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

Abstract

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.

Conflict of interest statement

Conflicts of interest

There are no conflicts of interest.

Patricia Brown and Alice Scott have no conflicts of interest.

Figures

FIGURE 1

Study cohort.

FIGURE 2

Preterm–term differences in plasma angiotensin-(1-7) by sex. Preterm: red; term: blue. Bar denotes median, diamond denotes mean, box indicates IQR, and whiskers include 1.5× or less IQR. Between-group comparisons by Wilcoxon rank-sum test. IQR, interquartile range.

FIGURE 3

Preterm–term differences in plasma angiotensin-(1-7) by overweight/obesity. Preterm: red; term: blue. Bar denotes median, diamond denotes mean, box indicates IQR, and whiskers include 1.5× or less IQR. Between-group comparisons by Wilcoxon rank-sum test. IQR, interquartile range.

FIGURE 4

Preterm–term differences in plasma angiotensin II/angiotensin-(1-7) by overweight/obesity. Preterm: red; term: blue. Bar denotes median, diamond denotes mean, box indicates IQR, and whiskers include 1.5× or less IQR. Between-group comparisons by Wilcoxon rank-sum test. IQR, interquartile range.

FIGURE 5

Preterm–term differences in urinary angiotensin-(1-7)/creatinine by overweight/obesity. Preterm: red; term: blue. Bar denotes median, diamond denotes mean, box indicates IQR, and whiskers include 1.5× or less IQR. Between-group comparisons by Wilcoxon rank-sum test. IQR, interquartile range.