as an important risk factor for the adverse events and complications of ACS and treatment (Rittger et al., 2012). In this study, both the men and women with ACS diagnosis were more often diabetic than the men and women without ACS. Many studies have described the association of diabetes with the typical symptoms of ACS (Langer et al., 1991; Stephen and Rosenfeld, 2008). The results of the Hasin et al. (2009) study showed that patients with diabetes have more previous diagnosis of cardiovascular disease, less typical symptom presentation and longer delay in seeking medical attention. It can be explained that the patients with diabetic neuropathy had impaired perception of cardiac pain (Langer et al., 1991). In this study, the men with ACS diagnosis were more likely to have hypercholesterolemia than the men without ACS and the women with ACS diagnosis were more often obese than the women without ACS. A high risk of coronary heart disease is among the wellestablished adverse health effects associated with excess weight. It has been suggested that physical activity may alleviate the cardiovascular risk associated with obesity (Buttar et al., 2005). The results of the Jensen et al. (2008) study showed the significant association between the obesity and high risk of ACS in the men and women. Furthermore, BMI was strongly associated with the risk of ACS among hypercholesterolemic participants. Canto (Canto et al., 2000) has found that hypercholesterolemia was associated with chest pain among patients with myocardial infarction. Wall thickening and dilatation are prominent structural changes that occur within large elastic arteries during aging. Beside physiological and pathological changes related to aging, older men are likely more affected by chronic conditions or risk factors. 4.1. Gender differences related to typical symptoms of ACS The primary complaint of patients with ACS diagnosis is characterized predominantly by a chest pain (Canto et al., 2000). Patients with ACS mostly present with a chest pain (Bayer et al., 1986; Kuhn et al., 2011). In this study, chest symptoms were the most reported typical symptom in the men and women. On the other hand, it was a more predictive symptom of ACS in the men than in the women. Likewise, previous studies showed that chest pain was one
of the most reported symptoms of ACS and was a positive predictor in both men and women (Cunningham et al., 1989; Goldberg et al., 1998; Milner et al., 2001; Noureddine et al., 2008). Stephen and Rosenfeld (2008) and Pelter et al. (2012) also reported that the men experienced chest pain more than the women. However, DeVon and Zerwic (2002) found a similar prevalence for the chest pain in the men and women. In the present study, arm pain was a predictor of ACS in the men more than the women. Goldberg et al. (1998) and Penque et al. (1998) showed that there was no difference in terms of sex in the reports of arm pain. But Willich et al. (1993) and Chiamvimonvat and Sternberg (1998) reported more arm pain in the women. Kuhn et al. (2011) showed that a significant proportion of the women have right-sided chest and arm pain. They stated that cardiovascular events in women are often heralded by nonspecific symptoms, making differentiation from other physiological and functional etiologies for them and ED personnel problematic. Arslanian-Engoren et al. (2006) and Mujtaba et al. (2012) showed that men are more likely to present arm pain. Pelter et al. (2012) reported that both men and women with ACS more often had arm pain and the patients with arm pain were more likely to have ACS. As the authors described before, arm pain was a potent significant predictor of ACS in the men more than the women. In the present study, diaphoresis was a predictor of ACS in the men more than the women. Similarly, Meshack et al. (1998) reported that the men presented with diaphoresis significantly more than the women. However, the results of Penque et al. (1998) did not show a difference in terms of sex in diaphoresis. In this study, jaw/neck pain was the less reported typical symptom among the other typical symptoms in the men and women with ACS diagnosis. However, in some previous studies, the women were reported to be more likely to have neck/jaw pain than the men (Everts et al., 1996; Goldberg et al., 1998; Milner et al., 1999). In this study, dyspnea was a predictor of ACS in the men more than the women. Although Arslanian-Engoren et al. (2006) reported that dyspnea was not a predictor of ACS in the men and the women, the studies of Goldberg et al. (1998), Meshack et al. (1998) and Milner (2002) showed that dyspnea was the most commonly reported non-chest pain symptom in both men and women, while Patel et al. (2004) reported that women had more dyspnea. 