Prevalence of Typical and Atypical Pain Sites of Coronary Artery Disease: A Cross-Sectional Study

Prevalence of Typical and Atypical Pain Sites of Coronary Artery Disease: A Cross-Sectional Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prevalence of Typical and Atypical Pain Sites of Coronary Artery Disease: A Cross-Sectional Study Mayar Abdullatef, Maya Omran, Anas Bitar, Bayan Alsaid This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4436785/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Aug, 2024 Read the published version in BMC Cardiovascular Disorders → Version 1 posted 16 You are reading this latest preprint version Abstract Study Objective This study aims to assess the prevalence of both typical and atypical pain in patients with ischemic heart disease, emphasizing the importance of recognizing and not disregarding atypical symptoms. Methods This cross-sectional study was conducted on patients diagnosed with coronary artery disease (CAD) who were admitted to two major hospitals in Damascus, Syria, from 2021 to 2023. Patients were asked to mark the sites of their pain on an anatomic illustration. Typical pain was identified as pain located in the precordial area, with or without radiating to the left shoulder or the left arm. Any other distribution of pain was considered atypical. Patients’ demographics and previous medical history were documented to investigate any potential associations with atypical pain. Results Among the 100 patients, 64% (64) had atypical pain, while 36% (36) had typical symptoms. Referred pain to areas like the left shoulder and left arm was reported by 81.9% of patients, with 47% and 41% of the sample mentioning discomfort in these regions, respectively. We found that smoking and previous heart disease were associated with atypical pain, with 73% of patients who experienced atypical pain being smokers. Conclusion The study found that atypical pain is common, affecting 64% of individuals primarily in the right shoulder, right arm, and back. This type of pain is associated with smoking and prior heart disease. Misdiagnosing coronary artery disease (CAD) can have serious consequences, as patients with atypical symptoms may miss important pre-hospital procedures like ECG. Coronary artery disease” CAD” Typical Atypical Ischemic heart disease Syria Figures Figure 1 Figure 2 Introduction Coronary artery disease (CAD) is one of the major cardiovascular diseases affecting the global human population.[ 1 ] Environmental factors, genetic factors, unhealthy lifestyle, chronic diseases and many other factors could cause (CAD) which leads in the end to cardiac infarction. Symptoms of cardiac infarction vary from case to another but the typical symptoms include heavy breathing and crushing substernal chest pain. This pain is often induced by doing effort such as running, walking for a long distance and even while resting in severe cases. Pain could radiate to other regions such as shoulders, arms, neck, jaw, teeth, and ear[ 2 ].This radiation may be caused by the convergence of the vagus, trigeminal and cervical spinal nerves (C2-C3)[ 3 , 4 ]. Patients with CAD can experience atypical pain as a sole symptom. A previous study found that craniofacial pain was the only complaint during the ischemic episode in some cases [ 4 ]. These patients are less likely to be diagnosed and consequently have a mortality rate three times lower than patients with typical angina symptoms [ 4 ]. Generally, Ischemic heart disease can be manifested as myocardial infarction (MI)and angina pectoris. Angina pectoris has two types: stable angina and unstable angina. Unlike stable angina, which is usually induced by exertion, unstable angina presents sudden symptoms even while at rest [ 5 ]. Patients with unstable angina have a worse prognosis and are more likely to develop MI. [ 5 ] Pain induced by CAD is called angina pectoris, which can be typical or atypical. Angina pectoris is a type of cardiac pain usually felt in the chest and upper left arm. Patients may experience atypical pain in the back, neck, or jaw instead. [ 6 ] However, the patient may present heterotopic pain (pain occurring in a region despite the real source being elsewhere in the body) in this region, with the real source potentially being of cardiac origin.[ 7 ] The cardiac heterotopic pain can lead to misdiagnosis and unnecessary medical procedures as was shown in several reports[ 8 ]. Misdiagnosed cases could develop lethal complications. Absence of chest pain and the lack of elevation of ST segment in electrocardiogram “ECG” were the main causes of misdiagnosis, as was shown in a previous study[ 9 ]. The objective of this study was to assess the prevalence of both typical and atypical anginal pain sites in individuals diagnosed with coronary artery disease (CAD). It aimed to determine the locations to which the atypical pain spreads and to emphasize the importance of healthcare providers being attentive to risk factors that may lead to atypical symptomatology. This, to our knowledge, is the first paper to study the prevalence of typical and atypical pain of cardiac origin in Syria. Materials and Methods This cross-sectional study examined 100 consecutive patients who were admitted to two cardiology departments in two major hospitals in Damascus, Syria (Assad University Hospital and University Heart Surgery Center) with signs and/or symptoms suggesting coronary artery disease (CAD), and the study period was divided into two time periods between November 2021 and December 2023, with a one-year gap in between. Angiography was performed on each of the patients to determine cardiac ischemia, and all patients included in this study met the criteria of having a cardiac ischemic episode verified according to the American College of Cardiologists’ (ACC) definition [ 10 ]. Each patient was shown an anatomical illustration that depicts the chest, abdomen, back, shoulders, arms, face, neck and mouth[ 4 ], and was asked to identify the location of their current pain, with the corresponding site of pain being marked. Additional required information was obtained from the patients: demographic details, risk factors (smoking, alcohol consumption, diabetes mellitus, hypertension, personal and family history of cardiac disease, and medication), personal medical and surgical history, recent dental examination and/or treatment and physical activity, and the information was recorded in data forms. Typical pain was identified as pain located in the precordial area, with or without radiating to the left shoulder or the left arm. [ 11 ] Any other distribution of pain was considered Atypical. Ethical approval: Informed consent was obtained from each patient and the participation of the patients was voluntary Consent for publication : the study protocol was approved by the Ethical Committee of Damascus University, Faculty of Medicine, Syria (document number: 4597, 25-10-2021). Excluding Criteria: Patients who had dental problems, psychiatric diseases, chronic headache or jaw masses were excluded, having not met the criteria of the study. Statistical analysis: The data presentation included frequencies (%) for categorical variables and mean ± standard deviation (SD) for continuous variables. The analysis was done using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, N.Y., USA). The Chi-Squared test was used to examine the relationship between the type of pain (typical or atypical) and the studied variables. The age variable was dichotomized based on the median of the patients’ age (58 years). For variables where the expected frequency was less than 5 in more than 20% of the cells, the Fisher exact test was used as an alternative to the chi-squared test. The absolute Phi (Φ) factor was calculated to assess the strength of the associations. The values of ‘1’ indicate a complete association, ‘0’ indicates no association, ‘0.1 indicates a small association, ‘0.3’ indicates a medium association, and ‘0.5’ indicates a large association. Phi (Φ) was only illustrated when there was a statistical significance when using a chi-squared test. Statistical significance was set at p ≤ 0.05. Results Characteristics of the included sample: The study included 100 participants with a mean age of 57.88 ± 9.05. Males (79%) constituted the majority of the sample. A significant portion of the patients (70%) lived in urban areas. Most of the patients were smokers (72%), while only a small percentage (9%) reported consuming alcohol. Diabetes was present in 38% of the patients, and more than half of them (53%) had hypertension and a history of heart disease. Additionally, 59% reported a familial history of heart disease. Detailed characteristics of the patients are presented in Table 1. Pain distribution: The precordial area was the most commonly reported pain site, experienced by 88% of the sample. This was followed by the left shoulder and left arm, reported by 47% and 41% of the sample, respectively. Common sites of pain also included the right shoulder (27%) and the back (24%). (Figure 1). Of the patients, 36% presented with typical pain, with 33.3% complaining of left shoulder pain and 36.1% experiencing left arm pain. Meanwhile, 64% of the patients presented with atypical pain, or pain radiating to other locations such as the right shoulder, right arm, abdomen, back, or the craniofacial area. Important areas of atypical pain were the right shoulder (42.2%), the back (37.5%), and the right arm (26.6%). (Figure 1). 