Cardiovascular disease (CVD) is a term used for blood vessel and heart disorders (World Health Organization (WHO), 2021). Coronary artery disease is a type of CVD that is caused when low-density lipoproteins (bad fats), also known as bad cholesterol, are deposited inside blood vessels, which causes them to narrow, blocking blood flow reaching the heart or the brain (WHO, 2021). CVD is known globally as a major cause of death (Zhao et al, 2020). According to WHO, in 2019 approximately 17.9 million deaths occurred from cardiovascular diseases, reflecting 32% of all deaths globally. Of that 32%, 85% were caused by myocardial infarction (MI) and strokes alone (WHO, 2021). Disease burden and deaths can be significantly reduced by early identification and treatment alongside awareness of possible risk factors. Possible risk factors include high blood pressure, high cholesterol levels, obesity and a family history of cardiovascular disease. Commencing drugs such as statins, maintaining a balanced diet and quitting smoking have been proven to reduce the risk of developing CVD (Gordon and Hsueh, 2021).
Although female patients present with a lower frequency of CVD than male patients, it has been observed that, following an acute cardiovascular event, female patients have a worse prognosis and higher mortality compared with male patients (Zhao et al, 2020). Research has shown that CVD results in 32% of all deaths in women and 27% of all deaths in men (Marti-Soler et al, 2014). Gender differences also affect how coronary heart disease, heart failure, stroke and aortic disease are treated (Gordon et al, 2021). For example, female patients' risk of CVD is generally underestimated because of the misconception that women are more protected than men against cardiovascular disease (Zhao et al, 2020). It is important to consider gender differences for the prevention, management, diagnosis and treatment of cardiovascular disease in female patients (Gordon et al, 2021).
In 1999, the first women-specific clinical recommendations for CVD prevention were developed by the American Heart Association (Ryan et al, 1999). This resulted in an increased awareness of female patients' risk of cardiovascular disease, and it has enhanced the management and treatment of CVD. In the same study, the American Heart Association also published female-specific guidelines for the management of stroke and atrial fibrillation (Ryan et al, 1999).
This narrative review aimed to identify gender-related differences in multiple cardiovascular disease treatments and to provide an overview of the possible causes. This will highlight the importance of gender differences in the establishment of a cardiovascular risk profile. It will provide a base for future research with an overall aim to close the gender gap and decrease the severity of CVD prognosis and mortality in female patients.
Methods
A narrative review methodology was used following the standards of the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) Statement (Page et al, 2021). A search of two databases, PubMed and CINAHL, sourced a total of 245 articles. This Boolean search aimed to identify studies assessing the relationship between gender discrimination and cardiovascular health among middle-aged adults. The key words ‘Cardiovascular disease’, ‘Treatment’, ‘Gender’ and filters including ‘English language’, ‘Published in the last 10 years’, ‘Middle ages: 45-65’ were applied.
Inclusion criteria were studies that followed quantitative or qualitative methodologies, literature reviews, systematic reviews and meta-analyses. Studies discussing gender differences in cardiovascular diseases have also been included. All studies that had recruited adults between the ages of 45 and 65 years were included. Exclusion criteria were studies that examined treatments for cardiovascular diseases without any mention of gender differences, those that exceeded the past-10-years limit and those that were electronically inaccessible. Studies that discussed screening methods and preventive strategies were also excluded. Limiters included articles from peer-reviewed journals that were written in English.
Of the 245 studies found in the initial search, seven met the inclusion criteria. The Critical Appraisal Skills Programme (CASP) (2018) checklist for systematic reviews was used to critically appraise the literature (Tod et al, 2022). Each of the seven studies scored over 80%, meeting the general quality criteria. Thematic analysis and coding were used to combine recurrent ideas that emerged from the literature (Braun and Clarke, 2006).
Results
Seven papers were included in this review (Table 1). These were four systematic reviews (Garcia et al, 2016; Panza et al, 2019; van Oosterhout et al, 2020; Zhao et al, 2020) and three cross-sectional studies (Marti-Soler et al, 2014; Scharm et al, 2020; Gordon et al, 2021). Three themes were identified from the analysis:
- Theme 1. Gender differences in the burden of CVD
- Theme 2. Gender differences in symptoms' presentation
- Theme 3. Gender differences in the management and treatment of CVD.
