Introduction

The Egyptian papyri from 2600 B.C. already recorded that patients with acute chest pain had a high risk of death [¹]. In our era, coronary heart disease (CHD) is one of the main health problems. As a major type of CHD, ischemic heart disease (IHD) causes more deaths and disability than any other condition and has a high economic burden in developed countries. The progressive increase in cardiovascular risk factors (CVRFs) has led to increasingly higher rates of patients affected by this disease [²].

Today, the term acute coronary syndrome (ACS) is used to designate the acute phases, where its clinical manifestations depend on the extent and severity of myocardial ischemia [³]. IC can be classified into two large groups: ST-elevation myocardial infarction (STEMI) or non-ST-segment elevation acute coronary syndrome (NSTE-ACS). This classification is not merely semantic but rather separates patients with completely different therapeutic management strategies after their arrival at the emergency department (ED). Although the prevalence of IC is greater among men, women with IC have higher fatality rates at 28 days and higher mortality rates at 6 months than men do. There are more hospitalized female AMI patients in all age groups [⁴].

When ACS is suspected, the basic tools for rapid evaluation in SUs are anamnesis, electrocardiograms (ECGs), physical examinations and the measurement of biochemical markers or cardiac enzymes. If high coronary risk is present in the Killip-Kimbal assessment for ACS with ST elevation or TIMI, for the staging of morbidity and mortality in ACS patients without ST elevation, percutaneous transluminal coronary angiography (PTCA) or revascularization surgery (PTCA) is performed [⁴-⁶].

Historically, health and disease in women have been understood from a reproductive perspective, without including women in the study of other diseases, and it has been observed that most of the processes, except those of a purely gynecological and obstetric nature, were investigated in men and then generalized in clinical practice to women. Clearly, biology establishes differences by sex, generating different health needs and problems according to sex and generating bias when applying male patterns of physiological and social functioning to all people [⁷-⁹]. This change in perspective, which begins to contemplate the real biological differences between the sexes, has made it possible to develop a new perspective on health according to sex and gender [⁹]. The concept of gender, which has been used in the social sciences since the 1960s, helps in understanding how sociocultural norms and power relations construct and maintain ideas about what is ‘feminine’ and ‘masculine’, influencing practices such as medical care [¹⁰], and contribute to the sociocultural construct of gender [¹¹,¹²]. This approach allows us to question and challenge gender biases in health care, such as when physicians assume that certain aspects, such as family, are only women's issues, promoting care that is more equitable and aware of social and cultural differences.

Methods

A mixed-methods explanatory descriptive study was carried out, which included a quantitative phase followed by a qualitative phase, with the purpose of obtaining qualitative data to help explain the results of the quantitative phase [²⁵]. The first phase consisted of a descriptive quantitative study that aimed to determine the characteristics of patients with ischemic coronary pathologies treated in the ED by selecting a consecutive sample that included all patients who were diagnosed with ACS and treated in the ED of the Hospital Universitario de Navarra (HUN) from 2016 to 2021. This type of sampling was chosen because it can be considered the best nonprobability sample since it includes all the available participants, which allows the sample to better represent the entire population.

The inclusion criteria were patients over 18 years of age who were admitted to the hospital emergency unit of the referral center with chest pain triage and who agreed to participate in the study. The exclusion criteria were patients with cardiac arrest or death at the time of admission to the ED and patients with previous cardiac surgery. Similarly, all patients who did not give their consent to be part of the study and those whose clinical data or treatment process was not properly collected were excluded from the study.

The variables studied were divided into sociodemographic data (upon first admission), clinical variables or anamnesis, physical examination, time (t1-t5), diagnostic test, therapeutic management and final evolution data (Table 1).

t1, or patient-time, is the time elapsed from the onset of symptoms to the request for medical care (either by calling 112 SOS-Navarra or by going to the primary care center or directly to the hospital ED); t2 or prehospital care time is the time elapsed from being brought to the attention of the SOS-Navarra health care team or a primary care center to the arrival of the user at the hospital; t3 or triage time is the time elapsed from the triage of the patient by means of an electrocardiogram (ECG) until the start of health care; t4 or door-needle time is the time elapsed from the ECG to treatment by means of fibrinolysis (recommended < 30 minutes); and t5 or balloon time is the time from ECG to PA (recommended < 90 minutes).

