Abstract P306: Preterm Birth is Associated with Increased Blood Pressure and Increased Urinary Angiotensinogen in Young Adults

Abstract

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality and hypertension (HTN) is a major risk factor for CVD. Preterm birth is an emerging risk factor for both CVD and HTN, but the underlying mechanisms are poorly described. The renin-angiotensin system (RAS) plays a key role in HTN and CVD, and adolescents born preterm have higher blood pressure (BP) with a shift in the balance of the classical and alternative pathways of the RAS exhibited as increased angiotensin II and reduced angiotensin-(1-7) as compared to term-born adolescents. Although numerous factors influence the expression of angiotensins, the precursor protein angiotensinogen in the kidney is implicated in the development of HTN and CVD and may contribute to higher angiotensin II. As the status of renal angiotensinogen in individuals born preterm is unknown, we hypothesized that urinary angiotensinogen is increased in young adults born preterm as compared to their term-born peers. Methods: We compared urinary excretion of angiotensinogen corrected for urine creatinine and systolic and diastolic BP in 142 young adults (mean age 19.9 years) born preterm with very low birth weight (<1500 g) to 32 young adults born term using Wilcoxon Rank-Sum test and t-test. We used generalized linear models to compare the ln(x) urinary angiotensinogen between the preterm and term groups adjusted for the potentially confounding factors race, maternal hypertensive pregnancy, and maternal smoking during pregnancy. Results: Compared to term, subjects born preterm had higher median urinary angiotensinogen (0.02 μg/g, IQR 0.01 to 0.04 vs. 0.01 μg/g, IQR 0.004 to 0.01, p < 0.001) and higher mean systolic BP (111 mmHg, SD 11 vs. 106 mmHg, SD 10, p = 0.03). On crude and adjusted analyses urinary angiotensinogen was associated positively with preterm birth (crude β : 0.82, 95% CI 0.47 to 1.16; adjusted β : 0.79, 95% CI 0.39 to 1.18). Discussion: In addition to higher BP, young adults born preterm demonstrated increased urinary angiotensinogen as compared to their term-born peers. Preterm birth may induce programming of the renal RAS leading to higher angiotensinogen and a higher angiotensin-to-angiotensin-(1-7) ratio, potentially contributing to the increased risk of HTN in individuals born preterm.