Cardiovascular disease and women: Is there a gender gap?

“Cardiovascular disease is the leading cause of death in women. It remains underdiagnosed, undertreated, and portends worse outcomes in women than men.”[i]

In this blog, our expert Nutritional Therapist, Ruth, explores the mechanisms that may be contributing to worsening risk factor profiles in women, before examining the ways in which women can support their optimal cardiovascular health.

Cardiovascular disease and females

According to the British Heart Foundation, here in the UK, over 3.6 million women are currently affected by ischaemic heart disease, which kills one in 14 women.[ii]

A 2024 review emphasised the gender bias associated with the prevention, diagnosis, and treatment of cardiovascular disease in women and identified the poor access to diagnostic tests and cardiovascular medicines for women compared to that for men.[iii]

Cardiovascular disease (CVD) has traditionally been perceived as a “man’s disease”, and this misconception has contributed to under-diagnosis and treatment for women worldwide.

In comparison to men, women are 50% more likely to be misdiagnosed with a heart attack even though they carry the same risk of developing CVDs as men.[iv]

Despite advances in its treatment and prevention, CVD remains the leading cause of death in women.[v] For the past three decades, dramatic declines in heart disease mortality for both men and women have been observed, especially in the older age group (>65 years).

However, recent data suggests stagnation in the improvements in incidence and mortality of coronary heart disease, specifically among younger women, under 55 years.[vi]

Anatomical differences may contribute to differing presentations of cardiovascular disease in women

There are several differences between the female and male anatomy, which is likely to account for the fact that women do not present with the “typical” CVD symptoms.

Women have smaller coronary arteries than men, and as a result, show a lower prevalence of anatomically obstructive coronary artery disease (CAD), but higher rates of myocardial ischaemia and mortality compared to men.[vii] The female paradox of more frequent angina, but less extensive CAD has been a focus of research.[viii]

Studies have demonstrated that over 2/3 of women with angina had no obstructive CAD and the majority of these had functional impairments in the coronary microcirculation, associated with significant impairments in health-related quality of life. Indeed, women have more non-obstructive CAD and functional ischaemic heart disease which are frequently overlooked and hence undertreated.[ix]

Sex-based comparisons demonstrate that women have more microvascular dysfunction (damage to the inner walls of the tiny blood vessels in the heart which can cause spasms and reduced blood flow, thus causing chest pain).[x] Women have also been shown to have more abnormal coronary reactivity[xi] and plaque rupture/vulnerability[xii]  at the root-cause of female loss of cardiac function.

As a result of these gender differences, women can experience more subtle and non-specific symptoms of cardiovascular disease[xiii] and, therefore, traditional diagnostic algorithms and screening and evaluation tools may be less effective for women.[xiv]

For example, women with acute myocardial infarction (MI) are reported to present with atypical symptoms including abdominal pain, dyspnoea, nausea, back and neck pain, indigestion, palpitations and unexplained fatigue; as opposed to a well-defined chest pain, which is the typical presentation in men and which is often better recognised by doctors.²

Gender bias in medical diagnosis and cardiovascular research

Bias towards angiographically defined obstructive CAD still exists, leading to underdiagnosis of the unique aspects of female pathophysiology and the potential for suboptimal treatment of women, poorer outcomes compared to men and a sex-based mortality gap.[xv]

Furthermore, women seem to have less knowledge of the symptoms and risks of CVD and are less likely to report their symptoms.[xvi]

While response to medical treatment differs in women, for decades they have been less represented in clinical trials.

In fact, meta-analyses suggests that only 10% of preclinical cardiovascular research focuses on female populations.[xvii]

This has widespread consequences in the overall evaluation, stratification, and treatment of women with CVD.[xviii] This underrepresentation leads to the extrapolation of study results from predominantly male trials to women, which have been shown to lead to more side effects and potentially worse outcomes.[xix]

Menopause & cardiovascular health: Does menopause present a female specific risk factor? 

The leading modifiable traditional cardiovascular risk factors in both men and women such as hypertension, smoking, diabetes, obesity, and dyslipidaemia together account for approximately 50% of preventable cardiovascular deaths.[xx]

Beyond sex differences in conventional cardiovascular risk factors, women-specific risk factors are also important across the lifespan. For example, menopause is the most striking example of how hormonal fluctuation impacts on cardiovascular health.

Menopause is a natural physiological event reflecting the loss of ovarian follicle function, decreasing ovarian hormone production, and permanent cessation of menstrual cycles. The average age of natural menopause is around 52 years, and as life expectancy continues to increase, women will often be considered post-menopause for about a third of their lives.[xxi] Because of rising life expectancy, by the year 2030, the global population of menopausal women is expected to include 1.2 billion people.[xxii]

Menopause represents a critical life stage in women, characterised by hormonal changes that significantly impact cardiovascular health.