4.2. Gender differences related to atypical symptoms of ACS In this study, dizziness/syncope was the most common atypical symptom in the women with ACS diagnosis and the most common atypical symptom in the men without ACS diagnosis. Furthermore, dizziness/syncope was a stronger predictor of non-ACS in the men than the women. Indigestion occurred more often in both men and women with non-ACS diagnosis. Furthermore, the male patients with indigestion were more likely to have a non-ACS diagnosis. On the other hand, there were no differences between the men and women in other atypical symptoms such as nausea/ vomiting, palpitation, fatigue and mid-back pain. Meshack et al. (1998) did not find a difference in terms of sex in dizziness/ syncope in the patients with ACS. But Ashton (1999) and Mujtaba et al. (2012) showed that women were more likely to have dizziness and syncope than the men. However, in the study of Pelter et al. (2012) dizziness/fainting occurred more often in the men with a non-ACS diagnosis. There was a trend for more dizziness/fainting in the women with non-ACS than the women with ACS. Furthermore, the patients with dizziness/fainting were three times more likely to have a non-ACS diagnosis. The results of Pelter et al. (2012) showed that there were no differences between the men and women with atypical symptoms such as palpitation, back or shoulder pain. In the study of Kuhn et al. (2011) women were more likely to present the complaints of unusual fatigue, dyspnea, dizziness, cold sweats,
Please cite this article in press as: Hossein Asgar Pour, Reza Norouzzadeh, Mohammad Reza Heidari, Gender differences in symptom predictors associated with acute coronary syndrome: A prospective observational study, International Emergency Nursing (2015), doi: 10.1016/j.ienj.2015.06.008
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nausea, weakness and indigestion. They reported the women’s tendency to experience atypical symptoms and signs for ACS. 4.3. Symptom predictors of ACS in men and women The results of this study showed that the typical symptoms such as chest symptoms, diaphoresis and dyspnea were more predictive of ACS in the men than the women. On the other hand, the atypical symptoms, of indigestion and dizziness/syncope were more predictive of ACS in the men than the women. In the multivariate analysis, the numbers of typical symptoms were more predictive of ACS diagnosis in the men than the women. Milner et al. (1999) showed that the typical symptoms of ACS were the strongest prognostic indicators in the women and also the total number of typical symptoms was a positive predictor of ACS. According to the results of this study, clinicians need to very carefully examine any man who has typical symptoms. 4.4. Study limitation In this study several emerging risk factors such as lipoprotein abnormalities, hypercoagulable states, elevated homocysteine levels, markers of inflammation and platelet glycoprotein were not evaluated. 5. Conclusion The results of this study showed that the typical symptoms and the number of the typical symptoms were more predictive of ACS in the men. According to the results of this study, clinicians need to very carefully examine any man who has typical symptoms. Accurate diagnosis of ACS on admission by clinical care providers could reduce hospital mortality and morbidity. This subject is more important for women who report less typical symptoms than men. The existence of some factors such as diabetes increases this challenge. However, it is necessary to consider electrocardiography findings, cardiac enzyme levels, serum levels of lipids, cardiac catheterization results for determining risk stratification and final prognosis. Given these study results, the following further research is recommended: – Differences between men and women in the correlate reports of time from the onset of signs and symptoms to arrival at the emergency department, – Evaluating the predictive power of presenting symptoms, according to sex differences and co-morbidities. Funding This study was supported by the Shahed University in Tehran, Iran. The authors thank all colleagues and patients who helped in conducting this research. Conflict of interest None of the authors has any potential conflicting interest in this study. Acknowledgement We thank all of our colleagues and patients who helped us in conducting this research. It is required to be listed here that this article is extracted from a research project with financial support from Shahed University. We thank all of our colleagues and patients who helped us in conducting this research.
