Shared Antecedents to Pre-term Birth and Cardiovascular Disease in Women

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PROJECT ABSTRACT Cardiovascular disease (CVD) is the leading cause of death among women and rates are rising in young women. Thus, prevention and early screening are essential. Women with preterm births (PTB) have excess CVD risk later in life compared to those with term births. It is unclear, however, if PTB unmasks, instigates or exacerbates a common predisposition. Mechanisms are not understood and pre-pregnancy measures are almost nonexistent. A few studies, including our own, raise the possibility that preterm birth may have lasting cardiometabolic effects that increase CVD risk, but longitudinal biomarker data have been unavailable to directly address this essential question. Inflammation and endothelial function are plausible but under-studied mechanisms linking PTB and CVD in women. The Coronary Artery Risk Development in Young Adults (CARDIA) study uniquely includes multiple assessments in women of reproductive age, both before and after pregnancies. Now in its third decade of follow-up with remarkably strong retention (72%), CARDIA will have conducted up to 9 in-person exams among 1,362 women (50% Black) who delivered 2,389 births from baseline to year 30. Uniquely, and just recently available, inflammatory and endothelial function markers have been measured in 900 CARDIA women from samples obtained both before and after pregnancies. We hypothesize that preterm birth is related to the pre-pregnancy profile, and additionally leaves a lasting pro-inflammatory signature that predisposes affected women to endothelial dysfunction, atherosclerosis and left ventricular remodeling. Our study aims are to 1) relate pre-pregnancy concentrations of high sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (s- ICAM) and tumor necrosis factor-α (TNF-α) to risk of PTB and determine if the change in these markers after delivery differs according to a history of PTB; and 2) evaluate the association of PTB and these profiles with atherosclerosis and cardiac remodeling in midlife. These novel studies will fill a major gap in our understanding of the link between PTB in susceptible women and the potential mechanisms underlying their increased risk of later CVD. These critical data will be the foundation for the discovery of novel mechanisms linking PTB to later CVD in women. The impact of this study is that it will be the first to use pre-pregnancy biomarkers of inflammation and endothelial function to understand the shared link between preterm birth and increased maternal risk of CVD later in life. These critical data will identify underlying inflammatory and endothelial mechanisms predisposing to both preterm birth and CVD in women, and pinpoint the timing and types of interventions needed to improve cardiovascular health in women.