For the treatment limitation variables, the following values were considered: the presence of associated comorbidities (previous renal, hepatic or pulmonary disease), the presence of bleeding risk, resistance or intolerance to any of the pharmacological treatments to be applied, and advanced age (>76 years). For the adverse event treatment variable, the presence of relative and absolute complications presented within 48 h after treatment, such as local or systemic allergic reactions; the presence of minor or major bleeding; alterations in blood pressure due to hypotension or hypertension; the presence of postintervention pain; the presence of cardiac arrhythmia, thrombosis or embolism; and failure of cardiac function, were considered.

For quantitative measures, the arithmetic mean and median were calculated for measures of central tendency, and the range and standard deviation were used as measures of dispersion. For qualitative variables, proportions were calculated as absolute frequencies, relative frequencies and percentages.

In the bivariate analysis, to establish the possible existence of statistically significant differences between qualitative variables, the chi-square test was performed once the application conditions were verified (an expected number of 5 or more in each cell). For the analysis of qualitative and quantitative variables with a normal distribution, the means of independent samples were compared with Student's t tests and ANOVA (after checking the homogeneity of the variances using the Levene test). In the case of nonnormal distributions, the Mann‒Whitney U test was used as a nonparametric test.

After the relationships between the study variables and the outcome variables (treatment application) were identified, statistically significant variables such as age, sex, and severity of the process were used to adjust both the univariate and multivariate binary logistic regression models. To study the association between sex and treatment, univariate and multivariate binary regression models were used, and the final multivariate model was adjusted for variables such as age, multiple pathologies and the final severity of the process. From these models, gross and adjusted odds ratio (OR) estimates with 95% confidence intervals were obtained for the sex variable. A probability of error of p <0.05 (alpha error = 5%) was considered to indicate statistical significance. The software used for the analysis was SPSS version 29.

The second phase, the qualitative study, was carried out using a phenomenological methodology to determine, in depth, the phenomenon or causes of the differences that occur in the immediate care and treatment of patients with coronary artery disease according to sex. The fundamental difference between phenomenology and other qualitative research methods is the emphasis on the individual and their subjective experience [²⁶]. The interviews were conducted with patients affected with IC after the first time they attended the HUN ED and the medical professionals who treated them. All interviews were conducted by the same researcher, using a preliminary outline established to avoid variability and digression in the content but allowing for the open development of the interviews. After the interviews were conducted, they were transcribed and analyzed by the same researcher. The transcripts were double-coded and peer-reviewed.

This process began with careful reading of each interview to become familiar with the content, followed by initial coding, where labels or categories were assigned to fragments of text that reflected relevant aspects of the experience. As the analysis progressed, these categories were refined and grouped into broader themes that captured the essence of shared perceptions and meanings. Interview saturation was assumed when, after further interviews, no additional categories or themes emerged, indicating that a sufficient level of depth had been reached to understand the experience in its entirety.

The development of data categorization was carried out by the study's principal investigator and two external subject matter experts. This principal investigator and the experts who collaborated have already developed several studies with the same methodology previously on the current topic and on trauma patients in the emergency department (ref?). The researcher created the transcripts directly from the recorder used in the interviews, an Olympus VN-712PC.

The analysis was carried out consecutively. As the interviews were carried out, they were transcribed and subsequently analyzed, which enabled a correct methodological process and progressive optimization of the subsequent interviews (Figure 1). For the saturation of the results, the criteria of sufficiency and adequacy of the data were taken into account. Two aspects were considered in the patient selection process.

Figure 1 Matrix of the methodology process. 

The first element assessed was that the coronary process was newly established to avoid biases in the perception of symptoms or knowledge from previous experiences; second, the sex of the patient was taken into account to carry out an alternation, allowing us to maintain the objective of making a comparison according to sex in the study and obtaining the perspectives of the lived experiences of both men and women. To ensure the absence of gender inequality, the interview process was carried out by randomizing male and female physicians consecutively, all of whom were specialized attending physicians in family medicine and emergencies.

These meetings were directed toward understanding the perspectives that informants (doctors and patients) have regarding the process of EC and the experiences lived; as a person who treats patients or as a person who suffers from EC; and as these individuals express their experiences in their own words. The purpose of the interviews was to gain insight into the informants' perspectives on the coronary process and lived experiences, both as caregivers and patients. The researcher and an expert reviewed the transcripts for accuracy. Data analysis followed a qualitative phenomenological methodology. Prior to the data collection and interview process, information about the project and a written request for informed consent were provided. Similarly, the study was presented to and accepted by the unit and emergency department chiefs and the center's management and medical directors. Finally, ethical approval was obtained from the Clinical Research Ethics Committee of Navarra before starting the study (EO/2013).