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International Emergency Nursing j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / a a e n
Gender differences in symptom predictors associated with acute coronary syndrome: A prospective observational study Hossein Asgar Pour BSc, RN, MSN, PhD (Assistant Professor) a,*, Reza Norouzzadeh BSc, RN, MSN (Lecturer) b, Mohammad Reza Heidari BSc, RN, MSN, PhD (Assistant Professor) b a b
Department of Surgical Nursing, Aydın Health School, Adnan Menderes University, Aydın, Turkey Faculty of Midwifery and Nursing, Shahed University, Tehran, Iran
A R T I C L E
I N F O
Article history: Received 25 August 2014 Received in revised form 26 June 2015 Accepted 28 June 2015 Keywords: Acute coronary syndrome Typical symptoms Symptom predictors
A B S T R A C T
Signs and symptoms (typical and atypical symptoms) of acute coronary syndromes (ACS) differ between men and women. Identification of gender differences has implications for both health care providers and the general public. The aim of this study was to determine the symptom predictors of the acute coronary syndromes in men and women. In this prospective study, nurse data collectors directly observed 256 men and 182 women (N = 438) with symptoms suggestive of ACS in the Emergency Departments of eight hospitals in Tehran. ACS was eventually diagnosed in 183 (57.2%) men and 137 (42.8%) women on the basis of standard electrocardiogram and cardiac enzyme (CPK-MB) level. In men, chest symptoms (OR = 3.22, CI = 0.137–0.756, P = 0.009), dyspnea (OR = 2.65, CI = 1.78–4.123 P = 0.001) and diaphoresis (OR = 2.175, CI = 1.020–4.639, P = 0.044) were significantly associated with the diagnosis of ACS 3.78, 2.72 and 1.87 times more than in women having these symptoms, respectively. These results indicated that chest symptoms, diaphoresis and dyspnea were the more pronounced typical symptoms of ACS in men compared to women. Additionally, the numbers of typical symptoms can be considered as more predictive of ACS in men (OR = 1.673, CI = 1.211–2.224, P < 0.001) than women (OR = 1.271, CI = 1.157–2.331, P = 0.212). Therefore, clinicians need to take men showing typical symptoms into consideration carefully. © 2015 Elsevier Ltd. All rights reserved.
1. Introduction Cardiovascular diseases mainly related to coronary artery disease (CAD) and its acute complications are one of the major causes of death in developing countries (Pankert et al., 2012). CAD remains the leading cause of morbidity and mortality in both men and women worldwide (Pelter et al., 2012). Acute coronary syndromes (ACS) are the most common causes of hospitalization for men and women in the United States (Biranvand and Asadpourpiranfar, 2006, Biranvand et al., 2008; McCaig and Nawar, 2006). ACS encompass a spectrum of coronary artery diseases, including unstable angina, ST-elevation myocardial infarction and non-ST elevation myocardial infarction with initial presentation and early management (Achar et al., 2005). Symptoms are often the initial clinical feature of ACS (Pelter et al., 2012). The accurate labeling of the symptoms of ACS as being cardiac in nature may reduce the time for treatment and expedite a timely
diagnosis (Hwang et al., 2009; McCaig and Nawar, 2006; Thygesen et al, 2007). Previous research studies suggest that the presentation of ACS and ACS symptoms may differ in both men and women (Arslanian-Engoren et al., 2006; Milner et al., 1999). Gender differences in the cardiovascular physiologic factors may further contribute to the differences between the men and women in the symptoms of ACS. Identification of the gender differences has implications for health care providers and the general public (DeVon and Zerwic, 2002; Patel et al., 2004). There are not enough studies regarding the differences of typical and atypical symptoms of ACS in both men and women (Milner et al., 1999). Therefore, the aim of this study was to determine the differences of typical and atypical symptom predictors of ACS in men and women. 2. Methods 2.1. Design, sample and setting
* Corresponding author. Department of Surgical Nursing, Aydın Health School, University of Adnan Menderes, P.O. Box: 09100, Aydın, Turkey. Tel.: +90 256 213 88 66; fax: +90 256 212 42 19. E-mail address: [email protected] (H. Asgar Pour).