Several mechanisms linking the drop in oestrogen during menopause and CVD have been proposed, including alteration in fat distribution and heightened blood pressure.

Postmenopausal women are also more susceptible to coronary vasomotor disorders due to a higher prevalence of systemic inflammation.  Women who experience early menopause (younger than aged 50) have a substantially increased risk of CVD[xxiii] so need to be more mindful of supporting cardiovascular health.

Hypertension

The prevalence of hypertension is lower in females compared with males, until around the 5^th decade of life, at which point the risk increases dramatically with ageing in females[xxiv] and in women over 60, hypertension is more likely to be uncontrolled.[xxv] Hypertension is the leading CVD risk factor and is estimated to be present in ∼75% of women post-menopause.[xxvi]

Vasomotor symptoms, such as hot flushes and night sweats are experienced by around 60-80% of women during and/or after menopause transition. In some females, these symptoms may only last for 6 months, but evidence has demonstrated that symptoms persisted for 4 years after menopause in 50% of females, lasting for up to 12 years in 10% of females, and up to 20 years in some women. Numerous studies have demonstrated that women with vasomotor symptoms are more likely to have adverse CVD risk profiles, compared to those without.[xxvii]

Vascular ageing and endothelial function

At the onset of menopause, there is an increase in vascular ageing – the progressive stiffening of the arteries with a decline in the ability of the vessels to dilate. Oestrogen is crucial to maintain normal endothelial function, where it increases the synthesis of nitric oxide (NO) by the vascular endothelium, which then diffuses into vascular smooth muscle cells, causing its relaxation.

This is called Endothelium-dependent vasodilation (EDV), and its impairment is a hallmark feature of endothelial dysfunction. Oestrogen preserves endothelial function, and declining ovarian hormones with reproductive ageing and menopause rapidly affects EDV – thus promoting vasoconstriction.²¹ As already discussed, endothelial dysfunction precedes the development of CVD in women.

Changes in lipid profile

Changes in the lipid profile of women are noted to start around the perimenopause years, with increases in total cholesterol, LDL cholesterol and triglycerides being observed, all of which are linked to endothelial dysfunction and increased risk of atherosclerosis. An increase in LDL in the perimenopause period is linked to an increased risk of carotid plaques post menopause.[xxviii] HDL cholesterol plays an independent cardioprotective role in younger women, but the same effect is not seen in peri and postmenopausal women. This may be due to changes in the quality of the HDL particles over the menopause transition.²¹

Metabolic Syndrome

Metabolic Syndrome is defined as a coexistence of several metabolic risk factors such as hypertension, dyslipidaemia, impaired glucose tolerance and central adiposity. Oestrogen plays an important part in fat storage and distribution. Before menopause, the fat is deposited in the thighs, buttocks, and hips. Women tend to gain weight (total body fat) during midlife and beyond as a function of chronological ageing.

However, when women go through menopause transition, there is a change in the body composition (fat: lean body mass) and the distribution of fat. Many women in peri and post menopause complain of gaining fat around the middle and difficulty losing weight despite maintaining a healthy lifestyle.[xxix] Therefore, we see that menopause transition may contribute to an increase in visceral fat, insulin resistance, diabetes, and inflammatory diseases, leading to the development or worsening of metabolic syndrome in women.²¹ 

Oxidative stress

Oxidative stress and ageing go hand in hand. Excessive generation of reactive oxygen species (ROS) leads to a state of oxidative stress, which is a major risk factor for the development and progression of atherosclerosis, a chronic inflammatory disease of the vascular system and the leading cause of CVD.[xxx]

The decrease in natural antioxidant defences, coupled with the gradual loss of oestrogen, which also exerts an antioxidant effect, is highly associated with the various sequelae of menopause such as heart disease and vasomotor disturbances in addition to non-cardiac effects such as osteoporosis. It is also important to consider that at low concentrations, oestrogen becomes pro-oxidative.²¹

How to support cardiovascular health after menopause

Social determinants of health are related to the health of women throughout the menopause transition. Cultural factors, family support, education level, economic status, marital status, employment, and lifestyles (nutrition, exercise, tobacco use, etc.) are the key mediators for cardiometabolic health.²²

The DASH diet & The Mediterranean Diet

Dietary intervention is considered one of the most important lifestyle modifications to prevent CVD risk. It is imperative to promote a diverse and healthy dietary pattern for CVD prevention due to the synergistic effects and interactions of nutrients, phytochemicals, and the food matrix. Well-balanced diets with all necessary nutrients are crucial for preventing or managing CVD in postmenopausal women.[xxxi]