12% of the patients presented with no precordial pain. The most common site of pain in those patients was the left chest (66.7%), followed by both the left arm and the back in 33.3% of patients. 8.3% complained from pain in the occipital area with no chest pain. (Figure 1). Variables associated with typical and atypical pain: We found that smoking and previous heart disease were associated with the type of pain. Most of the patients who were smokers presented with atypical pain (53 patients, 73.6%), compared to 19 smokers (26.4%) who presented with typical pain. More details about distribution of pain amongst smokers is shown in Table 2. Amongst non-smokers, 11 patients (39.3%) had atypical pain and 17 patients (60.7%) had typical pain, X2 (1, N = 100) = 10.31, p = 0.001, and the association was medium (Φ = 0.32). Patients with previous heart disease were more likely to have atypical pain than typical pain when compared with patients with no previous heart disease, X2 (1, N = 100) = 6.44, p = 0.01. The association between previous heart disease and the type of pain was small (Φ = 0.25). Other variables such as age, sex, and diabetes were not significantly associated with the type of pain. Details on the variables associated with typical and atypical pain are presented in Table 3. Discussion Cardiovascular disease (CVD) is a widespread cause of socio-economic and healthcare issues globally. Morbidity, mortality, and disability caused by CVD are on the rise annually[12], accounting for 30% of all-cause mortality. Coronary heart disease (CHD) is the primary cause of death globally. [13]. Patients who experience pain triggered by physical activity and relieved by rest are considered ideal candidates for cardiac pain diagnosis. Patients with coronary artery disease (CAD) may experience referred pain in different regions, such as the head, neck, arms, back, and abdominal region. [8] Several studies have explored the referred pain experienced by patients with ischemic heart disease. The objective of this study was to determine the frequency of typical and atypical pain and to caution doctors against disregarding atypical symptoms in hospitalized patients. Previous studies have indicated that men are more likely to report typical anginal pain, characterized by discomfort in the chest and upper arm, whereas women tend to experience atypical angina, manifested as pain in the jaw, neck, shoulders, and back. [6]. However, our study revealed that men experienced atypical pain more than women, with rates of 65.8% and 52.2%, respectively. This discrepancy may be attributed to the lower rates of alcohol consumption and smoking among women in our country, which reduces their risk of developing coronary artery disease (CAD). This aligns with our study results, which identified a correlation between smoking and atypical pain. Another study discovered that 30% of patients did not report chest pain [14], while our study indicated that the precordial area was the most frequently reported site of pain, experienced by 88% of the participants. It is noteworthy that 81.9% of the patients in our study reported experiencing referred pain, which is significant as many patients tend to overlook this type of pain. Various studies have linked referred pain to the convergence projection theory, which suggests that central neurons receive combined visceral and somatic stimuli, resulting in the perception of both visceral pain and referred somatic pain. Initial research focused on the spinothalamic tract (STT) and the spinoreticular tract (SRT) in the upper thoracic spinal cord due to their role in transmitting somatic pain signals and receiving sensory input from the heart. These pathways were chosen based on their established roles in transmitting somatic pain signals to the thalamus and reticular formation, respectively, and in receiving sensory input from the heart in the upper thoracic cord. Studies in animals demonstrated that stimulating cardiac spinal afferents activated around 80% of STT and SRT cells in the upper thoracic segments T1-T5. Neurons responsible for processing cardiac pain were identified in specific laminae of the spinal gray matter. These neurons exhibited responses to bradykinin applied either epicardially or intracardially to the heart, as well as to coronary artery occlusion. All neurons receiving input from the heart received somatic input, primarily nociceptive signals from the chest and upper limb muscles, which provides support for the convergence projection theory concerning STT and SRT neurons in the upper thoracic cord. They indicate that these neurons may play a role in generating sensations of angina and contributing to the referral of pain to nearby somatic structures [6]. However, 18.1% of the patients reported experiencing localized pain transmitted via spinal cardiac afferent fibers. In cases of CAD, fissures or erosions in atherosclerotic plaques lead to the release of various chemical mediators such as serotonin, histamine, thromboxane A2, bradykinin, reactive oxygen species including hydroxyl radicals, lactic acid causing proton release, and adenosine which triggers the production of prostaglandins (PGE2 and PGI2) within the coronary artery lumen. These chemical agents, either individually or in combination, interact with specific receptors primarily located on chemically sensitive terminals, resulting in the depolarization of cardiac visceral spinal afferent fibers [6]. Furthermore, our study highlighted that most smokers (73.6%) among our patients presented with atypical pain, indicating a potential link between smoking and atypical angina. Previous studies suggest that smokers are at a higher risk to develop back pain and other chronic pain conditions[15, 16]. Another study showed that among patients with chronic pain, smokers cmplained of higher pain intensity and inscreased number of pain sites[17, 18]. One underlying mechanism might be that cigarette smoking impairs oxygen delivery to tissues by increasing sympathetic outflow and carboxyhemoglobin levels and causing vasoconstriction. Thus, smoking may accelerate degenerative processes which make the body more vulnerable to injury. This can explain why smoking is a risk factor for osteoporosis, lumber disk diseases and impaired bone healing[19]. This alignes with the results of our study, which found that 25% of smokers had back pain, 26.4% had pain the the right shoulder and 19.4% had pain in the right arm. In our study, we found that only 36% of patients complained of typical pain, which indicates that the majority of patients suffered from atypical pain sites. This is a significant result, since atypical symptoms of AMI were associated with less invasive therapy and poor outcome, and in-hospital mortality was significantly higher in atypical than in typical group in a previous study conducted in Japan[20]. Moreover, 12% of patients presented with no precordial pain, whereas a study in Poland[21] showed that only 6.4% presented without chest pain.This is especially important because previously, if the patient did not report chest pain, then they were disadvantaged from even receiving a prehospital ECG[22]. Another important result of our research was that patients with previous heart disease where more likely to have atypical pain, which is consistent with the results of the Japanese study [20]. While in the Polish study [18], previous heart diseases and hypertention were more linked with typical symptoms of MI. It is extremely important to show all the different symptoms of MI because these symptoms are the cues for further diagnostic exams such as ECG and cardiac catheterization. There are a few limitations in this study. The sample included 100 patients, which might be considered slightly small. However, the long study period overcomes this disadvantage because it provides a wide range of changes in climate and conditions that enriches the results. The study was conducted in one city, therefor the results cannot be generalized. Nevertheless, Damascus is the capital of Syria, and the hospitals included in this study are amongst the largest in Syria. We suggest that future researchers who seek to study the same topic conduct their study on a larger sample and in more than one city to cover as much variations as possible. We also suggest studying the relation between smoking and atypical pain more precisely. Conclusion Our study found that atypical pain is common (64%), occurring mostly in the right shoulder, right arm and the back, and is associated with smoking and previous heart disease. Misdiagnosing coronary artery disease (CAD) can have fatal outcomes. Many patients with atypical CAD symptoms might be deprived of vital pre-hospital procedures, such as ECG, which can be lifesaving. This study underscores the importance of recognizing all symptoms, especially atypical ones, that might indicate CAD. Hopefully, it will assist doctors in acknowledging risk