This prospective observational study was conducted in the Emergency Departments of eight affiliated teaching hospitals in Tehran, Iran between March 2011 and June 2012. These departments were selected by a cluster sampling method. The voluntary patients having
http://dx.doi.org/10.1016/j.ienj.2015.06.008 1755-599X/© 2015 Elsevier Ltd. All rights reserved.
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at least one of the typical or atypical symptoms of ACS were considered for participation in the study. The typical symptoms of ACS were chest symptoms not related to trauma (chest pressure, heaviness, tightness/squeezing, or center or left chest pain), diaphoresis, shortness of breath (dyspnea) not related to pulmonary disorders, arm pain, and jaw/neck pain not related to trauma. Atypical symptoms were numbness, tingling, pricking, or stabbing in the chest (mid-back pain and chest pain in another location), palpitation, nausea/vomiting (not related to gastrointestinal diseases), dizziness or syncope, fatigue and indigestion (Milner et al., 2001). Patients with the history of stroke, neurologic disorders, trauma, chronic obstructive pulmonary diseases, pneumonia or pulmonary embolism were excluded. According to the results of a pilot study with p = 0.3 and d = 0.04 a selection of 530 patients was sufficient for the sample. Therefore, a total of 530 patients meeting study criteria were approached for the participation in the study. Of these, 438 patients agreed to participate and enrolled in this study. 2.2. Ethical approval The study was approved by the Institutional Ethics Committee of the Shahed University in Tehran. Written approvals were obtained from the Shahed University Institute of Health Sciences (March 2010), Ethics Board of the Shahed University Midwifery and Nursing Faculty (May 2010), and the affiliated teaching hospitals (June 2010). Written and verbal informed consents were obtained from all patients after explaining the aims and protocol of the study.
by electrocardiography changes (ST-segment and T-wave changes) and cardiac enzyme (creatine kinase-MB). For the more unified data collection, the investigators interviewed and trained the nurses before beginning the study. The data about symptoms were obtained by observing the patient–nurse interview, and the related symptoms of ACS expressed by the patients were documented in the ACS symptoms check list. The demographics data (sex, age, education) and the risk factors (history of hypertension, hypercholesterolemia, diabetes, smoking, and obesity) were collected from the medical records and by interviews with patients. Obesity was considered as body mass index (BMI) ≥ 30. 2.4. Data analysis The statistical analysis of data was performed by using the SPSS windows program (version 16.0). To examine the associations between the ACS and baseline characteristics and also presenting symptoms in women and men, the chi-squared test was used. The symptoms reported by at least 5% were included in the bivariate analyses. To determine symptom predictors in the men and women patients, the method of multiple logistic regressions with stepwise was performed. Logistic regression methods were used to identify the best model and the cutoff to stay in the model was P < 0.20 (Milner et al., 1999). Adjusted Odd ratios were estimated for each symptom predictor. The statistical significance was set at P < 0.05. 3. Results
2.3. Data collection, instruments and procedures 3.1. Risk factors and symptom predictors of ACS in men Data collecting instruments were developed based on a review of literature and from the specialists’ comments. The specialists were one ED physician, one ED nurse specialist, two ED staff nurses, one cardiologist, and a cardiac clinical nurse specialist. The checklist included the typical and atypical symptoms of ACS. To determine the validity of the checklist, each of the specialists was asked to note each symptom relevant or not relevant to the ACS. This process was done several times until the specialists were in 100% agreement. To determine the inter rater reliability two independent emergency nurse observers assessed twenty patients by using the checklist. The reliability of each item was calculated by using the percent agreement and the Kappa coefficient. The total percent agreement ranged from 86% to 100%, and the Kappa statistics ranged from 0.24 to 1. Therefore, providing the symptoms checklist was a reliable tool for identifying the symptoms of ACS. The data were collected by eight nurses who observed all the patients and met the study criteria as they were admitted to the ED during 6 hour shift intervals in a day for 7 days. ACS was defined as either unstable angina or acute myocardial infarction, confirmed
Out of 438 patients, 73.05% (N = 320) of them had ACS diagnosis. For the diagnosed patients with ACS, 57.2% (n = 183) were male and their mean age was 60.92 ± 1.24 years. Regarding the risk factors, the men with ACS usually had diabetes and hypercholesterolemia compared with men without ACS (P < 0.05). Additionally, men with ACS reported a higher number of typical and atypical symptoms (2.75 ± 1.36) compared to the men without ACS (1.78 ± 0.58) (P = 0.006) (Table 1). The most reported typical symptoms in the male patients with ACS were chest symptoms, diaphoresis and dyspnea (P < 0.05). The men with typical symptoms such as chest symptoms (P < 0.001), arm pain (P = 0.012), diaphoresis (P < 0.001) and dyspnea (P < 0.001) were significantly more likely to be diagnosed with ACS compared to the men who did not report these symptoms (Table 2). According to the atypical symptoms, there was a trend for more indigestion and dizziness/syncope in the men with non-ACS compared to the men with ACS, and the difference was statistically significant (P < 0.05) (Table 3).
