| SUMMARY |
|
| Epidemiology |
In Australia, 3 in 10 women die from CVD, including coronary artery disease (CAD). It is estimated that between the ages of 45 and 64, 1 in 9 women will develop some form of CVD, with an increase to 1 in 3 after age 65. Indigenous Australian women are particularly at risk, especially younger ones.
In 2016, Indigenous women ≥25 experienced an acute coronary event represented by myocardial infarction or unstable angina, at a rate 3.8 times higher than other Australian women. It is highlighted that in recent decades, mortality rates from CAD in Australia have been declining. From 2006 to 2016, the rate fell 46% for women (from 78 to 44/100,000 inhabitants) and 40% for men (from 135 to 84/100,000 inhabitants).
Furthermore, between 2001 and 2016, the prevalence of acute coronary events (myocardial infarction and unstable angina) in Australian women fell by 57% (from 465 to 215 events/100,000). However, rates of decline are lower in women <55 years of age, with an increase in strokes and myocardial infarctions.
| Cardiovascular risk factors |
There are several specific traditional sex-related risk factors that increase the risk of CVD in women.
> Traditional risk factors
These factors are frequently underrecognized and undertreated in women. Compared to men, they affect CVD risk differently in both sexes.
> Sex-specific risk factors
Several factors related to female sex increase the risk of CVD in women.
Hormonal contraceptives
Combined hormonal contraceptives increase the risk of acute myocardial infarction (AMI) 12-fold in women with hypertension and should be avoided in this subgroup. In women at higher risk of AMI, contraceptives to consider should be progesterone-only contraceptives. Before the use of hormonal contraceptives, there was no increased risk of subsequent CVD.
> Pregnancy-related disorders
Hypertensive and metabolic disorders of pregnancy are also independently associated with increased maternal CVD risk. These disorders include gestational hypertension, preeclampsia, eclampsia, and placental abruption (placenta abrupto).
The early onset of preeclampsia (<34 weeks) and its greater severity confer a particular increased risk of maternal CVD later in life, potentially due to the resulting endothelial dysfunction, which persists for many years after the affected pregnancy and is related to atherosclerosis. Women with gestational diabetes are at increased risk of subsequent CVD, and more than 50% will chronically develop type 2 diabetes mellitus.
> Menopause
After menopause, the risk of CVD increases substantially, possibly related to a significant increase in low-density lipoprotein cholesterol toward the end of the menstrual period. Lower estrogen and higher androgen concentrations contribute to the increased risk. Menopause before age 60 increases the risk of CVD.
> Hormonal treatment in menopause
Randomized, controlled trials have shown no primary or secondary prevention benefit from the use of hormone replacement therapy. The use of estrogens causes a small but significant increase in the risk of cardiovascular events, particularly in women who begin treatment 20 or more years after menopause, or at least after age 70. In women with AMI, menopausal hormone therapy should be discontinued.
> Other hormonal factors
Early menarche ( <12 years), early first pregnancy, history of abortion, stillbirth, preterm birth, and low birth weight infants are independently associated with an increased risk of CVD during pregnancy. rest of life. Possibly, this is mediated by an increased state of systemic inflammation and endothelial dysfunction, which accelerates atherosclerosis.
Polycystic ovary syndrome is associated with an increased risk of CVD, specifically CAD. The causes may be the association of insulin resistance, obesity and metabolic syndrome, which leads to type 2 diabetes, dyslipidemia and hypertension.
> Radiotherapy and chemotherapy for cancer
Radiation can cause endothelial injury of the coronary arteries leading to a proinflammatory state, rupture of the vascular wall, platelet aggregation, thrombosis and replacement of the damaged intima by myofibrosis, vascular stenosis and atherosclerosis. Women with a history of breast cancer treated with radiation therapy show a 7.4% relative increase in the risk of cardiovascular events with each gray of radiation exposure.
Furthermore, for unclear reasons, women treated with mantle field or mediastinal radiation for Hodgkin lymphoma have significantly higher rates of cardiovascular events and mortality compared with men, highlighting the need for increased surveillance. Lower specific cardiovascular surveillance has also been observed in women treated with radiation for cervical and uterine cancers.
| Cardiovascular risk assessment |
Cardiovascular risk must be evaluated differently in women than in men.
The Framingham Risk Score underestimates the risk of CVD in women. The Reynolds Risk Score is more suitable for women. This algorithm for predicting cardiovascular risk at 10 years, for women >45 years, includes 2 additional risk variants: high-sensitivity C-reactive protein concentration, a parental history of premature CAD before age 60.
Many specific risk assessments do not include sex-specific factors in relation to primary risk prevention. In this algorithm, risk assessment in women would be improved by more research promoting the incorporation of women-specific risk factors.
| Types of coronary artery disease (CAD) |
Between both sexes, differences are observed between the different types of CAD.
> Coronary artery disease (CAD)
In general, CAD has similar manifestations in both sexes, with the most common symptom being pain in the center of the chest. In women, there is a greater chance that the onset of pain will be at rest, during sleep, or if they are under mental stress. More commonly, women have atypical pain in the upper back, arms, neck, and jaw, as well as dyspnea, diaphoresis, indigestion, nausea, palpitations, dizziness, and weakness.
On the other hand, the proportion of women ≤55 who present with acute coronary syndrome without chest pain is significantly higher than that of men (19% vs. 13.7%). As a result, they are at greater risk of being discharged despite suffering from acute coronary syndrome; women with CAD also develop symptomatic heart failure more frequently than men . This may be due to the impact of the coexistence of arterial hypertension, an important risk factor for CAD, which leads to a higher incidence of left ventricular hypertrophy, responsible for the lower response to antihypertensive treatment in women, causing diastolic dysfunction and heart failure. cardiac with preserved ejection fraction.