factors and their contributions to different types of pain, ultimately aiding in the diagnosis of CAD across various atypical pain sites. Declarations Author Declarations: Ethics approval and consent to participate: The study protocol was approved by the Ethical Committee of Damascus University, Faculty of Medicine, Syria (document number: 4597, 25-10-2021). Informed consent was obtained from each patient and the participation of the patients was voluntary. Consent for publication: Not applicable. Data Availability: The data that support the findings of this study were uploaded in the 'Supplementary Files' section. Conflict of Interest: The authors declare no conflict of interest. Funding: the research was not funded Author Contributions: M.O. and M.A. contributed equally to this work. M.O. and M.A. are marked as first author. B.A. is the supervisor of the research and is responsible on Project administration. B.A.: Supervision, Project Administration, Conceptualization, Writing- Review & Editing, Methodology, Visualization, Validation. M.O.:Conceptualization, Methodology, Investigation, Resources, Writing-Original Draft, Writing- Review & Editing, Visualization, Validation. M.A.: Conceptualization, Methodology, Investigation, Resources, Writing-Original Draft, Writing- Review & Editing, Visualization, Validation. A.B.: Data Curation, Formal analysis, Writing- Original Draft, Writing- Review & Editing, Methodology, Visualization. Acknowledgments: Not applicable. References Malakar AK, et al. A review on coronary artery disease, its risk factors, and therapeutics. J Cell Physiol. 2019;234(10):16812–23. Myers DE. Vagus nerve pain referred to the craniofacial region. A case report and literature review with implications for referred cardiac pain. Br Dent J. 2008;204(4):187–9. Renton T. Tooth-Related Pain or Not? Headache. 2020;60(1):235–46. Kreiner M, et al. Craniofacial pain as the sole symptom of cardiac ischemia: a prospective multicenter study. J Am Dent Assoc. 2007;138(1):74–9. Fazlyab M, et al. Craniofacial Pain as the Sole Sign of Prodromal Angina and Acute Coronary Syndrome: A Review and Report of a Rare Case. Iran Endod J. 2015;10(4):274–80. Foreman RD, Garrett KM, Blair RW. Mechanisms of cardiac pain. Compr Physiol. 2015;5(2):929–60. López-López J, et al. Orofacial pain of cardiac origin: review literature and clinical cases. Med Oral Patol Oral Cir Bucal. 2012;17(4):e538–44. McCarthy BD, et al. Missed diagnoses of acute myocardial infarction in the emergency department: results from a multicenter study. Ann Emerg Med. 1993;22(3):579–82. Chan WK, et al. Undiagnosed acute myocardial infarction in the accident and emergency department: reasons and implications. Eur J Emerg Med. 1998;5(2):219–24. 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A meta-analysis of cigarette smoking, bone mineral density and risk of hip fracture: recognition of a major effect. BMJ. 1997;315(7112):841–6. Fujino M, et al. Impact of symptom presentation on in-hospital outcomes in patients with acute myocardial infarction. J Cardiol. 2017;70(1):29–34. Zdzienicka J et al. Patients with non-ST-elevation myocardial infarction and without chest pain are treated less aggressively and experience higher in-hospital mortality. Kardiol Pol, 2007. 65(7): p. 769 – 75; discussion 776-7. Zegre-Hemsey JK, et al. A Statewide Assessment of Prehospital Electrocardiography Approaches of Acquisition and Interpretation for ST-Elevation Myocardial Infarction Based on Emergency Medical Services Characteristics. Prehosp Emerg Care. 2020;24(4):550–6. Tables Table 1 Patients’ characteristics. (n = 100). Variable Frequency / Mean ± SD Age (yrs) (Min: 32 - Max: 75) 57.88 ± 9.05 Sex Females 21 Males 79 Residency type Rural Urban Smoking No Yes Alcohol consumption No Yes Diabetes No Yes Hypertension No Yes Previous heart disease No Yes Familial history of heart disease No Yes Recent dental procedure No Yes Sports No Yes 29 71 28 72 91 9 62 38 47 53 47 53 41 59 85 15 71 29 Table 2 Sites of pain in smokers Site of Pain Percentage Precordial area Left shoulder Left arm Right shoulder Back Left chest Right arm Abdomen Right chest Neck Right mandible Occipital area Left mandible Right temporal area Left temporal area Right maxillary 83.3% 43.1% 40.3% 26.4% 25% 23.6% 19.4% 11.1% 8.4% 5.6% 4.2% 4.2% 2.8% 2.8% 1.4% 1.4% Table 3 Variables associated with typical and atypical presentation using Chi-Squared test. a Variable Atypical (n = 64) Typical (n = 36) X 2 p Age 57 and less 34 (72.3%) 13 (27.7%) 2.68 0.10 58 and more 30 (56.6%) 23 (43.4%) Sex Female 12 (57.1%) 9 (42.9%) 0.54 0.46 Male 52 (65.8%) 27 (34.2%) Residency Rural 17 (58.6%) 12 (41.4%) 0.51 0.47 Urban 47 (66.2%) 24 (33.8%) Smoking No 11 (39.3%) 17 (60.7%) 10.31 0.001 Φ = 0.32 Yes 53 (73.6%) 19 (26.4%) Alcohol No 58 (63.7%) 33 (36.3%) - 1.0 Yes 6 (66.7%) 3 (33.3%) Diabetes No 40 (64.5%) 22 (35.5%) 0.02 0.89 Yes 24 (63.2%) 14 (36.8%) Hypertension No 32 (68.1%) 15 (31.9%) 0.64 0.42 Yes 32 (60.4%) 21 (39.6%) Familial history of heart disease No 26 (63.4%) 15 (36.6%) 0.01 0.92 Yes 38 (64.4%) 21 (35.6%) Previous heart disease No 24 (51.1%) 23 (48.9%) 6.44 0.01 Φ = 0.25 Yes 40 (75.5%) 13 (24.5%) Recent dental procedure No 57 (67.1%) 28 (32.9%) 2.30 0.13 Yes 7 (46.7%) 8 (53.3%) Sports No 45 (63.4%) 26 (36.6%) 0.04 0.84 Yes 19 (65.5%) 10 (34.5%) Additional Declarations No competing interests reported. Supplementary Files results.xlsx Cite Share Download PDF Status: Published Journal Publication published 24 Aug, 2024 Read the published version in BMC Cardiovascular Disorders → Version 1 posted Editorial decision: Revision requested 29 Jun, 2024 Reviews received at journal 18 Jun, 2024 Reviews received at journal 18 Jun, 2024 Reviews received at journal 13 Jun, 2024 Reviewers agreed at journal 12 Jun, 2024 Reviewers agreed at journal 11 Jun, 2024 Reviewers agreed at journal 10 Jun, 2024 Reviewers agreed at journal 10 Jun, 2024 Reviewers agreed at journal 10 Jun, 2024 Reviewers agreed at journal 10 Jun, 2024 Reviewers agreed at journal 10 Jun, 2024 Reviewers invited by journal 10 Jun, 2024 Editor assigned by journal 29 May, 2024 Editor invited by journal 20 May, 2024 Submission checks completed at journal 20 May, 2024 First submitted to journal 17 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4436785","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":308147929,"identity":"93120f4e-5505-4411-ac6e-2584dfae3fb4","order_by":0,"name":"Mayar Abdullatef","email":"data:image/png;base64,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","orcid":"","institution":"Damascus University","correspondingAuthor":true,"prefix":"","firstName":"Mayar","middleName":"","lastName":"Abdullatef","suffix":""},{"id":308147930,"identity":"a47240b5-f71f-40de-b622-f3b984005529","order_by":1,"name":"Maya Omran","email":"","orcid":"","institution":"Damascus University","correspondingAuthor":false,"prefix":"","firstName":"Maya","middleName":"","lastName":"Omran","suffix":""},{"id":308147931,"identity":"51db458f-2642-43d9-8cb8-99d08038758f","order_by":2,"name":"Anas Bitar","email":"","orcid":"","institution":"Damascus University","correspondingAuthor":false,"prefix":"","firstName":"Anas","middleName":"","lastName":"Bitar","suffix":""},{"id":308147932,"identity":"56ed8213-6dca-45db-8831-031eb8047a53","order_by":3,"name":"Bayan Alsaid","email":"","orcid":"","institution":"Damascus University","correspondingAuthor":false,"prefix":"","firstName":"Bayan","middleName":"","lastName":"Alsaid","suffix":""}],"badges":[],"createdAt":"2024-05-17 12:37:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4436785/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4436785/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12872-024-04127-z","type":"published","date":"2024-08-24T15:57:32+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":57802450,"identity":"11d23b0f-8eb7-45c5-8feb-081ff9a88f66","added_by":"auto","created_at":"2024-06-05 22:34:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":529800,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4436785/v1/f4c1d94ce3b892b56198641b.png"},{"id":57802451,"identity":"9b03f7d3-0b92-4b35-8686-399907333839","added_by":"auto","created_at":"2024-06-05 22:34:49","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":825120,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4436785/v1/41f0c9dd71c04b63dfa01475.png"},{"id":63300899,"identity":"5a2a99ff-6834-420e-8ecc-6d6dc38b250b","added_by":"auto","created_at":"2024-08-26 16:17:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1616876,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4436785/v1/b6032bf2-a725-459a-9ddb-24eaaf4dd4b3.pdf"},{"id":57802452,"identity":"fe537636-b49e-4dfb-92e5-c89ee50af32b","added_by":"auto","created_at":"2024-06-05 22:34:49","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":32998,"visible":true,"origin":"","legend":"","description":"","filename":"results.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4436785/v1/317e2c64e412fd142bb4348d.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prevalence of Typical and Atypical Pain Sites of Coronary Artery Disease: A Cross-Sectional Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCoronary artery disease (CAD) is one of the major cardiovascular diseases affecting the global human population.