Association between cardiometabolic pregnancy complications and cardiovascular diseases

Background: Cardiometabolic pregnancy complications including hypertensive disorders of pregnancy (HDP) and gestational diabetes (GDM) each double the risk of cardiovascular disease (CVD) later in life. Two hypotheses have been posited to explain this increase in risk: shared burden of atherosclerotic risk factors, and persistent vascular impairment after the affected pregnancy. Thus, the aim of this work is to explore the biological mechanism underlying the association between pregnancy complications and CVD as well as the clinical outcomes at the time of an ischemic event. Methods: 1. Through a systematic review and meta-analysis, we summarized and updated evidence for sustained vascular dysfunction at least three months after HDP, as measured by imaging modalities and serum biomarkers. We pooled results of modalities reported in more than three studies using a random effects model. 2. Using data from the GENESIS-PRAXY prospective cohort, we studied 251 parous women (≤ 55 years old) hospitalized with an acute coronary syndrome (ACS) in whom detailed medical and obstetric history as well as biological data were available. We compared clinical presentation, traditional risk factors and biomarkers of endothelial dysfunction at ACS diagnosis in women with versus without a prior history of complicated pregnancy (HDP and/or GDM). Major adverse cardiac events (MACE) were captured at 12 months.Results: 1. By summarizing more than 70 studies, we found evidence of sustained vascular dysfunction after pregnancies complicated with HDP. There was evidence of vascular dysfunction in women post HDP compared to women with prior normal pregnancy when measured by carotid-femoral pulse-wave velocity (0.64m/s [0.17 to 1.11]), carotid intima-media thickness (0.025mm [0.004 to 0.045]) and augmentation index (5.48% [1.58 to 9.37]), as well as mean levels of soluble fms-like tyrosine kinase (6.12pg/ml [1.91 to 10.33]). Vascular dysfunction was more pronounced in younger women (< 40 years) and closer to the index pregnancy. 2. At the time of the ACS, women with previous pregnancy complications were younger (47.4 ± 6.2 vs. 49.1 ± 5.6 years, p=0.002), and had a greater burden of traditional atherosclerotic risk factors compared with women with prior normal pregnancy. Of note, women with prior preeclampsia were more likely to have chronic hypertension and to present with ST-elevation myocardial infarction as compared to women with prior unaffected pregnancy (adjusted OR 2.76 [1.04, 7.29]). At 12 months, there was a trend for increased risk of MACE in women with prior pregnancy complications, mostly driven by an increased risk of recurrent ACS in women with prior preeclampsia.Conclusion: Pooled data from studies evaluating vascular imaging suggest that some vascular dysfunction persists in women with prior HDP as compared to women with prior normal pregnancy. Women with prior pregnancy complications also present with ACS at a younger age, and with a high burden of atherosclerotic risk factors. In particular, preeclampsia was associated with more severe ACS at presentation and a higher likelihood of recurrence. Further studies are needed to understand the precise trajectory between cardiometabolic pregnancy complications and development of CVD, and the development and testing of tailored interventions.

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