Table 1. Summary of included studies
| Authors | Type of study | Aim | Data collection | Population, gender breakdown (men/women) and age (years) | Main findings |
|---|---|---|---|---|---|
| Marti-Soler et al, 2014 Switzerland | Cross-sectional study | To assess the seasonality of cardiovascular risk factors in a large set of population-based studies | Data gathered by the Prevention, Epidemiology and Population Science section of the European Association for Cardiovascular Prevention and Rehabilitation (EACPR) | 237 979 (51%/49%)Adult: 19−44Middle aged: 45−65 | The risk of dying from cardiovascular disease was higher in men than women aged 45 to 65 years |
| Garcia et al, 2016 USA | Systematic review | To assess aspects of cardiovascular health in women and examine gender differences in prevention, diagnosis and treatment | Data was evaluated using the Newcastle-Ottawa Scale (NOS) | 3,349,852 (60%/40%)Middle aged: 45–65 | Women's cardiovascular disease symptoms presentation differs compared with men. Women experience non-traditional risk factors that can lead to CVD. These include gestational diabetes mellitus, hypertensive pregnancy disorders, preterm delivery, weight gain after pregnancy, autoimmune diseases (rheumatoid arthritis), menopause, radiation and chemotherapy for breast cancer |
| Panza et al, 2019 Canada | Systematic review | To evaluate the links between discrimination and cardiovascular health among socially stigmatised groups, including gender | Data was evaluated using the NOS | 2 590 560 (72%/28|%)Adult: (20−44)Middle aged: 45−65 | Barriers such as gender, race, age, weight and sexual orientation have been identified |
| van Oosterhout et al, 2020 USA | Systematic review and meta-analysis | To examine sex differences in symptom presentation in acute coronary syndromes | Data was evaluated using the NOS | 1 226 163 (59%/41%)Middle aged: 45−65 | Women with acute coronary syndromes have different symptoms at presentation than men with acute coronary syndromes |
| Scharm et al, 2020 Germany | Cross-sectional study | To assess treatment motivation in patients with cardiovascular diseases | Data gathered from Rasch-based short screenings | 1,168 (66%/34%)Middle aged: 45−65 | Women reported a higher treatment motivation than men. This resulted in a transfer of learnt techniques into daily life |
| Zhao et al, 2020 UK | Systematic review and meta-analysis | To examine sex differences in cardiovascular medication prescription in primary care | Data was evaluated using the NOS | 2,264,600 (28%/72%)Middle aged: 45−65 | Women reported with a lower precedence of aspirin, statins and angiotensin-converting enzyme inhibitors (ACE inhibitors) prescribed than men. Men reported with a lower prevalence of diuretics prescribed than women |
| Gordon et al, 2021 USA | A cross-sectional study | To identify racial, ethnic, gender and age group differences in cardiometabolic risks among adults | Data gathered from the 2014/2015 and 2017 Kaiser Permanente Northern California Member Health Survey | 1,027,079 (54%/46%)Middle aged: (45−65) | Women reported to be more likely than their male counterparts to be in the healthy weight range, not to smoke, stay within their daily alcohol intake and to avoid high sodium |
Theme 1 includes data from all the studies on gender differences in the burden of coronary heart disease (CHD), heart failure, and stroke and carotid stenosis. Theme 2 includes data from three studies (Garcia et al, 2016; Panza et al, 2019; van Oosterhout et al, 2020) on gender differences in symptoms' presentation in CHD, heart failure and arrhythmias. Theme 3 included data from three studies (Garcia et al, 2016; Scharm et al, 2020; Zhao et al, 2020) on gender differences in the management and treatment of CVD, which included medications such as statins, aspirin and blood pressure medications.
Theme 1.
Gender differences in the burden of CVD
All of the studies included in this review stated that an increase in mortality in female patients is caused by a lack of management of CVD in women. Five of these studies stated that CHD is the leading cause of death for both male and female patients, accounting for one-third of all deaths in women (Marti-Soler et al, 2014; Garcia et al, 2016; Panza et al, 2019; Scharm et al, 2020; Gordon et al, 2021). In addition, it had been considered that CHD affects male patients more than female patients (WHO, 2021). However, according to Marti-Soler (2014) and Garcia (2016), it has been observed that, although female patients have an overall poor primary prevention rate, they are diagnosed with CHD at an older age and present with a higher pool of cardiovascular risk factors compared with male patients. Gordon (2021), in agreement with Marti-Soler (2014) and Garcia (2016), added that there is a greater frequency of CHD death in older female patients compared with younger female patients. It should be highlighted that in women younger than 55 years, CHD morbidity and fatality has remained static. In contrast, Scharm (2020) found that mortality rates in female patients with CHD are reported to be only half that of their male counterparts, although there has been an increase in morbidity in older female patients with CHD compared with male patients.
Theme 2.