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Environmental factors, genetic factors, unhealthy lifestyle, chronic diseases and many other factors could cause (CAD) which leads in the end to cardiac infarction. Symptoms of cardiac infarction vary from case to another but the typical symptoms include heavy breathing and crushing substernal chest pain. This pain is often induced by doing effort such as running, walking for a long distance and even while resting in severe cases. Pain could radiate to other regions such as shoulders, arms, neck, jaw, teeth, and ear[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].This radiation may be caused by the convergence of the vagus, trigeminal and cervical spinal nerves (C2-C3)[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePatients with CAD can experience atypical pain as a sole symptom. A previous study found that craniofacial pain was the only complaint during the ischemic episode in some cases [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. These patients are less likely to be diagnosed and consequently have a mortality rate three times lower than patients with typical angina symptoms [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGenerally, Ischemic heart disease can be manifested as myocardial infarction (MI)and angina pectoris. Angina pectoris has two types: stable angina and unstable angina. Unlike stable angina, which is usually induced by exertion, unstable angina presents sudden symptoms even while at rest [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Patients with unstable angina have a worse prognosis and are more likely to develop MI. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e \u003cp\u003ePain induced by CAD is called angina pectoris, which can be typical or atypical. Angina pectoris is a type of cardiac pain usually felt in the chest and upper left arm. Patients may experience atypical pain in the back, neck, or jaw instead. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] However, the patient may present heterotopic pain (pain occurring in a region despite the real source being elsewhere in the body) in this region, with the real source potentially being of cardiac origin.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] The cardiac heterotopic pain can lead to misdiagnosis and unnecessary medical procedures as was shown in several reports[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Misdiagnosed cases could develop lethal complications. Absence of chest pain and the lack of elevation of ST segment in electrocardiogram \u0026ldquo;ECG\u0026rdquo; were the main causes of misdiagnosis, as was shown in a previous study[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe objective of this study was to assess the prevalence of both typical and atypical anginal pain sites in individuals diagnosed with coronary artery disease (CAD). It aimed to determine the locations to which the atypical pain spreads and to emphasize the importance of healthcare providers being attentive to risk factors that may lead to atypical symptomatology.\u003c/p\u003e \u003cp\u003eThis, to our knowledge, is the first paper to study the prevalence of typical and atypical pain of cardiac origin in Syria.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis cross-sectional study examined 100 consecutive patients who were admitted to two cardiology departments in two major hospitals in Damascus, Syria (Assad University Hospital and University Heart Surgery Center) with signs and/or symptoms suggesting coronary artery disease (CAD), and the study period was divided into two time periods between November 2021 and December 2023, with a one-year gap in between.\u003c/p\u003e \u003cp\u003eAngiography was performed on each of the patients to determine cardiac ischemia, and all patients included in this study met the criteria of having a cardiac ischemic episode verified according to the American College of Cardiologists\u0026rsquo; (ACC) definition [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEach patient was shown an anatomical illustration that depicts the chest, abdomen, back, shoulders, arms, face, neck and mouth[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and was asked to identify the location of their current pain, with the corresponding site of pain being marked.\u003c/p\u003e \u003cp\u003eAdditional required information was obtained from the patients: demographic details, risk factors (smoking, alcohol consumption, diabetes mellitus, hypertension, personal and family history of cardiac disease, and medication), personal medical and surgical history, recent dental examination and/or treatment and physical activity, and the information was recorded in data forms.\u003c/p\u003e \u003cp\u003eTypical pain was identified as pain located in the precordial area, with or without radiating to the left shoulder or the left arm. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] Any other distribution of pain was considered Atypical.\u003c/p\u003e\n\u003cp\u003eEthical approval: Informed consent was obtained from each patient and the participation of the patients was voluntary\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003ethe study protocol was approved by the Ethical Committee of Damascus University, Faculty of Medicine, Syria (document number: 4597, 25-10-2021).\u003c/p\u003e\n\u003cp\u003eExcluding Criteria: Patients who had dental problems, psychiatric diseases, chronic headache or jaw masses were excluded, having not met the criteria of the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStatistical analysis: The data presentation included frequencies (%) for categorical variables and mean \u0026plusmn; standard deviation (SD) for continuous variables. The analysis was done using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, N.Y., USA). The Chi-Squared test was used to examine the relationship between the type of pain (typical or atypical) and the studied variables. The age variable was dichotomized based on the median of the patients\u0026rsquo; age (58 years). For variables where the expected frequency was less than 5 in more than 20% of the cells, the Fisher exact test was used as an alternative to the chi-squared test. The absolute Phi (\u0026Phi;) factor was calculated to assess the strength of the associations. The values of \u0026lsquo;1\u0026rsquo; indicate a complete association, \u0026lsquo;0\u0026rsquo; indicates no association, \u0026lsquo;0.1 indicates a small association, \u0026lsquo;0.3\u0026rsquo; indicates a medium association, and \u0026lsquo;0.5\u0026rsquo; indicates a large association. Phi (\u0026Phi;) was only illustrated when there was a statistical significance when using a chi-squared test. Statistical significance was set at p \u0026le; 0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eCharacteristics of the included sample:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study included 100 participants with a mean age of 57.88 ± 9.05. Males (79%) constituted the majority of the sample. A significant portion of the patients (70%) lived in urban areas. Most of the patients were smokers (72%), while only a small percentage (9%) reported consuming alcohol. Diabetes was present in 38% of the patients, and more than half of them (53%) had hypertension and a history of heart disease. Additionally, 59% reported a familial history of heart disease. Detailed characteristics of the patients are presented in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePain distribution:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe precordial area was the most commonly reported pain site, experienced by 88% of the sample. This was followed by the left shoulder and left arm, reported by 47% and 41% of the sample, respectively. Common sites of pain also included the right shoulder (27%) and the back (24%). (Figure 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOf the patients, 36% presented with typical pain, with 33.3% complaining of left shoulder pain and 36.1% experiencing left arm pain. Meanwhile, 64% of the patients presented with atypical pain, or pain radiating to other locations such as the right shoulder, right arm, abdomen, back, or the craniofacial area. Important areas of atypical pain were the right shoulder (42.2%), the back (37.5%), and the right arm (26.6%). \u0026nbsp; (Figure 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e12% of the patients presented with no precordial pain. The most common site of pain in those patients was the left chest (66.7%), followed by both the left arm and the back in 33.3% of patients.\u003c/p\u003e\n\u003cp\u003e8.3% complained from pain in the occipital area with no chest pain.