> Ischemia with non-obstructive coronary artery disease
Nonobstructive CAD ischemia is a condition caused by coronary microvascular dysfunction or spasm of the epicardial vasculature.
It is more common in women, especially between 45 and 65 years old. If this condition or coronary stenosis is not diagnosed, the mistake can be made of ignoring the presence of heart disease and not being treated, which increases the risk of cardiac events. A meta-analysis has revealed an estimated overall increase in the incidence of overall mortality or myocardial infarction of 0.98 per 100 person-years in patients with non-obstructive CAD compared with 0.2 per 100 person-years in the general population. comparable.
Furthermore, 50% of patients with non-obstructive CAD will experience repeated episodes of ischemic chest pain, similar to those with obstructive CAD, further attenuating the significance of the condition. To evaluate macroscopic resistance, coronary flow reserve, and microvascular resistance, functional coronary angiography is necessary to confirm the diagnosis, which may otherwise be missed by routine noninvasive studies.
> Myocardial infarction with non-obstructive coronary artery disease
This type of CAD is about 3 times more common in women than in men, according to an analysis of 10 pooled studies that enrolled patients with nonobstructive CAD and patients with myocardial infarction and obstructive CAD. Likewise, almost 25% of patients in the first group presented angina, equivalent to the prevalence in patients with obstructive CAD.
In approximately one quarter of nonobstructive CAD cases, the pathophysiology is unknown. It is believed that the process involving disease of the epicardial vessels and coronary microvasculature is responsible, which hinders the increase in myocardial blood flow in response to increased oxygen demand. It may also be an overlap with mild forms of Takotsubo syndrome.
> Takotsubo syndrome
This syndrome is responsible for 7.5% of AMI cases in women; 90% occur in postmenopause, between 50 and 75 years of age. It is triggered by emotional or physical stress , which is associated with increased sympathetic activity. Patients present with chest pain and electrocardiographic changes characteristic of acute coronary syndrome, but without obstructive CAD on angiography. These patients present reversible ventricular dilation. Cardiac arrest occurs in 5.9% of patients.
> Spontaneous coronary artery dissection
In up to 25% of women ≤60 years of age, this condition causes AMI in the absence of conventional risk factors. It is the most common cause of myocardial infarction associated with pregnancy. It mainly occurs in the third trimester or postpartum. There is a high risk of recurrence, with an independent pathological process of atherosclerotic disease. Although strategies to prevent spontaneous coronary artery dissection include avoiding hormonal therapy and future pregnancies, there is currently no evidence to establish therapeutic guidelines.
| Treatment of cardiovascular disease |
The management of CVD in women should take into account sex-specific factors including coronary artery size, bleeding risk and hormonal status, as well as potential pharmacokinetic and pharmacodynamic differences.
> Revascularization
Compared with men, women are more likely to undergo percutaneous coronary angioplasty but less likely to receive coronary bypass .
It is unclear whether this represents an inconvenient or appropriate treatment given the increased mortality in women after coronary bypass linked to increased comorbidities, including smaller coronary vessels.
> Cardiovascular pharmacotherapy
In younger women, dual antiplatelet therapy results in an increased risk of hypermenorrhea and anemia, with the need for closer monitoring.
It is important to discuss contraception with the patient, since statins and angiotensin-converting enzyme inhibitors are contraindicated in pregnancy. The prescription may differ in women depending on their reproductive age, other hormonal treatments, and use of contraceptives. Women with CVD are more likely to be treated with nitrates, calcium channel blockers, and sedatives, and less likely to receive aspirin and statins than men, possibly explaining the higher prevalence of non-atherosclerotic CVD.
Statins after AMI are also significantly less indicated in women than in men, which In part, it depends on the doctors, and may be appropriate when the myocardial infarction is caused by non-obstructive CAD, which is more common in women. However, lower statin use in women with obstructive CAD may be related to physicians’ lower concern about the risks of recurrent heart disease in women and a lower likelihood of considering heart disease as the primary threat to their survival. female health. Even women themselves often consider that the greatest threat to their health is cancer. This may explain why women receive statins less frequently after a myocardial infarction, compared to men. So far, there is no evidence to support that statin use is safer in men than in women.
A meta-analysis suggests that statins indicated to prevent major cardiovascular events have a similar effect in both sexes and that, therefore, the lower effect in women would be the result of current practice.
| Conclusion |
Current guidelines for the diagnosis, investigation, and treatment of CAD do not discriminate between sexes and are based on studies with larger numbers of men. Women are more likely to experience delays in diagnosis and less likely to receive medical care based on established guidelines.
To reduce the risk of CVD in women, it is essential to address the different contributions of traditional risk factors, such as diabetes, adherence by physicians to established guidelines for the management of hyperlipidemia, and a focus on the lifestyle factors. Furthermore, recognizing the importance of sex-specific risk factors, such as hypertensive and metabolic disorders of pregnancy, is vital to improve outcomes.
While sex-specific cardiovascular research has increased significantly in recent years, this has not translated into changes in guideline-recommended care, nor has it improved clinical outcomes for women.
Fundamentally, CVD in women remains understudied, underdiagnosed and undertreated. Until this is changed, women will continue to experience disproportionately high cardiovascular morbidity and mortality.
