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

doi:10.21203/rs.3.rs-4436785/v1

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

https://doi.org/10.21203/rs.3.rs-4436785/v1

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published 24 Aug, 2024

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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

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.

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.

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.

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.

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.

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.

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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%

2.8%

1.4%

Table 3 Variables associated with typical and atypical presentation using Chi-Squared test.^a
Variable		Atypical (n = 64)	Typical (n = 36)	X²	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%)

No competing interests reported.

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You are reading this latest preprint version

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

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Abstract

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