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;(Figure 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eVariables associated with typical and atypical pain:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe found that smoking and previous heart disease were associated with the type of pain. Most of the patients who were smokers presented with atypical pain (53 patients, 73.6%), compared to 19 smokers (26.4%) who presented with typical pain. More details about distribution of pain amongst smokers is shown in Table 2. Amongst non-smokers, 11 patients (39.3%) had atypical pain and 17 patients (60.7%) had typical pain, X2 (1, N = 100) = 10.31, p = 0.001, and the association was medium (Φ = 0.32). Patients with previous heart disease were more likely to have atypical pain than typical pain when compared with patients with no previous heart disease, X2 (1, N = 100) = 6.44, p = 0.01. The association between previous heart disease and the type of pain was small (Φ = 0.25).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOther variables such as age, sex, and diabetes were not significantly associated with the type of pain. Details on the variables associated with typical and atypical pain are presented in Table 3.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCardiovascular disease (CVD) is a widespread cause of socio-economic and healthcare issues globally. \u0026nbsp;Morbidity, mortality, and disability caused by CVD are on the rise annually[12], accounting for 30% of all-cause mortality. Coronary heart disease (CHD) is the primary cause of death globally.\u0026nbsp;[13].\u003c/p\u003e\n\u003cp\u003ePatients who experience pain triggered by physical activity and relieved by rest are considered ideal candidates for cardiac pain diagnosis. Patients with coronary artery disease (CAD) may experience referred pain in different regions, such as the head, neck, arms, back, and abdominal region.\u0026nbsp;[8]\u0026nbsp;Several studies have explored the referred pain experienced by patients with ischemic heart disease.\u003c/p\u003e\n\u003cp\u003eThe objective of this study was to determine the frequency of typical and atypical pain\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eand\u0026nbsp;to caution doctors against disregarding atypical symptoms\u0026nbsp;in hospitalized patients.\u003c/p\u003e\n\u003cp\u003ePrevious studies have indicated that men are more likely to report typical anginal pain, characterized by discomfort in the chest and upper arm, whereas women tend to experience atypical angina, manifested as pain in the jaw, neck, shoulders, and back.\u0026nbsp;[6]. However, our study revealed that men experienced atypical pain more than women, with rates of 65.8% and 52.2%, respectively.\u003c/p\u003e\n\u003cp\u003eThis discrepancy may be attributed to the lower rates of alcohol consumption and smoking among women in our country, which reduces their risk of developing coronary artery disease (CAD). This aligns with our study results, which identified a correlation between smoking and atypical pain. Another study discovered that 30% of patients did not report chest pain\u0026nbsp;[14], while our study indicated that the precordial area was the most frequently reported site of pain, experienced by 88% of the participants.\u003c/p\u003e\n\u003cp\u003eIt is noteworthy that 81.9% of the patients in our study reported experiencing referred pain, which is significant as many patients tend to overlook this type of pain. Various studies have linked referred pain to the convergence projection theory, which suggests that central neurons receive combined visceral and somatic stimuli, resulting in the perception of both visceral pain and referred somatic pain. Initial research focused on the spinothalamic tract (STT) and the spinoreticular tract (SRT) in the upper thoracic spinal cord due to their role in transmitting somatic pain signals and receiving sensory input from the heart.\u003c/p\u003e\n\u003cp\u003eThese pathways were chosen based on their established roles in transmitting somatic pain signals to the thalamus and reticular formation, respectively, and in receiving sensory input from the heart in the upper thoracic cord.\u003c/p\u003e\n\u003cp\u003eStudies in animals demonstrated that stimulating cardiac spinal afferents activated around 80% of STT and SRT cells in the upper thoracic segments T1-T5. Neurons responsible for processing cardiac pain were identified in specific laminae of the spinal gray matter. These neurons exhibited responses to bradykinin applied either epicardially or intracardially to the heart, as well as to coronary artery occlusion.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll neurons receiving input from the heart received somatic input, primarily nociceptive signals from the chest and upper limb muscles, which provides support for the convergence projection theory concerning STT and SRT neurons in the upper thoracic cord. They indicate that these neurons may play a role in generating sensations of angina and contributing to the referral of pain to nearby somatic structures\u0026nbsp;[6].\u003c/p\u003e\n\u003cp\u003eHowever, 18.1% of the patients reported experiencing localized pain transmitted via spinal cardiac afferent fibers.\u003c/p\u003e\n\u003cp\u003eIn cases of CAD, fissures or erosions in atherosclerotic plaques lead to the release of various chemical mediators such as serotonin, histamine, thromboxane A2, bradykinin, reactive oxygen species including hydroxyl radicals, lactic acid causing proton release, and adenosine which triggers the production of prostaglandins (PGE2 and PGI2) within the coronary artery lumen.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThese chemical agents, either individually or in combination, interact with specific receptors primarily located on chemically sensitive terminals, resulting in the depolarization of cardiac visceral spinal afferent fibers [6].\u003c/p\u003e\n\u003cp\u003eFurthermore, our study highlighted that most smokers (73.6%) among our patients presented with atypical pain, indicating a potential link between smoking and atypical angina. Previous studies suggest that smokers are at a higher risk to develop back pain and other chronic pain conditions[15, 16]. Another study showed that among patients with chronic pain, smokers cmplained of higher pain intensity and inscreased number of pain sites[17, 18].\u003c/p\u003e\n\u003cp\u003eOne underlying mechanism might be that cigarette smoking impairs oxygen delivery to tissues by increasing sympathetic outflow and carboxyhemoglobin levels and causing vasoconstriction. Thus, smoking may accelerate degenerative processes which make the body more vulnerable to injury. This can explain why smoking is a risk factor for osteoporosis, lumber disk diseases and impaired bone healing[19].\u003c/p\u003e\n\u003cp\u003eThis alignes with the results of our study, which found that 25% of smokers had back pain, 26.4% had pain the the right shoulder and 19.4% had pain in the right arm.\u003c/p\u003e\n\u003cp\u003eIn our study, we found that only 36% of patients complained of typical pain, which indicates that the majority of patients suffered from atypical pain sites. This is a significant result, since atypical symptoms of AMI were associated with less invasive therapy and poor outcome, and in-hospital mortality was significantly higher in atypical than in typical group in a previous study conducted in Japan[20].\u003c/p\u003e\n\u003cp\u003eMoreover, 12% of patients presented with no precordial pain, whereas a study in Poland[21]\u0026nbsp;showed that only 6.4% presented without chest pain.This is especially important because previously, if the patient did not report chest pain, then they were disadvantaged from even receiving a prehospital ECG[22].\u003c/p\u003e\n\u003cp\u003eAnother important result of our research was that patients with previous heart disease where more likely to have atypical pain, which is consistent with the results of the Japanese study [20]. While in the Polish study [18], previous heart diseases and hypertention were more linked with typical symptoms of MI. It is extremely important to show all the different symptoms of MI because these symptoms are the cues for further diagnostic exams such as ECG and cardiac catheterization.\u003c/p\u003e\n\u003cp\u003eThere are a few limitations in this study. The sample included 100 patients, which might be considered slightly small.\u0026nbsp;However, the long study period overcomes this disadvantage because it provides a wide range of changes in climate and conditions that enriches the results. The study was conducted in one city, therefor the results cannot be generalized. Nevertheless, Damascus is the capital of Syria, and the hospitals included in this study are amongst the largest in Syria.\u003c/p\u003e\n\u003cp\u003eWe suggest that future researchers who seek to study the same topic conduct their study on a larger sample and in more than one city to cover as much variations as possible. We also suggest studying the relation between smoking and atypical pain more precisely.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur study found that atypical pain is common (64%), occurring mostly in the right\u0026nbsp; shoulder, right arm and the back, and is associated with smoking and previous\u0026nbsp; heart disease. Misdiagnosing coronary artery disease (CAD) can have fatal\u0026nbsp; outcomes. Many patients with atypical CAD symptoms might be deprived of vital\u0026nbsp; pre-hospital procedures, such as ECG, which can be lifesaving. This study\u0026nbsp; underscores the importance of recognizing all symptoms, especially atypical ones,\u0026nbsp; that might indicate CAD. Hopefully, it will assist doctors in acknowledging risk\u0026nbsp; factors and their contributions to different types of pain, ultimately aiding in the\u0026nbsp; diagnosis of CAD across various atypical pain sites.