ABSTRACT
Adverse pregnancy outcomes (APOs), such as hypertensive disorders of pregnancy, intrauterine growth
restriction, and preterm birth, occur in about 20% of pregnancies and are associated with excess lifelong
cardiovascular disease (CVD) risk for women. However, levels of traditional CVD risk factors may not identify
all women progressing towards CVD after an APO. Data suggest that more sensitive measures are needed to
identify premenopausal women on track to develop CVD after APOs, especially non-hypertensive APOs.
Pulsatile hemodynamic dysfunction, i.e., high arterial pressure wave reflection magnitude, high systolic
pressure augmentation, and high central arterial stiffness, can precede left ventricular structural abnormalities,
diastolic dysfunction, hypertension, and overt CVD and can be improved or reversed with lifestyle modification.
Small, single center studies have reported changes in vascular function during pregnancies with and without
APOs and vascular dysfunction in women after some types of APOs. The NHLBI recently funded a
continuation of the nuMoM2b Heart Health Study (HHS2; 1U01HL145358-01A1; PIs: McNeil, Greenland, and
Saade), which will be conducted in >4,000 demographically diverse women. The HHS2 was designed to
further understanding of early CVD development after APOs. Women were initially enrolled at the beginning of
their first pregnancy, and available data include detailed pregnancy information, biospecimens, and CVD risk
factor assessment over 7 years of follow-up. We propose the addition of non-invasive pulsatile hemodynamic
measurements to data collection procedures for a subset of participants enrolled in HHS2, including central
arterial stiffness and arterial wave reflection measurements. Our Aims are as follows: Aim 1: Compare
vascular function measurements between women who did and did not have an APO. Account for lifestyle
behaviors and APO types. Aim 2. Define associations of early pregnancy biomarkers with poor pulsatile
hemodynamics. Our study will aid in sex-specific identification of higher-risk individuals with normal levels of
traditional CVD risk factors and define associations with molecular phenotypes in early pregnancy. We will
reveal modifiable lifestyle factors associated with pulsatile hemodynamics, thus informing preventive strategies
and setting the stage for interventions. The measurements will enrich the HHS2 dataset. The study will fill a
key knowledge gap regarding silent CVD in premenopausal women and directly aligns with the objective of
improving understanding and identification of early CVD development after different APOs.