Table 1 Relationship between baseline characteristics and ACS in men and women. Characteristics
Hypertension Diabetes mellitus Currently smoking Hypercholesterolemia Obesity (BMI ≥ 30) Menopause Age (years) Number of presenting symptoms
Men
Women
With ACS (n = 183)
Without ACS (n = 73)
N
N
% 126 152 83 93 46
Mean ± SD 60.92 ± 1.24 2.75 ± 1.36
70 84.9 46.4 55.4 74.2
P
% 54 27 96 75 16
56.32 ± 1.11 1.78 ± 0.58
30 15.1 53.6 44.6 25.8
0.103 0.000 0.543 0.040 0.148
0.011 0.006
With ACS (n = 137)
Without ACS (n = 45)
N
%
N
50 88 123 64 63 103 Mean ± SD 63.29 ± 3.84 2.94 ± 1.78
39.4 65.2 90.4 50.4 80.8 74.1
77 47 13 63 15 36
P
% 60.6 34.8 9.6 49.6 19.2 25.9
0.722 0.033 0.764 0.860 0.034 0.660
59.13 ± 2.17 1.56 ± 0.69
0.020 0.018
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Table 2 Relationship between presenting typical symptoms and ACS in men and women. Presentation symptoms
Men
Women
ACS (n = 183)
Chest symptoms Arm pain Diaphoresis Jaw/Neck pain Dyspnea
No ACS (n = 73)
p
N
%
N
%
169 108 158 34 141
92.3 59 86.3 18.6 77
14 75 25 149 42
7.7 41 13.7 81.4 23
ACS (n = 137)
0.000 0.012 0.000 0.129 0.000
No ACS (n = 45)
p
N
%
N
%
124 75 118 36 100
90.5 54.7 86.1 26.3 73
13 62 19 101 37
9.5 45.3 13.9 73.7 27
0.000 0.606 0.000 0.161 0.000
Table 3 Relationship between presenting atypical symptoms and ACS in men and women. Presentation symptoms
Men
Women
ACS (n = 183)
Nausea/Vomiting Palpitation Fatigue Indigestion Mid-back pain (between shoulder blades) Dizziness/Syncope Chest pain in other location
No ACS (n = 73)
p
ACS (n = 137)
No ACS (n = 45)
p
N
%
N
%
N
%
N
%
59 48 71 44 59
32.2 26.2 38.8 24 32.2
124 135 112 139 124
67.8 73.8 61.2 76 67.8
0.770 0.282 0.316 0.041 0.291
52 30 48 26 52
38 21.9 35 19 38
85 107 89 111 85
62 78.1 65 81 62
0.002 0.003 0.474 0.005 0.069
78 43
42.6 23.5
105 140
57.4 76.5
0.001 0.741
70 49
51.1 35.8
67 88
48.9 64.2
0.001 0.480
3.2. Risk factors and symptom predictors of ACS in women For the patients with ACS diagnosis, 42.8% (n = 137) were female and the mean age of women diagnosed with ACS was 63.29 ± 3.84 years. The women with ACS diagnosis were older than the men with ACS diagnosis (P < 0.05). Regarding the risk factors, the women with ACS diagnosis were more often diabetic and obese than the women without ACS (P < 0.05). Additionally, the number of reported symptoms in women with ACS (2.94 ± 1.78) was more than the women without ACS (1.56 ± 0.69) (P = 0.018) (Table 1). The most reported typical symptoms in the women patients with ACS diagnosis were chest symptoms, diaphoresis and dyspnea (P < 0.05). The women with typical symptoms such as chest symptoms (P < 0.001), diaphoresis (P < 0.001) and dyspnea (P < 0.001) were significantly more likely to be diagnosed with ACS compared to the women who did not report these symptoms (Table 2). According to the atypical symptoms, there was a trend for more nausea/vomiting, palpitation and indigestion in the women with non-ACS compared to the women with ACS, and the difference was statistically significant (P < 0.05). There was a trend for more dizziness/syncope in the women with ACS compared to the women
with non-ACS, and the difference was statistically significant (P < 0.001) (Table 3).