Gender differences in symptoms' presentation
There is a knowledge deficit about CHD in female patients that can result in both patients and doctors delaying reporting an MI or delaying diagnosis (Garcia et al, 2016; Panza et al, 2019; van Oosterhout et al, 2020). Although CVD occurrence is less frequent in women before menopause, there is a noticeable increase in the frequency of CVD in women after menopause (van Oosterhout et al, 2020). Additionally, numerous common CVD symptoms are largely based on studies with a population breakdown in favour of male patients. For example, Garcia (2016) stated that chest pain is known as a common symptom of an MI. However, while chest pain can be experienced by both genders, it is more common for women to experience symptoms that are considered atypical. These symptoms include nausea or vomiting, shortness of breath, dizziness or no symptoms at all (Garcia et al, 2016; van Oosterhout et al, 2020).
Such ‘silent MIs’ can lead to female patients experiencing more acute MI (AMI) complications compared with male patients (van Oosterhout et al, 2020). Panza et al (2019) stated that, in female patients, there is a correlation between those who have diabetes mellitus or heart failure and the occurrence of a first AMI experience. Data from three of the studies found that female patients experience symptoms such as back pain, jaw and neck pain, dyspnoea, indigestion, nausea or vomiting and weakness (Garcia et al, 2016; Panza et al, 2019; van Oosterhout et al, 2020). van Oosterhout et al (2020) stated that symptoms before the onset of an AMI in female patients are reported as unusual fatigue (70.7%), sleep disturbances (47.8%) and shortness of breath (42.1%). The rate of undetected AMIs and untreated acute coronary syndromes and higher hospital morbidity and mortality may be explained by these ‘atypical’ presentations of symptoms in female patients (Garcia et al, 2016).
Heart failure is a major disorder worldwide. Three studies (Marti-Soler et al, 2014; Panza et al, 2019; Scharm et al, 2020) found that there are higher rates of hospitalisation and death in female patients compared with male patients after experiencing heart failure. In addition, Gordon (2021) stated that the types of heart failure vary between genders because female patients are reported to be less likely to suffer from reduced ejection fraction heart failure and coronary artery disease compared with their male counterparts.
The gender differences in clinical presentation and treatment outcomes in heart failure may lead to different health outcomes. Panza et al (2019) and van Oosterhout et al (2020) both stated that female patients present more frequently with hypertension and diabetes mellitus. Garcia (2016) stated that additional risk factors such as diabetes mellitus contribute to the development of heart failure in women. Female patient-only risk factors include chemotherapy undertaken to treat breast cancer (van Oosterhout et al, 2020), gestational diabetes and hypertensive pregnancy disorders (Garcia et al, 2016).
Panza et al (2019) and van Oosterhout et al (2020) also reported that the segment on an electrocardiogram (ECG) that reflects the change in the heart rhythm (the QT interval) differs between the genders. The QT interval is reported to be longer in female patients compared with that in male patients. This can be observed at a higher definition in women with a low heart rate. The frequency of inappropriate tachycardia is higher in women compared to men, and atrial fibrillation is more symptomatic in women (Panza et al, 2019). Female patients may also present with more frequent embolic strokes, higher heart rates and experience delays in symptom recognition and treatment compared with their male counterparts (van Oosterhout et al, 2020).
Theme 3.
Gender differences in the management and treatment of CVD
Data from Panza et al (2019) and van Oosterhout et al (2020) showed that female patients receive less aggressive treatments with fewer catheter ablations and cardioversions.
Three studies concluded that the less aggressive treatment strategies in female patients are the result of neglect of CVD in women and possible gender differences in presentation (Garcia et al, 2016; Scharm et al, 2020; Zhao et al, 2020). These studies stated that angiograms and interventional procedures are less frequently performed to aid diagnoses in female patients compared with male patients. There has been concern expressed for many years that, due to the existence of gender-related differences in cardiovascular physiology, therapeutic approaches should be gender specific (Scharm et al, 2020; Zhao et al, 2020).
As a result, recent diagnostic definitions and referral requirements have been developed to take gender differences into consideration. For example, the CHA2DS2-VASc scoring system introduced gender as a factor for stroke in atrial fibrillation. Although a CHA2DS2-VASc score of 0 indicates an extremely low risk of stroke, a female would be allocated 1 point in this scoring system from birth (Philippart et al, 2015). Treatments such as percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery now take gender into consideration (Garcia et al, 2016). However, overall, these studies found that diagnostic criteria and surgical thresholds for CVD do not take gender into account, which results in poorer cardiovascular disease outcomes in female patients compared with males. Scharm (2020) stated that taking gender-related differences into account in pharmacokinetics and pharmacodynamics is extremely important because the efficiency and side-effects of medicine differ between the genders. Thus, gender differences such as enzyme formation and drug compatibility are important when setting out risk profiles (Zhao, 2020).