Results

The sample of 478 patients consisted mostly of men (70.51%), with an average age of 66.43 years, compared to women, who had an average age of 72.54 years (p<0.001). This coincides with the perceptions of doctors, who consider that cardiovascular disease mainly affects men. With respect to coronary involvement, there were 249 cases of STEMI and 229 cases of NSTEMI (Table 2). The most prevalent cardiovascular risk factor was smoking, followed by hypertension and dyslipidemia.

Enzyme level analysis revealed greater initial and final elevations in male patients with STEMI (p<0.05). Time analysis revealed a 2-hour delay in women at t1 (p<0.001) and slightly greater delays at t3 (p=0.001) (Table 2). The average time t1 generated by the patient was 117 minutes longer in women with STEMI and 148 minutes longer in the NSTE-ACS group (P<0.001). These delays are reflected in interviews with patients, where women reported that, after experiencing symptoms such as chest pain, they first finished household chores or waited to see if the pain would go away before seeking help, which may contribute to these delays.

Discussion

This study confirms the persistent gender disparities in the treatment of acute coronary syndrome (ACS), aligning with previous research that highlights differences in pharmacological therapy and revascularization procedures [¹⁴,²⁰,²⁷-²⁹]. By combining quantitative data with qualitative insights from patients and healthcare professionals, we gain a deeper understanding of the factors underlying these disparities.

The distribution of the sample by sex reflects the epidemiological trend reported in numerous studies: men are more frequently diagnosed with coronary artery disease (CAD) [⁴,²⁹,³⁰]. Although women with ischemic conditions tend to be older, our study did not find a significant age difference between sexes, suggesting that age alone may not influence treatment disparities in our cohort. Nonetheless, existing literature associates older age in women with increased multimorbidity [³⁰], which can complicate management.

Interestingly, our analysis revealed that cardiovascular risk factors such as hypertension, hyperlipidemia, and smoking are more prevalent in men, potentially leading healthcare providers to prioritize their care. However, recent studies suggest that psychosocial factors-such as anxiety, chronic stress, caregiver burden, and socioeconomic disadvantages-are more common in women and may contribute to microvascular dysfunction and vasomotor reactivity, factors often overlooked in traditional assessments [³⁰-³³].

Analysis of cardiac enzyme levels revealed greater elevations in men. These higher enzyme ranges in men may also be affected by their larger body and muscle size, and future studies should assess whether the range of pathology should be the same for both sexes. Such differences may represent a key factor influencing the reduced use of pharmacological therapies in women [³⁴]. However, this would not justify the lower administration or longer delay in the application time of treatment in women, since their results, together with the rest of the clinical manifestations, continue to show increases suggestive of pathology and, therefore, the need for treatment.

Diagnostic procedures such as cardiac catheterization and stress testing have historically shown sex-based differences, with men more frequently undergoing these tests [³⁴,³⁵]. Our findings align with this, as stress testing was performed less often in women, even after controlling for age. This suggests potential biases or systemic barriers affecting diagnostic pathways.

Binary logistic regression revealed that men with any type of CI are more likely to receive pharmacological treatment, as well as fibrinolysis or PCI. This difference remained significant after adjusting for age and severity of the process. Indeed, men had nearly double the odds of receiving fibrinolysis or PCI after adjustment [²⁰,²⁹,³⁶-³⁸]. This indicates a treatment gap that is not solely explained by clinical factors but may be influenced by perceptions and biases.

The analyzed data, as well as the phenomenological study of the experience lived by patients, revealed similar symptomatology experienced and expressed at the onset and immediate evolution of CI; therefore, the diagnostic difficulty by sex would be similar. This finding refutes hypotheses raised in other studies of men [³⁴,³⁹,⁴⁰], where they suggest that unequal treatment by sex is due to the presentation of atypical or more nonspecific symptoms in women. In contrast, our study shows that both men and women presented clear symptomatology and enzyme elevations indicative of a coronary process, which does not justify delays in treatment initiation or the reduced therapeutic effort with invasive procedures.

Qualitative data from patient interviews revealed that symptom recognition and expression are similar across genders, contradicting hypotheses that women experience or report atypical symptoms more frequently. Both men and women expressed clear symptoms and enzyme elevations, indicating that diagnostic difficulty by sex is minimal. However, women tend to delay seeking care [²⁰], -averaging 117 minutes longer in STEMI and 148 minutes longer in NSTE-ACS-primarily due to psychosocial factors such as social responsibilities, caregiving roles, and fear of burdening others. These delays, identified both through patient narratives and timing analyses, can prolong ischemic time and negatively impact outcomes.

