Adverse Pregnancy Outcomes Are Associated with Reduced Coronary Flow Reserve in Women With Signs and Symptoms of Ischemia Without Obstructive Coronary Artery Disease: A Report from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction Study.

Background: We assessed history of adverse pregnancy outcomes (APOs) and coronary microvascular dysfunction (CMD) in the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) cohort of women with signs and symptoms of ischemia without obstructive coronary artery disease (CAD). We hypothesized that women with CMD with symptoms and signs of ischemia, without obstructive CAD, are more likely to have a history of APO. Materials and Methods: WISE-CVD recruited women with suspected ischemia found to have no obstructive CAD ( n  = 324). A subset of these women underwent coronary reactivity testing, including coronary flow reserve (CFR) ( n  = 185). Relationship between history of any APO and CMD was assessed by multivariable linear regression analyses. APOs included any of the following: hypertension during pregnancy, preeclampsia, eclampsia, gestational diabetes, or intrauterine growth restriction (low-birth-weight child). Results: Overall, 79/324 (24%) women reported at least one APO. Women with APOs were younger (52 vs. 56 years, p  = 0.001), were more likely obese (body mass index 32 vs. 29 kg/m ² , p  = 0.004), and had a history of hypertension (56% vs 36%, p  = 0.002), but otherwise had no additional differences in cardiac risk variables versus women without APOs. Among the subgroup who underwent invasive CFR testing ( n  = 185), those with an APO had lower CFR (2.53 vs. 2.76, p  = 0.016) versus those without APO. Conclusions: History of APOs in women with signs and symptoms of ischemia without obstructive CAD is associated with lower CFR indicative of CMD. Whether common pathways involving diffuse microvascular dysfunction may account for this suggested association remains unclear. Further investigation is needed to expand on these exploratory findings.