3.3. Comparison of symptom predictors of ACS in men and women The results of the multiple logistic analyses of the symptom predictors of ACS in the men and women are shown in Table 4. Among the typical symptoms, chest symptoms were observed as a positive predictor of ACS in both men and women (P < 0.05), while diaphoresis and dyspnea were the positive predictors of ACS in the men (P < 0.05). Among the atypical symptoms, indigestion and dizziness/ syncope were the more predominant predictors of non-ACS in the men (P < 0.05). Comparison of the odd ratios (OR) showed that the men with typical symptoms such as chest symptoms (odds ratio [OR] = 3.22, confidence interval [CI] = 0.137–0.756, P = 0.009), diaphoresis (OR = 2.17, CI = 1.020–4.639, P = 0.044) and dyspnea (OR = 2.65, CI = 1.78–4.123, P = 0.001) were 3.78, 2.72 and 1.87 times more likely to have a diagnosis of ACS. This indicates that these symptoms might be helpful in the assessment during the triage process. The number of typical symptoms was an independent predictor of
Table 4 Symptom predictors of ACS in men and women by logistic regression analysis. Model and variable
Adjusted OR
Chest symptomsa Diaphoresis Dyspnea Indigestion Dizziness/Syncope Number of typical symptoms
3.222 2.175 2.654 2.545 2.191 1.673
95% (CI)
P
Adjusted OR
0.137–0.756 1.020–4.639 1.780–4.123 1.207–5.367 1.152–4.169 1.121–2.224
0.009 0.044 0.001 0.014 0.017 0.001
0.852 0.973 1.039 0.823 0.750 1.271
Men
a
95% (CI)
P
0.558–1.302 0.655–1.443 0.688–1.569 0.544–1.245 0.466–1.208 1.157–2.331
0.039 0.890 0.856 0.357 0.237 0.212
Women
Chest pressure, heaviness, tightness/squeezing, or center or left chest pain.
