An exploratory descriptive analysis was carried out. Categorical variables were expressed as absolute numbers and percentages, and quantitative ones as mean and standard deviation. Significant differences were assessed using the Chi-square test or the Fisher test in the first case, and the Wilcoxon rank sum test in the second one. Crude attendance rates for cardiology consultations were calculated based on the total reference population of the hospital. All analysis were performed using R software (R Core Team, 2021).

The most common symptoms presenting to cardiology consultations were palpitations in women (676 patients; 19.2%) and ECG abnormalities in men (570 patients; 23.2%) (Table 1). There were important differences in the reasons for consultation according to age and sex [Table 1, Supplementary Figure S2, S3]. In the younger population (<65 years), palpitations were the most common reason for consultation in women, whereas ECG abnormalities were the most common in men. In the group aged ≥65 years, dyspnoea was the most common situation leading to a cardiology consultation in women, and ECG abnormalities remained the most common in men. Two reasons for referral were most common in women: palpitations (969 patients, 676 women, 69.8%) and dyspnoea (858 patients, 626 women, 72.8%).

An electrocardiogram (ECG) was performed in all patients and a bedside echocardiogram was performed in more than half of the patients as part of the initial assessment in the cardiology clinic, with no difference by sex or reason for presentation (1,327 [54.1%] men and 1,944 [55.2%], P = 0.573). Additional tests were ordered in 917 (37.4%) men and 1,243 (35.3%) women (P = 0.09). The time from the cardiology visit to the performance of the additional tests was 93.5 ± 85.9 days in men and 95.9 ± 103.9 days in women (P = 0.474). Supplementary Table S1 shows the most common tests ordered after the consultation by sex and reason for the consultation. Coronary angiography was ordered in 19 [4.1%] men and 8 [1.4%] women with chest pain (P = 0.006). Non-invasive testing for ischaemia was performed more often in women aged ≥65 years than in men (239 [34%] vs. 106 [27%], P = 0.018). In patients who underwent an ischaemia test, 4 deaths were observed during follow-up, both in the >65 age group (3 in men and 1 in women).

Of the total cohort of patients seen in the cardiology clinic, 1,306 men (53.3%) and 1,952 women (55.4%, P = 0.062) were discharged to primary care without further tests or visits (men aged ≥65 years were more likely than women to be referred for a subsequent cardiology visit [41.8% men vs. 37.4% women aged ≥65 years (P = 0.016)].

During a mean follow-up of 23.7 ± 1.7 months after the cardiology consultation, emergency department visits were more frequent in women (55.0% vs. 47.7%; P < 0.001), especially in younger (<65 years) women (48.5% vs. 39.9%; P < 0.001; Figure 1, Table 2). In contrast, hospital admissions were more frequent in men aged ≥65 years (22.6% vs. 21.6%, P < 0.001), especially to the cardiology department in the overall study population (9.3% vs. 5.8%, P < 0.001), but the difference in hospital admissions to the cardiology department between men and women was statistically significant for specific reasons for consultation [chest pain 15.5% vs. 8.8%, P < 0.001; and syncope 10.2% vs. 2.5%, P < 0.001 (Table 2)]. All-cause mortality was higher in men than in women (2.8% vs. 1.9%, P = 0.035). However, this difference was statistically significant only in the group of patients aged ≥65 years (6.0% vs. 3.3%; P < 0.001), but not in younger patients (0.2% vs. < 0.1%; P = 0.4).

We found significant differences according to patient age and sex. Palpitations are a very common reason for consulting a general practitioner (15% of primary care visits) (24, 25) and the main reason for referral in younger women, whereas it was much less common in men. Palpitations are a benign symptom in the majority of cases, but cause significant discomfort and disability in patients (26, 27). Although palpitations are occasionally related to emotional or psychosomatic causes (>30%) (28), and women with palpitations are even more likely than men to be diagnosed with anxiety disorders (26, 29), in our experience palpitations remain a cause of concern for our primary care physicians and referral for cardiology consultation. Unfortunately, we have not been able to determine the proportion of men and women seen by general practitioners with palpitations who are not referred to cardiology.

Dyspnea was a more frequent cause for referral in older patients, particularly among women. A previous study also reported that women have a higher prevalence and severity of dyspnea than men (30). The reasons for this difference are probably multifactorial, including greater prevalence of obesity, anemia, physical deconditioning, a reduced maximum ventilatory capacity in women and, eventually, a role for emotional factors (30–33). Since dyspnea is an individual and subjective sensation, it is affected by emotional factors (33). Women more commonly suffer from anxiety and mood disorders, and these may worsen the frequency and intensity of dyspnea (33–35). However, dyspnea is an important symptom with prognostic impact since it may reflect underlying heart disease, such as ischemic heart disease, also in women. In a large cohort of patients referred for cardiac noninvasive imaging tests, those presenting with dyspnea had a much higher CV and all-cause mortality than patients without dyspnea (36). As mentioned, dyspnea is more common in women and its assessment should be incorporated into the routine clinical care of these patients, in view of its important prognostic value.

ECG abnormalities were the main reason for consultation in men at all ages. The higher incidence of ECG abnormalities in men compared with women has been described previously (37, 38), and may be partly explained by the higher incidence of cardiovascular disease in men, particularly ischaemic heart disease, which occurs at a younger age (39). The reason for the higher referral rate may be that general practitioners may be more concerned about the presence of structural heart disease in men with ECG abnormalities.

Apart from the ECG, which was performed on all patients, and the bedside echocardiogram, which was performed by the attending cardiologist, we found significant differences in the proportion of additional tests ordered, especially in younger patients. Overall, the pattern of additional tests may reflect a greater concern about CVD in men compared with women. One study found that general practitioners considered women to be less likely than men to have ischaemic heart disease, despite having equivalent symptoms or Framingham risk scores to men, and this was associated with a lower indication for diagnostic testing in women (40).