Drugs such as statins, aspirin and blood pressure medications are used as preventive measures against CVD. They are also used to prevent the escalation of an existing condition. Statins are a type of drug that lower cholesterol, while aspirin is prescribed for people who have coronary artery disease or have experienced an MI. Blood pressure medications include drugs such as angiotensin-converting-enzyme (ACE) inhibitors, diuretics, beta blockers and calcium channel blockers (Zhao et al, 2020). According to Garcia (2016) female patients are reported to be frequently prescribed diuretics and are less likely to be prescribed aspirin, statins, ACE inhibitors and beta blockers compared with male patients.
Garcia (2016) stated that the less frequent diagnosis and less aggressive treatments in female patients are the result of underlying physiological differences. Women are reported to experience disease of the peripheral arteries present in the vessels that carry blood from the heart to the legs, while men are reported to experience blockages in the central arteries present in the heart that supply blood primarily to the right atrium and right ventricle (Garcia et al, 2016). This results in a more challenging treatment in women compared to men, as to date there is no permanent treatment available for patients who experience disease of peripheral arteries disease unlike those who have central arteries blockages (Yu and McEniery, 2020). In addition, heart cauterisations occur later during the course of an MI and also less frequently in female patients compared with male patients (Scharm et al, 2020; Zhao et al, 2020). The incidence of CVD in male patients between the ages of 45 and 65 years is about three times that of female patients in the same age bracket. Male patients also report with CVD 10 years earlier than female patients, which could be the result of the misperception that women are more protected against cardiovascular diseases than men (Garcia et al, 2016; van Oosterhout et al, 2020; Scharm et al, 2020; Zhao et al, 2020).
Additionally, according to both Garcia (2016) and Zhao (2020), female patients may be less aware of the severity of their cardiovascular disease and of appropriate treatments as a result of a lack of health education in this area, which can lead to female patients being less likely to report symptoms to healthcare services and result in less frequent use of such healthcare services compared with male patients. However, data from Garcia (2016), Scharm (2020) and Zhao (2020) suggested that female patients may experience a delay in receiving medical treatment to decrease the risk of incidences of cardiac events or to prevent recurrent cardiac events and reported suffering adverse reactions at a higher rate compared with male patients, which may have led to women doubting the effectiveness and safety of cardiovascular medications. This may result in female patients having a higher discontinuation rate of cardiovascular medications compared with male patients (Zhao et al, 2020).
Stroke
Four studies stated that haemorrhagic stroke and ischaemic stroke are the leading causes of hospitalisation and death worldwide (Marti-Soler et al, 2014; Panza et al, 2019; Scharm et al, 2020; Gordon et al, 2021). Around 20% of ischaemic stroke cases are estimated to be triggered by a carotid stenosis or occlusion (Scharm et al, 2020). Women have an increased lifetime incidence of stroke compared with men, largely because of a sharp increase in stroke risk in older postmenopausal women (Scharm et al, 2020). Gender differences in stroke types have also been observed, with women being more likely to have cardioembolic and lacunar strokes (Panza et al, 2019).
Marti-Soler (2014), Panza et al (2019), Scharm (2020) and Gordon (2021) also stated that male patients have presented more frequently with carotid stenosis compared with female patients. Marti-Soler (2014), Garcia (2016) and Panza et al (2019) reported that, although female patients are at a higher risk of stroke, it has been observed that after carotid endarterectomy men have lower perioperative stroke rates and mortality. Carotid repair differs in female patients and male patients due to biological, anatomical and hormonal differences. In women, the development of arteriosclerosis can result in unusual plaque patterns and lead to a different carotid repair cycle compared with men (Scharm et al, 2020). Women are thus less likely to benefit from carotid endarterectomy than men.
Discussion
This narrative review aimed to provide an overview of gender-related differences in several typical cardiovascular disease treatments and to identify the possible causes. Three main themes emerged from this analysis: gender differences in the burden of CVD, in symptoms presentation and in the management and treatment of CVD. This review highlighted clear gender-related differences in several typical cardiovascular disease treatments.