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Declarations:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the Ethical Committee of Damascus University, Faculty of Medicine, Syria (document number: 4597, 25-10-2021).\u0026nbsp;Informed consent was obtained from each patient and the participation of the patients was voluntary.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study were uploaded in the 'Supplementary Files' section.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ethe research was not funded\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eM.O. and M.A. contributed equally to this work. M.O. and M.A. are marked as first author.\u003c/p\u003e\n\u003cp\u003eB.A. is the supervisor of the research and is responsible on Project administration.\u003c/p\u003e\n\u003cp\u003eB.A.: Supervision, Project Administration, Conceptualization, Writing- Review \u0026amp; Editing, Methodology, Visualization, Validation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eM.O.:Conceptualization, Methodology, Investigation, Resources, Writing-Original Draft, Writing- Review \u0026amp; Editing, Visualization, Validation.\u003c/p\u003e\n\u003cp\u003eM.A.: Conceptualization, Methodology, Investigation, Resources, Writing-Original Draft, Writing- Review \u0026amp; Editing, Visualization, Validation.\u003c/p\u003e\n\u003cp\u003eA.B.: Data Curation, Formal analysis, Writing- Original Draft, Writing- Review \u0026amp; Editing, Methodology, Visualization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMalakar AK, et al. A review on coronary artery disease, its risk factors, and therapeutics. J Cell Physiol. 2019;234(10):16812\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMyers DE. Vagus nerve pain referred to the craniofacial region. A case report and literature review with implications for referred cardiac pain. Br Dent J. 2008;204(4):187\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRenton T. Tooth-Related Pain or Not? Headache. 2020;60(1):235\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKreiner M, et al. Craniofacial pain as the sole symptom of cardiac ischemia: a prospective multicenter study. J Am Dent Assoc. 2007;138(1):74\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFazlyab M, et al. Craniofacial Pain as the Sole Sign of Prodromal Angina and Acute Coronary Syndrome: A Review and Report of a Rare Case. Iran Endod J. 2015;10(4):274\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eForeman RD, Garrett KM, Blair RW. Mechanisms of cardiac pain. Compr Physiol. 2015;5(2):929\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eL\u0026oacute;pez-L\u0026oacute;pez J, et al. Orofacial pain of cardiac origin: review literature and clinical cases. Med Oral Patol Oral Cir Bucal. 2012;17(4):e538\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcCarthy BD, et al. Missed diagnoses of acute myocardial infarction in the emergency department: results from a multicenter study. Ann Emerg Med. 1993;22(3):579\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChan WK, et al. Undiagnosed acute myocardial infarction in the accident and emergency department: reasons and implications. Eur J Emerg Med. 1998;5(2):219\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGulati M, Levy PD, Mukherjee D, Amsterdam E, Bhatt DL, Birtcher KK, Blankstein R, Boyd J, Bullock-Palmer RP, Conejo T, Diercks DB, Gentile F, Greenwood JP, Hess EP, Hollenberg SM, Jaber WA, Jneid H, Joglar JA, Morrow DA, O'Connor RE, Ross MA, Shaw LJ, 2021 AHA/ACC/ASE/CHEST/, SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021;144(22):e368-e454. doi: 10.1161/CIR.0000000000001029. Epub 2021 Oct 28. Erratum in: Circulation. 2021;144(22):e455. Erratum in: Circulation. 2023;148(24):e281. PMID: 34709879.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWalker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. Editors: Boston; 1990.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoth GA, et al. Global Burden of Cardiovascular Diseases and Risk Factors, 1990\u0026ndash;2019: Update From the GBD 2019 Study. J Am Coll Cardiol. 2020;76(25):2982\u0026ndash;3021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGaziano TA, et al. Growing epidemic of coronary heart disease in low- and middle-income countries. Curr Probl Cardiol. 2010;35(2):72\u0026ndash;115.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeVon HA, Mirzaei S, Zegre-Hemsey J. Typical and Atypical Symptoms of Acute Coronary Syndrome: Time to Retire the Terms? J Am Heart Assoc. 2020;9(7):e015539.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAndersson H, Ejlertsson G, Leden I. Widespread musculoskeletal chronic pain associated with smoking. An epidemiological study in a general rural population. Scand J Rehabil Med. 1998;30(3):185\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePower C, et al. Predictors of low back pain onset in a prospective British study. Am J Public Health. 2001;91(10):1671\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrhurhu VJ, Pittelkow TP, Hooten WM. Prevalence of smoking in adults with chronic pain. Tob Induc Dis. 2015;13(1):17.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVogt MT, et al. Influence of smoking on the health status of spinal patients: the National Spine Network database. Spine (Phila Pa 1976). 2002;27(3):313\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLaw MR, Hackshaw AK. A meta-analysis of cigarette smoking, bone mineral density and risk of hip fracture: recognition of a major effect. BMJ. 1997;315(7112):841\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFujino M, et al. Impact of symptom presentation on in-hospital outcomes in patients with acute myocardial infarction. J Cardiol. 2017;70(1):29\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZdzienicka J et al. Patients with non-ST-elevation myocardial infarction and without chest pain are treated less aggressively and experience higher in-hospital mortality. Kardiol Pol, 2007. 65(7): p. 769\u0026thinsp;\u0026ndash;\u0026thinsp;75; discussion 776-7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZegre-Hemsey JK, et al. A Statewide Assessment of Prehospital Electrocardiography Approaches of Acquisition and Interpretation for ST-Elevation Myocardial Infarction Based on Emergency Medical Services Characteristics. Prehosp Emerg Care. 2020;24(4):550\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"397\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e Patients\u0026rsquo; characteristics. (n = 100).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.2015113350126%\" valign=\"top\" style=\"width: 70.3794%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.7984886649874%\" valign=\"top\" style=\"width: 29.3687%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFrequency / Mean \u0026plusmn; SD\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.2015113350126%\" valign=\"top\" style=\"width: 70.3794%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (yrs)\u0026nbsp;\u003c/strong\u003e(Min: 32 - Max: 75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.7984886649874%\" valign=\"top\" style=\"width: 29.3687%;\"\u003e\n \u003cp\u003e57.88 \u0026plusmn; 9.05\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.2015113350126%\" valign=\"top\" style=\"width: 70.3794%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eFemales\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.7984886649874%\" valign=\"top\" style=\"width: 29.3687%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.2015113350126%\" valign=\"top\" style=\"width: 70.3794%;\"\u003e\n \u003cp\u003eMales\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.7984886649874%\" valign=\"top\" style=\"width: 29.3687%;\"\u003e\n \u003cp\u003e79 \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.2015113350126%\" style=\"width: 70.3794%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eResidency type\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eRural\u003c/p\u003e\n \u003cp\u003eUrban\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSmoking\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAlcohol consumption\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDiabetes\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHypertension\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePrevious heart disease\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFamilial history of heart disease\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRecent dental procedure\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSports\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.7984886649874%\" valign=\"top\" style=\"width: 