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A gender difference in heart disease

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A gender difference in heart disease

Dr Raffi Kaprielian MB BS MA MD FRCP is a cardiologist at Bupa Cromwell Hospital and West Middlesex Hospital.

Cardiovascular disease is NOT just a man’s disease

Cardiovascular disease remains the leading cause of death in women in most developed countries including the UK, exceeding the combined deaths from stroke, lung cancer, chronic obstructive pulmonary disease and breast cancer.

The rates of population and in-hospital cardiovascular mortality have significantly declined in Europe and USA since the year 2000, but higher rates of cardiovascular deaths in women continue to exist (in Europe 54 percent of all female deaths are from CVD compared with 43 percent in men).

Despite the prevalence of heart disease in women, many doctors, and indeed the public themselves, may still regard heart disease as a man’s disorder. As a consequence, the success of tackling the known risk factors for primary prevention for the development of heart disease in women - and even treatment of symptomatic women presenting with established heart disease - remains sub-optimal and significantly worse outcomes than for men.

GPs and obstetrician/gynecologists can play important roles in tackling heart disease in women. This includes increased patient education and prevention, screening in the primary care setting, increased treatment in primary care and increased referral to cardiologists (especially for assessment of symptoms and for primary prevention in moderate to high-risk patients).

Does primary prevention differ between the sexes?

The risk factors for developing heart disease are very similar between men and women5. These include:

  • diabetes mellitus*
  • hypertension*
  • hypercholesterolaemia
  • smoking
  • central obesity
  • sedentary lifestyle*
  • adverse family history
  • lack of exercise
  • dietary patterns

*stronger effect on CV risk then men

The perception that women are relatively protected means these risk factors may not be treated aggressively. However, women have an accelerated incidence of ischaemic heart disease in the post-menopausal years, presenting approximately 5-10 years after men on average.

These presentations are with higher incident mortality, higher mortality of cardiac intervention including invasive procedures such as coronary angioplasty and coronary artery bypass surgery and poorer control of cardiovascular symptoms (despite their documented lower angiographic disease burden - see below).

How is cardiovascular disease associated with menopause?

After menopause, a woman’s risk of cardiovascular disease increases with reduced levels of oestrogen. In women who have undergone early menopause (before age 50) or surgical menopause, the risk of cardiovascular disease is also higher, especially when combined with other risk factors.

A reduced level of oestrogen causes:

  • increased rate of development of atherosclerosis
  • measurable changes in the plasma lipids: increase in LDL and decrease in levels of HDL
  • an increase in fibrinogen levels (pro-thrombotic)

What is the role of hormone replacement therapy (HRT)?

Preliminary observational research showed that HRT could reduce the risk of heart disease in post-menopausal women. However it now appears that this effect was likely due to the lifestyles of women taking HRT rather than the medical benefits.

More recent large-scale studies of women, such as the Heart and Estrogen/Progestin Replacement Study (HERS) and the Women’s Health Initiative (WHI) concluded that the overall health risks of HRT exceeded the benefits.

Women in the HERS study had an increased risk of heart attack and stroke during the first year of taking HRT. After two years of treatment, this risk appeared to be reduced.

Women in the WHI study had an increased risk for breast cancer, coronary heart disease (including nonfatal heart attacks), stroke, venous thrombosis, and gall bladder disease.

Thus:

  • HRT should not be used for cardiovascular protection.
  • The use of HRT for preventing osteoporosis should be carefully considered and the risks weighed against the benefits. Women who have existing coronary artery disease should consider other options.
  • HRT may be used for short-term treatment of menopausal symptoms.
  • Long-term use is discouraged because of increased risk for heart attack, stroke, and breast cancer.

How does heart disease prevent differently between the sexes?

It is now clear that the basic pathophysiological mechanisms and presentation of cardiac disease (both ischemic heart disease and cardiac failure) differ between the sexes.

Ischaemic heart disease

Presentation

The symptoms of cardiac ischaemia in women are often unusual. Instead of the classic crushing chest pain, sweating and shortness of breath that is described in the text books, women also often complain of vague symptoms -  fatigue, an upset stomach, or pain in the jaw or shoulders. This may often lead to delays in diagnosis and referral.

Men present more often than women with ST-segment elevation myocardial infarction and have a higher prevalence of CAD adjusted to age. However, women present more frequently for the evaluation of chest pain and are more frequently hospitalised for it.

Pathophysiological differences

These clinical differences reflect basic pathophysiological differences between the sexes. Important factors in women include smaller coronary artery size and less obstructive coronary artery disease seen along the entire spectrum of acute coronary syndromes and across all age groups8. This ‘advantage’ appears more marked in the coronary tree than in other vascular beds. The burden of coronary atheroma appears less using CT calcium scores9 or with intravascular ultrasound10. Women are seen to have more concentric atheroma than men (as opposed to eccentric obstructing plaques).

Coronary microvascular dysfunction in women is postulated as an important aetiological factor for IHD in women and a frequent determinant of chest pain in the absence of significant coronary obstruction. The presence of microvascular dysfunction is not benign: it has been significantly related to increased risk of major adverse outcomes (death or hospitalisation for non-fatal AMI, congestive heart failure or stroke), with an adjusted hazards ratio of 1.14 per unit decrease in log-transformed coronary flow reserve.

Cardiac failure

Cardiac failure is a disease of the elderly with incidence and prevalence rising steeply above the age of 70 years. The prevalence is in fact more common in men, apart from in the 80+ age group.  Women with clinical heart failure (breathlessness, easy fatigue, ankle oedema, orthopnoea, raised BNP) will tend (in comparison with men) to:

  • be older - often over 80 years
  • have preserved systolic function (so-called diastolic heart failure)
  • have a history with atrial fibrillation
  • have a history of hypertension
  • have a poorer response to therapy; indeed there are few proven therapies to be effective in diastolic heart failure (eg candesartan)

Recognition of the syndrome, accurate diagnosis and institution of effective therapies especially in systolic failure (including ACE inhibitors, beta-blockers, angiotensin antagonists, aldosterone antagonists and anticoagulation), has improved although there is clearly an ongoing need for better care coordination, including the close consultation of primary care physicians with cardiologists.

When should you refer to a cardiologist

Primary prevention

If you have a female patient with one or more cardiovascular risk factors (ie moderate to high risk for future events) and you are uncertain whether to commence pharmacological intervention, then a referral for a full cardiovascular assessment is justified. Intervention in women from a younger age will help prevent the development of the atherosclerotic process.

Hypertension and heart failure

Development of heart failure with preserved function is a common presentation in women over 80 years of age. This condition is difficult to manage. Referral to a cardiologist should be considered for early recognition and treatment of hypertension to prevent the onset of symptoms, as well as for assessment and treatment in symptomatic patients.

Ischaemic heart disease

The development of exertional symptoms, even if not typical for angina or heart failure, warrants referral to a cardiologist for a full assessment. Detailed investigations including functional testing with imaging modalities such as stress echocardiography and CT angiography can be used to establish diagnosis and assess the need for invasive tests and revascularisation.

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