Sex and Gender Differences in Acute Coronary Syndrome

Haider A, Bengs S, Luu J, et al.
Sex and Gender in Cardiovascular Medicine: Presentation and Outcomes of Acute Coronary Syndrome. Eur Heart J 2020;41:1328-1336.

The following are key points to remember from this update on the difference in presentation and outcomes of acute coronary syndrome (ACS) between men and women:

  1. Despite declines in cardiovascular disease (CVD) over recent decades, an increased mortality rate has been observed among younger women (<55 years of age). Women have longer time from symptom onset to presentation and are less likely to have diagnostic testing such as electrocardiogram and troponins, particularly younger women.
  2. ACS presentation can be similar between men and women; over 80% of both report chest pain when presenting with ACS. However, more women report additional non-chest pain symptoms. In addition, among those who present without chest pain, female sex is more common.
  3. Atherosclerotic plaque characteristics may differ by sex. Sex-related differences in coronary biology include higher myocardial blood flow in women compared to men, which may contribute to differences in shear stress and susceptibility to coronary artery disease. Furthermore, hormonal-mediated differences may contribute to sex-related differences in vascular stiffness. These differences may contribute to the observation that women display different coronary plaque characteristics (more diffuse, nonobstructive, and reduced overall plaque burden) compared to men. Evidence also suggests that coronary artery calcium scoring may be a stronger risk factor among women as compared to men.
  4. Women are twice as likely to experience microvascular angina as men, which is associated with an increase in ACS events and heart failure with preserved ejection fraction. Evidence suggests that a blunted heart rate response during pharmacological stress testing is a predictor of impaired coronary flow reserve in women.
  5. In addition to microvascular-related ACS, women are more likely to experience spontaneous coronary artery dissection (SCAD), or Takotsubo cardiomyopathy. Takotsubo is more prevalent among postmenopausal women than other groups, while SCAD is more prevalent among young women presenting with ACS. Up to 33% of women have no culprit coronary lesion on angiography.
  6. The menopausal transition with changes in estrogen may contribute to changes in a woman’s risk for CVD. Estrogen decline in menopause has been associated with changes in body fat distribution, endothelial dysfunction, vascular inflammation, sympathetic tone, and insulin resistance. Large trials of hormonal replacement did not reduce CV events though. However, a re-analysis of the Women’s Health Initiative suggests that hormonal replacement in the early menopausal period may be beneficial among women with no prior history of CVD.
  7. Women are more likely to have worse health status than are men at the time of ACS. Smoking and diabetes may be stronger risk factors among women compared to men. Smoking CV risk is highest among young and middle-aged women. Sex-difference in socioeconomic status, psychosocial burden, and mental health may contribute to CV risk among women. Evidence suggests that depression and perceived stress are predictive of CV risk in young and middle-aged women.
  8. Pregnancy may be a time when a woman’s CV risk can be assessed. Pregnancy complications, including preeclampsia, placental abruption, gestational hypertension, and diabetes, appear to increase a woman’s risk for further CVD. Preterm delivery may also be associated with future CV risk.

Clinical Topics: Acute Coronary Syndromes, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Stable Ischemic Heart Disease, Vascular Medicine, Interventions and ACS, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging, Hypertension, Chronic Angina

Keywords: Acute Coronary Syndrome, Chest Pain, Coronary Angiography, Depression, Diagnostic Imaging, Diabetes Mellitus, Electrocardiography, Estrogens, Hypertension, Pregnancy-Induced, Microvascular Angina, Plaque, Atherosclerotic, Pre-Eclampsia, Pregnancy, Postmenopause, Primary Prevention, Risk Factors, Takotsubo Cardiomyopathy, Troponin, Vascular Stiffness, Women

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