29.3687%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e71\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e72\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e91\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e62\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e47\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e53\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e47\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e53\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e41\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e59\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e85\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e71\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e Sites of pain in smokers\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"61.6822429906542%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSite of Pain\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.3177570093458%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePercentage\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"61.6822429906542%\" valign=\"top\"\u003e\n \u003cp\u003ePrecordial area\u003c/p\u003e\n \u003cp\u003eLeft shoulder\u003c/p\u003e\n \u003cp\u003eLeft arm\u003c/p\u003e\n \u003cp\u003eRight shoulder\u003c/p\u003e\n \u003cp\u003eBack\u003c/p\u003e\n \u003cp\u003eLeft chest\u003c/p\u003e\n \u003cp\u003eRight arm\u003c/p\u003e\n \u003cp\u003eAbdomen\u003c/p\u003e\n \u003cp\u003eRight chest\u003c/p\u003e\n \u003cp\u003eNeck\u003c/p\u003e\n \u003cp\u003eRight mandible\u003c/p\u003e\n \u003cp\u003eOccipital area\u003c/p\u003e\n \u003cp\u003eLeft mandible\u003c/p\u003e\n \u003cp\u003eRight temporal area\u003c/p\u003e\n \u003cp\u003eLeft temporal area\u003c/p\u003e\n \u003cp\u003eRight maxillary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.3177570093458%\" valign=\"top\"\u003e\n \u003cp\u003e83.3%\u003c/p\u003e\n \u003cp\u003e43.1%\u003c/p\u003e\n \u003cp\u003e40.3%\u003c/p\u003e\n \u003cp\u003e26.4%\u003c/p\u003e\n \u003cp\u003e25%\u003c/p\u003e\n \u003cp\u003e23.6%\u003c/p\u003e\n \u003cp\u003e19.4%\u003c/p\u003e\n \u003cp\u003e11.1%\u003c/p\u003e\n \u003cp\u003e8.4%\u003c/p\u003e\n \u003cp\u003e5.6%\u003c/p\u003e\n \u003cp\u003e4.2%\u003c/p\u003e\n \u003cp\u003e4.2%\u003c/p\u003e\n \u003cp\u003e2.8%\u003c/p\u003e\n \u003cp\u003e2.8%\u003c/p\u003e\n \u003cp\u003e1.4%\u003c/p\u003e\n \u003cp\u003e1.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"623\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 3\u0026nbsp;\u003c/strong\u003eVariables associated with typical and atypical presentation using Chi-Squared test.\u003csup\u003ea\u003c/sup\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.17307692307692%\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.07051282051282%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAtypical (n = 64)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.55128205128205%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTypical (n = 36)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.33974358974359%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eX\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.865384615384615%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.97752808988764%\" rowspan=\"2\"\u003e\n \u003cp\u003eAge\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.088282504012842%\" valign=\"top\"\u003e\n \u003cp\u003e57 and less\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10112359550562%\" valign=\"top\"\u003e\n \u003cp\u003e34 (72.3%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.582664526484752%\" valign=\"top\"\u003e\n \u003cp\u003e13 (27.7%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.359550561797754%\" rowspan=\"2\"\u003e\n \u003cp\u003e2.68\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.890850722311397%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.10\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.059701492537314%\" valign=\"top\"\u003e\n \u003cp\u003e58 and more\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.52238805970149%\" valign=\"top\"\u003e\n \u003cp\u003e30 (56.6%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.417910447761194%\" valign=\"top\"\u003e\n \u003cp\u003e23 (43.4%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.97752808988764%\" rowspan=\"2\"\u003e\n \u003cp\u003eSex\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.088282504012842%\" valign=\"top\"\u003e\n \u003cp\u003eFemale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10112359550562%\" valign=\"top\"\u003e\n \u003cp\u003e12 (57.1%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.582664526484752%\" valign=\"top\"\u003e\n \u003cp\u003e9 (42.9%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.359550561797754%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.54\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.890850722311397%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.46\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.059701492537314%\" valign=\"top\"\u003e\n \u003cp\u003eMale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.52238805970149%\" valign=\"top\"\u003e\n \u003cp\u003e52 (65.8%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.417910447761194%\" valign=\"top\"\u003e\n \u003cp\u003e27 (34.2%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.97752808988764%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eResidency\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.088282504012842%\" valign=\"top\"\u003e\n \u003cp\u003eRural\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10112359550562%\" valign=\"top\"\u003e\n \u003cp\u003e17 (58.6%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.582664526484752%\" valign=\"top\"\u003e\n \u003cp\u003e12 (41.4%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.359550561797754%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.51\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.890850722311397%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.47\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.059701492537314%\" valign=\"top\"\u003e\n \u003cp\u003eUrban\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.52238805970149%\" valign=\"top\"\u003e\n \u003cp\u003e47 (66.2%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.417910447761194%\" valign=\"top\"\u003e\n \u003cp\u003e24 (33.8%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.97752808988764%\" rowspan=\"2\"\u003e\n \u003cp\u003eSmoking\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.088282504012842%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10112359550562%\" valign=\"top\"\u003e\n \u003cp\u003e11 (39.3%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.582664526484752%\" valign=\"top\"\u003e\n \u003cp\u003e17 (60.7%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.359550561797754%\" rowspan=\"2\"\u003e\n \u003cp\u003e10.31\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.890850722311397%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026Phi; = 0.32\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.059701492537314%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.52238805970149%\" valign=\"top\"\u003e\n \u003cp\u003e53 (73.6%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.417910447761194%\" valign=\"top\"\u003e\n \u003cp\u003e19 (26.4%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.97752808988764%\" rowspan=\"2\"\u003e\n \u003cp\u003eAlcohol\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.088282504012842%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10112359550562%\" valign=\"top\"\u003e\n \u003cp\u003e58 (63.7%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.582664526484752%\" valign=\"top\"\u003e\n \u003cp\u003e33 (36.3%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.359550561797754%\" rowspan=\"2\"\u003e\n \u003cp\u003e-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.890850722311397%\" rowspan=\"2\"\u003e\n \u003cp\u003e1.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.059701492537314%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.52238805970149%\" valign=\"top\"\u003e\n \u003cp\u003e6 (66.7%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.417910447761194%\" valign=\"top\"\u003e\n \u003cp\u003e3 (33.3%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.97752808988764%\" rowspan=\"2\"\u003e\n \u003cp\u003eDiabetes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.088282504012842%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10112359550562%\" valign=\"top\"\u003e\n \u003cp\u003e40 (64.5%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.582664526484752%\" valign=\"top\"\u003e\n \u003cp\u003e22 (35.5%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.359550561797754%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.02\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.890850722311397%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.89\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.059701492537314%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.52238805970149%\" valign=\"top\"\u003e\n \u003cp\u003e24 (63.2%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.417910447761194%\" valign=\"top\"\u003e\n \u003cp\u003e14 (36.8%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.97752808988764%\" rowspan=\"2\"\u003e\n \u003cp\u003eHypertension\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.088282504012842%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10112359550562%\" valign=\"top\"\u003e\n \u003cp\u003e32 (68.1%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.582664526484752%\" valign=\"top\"\u003e\n \u003cp\u003e15 (31.9%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.359550561797754%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.64\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.890850722311397%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.42\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.059701492537314%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.52238805970149%\" valign=\"top\"\u003e\n \u003cp\u003e32 (60.4%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.417910447761194%\" valign=\"top\"\u003e\n \u003cp\u003e21 (39.6%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.97752808988764%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eFamilial history of heart disease\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.088282504012842%\"\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10112359550562%\"\u003e\n \u003cp\u003e26 (63.4%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.582664526484752%\"\u003e\n \u003cp\u003e15 (36.6%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.359550561797754%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.01\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.890850722311397%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.92\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.059701492537314%\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.52238805970149%\"\u003e\n \u003cp\u003e38 (64.4%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.417910447761194%\"\u003e\n \u003cp\u003e21 (35.6%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.97752808988764%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePrevious heart disease\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.088282504012842%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10112359550562%\" valign=\"top\"\u003e\n \u003cp\u003e24 (51.1%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.582664526484752%\" valign=\"top\"\u003e\n \u003cp\u003e23 (48.9%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.359550561797754%\" rowspan=\"2\"\u003e\n \u003cp\u003e6.44\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.890850722311397%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.01\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026Phi; = 0.25\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.059701492537314%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.52238805970149%\" valign=\"top\"\u003e\n \u003cp\u003e40 (75.5%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.417910447761194%\" valign=\"top\"\u003e\n \u003cp\u003e13 (24.5%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.97752808988764%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRecent dental procedure\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.088282504012842%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10112359550562%\" valign=\"top\"\u003e\n \u003cp\u003e57 (67.1%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.582664526484752%\" valign=\"top\"\u003e\n \u003cp\u003e28 (32.9%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.359550561797754%\" rowspan=\"2\"\u003e\n \u003cp\u003e2.30\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.890850722311397%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.13\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.059701492537314%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.52238805970149%\" valign=\"top\"\u003e\n \u003cp\u003e7 (46.7%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.417910447761194%\" valign=\"top\"\u003e\n \u003cp\u003e8 (53.3%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.97752808988764%\" rowspan=\"2\"\u003e\n \u003cp\u003eSports\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.088282504012842%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.10112359550562%\" valign=\"top\"\u003e\n \u003cp\u003e45 (63.4%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.582664526484752%\" valign=\"top\"\u003e\n \u003cp\u003e26 (36.6%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.359550561797754%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.04\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.890850722311397%\" rowspan=\"2\"\u003e\n \u003cp\u003e0.84\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.059701492537314%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.52238805970149%\" valign=\"top\"\u003e\n \u003cp\u003e19 (65.5%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.417910447761194%\" valign=\"top\"\u003e\n \u003cp\u003e10 (34.5%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Coronary artery disease” CAD”, Typical, Atypical, Ischemic heart disease, Syria","lastPublishedDoi":"10.21203/rs.3.rs-4436785/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4436785/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eStudy Objective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study aims to assess the prevalence of both typical and atypical pain in patients with ischemic heart disease, emphasizing the importance of recognizing and not disregarding atypical symptoms.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis cross-sectional study was conducted on patients diagnosed with coronary artery disease (CAD) who were admitted to two major hospitals in Damascus, Syria, from 2021 to 2023. Patients were asked to mark the sites of their pain on an anatomic illustration. Typical pain was identified as pain located in the precordial area, with or without radiating to the left shoulder or the left arm. Any other distribution of pain was considered atypical. Patients’ demographics and previous medical history were documented to investigate any potential associations with atypical pain.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 100 patients, 64% (64) had atypical pain, while 36% (36) had typical symptoms. Referred pain to areas like the left shoulder and left arm was reported by 81.9% of patients, with 47% and 41% of the sample mentioning discomfort in these regions, respectively. We found that smoking and previous heart disease were associated with atypical pain, with 73% of patients who experienced atypical pain being smokers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study found that atypical pain is common, affecting 64% of individuals primarily in the right shoulder, right arm, and back. This type of pain is associated with smoking and prior heart disease. Misdiagnosing coronary artery disease (CAD) can have serious consequences, as patients with atypical symptoms may miss important pre-hospital procedures like ECG.\u003c/p\u003e","manuscriptTitle":"Prevalence of Typical and Atypical Pain Sites of Coronary Artery Disease: A Cross-Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-05 22:34:44","doi":"10.21203/rs.3.rs-4436785/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-30T03:23:28+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-18T19:14:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-18T16:28:44+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-13T20:13:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"25632719275282286719270400580178436826","date":"2024-06-12T22:45:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"23845346819652027774798335404821569799","date":"2024-06-11T19:20:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"20179815356184185011736641635822018345","date":"2024-06-10T23:21:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"71919355117874679089291975394151737007","date":"2024-06-10T17:31:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"126164423285853714683572938245549251751","date":"2024-06-10T15:28:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"199926863123478089511737122734827249151","date":"2024-06-10T15:21:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"213676052739410569407168159805404677624","date":"2024-06-10T15:20:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-10T15:02:42+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-29T10:12:31+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-05-21T03:58:23+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-21T03:56:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2024-05-17T12:35:58+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6e4e2c01-61e9-42c2-b929-ec40c07b509a","owner":[],"postedDate":"June 5th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-26T16:12:37+00:00","versionOfRecord":{"articleIdentity":"rs-4436785","link":"https://doi.org/10.1186/s12872-024-04127-z","journal":{"identity":"bmc-cardiovascular-disorders","isVorOnly":false,"title":"BMC Cardiovascular Disorders"},"publishedOn":"2024-08-24 15:57:32","publishedOnDateReadable":"August 24th, 2024"},"versionCreatedAt":"2024-06-05 22:34:44","video":"","vorDoi":"10.1186/s12872-024-04127-z","vorDoiUrl":"https://doi.org/10.1186/s12872-024-04127-z","workflowStages":[]},"version":"v1","identity":"rs-4436785","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4436785","identity":"rs-4436785","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}