As discussed, hypertension is a leading CVD risk factor post-menopause. The DASH diet is a well-known dietary pattern consistently shown to reduce blood pressure in diverse populations. The DASH diet emphasises the consumption of fruits, vegetables, wholegrains, legumes, nuts, lean protein, and low-fat dairy products. Furthermore, it focuses on limited intakes of salt, added sugar, and saturated fat.[xxxii] While the literature is limited regarding the beneficial effects of a DASH diet in postmenopausal women, a systematic review and meta-analysis revealed that the DASH diet improved CVD risk biomarkers of total cholesterol and low-density lipoprotein cholesterol in adults with and without co-morbidities.[xxxiii]

Postmenopausal women incur an increased risk of endothelial dysfunction due at least in part to oxidative stress as well as elevated levels of proinflammatory cytokines. Oxidative stress and systemic inflammation contribute to the development of endothelial dysfunction, which is the initial step in atherosclerosis development.[xxxiv]

The Mediterranean Diet tends to be rich in olive oil, nuts, legumes, fruit and vegetables, and fish, with low intake of sugary and processed foods, and adherence has shown to lower oxidative stress and inflammation and improve endothelial function.[xxxv]

Exercise

Exercise plays a key role in supporting the health of postmenopausal women by addressing many physiological changes associated with menopause.

• Hypertension: Aerobic exercises such as cycling, walking and swimming help to lower blood pressure. This decrease is partly attributed to improved endothelial function, which enhances blood vessel flexibility and reduces arterial stiffness.”[xxxvi] Exercise also increases the production of NO, which helps dilate blood vessels.[xxxvii]
• Lipid Profiles: Exercise can help to lower total cholesterol and triglycerides and raise HDL cholesterol.[xxxviii] Both aerobic and strength training exercises may also help mitigate the loss of muscle mass and increase in abdominal fat that often accompanies menopause. The anti-inflammatory effect of regular exercise is associated with a decrease in visceral fat mass and therefore a decrease in the release of pro-inflammatory adipokines.[xxxix]
• Metabolic Syndrome: Exercise can help increase energy expenditure, improve insulin sensitivity, regulate blood sugar, and lower blood pressure. During exercise, muscle contractions increase the uptake of glucose from the bloodstream into the muscle cells. Regular exercise also helps reduce body fat, most notably visceral fat, which is associated with insulin resistance.
• Oxidative Stress: Regular, moderate exercise boosts antioxidant defences by increasing the production of antioxidant enzymes such as glutathione peroxidase and superoxide dismutase.  It also improves mitochondrial function, leading to more efficient energy production and less free radical generation. However, extreme or excessive exercise can increase oxidative stress due to the higher production of ROS. While this increase is usually temporary and the body adapts by strengthening its defences, it can lead to damage if not balanced with sufficient recovery and nutrition.

Exercise can also enhance mood and mental health through endorphin release, improve sleep quality, and may reduce the frequency and severity of many menopause-associated symptoms.

Cardiovascular health supportive nutrients

Isoflavones are natural plant compounds found in soybeans and other legumes. The main isoflavones are genistein, daidzein, and glycitein. Isoflavones are a type of phytoestrogen and can weakly occupy oestrogen receptors within the body and stimulate a gentle oestrogenic response. Phytoestrogen-rich foods, which are common in traditional Asian diets, are related to a lower incidence of menopausal symptoms and have gained wide attention for being able to help attenuate hormonal fluctuations that occur in menopausal women and also provide a protective influence against longer-term more serious conditions such as CVD.[1]

Omega 3 – has been widely studied for its protective role in cardiovascular health. It has been shown to lower blood pressure, improve lipid profile and counteract oxidative stress through several mechanisms including vasodilation, anti-thrombotic, inflammation and blood triglyceride reduction.[2]

Antioxidants – Antioxidant nutrients such as vitamin C, E, selenium and a wide range of polyphenols contribute to cardiovascular health by protecting the body from oxidative stress. This helps to prevent damage to blood vessels and the oxidation of LDL. Many antioxidants also exhibit anti-inflammatory effects.

Pre/probiotics – During menopause, the decline in oestrogen levels can disrupt the balance of gut bacteria. A healthy gut microbiome helps to regulate inflammation and also plays a role in immunity, metabolism and fat storage. An imbalance in gut bacteria can therefore lead to chronic inflammation, weight gain and metabolic issues, all of which are risk factors for CVD. Including prebiotics and probiotics can help to support the health of the gut.

Summary

Awareness of the increased risk of CVD in women after menopause is crucial as hormonal changes, particularly the decline in oestrogen, significantly impact health. Oestrogen has protective effects on cardiovascular health, and its decrease can lead to inflammation, higher cholesterol levels, and changes in blood vessel function.

In addition, weight gain and metabolic changes further elevate CVD risk. Being conscious of the more subtle and non-specific symptoms that occur in women is also key and can help to improve the prevention, recognition, diagnosis, and treatment of CVD in women. 

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References:

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Last updated on 27th February 2025 by cytoffice