Although the greater use of coronary angiography in male compared with female patients with chest pain and coronary artery disease has been consistently reported for decades (41–45), it is concerning to find this difference 30 years after the description of the Yentl syndrome (41). Gender stereotypes drive differences in the indication for tests such as coronary angiography (43), device implantation (cardioverter defibrillator, cardiac resynchronisation therapy, or mechanical circulatory support) (46), or the performance of invasive procedures such as percutaneous coronary intervention, coronary artery bypass grafting (43), or heart transplantation (47), leading to health inequities. However, it is unlikely that a lower perceived risk of coronary heart disease in women (44) by the consulting cardiologist explains this difference, especially now that the proportion of female cardiologists is high (45% in our department). Rather, this difference may be interpreted as a different perception of patient risk or a higher likelihood of angina with normal coronary arteries in women (45), but an implicit gender bias among cardiologists caring for women with CVD, favouring men who are seen as more robust and willing to take the risk of invasive procedures and interventions than women, has also been described (7, 48). This persistent difference warrants prospective investigation and future corrective action.

Men with ECG abnormalities were more likely than women to undergo a specialised echocardiogram, reinforcing the idea of a higher perceived risk of heart disease in men.

Although mortality was generally low, there were differences between women and men and in other outcomes. Women, especially younger women and those with palpitations, had more emergency department visits than men. In fact, more than half of the people who go to the emergency department for palpitations are women (49). An alternative explanation for a gender bias in the referral rate and use of additional tests in the palpitations group is that in a tax-funded health care system with universal free access to specialist care at the discretion of the general practitioner, women with palpitations may be more likely to consult a physician. Finally, given that many palpitations are benign and/or non-cardiac in origin, the proportion of true positives among those referred for evaluation may be lower in women than in men. Therefore, the current indication for additional testing could be considered efficient, as fewer tests are indicated in women, who ultimately have fewer hospital admissions and lower mortality. It could also be argued that men are referred to the cardiologist less often than necessary and that this may have a negative impact on hospitalisation and mortality, which are higher in men than in women.

Interestingly, despite having more emergency department visits, women were less likely to be admitted to hospital than men, a finding consistent with previous reports (50). The reasons for this difference are unclear. Given that patients in our cohort did not have previous CV comorbidities requiring specific cardiology consultation, the lower cardiology admission in women is unlikely to be justified by a more favourable clinical profile, so it may be necessary to look at social aspects to explain these differences. A Danish study found similar results, with men having more hospital admissions but higher mortality (19, 20). It has been suggested in previous studies that men seek medical advice later and therefore “under-react” to severe symptoms (19, 20). One of the reasons that could explain the higher frequentation rate among women in the outpatient setting is a greater symptom awareness and disease concern with symptoms of subacute/chronic evolution. It may be possible that women minimized symptoms due to social factors (i.e., family burden, people under their care) particularly in the acute context of emergency visits or hospital admissions. As women most often take most of the housework and are the caregivers for most relatives, they may consciously or unconsciously minimize symptoms or delay in seeking care after they have coped with what they may consider their main responsibilities.

Mortality during follow-up was higher in men. The shorter life expectancy of men is known to be due to a higher incidence of coronary heart disease and cancer (51).

However, CVD in women should not be neglected, as it is also the leading cause of death in women (52), and women also have worse functional status, symptom control and disability than men, known as the “female disadvantage” (6). Despite the fact that CVD is the leading cause of mortality in women, clinicians routinely underestimate the risk of heart disease in them (6, 16, 40, 41, 53, 54). A number of underlying factors lead to inequities in health care between men and women, with a final disadvantage for women (“female disadvantage”). These are found in two main dimensions, The first one, is biological (sex differences), where a lack of understanding of pathophysiological mechanisms and the natural history of CVD in women occurs, with CVD risk assessment being often incomplete and specific female gender factors not taken into account. The second dimension is socio-cultural (gender gap), where stereotypes and social roles of women lead healthcare professionals to consider women less likely to suffer from heart disease, less able to make decisions about their health, and to be treated differently by physicians who routinely treat women (17, 40). Gender biases in the healthcare of CVD start in research, are uncritically transmitted in teaching pathways (health sciences, medical schools), and reproduced in daily clinical practice (17, 40, 53). Interestingly, it has been suggested that women with CVD seen by female cardiologists may have better outcomes than those seen by a male cardiologist (55).

The results of this work help to highlight differences in health care between men and women. Actions are needed at several levels to reduce health inequalities. Healthcare professionals should receive medical training that is sensitive to the differences between men and women. A gender-sensitive medicine approach needs to be promoted to change the medical culture to be more female-friendly, including an increase in the leadership of female cardiologists and other specialists. The socio-economic context of patients needs to be considered in daily clinical practice. More studies are needed to promote women's participation in clinical trials and to deepen the understanding of sex- and gender-related differences and its causes. The empowerment of women as patients should be promoted through education and cultural change that minimise gender stereotypes.

There are some limitations to this study. The reason for consultation was obtained from the GPs' interpretation of the patients' symptoms or reasons for consultation, and the final diagnosis was not available. It was not possible to assess differences in consultation, emergency department visits or hospital admission according to socio-economic variables (education level, income, occupation) because of the lack of such information. Further analysis using this approach is needed to fully understand the complexity of these processes. In addition, our data refer to a specific metropolitan health area, from a tertiary care hospital, so there could be differences in other health areas and other clinics. External validity may be limited and further multicenter analyses are needed. No information was available on the uncertainty of the patients' symptoms.

It is desirable that future studies include sex-specific analyses in order to assess and reduce inequities and the gender gap that is still present in the management of CVD.