Association of adverse pregnancy outcomes with coronary microvascular dysfunction: a systematic review and...

Adverse pregnancy outcomes (APOs) are recognized cardiovascular risk enhancers, yet their association with coronary microvascular dysfunction (CMD) has not been systematically quantified.

To evaluate the association between APOs and CMD and to provide pooled estimates of CMD prevalence and severity in women with APO history.

PubMed, Embase, Cochrane Library, and Web of Science were searched through December 2025. Observational studies evaluating coronary microvascular function using PET, Doppler echocardiography, stress CMR, or invasive physiology in women with APOs versus controls were included. Multivariate random-effects meta-analysis was performed to account for non-independent effect estimates arising from shared control groups. Risk of bias was assessed using NOS; certainty of evidence using GRADE.

Five studies (1,183 participants; 583 APO, 600 controls) were included. Women with APO history demonstrated significantly reduced CFR (SMD -0.94; 95% CI, -1.43 to -0.45; p<0.0001; I²=88.2%) and elevated CMD prevalence (OR 6.74; 95% CI, 1.55-29.42; p0.011; I²=92.2%). An exploratory graded pattern was observed, with combined preeclampsia and gestational diabetes associated with the largest CFR reduction (SMD -1.27); however, this was driven primarily by a single study with shared controls. Publication bias assessment was non-significant for CFR (p0.312) but borderline for CMD prevalence (p0.078).

APOs are associated with reduced CFR and elevated CMD prevalence, suggesting CMD may represent a plausible intermediate phenotype linking pregnancy complications to long-term cardiovascular disease. Given low to very low certainty evidence and substantial heterogeneity, these findings are hypothesis-generating and support further prospective research.