38 CLINICAL FOCUS
38 CLINICAL FOCUS
12 JULY 2024 ausdoc . com . au
| THE | HEARTS AND MINDS SPECIAL
Therapy Update
Cardiovascular
disease in women
Associate Professor Sarah Zaman MBBS , PhD , academic interventional cardiologist at Westmead Applied Research Centre , University of Sydney , and Department of Cardiology , Westmead Hospital , Sydney .
Anushriya Pant BMedSci , PhD student at Westmead Applied Research Centre , University of Sydney .
Understanding the sex-specific differences of CVD in women is essential to the delivery of better , individualised prevention and improved outcomes for patients .
CARDIOVASCULAR disease ( CVD ) is a leading cause of death in women . 1 , 2 Global efforts to improve cardiovascular outcomes have seen a decrease in cardiac deaths over the past two decades , however the overall rates of CVD remain stagnant . 1
Despite the increased recognition of CVD in women , most research is conducted in men . Women continue to underestimate their risk of CVD , such that only one-fifth of Australian women recognise that CVD is a leading cause of all female deaths . 2
This article summarises sex-specific risk factors for CVD , biological differences in risk factors and cardiovascular conditions , and diagnostic and management challenges of CVD in women . By understanding these sex differences ( see figure 1 ), healthcare providers can deliver better , individualised prevention and improve cardiovascular outcomes for female patients .
Traditional and non-traditional risk factors in women
Sex differences may influence the presentation and prevalence of traditional risk factors for CVD in women and men . Some cardiovascular risk factors have higher impact in women than in men . Type 2 diabetes mellitus ( T2DM ), hypertension and smoking , for example , all confer a greater risk for myocardial infarction ( MI ) in women than men . 3 Further , in women with T2DM , heart attacks occur earlier in life , compared to men with T2DM . 4
Additionally , there are non-traditional risk factors that are unique to , or more prevalent , in women . These include early menopause , polycystic ovarian syndrome ( PCOS ), and pregnancy complications of gestational diabetes ( GDM ), hypertensive disorders of pregnancy ( HDP ) such as gestational hypertension and pre-eclampsia , having small-for-gestational-age infants , and preterm delivery . 5 , 6 Several meta-analyses have established these pregnancy-related complications as risk factors for CVD . 7 Additionally , in women with previous GDM , the subsequent risk of T2DM is increased by up to 10-fold , which is an important modifiable risk factor for CVD . 8 Also , in women with PCOS , there is a nearly twofold increased risk of developing CVD . 9
Furthermore , some female-predominant autoimmune inflammatory conditions , such as systemic lupus erythematosus and rheumatoid arthritis , have been associated with premature CVD . 3 , 10
Oestrogen and menopause In women , oestrogen has a protective effect against CVD , likely due to vasodilation of arteries , effects on cholesterol levels , and reductions in oxidative stress and fibrosis . 5 , 11 Oestrogen levels decrease when women transition into menopause , usually between the ages of 45 and 55 years . 12 As a result , CVD tends to develop seven years later , on average , in women than men . 5 , 11
The risk of CVD increases as oestrogen levels decrease after menopause , and those with early menopause ( aged under 44 years , but particularly those aged under 40 years ) have a greater risk of developing CVD . 5 , 6 Changes during and after menopause have been linked to vascular dysfunction and resultant elevated blood pressure . 5
Menopause has been associated with changes in lipid profile , with subsequent dyslipidaemia ( for example , elevated triglycerides and LDL cholesterol and decreased HDL cholesterol ), increased visceral fat and subsequent obesity , and increased glucose intolerance / insulin
5 , 12 , 13 resistance with increased risk for T2DM .
Sex-specific differences in CVD presentation and outcomes
Heart attack symptoms in women There are several sex differences in MI symptomology . Women often have atypical symptoms , despite presenting with chest pain , and this can lead to delays in care . Differences in MI symptoms , be they real or perceived differences due to clinician and patient bias , contribute to delayed diagnosis of MI in women . 2 , 14 Chest pain remains the most common symptom of MI in both sexes , however women are more likely to have additional non-chest pain symptoms that distract from the diagnosis , including fatigue , weakness , breathlessness or dizziness . 2 , 14 Women may also describe different additional non-chest pain , including intense upper abdominal pain , intense back pain and indigestion . 15 It is important to consider an MI diagnosis in anyone who presents with chest pain , irrespective of other symptoms , and to perform an urgent electrocardiogram to exclude ST-elevation MI . These differences in MI presentation may explain why women are less likely than men to receive timely treatment . 3 , 14
MI in women versus men Atherosclerosis is the underlying cause of MI in both women and men , however there
Differences in MI symptoms , be they real or perceived differences due to clinician and patient bias , contribute to delayed diagnosis of MI in women . are sex differences related to plaque and vascular morphology . 16 In women , coronary artery plaques are generally smaller , with less dense fibrous tissue , and are more prone to plaque erosion than rupture , compared to men . 14 , 16 In women , atherosclerotic CVD is more likely to be diffuse , presenting in the microvasculature , while men tend to exhibit focal plaques and obstructive macrovascular disease . 17 These differences in plaque morphology can mean that women are more likely to have MI with non-obstructive coronary arteries ( MINOCA ) on coronary angiography . 3 , 18 , 19 This results in appropriately lower rates of coronary stenting in women than men with MI .
