Effect of reproductive history on longitudinal change in cardiac, vascular and lipid parameters

Abstract Pregnancy is often described as a physiologic “stress test” that may uncover latent risk for hypertension, diabetes and CVD. Even in uncomplicated pregnancies, women experience rapid cardiometabolic changes to support fetal development. While many of these adaptations normalize soon after delivery, some changes persist, including echocardiographic changes in cardiac structure and lower high-density lipoprotein cholesterol (HDL-C). Whether these pregnancy-related changes, or alterations in HDL particle structure or function, contribute to long-term cardiovascular risk is unknown. Parity, or the total number of live births, among post- menopausal women is also associated with greater risk of cardiovascular disease and alterations in HDL-C levels, HDL structure and function, and cardiac and vascular function. However, a significant research gap exists in linking observed cardiovascular changes across pregnancy to the observed associations of parity with cardiovascular health post-menopause. We will address this gap by leveraging existing data and samples from the NHLBI Growth and Health Study (NGHS) and conduct a new in-person visit in 350 participants at median age 46, when the women will be pre- or peri-menopausal. NGHS enrolled 871 girls (50% African- American and 50% white) in 1987 at age 9 or 10 and examined them up to 17 times, to age 27, including 7 echocardiograms between ages 20-27, multiple saved samples and reproductive history questionnaires. This study will conduct detailed lipoprotein sizing and functionality assessments from stored and new samples and conduct cardiovascular imaging and repeat echocardiograms at median age 46 to: 1) Determine the specific lipoprotein particle size distribution and function changes which occur from before to short- and long-term post pregnancy; 2) Determine whether pregnancy-related cardiac adaptations result in long-term alterations in cardiac structure and function, thereby increasing CVD risk for women in their forties; and 3) Test whether parity increases CV risk independently of socioeconomic status (SES) in African-American and white women. With the completion of our aims, we will have determined the prospective pathways between pregnancy-related lipoprotein and cardiovascular changes and pre-menopausal cardiovascular health for women in their forties. Results from our proposed studies will fill a critical gap in our understanding of how such risks may accumulate during a woman's reproductive life, as well as how socioeconomic status contributes to parity- related risk long-term. Women in this study have also been exposed to the obesity epidemic, lending greater understanding to contemporary reproductive development.