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ACS in the men (P < 0.05), while the number of typical symptoms was not an independent predictor of ACS in the women (P > 0.05). 4. Discussion The diagnosis of ACS symptoms in men and women is important. The inability of patients to detect the symptoms of ACS leads to a delay in treatment, infarct expansion and worse prognosis (Brieger et al., 2004). Identifying the symptoms of ACS and factors related to early symptoms is important for successful management and may help in the early detection and appropriate medical treatments (Calle et al., 1994; Nobahar and Vafaee, 2005; Paul et al., 1996). ACS is a major cause of mortality in the elderly (Dessotte et al., 2011; McCaig and Nawar, 2006; Thygesen et al., 2007). Sixty percent of all deaths reported are due to acute myocardial infarction in older patients and the mortality rate is about three times higher compared to younger patients (Biranvand and Asadpourpiranfar, 2006). Furthermore, the complication rates related to ACS have increased with age (Rittger et al., 2012). In our study, the men and women with ACS diagnosis were older than the men and women without ACS. In explanation, ageassociated changes in the arterial properties of individuals who are otherwise considered healthy may have relevance to the exponential increase in cardiovascular disease. Cross sectional studies in humans have found that wall thickening and dilatation are the prominent structural changes that occur within the large elastic arteries during aging (Wilbert and Aronow, 2005). The elderly constitute an increasing proportion of all patients with ACS and increased age has been identified as an important risk factor for the adverse events and complications of ACS and treatment (Rittger et al., 2012). In this study, both the men and women with ACS diagnosis were more often diabetic than the men and women without ACS. Many studies have described the association of diabetes with the typical symptoms of ACS (Langer et al., 1991; Stephen and Rosenfeld, 2008). The results of the Hasin et al. (2009) study showed that patients with diabetes have more previous diagnosis of cardiovascular disease, less typical symptom presentation and longer delay in seeking medical attention. It can be explained that the patients with diabetic neuropathy had impaired perception of cardiac pain (Langer et al., 1991). In this study, the men with ACS diagnosis were more likely to have hypercholesterolemia than the men without ACS and the women with ACS diagnosis were more often obese than the women without ACS. A high risk of coronary heart disease is among the wellestablished adverse health effects associated with excess weight. It has been suggested that physical activity may alleviate the cardiovascular risk associated with obesity (Buttar et al., 2005). The results of the Jensen et al. (2008) study showed the significant association between the obesity and high risk of ACS in the men and women. Furthermore, BMI was strongly associated with the risk of ACS among hypercholesterolemic participants. Canto (Canto et al., 2000) has found that hypercholesterolemia was associated with chest pain among patients with myocardial infarction. Wall thickening and dilatation are prominent structural changes that occur within large elastic arteries during aging. Beside physiological and pathological changes related to aging, older men are likely more affected by chronic conditions or risk factors. 4.1. Gender differences related to typical symptoms of ACS The primary complaint of patients with ACS diagnosis is characterized predominantly by a chest pain (Canto et al., 2000). Patients with ACS mostly present with a chest pain (Bayer et al., 1986; Kuhn et al., 2011). In this study, chest symptoms were the most reported typical symptom in the men and women. On the other hand, it was a more predictive symptom of ACS in the men than in the women. Likewise, previous studies showed that chest pain was one
of the most reported symptoms of ACS and was a positive predictor in both men and women (Cunningham et al., 1989; Goldberg et al., 1998; Milner et al., 2001; Noureddine et al., 2008). Stephen and Rosenfeld (2008) and Pelter et al. (2012) also reported that the men experienced chest pain more than the women. However, DeVon and Zerwic (2002) found a similar prevalence for the chest pain in the men and women. In the present study, arm pain was a predictor of ACS in the men more than the women. Goldberg et al. (1998) and Penque et al. (1998) showed that there was no difference in terms of sex in the reports of arm pain. But Willich et al. (1993) and Chiamvimonvat and Sternberg (1998) reported more arm pain in the women. Kuhn et al. (2011) showed that a significant proportion of the women have right-sided chest and arm pain. They stated that cardiovascular events in women are often heralded by nonspecific symptoms, making differentiation from other physiological and functional etiologies for them and ED personnel problematic. Arslanian-Engoren et al. (2006) and Mujtaba et al. (2012) showed that men are more likely to present arm pain. Pelter et al. (2012) reported that both men and women with ACS more often had arm pain and the patients with arm pain were more likely to have ACS. As the authors described before, arm pain was a potent significant predictor of ACS in the men more than the women. In the present study, diaphoresis was a predictor of ACS in the men more than the women. Similarly, Meshack et al. (1998) reported that the men presented with diaphoresis