Association between preterm birth and the renin−angiotensin system in adolescence: influence of sex and obesity

OBJECTIVES: Preterm birth appears to contribute to early development of cardiovascular disease, but the mechanisms are unknown. Prematurity may result in programming events that alter the renin-angiotensin system. We hypothesized that prematurity is associated with lower angiotensin-(1-7) in adolescence and that sex and obesity modify this relationship. METHODS: We quantified angiotensin II and angiotensin-(1-7) in the plasma and urine of 175 adolescents born preterm and 51 term-born controls. We used generalized linear models to estimate the association between prematurity and the peptides, controlling for confounding factors and stratifying by sex and overweight/obesity. RESULTS: Prematurity was associated with lower plasma angiotensin II (β: -5.2 pmol/l, 95% CI: -10.3 to -0.04) and angiotensin-(1-7) (-5.2 pmol/l, 95% CI: -8.4 to -2.0) but overall higher angiotensin II:angiotensin-(1-7) (3.0, 95% CI: 0.9-5.0). The preterm-term difference in plasma angiotensin-(1-7) was greater in women (-6.9 pmol/l, 95% CI: -10.7 to -3.1) and individuals with overweight/obesity (-8.0 pmol/l, 95% CI: -12.2 to -3.8). The preterm-term difference in angiotensin II:angiotensin-(1-7) was greater among those with overweight/obesity (4.4, 95% CI: 0.6-8.1). On multivariate analysis, prematurity was associated with lower urinary angiotensin II:angiotensin-(1-7) (-0.13, 95% CI: -0.26 to -0.003), especially among the overweight/obesity group (-0.38, 95% CI: -0.72 to -0.04). CONCLUSION: Circulating angiotensin-(1-7) was diminished whereas urinary angiotensin-(1-7) was increased relative to angiotensin II in adolescents born preterm, suggesting prematurity may increase the risk of cardiovascular disease by altering the renin-angiotensin system. Perinatal renin-angiotensin system programming was more pronounced in women and individuals with overweight/obesity, thus potentially augmenting their risk of developing early cardiovascular disease.