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Table 1 Variables affecting women across their lifespan

From: Strategies and methods to study female-specific cardiovascular health and disease: a guide for clinical scientists

I. Reproductive health
Hypoestrogenemic conditions Polycystic ovarian syndrome is associated with vascular changes [20, 229, 230]
Stress reduces pituitary LH and FSH secretion leading to anovulation and secondary hypoestrogenemia [31, 32].
Pregnancy hypertension A women’s recall of pregnancy hypertensive disorders is specific but sensitivity varies and the positive predictive value is low [65]. Investigators have suggested standardization of study design for research involving women with preeclampsia [231]
Maternal/fetal exposure to other pregnancy disorders Women with histories of preeclampsia, gestational diabetes, small-for-gestational-age deliveries, or preterm deliveries (whether spontaneous or medically indicated) are at about twofold the increased risk of coronary heart disease and stroke compared with women who have had pregnancies uncomplicated by these factors [12]
Microchimerism Fetal cells passage transplacentally into the maternal circulation during pregnancy and persist for decades (this is termed fetal microchimerism or FMC). FMC is potentially associated with detrimental effects, e.g., preeclampsia and autoimmune disease, and with beneficial effects, e.g., female longevity due to regeneration and repair due to FMC. FMC has been identified in explanted idiopathic cardiomyopathy hearts [77] and the frequency and concentration are higher in women with preeclampsia [78, 232]
Early menopause Associated with greater coronary artery disease and stroke risk [58]
II. Sex hormones
Endogenous sex hormones Sex hormone levels are associated with body composition, incident diabetes, and other risk factors [233].
Hormone therapy and age of therapy Sub-analyses from Women’s Health Initiative indicate age of hormone therapy (HT) may impact risk/benefit. The KEEPS trial showed no difference in progression of carotid intima-media thickness in women treated early post-menopause with oral or transdermal estrogen [46]
III. Psychosocial issues
Depression More common in women and associated with incident CVD and worse prognosis [234, 235]. The AHA has recognized depression as a risk factor for poor prognosis among patients with acute coronary syndrome [236]
Stress Reduces pituitary LH and FSH secretion leading to anovulation and secondary hypoestrogenemia [31, 32]
Elderly age Women are the majority of the elderly with high burden of CVD [161]
IV. Other variables
Impact of diabetes DM confers greater risk in women than men [171]
Non-atherosclerotic coronary disease Vasomotor dysfunction and coronary microvascular disease are often not considered despite women having lower prevalence of obstructive CAD [34]
Inflammatory autoimmune disease Rheumatologic disorders, particularly systemic lupus erythematosus and rheumatoid arthritis, are more prevalent in women and are associated with more prevalent CVD [176, 237, 238]