Healthcare professionals acknowledged that women often arrive later and face delays at triage and treatment initiation stages. While physicians perceive women as more expressive of their symptoms, paradoxically, they do not always prioritize their care accordingly. This discrepancy may stem from biases that associate women’s symptoms with emotional or musculoskeletal issues rather than cardiac pathology. Moreover, some clinicians consider women to be more fragile due to age or comorbidities, but our data show that men often have more contraindications and experience more post-treatment complications, suggesting that biological factors should not justify differential treatment.

The phenomenological analysis further revealed that women’s delays are influenced by psychosocial elements-such as prioritizing family duties or avoiding being a burden-rather than a lack of symptom awareness. These self-generated delays prolong the course of the coronary process, potentially affecting the progression of the process and limiting therapy [⁸,³⁸,⁴¹-⁴³]. Women tend to overestimate the severity of their symptoms yet still postpone seeking help, whereas men often inform female relatives promptly. Physicians’ perceptions of women’s emotional expressiveness and age-related fragility influence clinical decisions, sometimes leading to less aggressive treatment for women despite similar or more severe presentations.

These findings underscore the importance of addressing both biological and psychosocial factors contributing to gender disparities. Interventions should include targeted education for healthcare providers to recognize and counteract biases, as well as community-based strategies to empower women to seek prompt care. Incorporating additional risk factors-such as anxiety, chronic stress, and social vulnerability-into cardiovascular risk assessments could improve early detection and management.

The greater prevalence of CAD in men, along with physicians' perception of the greater severity of CAD in men, reflects a possible bias that would condition a more aggressive and priority therapeutic effort in men [²⁹,⁴¹,⁴⁴]. However, the analysis of post-ACS evolution revealed a similar severity level by sex [²⁹,⁴¹,⁴²,⁴⁵,⁴⁶], demonstrating that this perception can be incorrect and may act as a conditioning factor of gender inequality for women.

Although there are no differences in limitations based on gender, there are differences in the application of therapy. Procedures such as fibrinolysis and angioplasty were performed more frequently in men. This may be related to the perception of physicians, who consider that women, although they express their symptoms more intensely and quickly, often have limitations in treatment, perhaps due to delays in seeking help or other factors not initially detected.

Phenomenological analysis also revealed that certain psychosocial factors associated with women, such as higher emotional or educational levels, favor earlier seeking of assistance or overestimation of their symptoms. Physicians interpret that men express the pathological process to a lesser extent and therefore prioritize their assistance, considering that they may be worse off. In this context, physicians correctly perceived that women expressed the severity of their symptoms more clearly, yet their actions were contradictory, as they did not prioritize access to healthcare even though they acknowledged the seriousness of the situation. Women, in addition to experiencing symptoms similar to those of men, tended to wait longer before seeking help, concerned about not worrying their families, while men tended to quickly inform a female relative. Doctors also noted that, although they treat both sexes equally, they believe that women have a greater ability to express their symptoms, which influences clinical decisions and treatment times.

They also mentioned the possibility of generating a perception bias with women, since they associated symptomatological manifestations in women as a suspicion of psychoemotional involvement (anxiety crisis, hysterical ballooning) or musculoskeletal or digestive disorders, but not cardiological ones.

Ultimately, addressing these disparities requires a comprehensive, multifaceted approach involving healthcare providers, policymakers, and community organizations. Educational initiatives should aim to raise awareness among clinicians about gender biases and the importance of equitable treatment, while community programs can empower women to seek care promptly and reduce psychosocial barriers. Incorporating additional risk factors such as anxiety, chronic stress, and social vulnerability into cardiovascular assessments will help identify at-risk women earlier and tailor interventions accordingly.

Moreover, establishing sex-specific reference ranges for cardiac biomarkers, like enzymes, could improve diagnostic precision and prevent underestimation of pathology in women. Public health campaigns should also focus on community-level interventions to promote awareness of ACS symptoms in women, emphasizing the importance of early medical attention regardless of social or emotional factors.

In clinical practice, protocols should be reviewed and adapted to ensure that treatment decisions are based on objective clinical indicators rather than gendered perceptions. Training healthcare professionals to recognize and counteract unconscious biases is essential to promote equitable care. Additionally, fostering a healthcare environment that values gender-sensitive approaches can help reduce delays and improve outcomes for women experiencing ACS.

In conclusion, this study highlights the complex interplay of biological, psychosocial, and systemic factors contributing to gender disparities in ACS treatment. By implementing targeted strategies that address these multifactorial influences, we can move toward more equitable healthcare delivery, ultimately improving prognosis and quality of life for all patients affected by coronary artery disease.

Conclusions