significantly more than the women. However, the results of Penque et al. (1998) did not show a difference in terms of sex in diaphoresis. In this study, jaw/neck pain was the less reported typical symptom among the other typical symptoms in the men and women with ACS diagnosis. However, in some previous studies, the women were reported to be more likely to have neck/jaw pain than the men (Everts et al., 1996; Goldberg et al., 1998; Milner et al., 1999). In this study, dyspnea was a predictor of ACS in the men more than the women. Although Arslanian-Engoren et al. (2006) reported that dyspnea was not a predictor of ACS in the men and the women, the studies of Goldberg et al. (1998), Meshack et al. (1998) and Milner (2002) showed that dyspnea was the most commonly reported non-chest pain symptom in both men and women, while Patel et al. (2004) reported that women had more dyspnea. 4.2. Gender differences related to atypical symptoms of ACS In this study, dizziness/syncope was the most common atypical symptom in the women with ACS diagnosis and the most common atypical symptom in the men without ACS diagnosis. Furthermore, dizziness/syncope was a stronger predictor of non-ACS in the men than the women. Indigestion occurred more often in both men and women with non-ACS diagnosis. Furthermore, the male patients with indigestion were more likely to have a non-ACS diagnosis. On the other hand, there were no differences between the men and women in other atypical symptoms such as nausea/ vomiting, palpitation, fatigue and mid-back pain. Meshack et al. (1998) did not find a difference in terms of sex in dizziness/ syncope in the patients with ACS. But Ashton (1999) and Mujtaba et al. (2012) showed that women were more likely to have dizziness and syncope than the men. However, in the study of Pelter et al. (2012) dizziness/fainting occurred more often in the men with a non-ACS diagnosis. There was a trend for more dizziness/fainting in the women with non-ACS than the women with ACS. Furthermore, the patients with dizziness/fainting were three times more likely to have a non-ACS diagnosis. The results of Pelter et al. (2012) showed that there were no differences between the men and women with atypical symptoms such as palpitation, back or shoulder pain. In the study of Kuhn et al. (2011) women were more likely to present the complaints of unusual fatigue, dyspnea, dizziness, cold sweats,
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nausea, weakness and indigestion. They reported the women’s tendency to experience atypical symptoms and signs for ACS. 4.3. Symptom predictors of ACS in men and women The results of this study showed that the typical symptoms such as chest symptoms, diaphoresis and dyspnea were more predictive of ACS in the men than the women. On the other hand, the atypical symptoms, of indigestion and dizziness/syncope were more predictive of ACS in the men than the women. In the multivariate analysis, the numbers of typical symptoms were more predictive of ACS diagnosis in the men than the women. Milner et al. (1999) showed that the typical symptoms of ACS were the strongest prognostic indicators in the women and also the total number of typical symptoms was a positive predictor of ACS. According to the results of this study, clinicians need to very carefully examine any man who has typical symptoms. 4.4. Study limitation In this study several emerging risk factors such as lipoprotein abnormalities, hypercoagulable states, elevated homocysteine levels, markers of inflammation and platelet glycoprotein were not evaluated. 5. Conclusion The results of this study showed that the typical symptoms and the number of the typical symptoms were more predictive of ACS in the men. According to the results of this study, clinicians need to very carefully examine any man who has typical symptoms. Accurate diagnosis of ACS on admission by clinical care providers could reduce hospital mortality and morbidity. This subject is more important for women who report less typical symptoms than men. The existence of some factors such as diabetes increases this challenge. However, it is necessary to consider electrocardiography findings, cardiac enzyme levels, serum levels of lipids, cardiac catheterization results for determining risk stratification and final prognosis. Given these study results, the following further research is recommended: – Differences between men and women in the correlate reports of time from the onset of signs and symptoms to arrival at the emergency department, – Evaluating the predictive power of presenting symptoms, according to sex differences and co-morbidities. Funding This study was supported by the Shahed University in Tehran, Iran. The authors thank all colleagues and patients who helped in conducting this research. Conflict of interest None of the authors has any potential conflicting interest in this study. Acknowledgement We thank all of our colleagues and patients who helped us in conducting this research. It is required to be listed here that this article is extracted from a research project with financial support from Shahed University. We thank all of our colleagues and patients who helped us in conducting this research.
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Please cite this article in press as: Hossein Asgar Pour, Reza Norouzzadeh, Mohammad Reza Heidari, Gender differences in symptom predictors associated with acute coronary syndrome: A prospective observational study, International Emergency Nursing (2015), doi: 10.1016/j.ienj.2015.06.008