The treatment of MI due to atherosclerosis but without obstructive disease or need for coronary stents remains the same , that is , intensive medical therapy with dual antiplatelets and statins as well as angiotensin-converting enzyme ( ACE ) inhibitors , and beta blockers , where appropriate .
Patients with MINOCA have poor outcomes , similar to patients with classical MI from plaque rupture , even though they do not have severe coronary artery stenosis . Another challenge is that patients with MINOCA ( who are predominantly female ), are less often prescribed standard post-MI secondary prevention agents or referred to cardiac rehabilitation . 3 It is important to remember to prescribe or continue secondary prevention therapies even in MI without obstructive coronary disease .
Non-atherosclerotic causes of MI in women Although CVD-related mortality is decreasing in Australia , there has been a rise in heart attacks in women , notably in women under the age of 55 . 2 This is possibly due to improved diagnosis of less common causes of heart attacks that are more common in younger women . Spontaneous coronary artery dissection ( SCAD ) is a non-atherosclerotic tear or bleed within the coronary artery wall that results in acute obstruction to coronary blood flow . 20 The result is MI and , in some cases , ventricular tachyarrhythmia and sudden death . SCAD is unrelated to traditional cardiovascular risk factors , and most people with the condition are young and healthy . It predominantly affects women ( 80-90 % female
NEED TO KNOW
Cardiovascular disease in women is under-recognised and undertreated .
The traditional risk factors of hypertension , diabetes and smoking increase the risk of cardiovascular events to a greater extent in women compared with men .
Non-traditional risk factors that are unique to , or more prevalent in , women include early menopause , pregnancy-related complications , and chronic inflammatory conditions such as systemic lupus erythematosus .
Myocardial infarction can present differently in women than in men , with non-obstructive coronary arteries and spontaneous coronary artery dissection more common .
The 2023 update to the Australian CVD risk guidelines includes consideration of these female-specific risk factors .
predominance ), particularly young and middle-aged women ( average age 51 years ), and causes an estimated 25 % of MIs in women under 50 . 21 Hormonal triggers are well described , with SCAD being the most common cause of heart attacks in pregnant women and women up to six months postpartum . 20
The diagnosis should be considered in younger women , without CVD risk factors , who present with chest pain and elevated troponin consistent with MI . 20 At this stage , invasive coronary angiography is required to make a definitive diagnosis . It is also recommended that all people with SCAD undergo screening for fibromuscular dysplasia ( a common overlapping syndrome ), and are referred after their MI for cardiac rehabilitation . 20 , 22 Antiplatelets ( for example , aspirin ) are frequently used ; however , in the absence of atherosclerosis , statins are often stopped .
Current guidelines
The past two decades have seen global changes to guidelines on CVD prevention and management that include recommendations specific to women , and the acknowledgement of sex-specific risk factors in the evaluation of cardiovascular
14 , 23 , 24 risk .
Prior pregnancy-related complications and premature menopause (< 40 years ) have been identified as risk-enhancing factors for CVD in the 2019 American Heart Association ( AHA )/ American College of Cardiology ( ACC ) guideline . 25 Monitoring women with GDM at 4-12 weeks postpartum , followed by lifelong screening for T2DM every 1-3 years is recommended in the American Diabetes Association ’ s Standards of Care in Diabetes ( 2023 ). 26
Additionally , the higher prevalence and burden of SCAD in younger women and potential for pregnancy to trigger the condition , is acknowledged in the 2023 AHA / ACC / ACCP / ASPC / NLA / PCNA Guideline for the Management of Patients With Chronic Coronary Disease . 27
Recently , the updated 2023 Australian CVD risk guideline acknowledged sex differences in CVD risk and the need for sex-specific advice . 28 Updates to the Australian guideline include information on pregnancy complications , recommending physicians to consider pregnancy history in a CVD risk