Five studies (Marti-Soler et al, 2014; Garcia et al, 2016; Panza et al, 2019; Scharm et al, 2020; Gordon et al, 2021) indicated that the incidence of fatal CHD is higher in older female patients, with associated morbidity increasing with age because elderly women experience greater incidences of heart disease. These studies have also indicated that there is a gender difference in the type of heart failure with which patients present. For example, female patients report less frequently with reduced ejection fractions compared with male patients. It has been highlighted that there is also a gender difference in the aetiology of heart failure because female patients are less likely to report with coronary artery disease. It has been observed that one of the additional risk factors for female patients that contributes to the development of heart failure is diabetes mellitus. Another cause of heart failure specific to women includes chemotherapy used to treat breast cancer. It has been observed that the development and progression of abdominal aortic aneurysms (AAA) in female patients is different to that of male patients. For example, female patients have a higher risk of aneurysm and surgery morbidity compared with their male counterparts. Studies have reported that the risk of AAA is higher after menopause because female patients are no longer protected by hormones.
Studies indicate that female patients have ‘atypical’ symptoms such as back pain, dyspnoea, indigestion, nausea/vomiting and weakness. Symptoms before the onset of AMI in female patients was reported such as unusual fatigue, sleep disturbances and shortness of breath. The missed AMI diagnosis in female patients and undertreatment of acute coronary syndromes can be explained by the atypical symptoms presentation, which leads to poorer health outcomes and increased rates of morbidity and mortality.
However, according to Scharm (2020), women have continuously reported a higher treatment motivation than males, resulting in a transfer of learned techniques that promote heart health into daily life. Female patients are reportedly more likely than their male counterparts to be in a healthy weight range, avoid smoking, stay within their daily alcohol intake and avoid high sodium foods (Gordon et al, 2021).
It has been observed that women over the age of 65 years have a higher occurrence of stroke, with a lifetime risk of suffering from post-stroke disability. Gender differences in stroke types have also been observed, with female patients being more likely to have cardioembolic and lacunar strokes. Also, atrial fibrillation is more symptomatic in female patients because they present with a higher heart rate and an increased incidence of embolic strokes compared with male patients. They also experience delays in symptoms recognition and treatment. These findings demonstrate that female patients are usually treated less aggressively, with fewer cardioversion and catheter ablation procedures. It has been reported that women experience major bleeding events and strokes more frequently after undergoing anticoagulation therapy compared with men.
These findings have indicated that, in the past, gender was not taken into account when setting diagnostic criteria and surgical thresholds. Thus, according to the seven studies, female patients are less likely to be prescribed aspirin, statins, beta blockers and ACE inhibitors compared with male patients, while being more likely to be prescribed diuretics. Gender-related physiological differences in CVD lead to less frequent diagnosis and treatment in women. Female patients are reported to suffer from disease of the peripheral heart arteries, while male patients are reported to suffer from blockages in central heart arteries, which results in a more challenging treatment in women compared with men. Heart cauterisations occur later during the course of an MI and also less frequently in women compared with men.
Limitations
There were some limitations to this study. First, the use of only two databases, CINAHL and PubMed, may have limited the number of studies available for review. Second, the use of a narrative approach may have limited the depth of the findings and the number of articles retrieved. Only seven studies have been included in this narrative review. However, the low number of studies may reflect the lack of healthcare funding provided to complete adequate research. Another possible limitation is the age profile of the participants in the studies. The studies included in this narrative review had an age profile of only middle-aged adults ranging between 45 and 65 years of age. Finally, most studies included in this narrative review involved more men than women, which may lead to an overall gender bias. Further research is required to provide a better overview of women's CVD symptoms, presentation, management and treatment.
Conclusion
Data from the past decade have shown that female patients have a higher 30-day mortality after an AMI compared with male patients and it is now recognised that these gender differences are largely explained by clinical differences at presentation. Since CVD can present differently in male and female patients it potentially requires different approaches to diagnosis and treatment. This suggests that more attention should be focused on how to define and add gender-related indicators to current risk assessments and management strategies. These findings are in agreement with previous research and provide an overview of the gender differences reported in the literature within the past 10 years.
KEY POINTS
- Although cardiovascular diseases are more prevalent in males than in females, numerous studies have revealed that following an acute cardiovascular event female patients have a higher rate of mortality and poorer prognosis compared with male patients
- The neglect of cardiovascular disease in females results in less aggressive treatment strategies and a higher mortality
- Three recurrent themes emerged from the literature: gender differences in the burden of CVD, gender differences in symptom presentation and gender differences management and treatment of CVD
- Different approaches to diagnosis and treatment are required, which would lead to different outcomes
CPD reflective questions
- Women have historically been under-represented in cardiovascular clinical trials, resulting in a lack of sex-specific data. What gender and health issues do you see present in modern day healthcare practice?
- Can you name some of the structural factors influencing women's and men's health, that is, factors that are out of an individual's control?
- Do you think gender norms, that is, ideas about masculinity and femininity, affect the way that these issues are perceived or addressed?