South Andrew M, Nixon Patricia A, Chappell Mark C, Diz Debra I, Russell Gregory B, Snively Beverly M, Shaltout Hossam A, Rose James C, O'Shea T Michael, Washburn Lisa K
Department of Pediatrics, Wake Forest School of Medicine, Winston Salem, North Carolina.
Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston Salem, North Carolina.
Pediatr Res. 2017 Jan;81(1-1):88-93. doi: 10.1038/pr.2016.179. Epub 2016 Sep 16.
Antenatal corticosteroid (ANCS) treatment hastens fetal lung maturity and improves survival of premature infants, but the long-term effects of ANCS are not well-described. Animal models suggest that ANCS increases the risk of cardiovascular disease through programmed changes in the renin-angiotensin (Ang)-aldosterone system (RAAS). We hypothesized that ANCS exposure alters the RAAS in adolescents born prematurely.
A cohort of 173 adolescents born prematurely was evaluated, of whom 92 were exposed to ANCS. We measured plasma and urine Ang II and Ang-(1-7) and calculated Ang II/Ang-(1-7) ratios. We used general linear regression models to estimate the difference in the RAAS between the ANCS-exposed and unexposed groups, adjusting for confounding variables.
In unadjusted analyses, and after adjustment for sex, race, and maternal hypertension, ANCS exposure was associated with increased urinary Ang II/Ang-(1-7) (estimate 0.27 (95% CI 0.03, 0.5), P = 0.03), increased plasma Ang-(1-7) (0.66 (0.26, 1.07), P = 0.002), and decreased plasma Ang II/Ang-(1-7) (-0.48 (-0.91, -0.06), P = 0.03).
These alterations indicate an imbalance in the urinary RAAS, promoting the actions of Ang II at the expense of Ang-(1-7), which over time may increase the risk of renal inflammation and fibrosis and ultimately hypertension and renal disease.
产前使用糖皮质激素(ANCS)可加速胎儿肺成熟并提高早产儿存活率,但ANCS的长期影响尚未得到充分描述。动物模型表明,ANCS通过肾素-血管紧张素(Ang)-醛固酮系统(RAAS)的程序性变化增加心血管疾病风险。我们假设,暴露于ANCS会改变早产出生青少年的RAAS。
对173名早产出生的青少年进行队列研究,其中92人暴露于ANCS。我们测量了血浆和尿液中的Ang II和Ang-(1-7),并计算了Ang II/Ang-(1-7)比值。我们使用一般线性回归模型来估计暴露于ANCS组和未暴露组之间RAAS的差异,并对混杂变量进行了调整。
在未调整分析中,以及在对性别、种族和母亲高血压进行调整后,暴露于ANCS与尿Ang II/Ang-(1-7)升高(估计值0.27(95%CI 0.03,0.5),P = 0.03)、血浆Ang-(1-7)升高(0.66(0.26,1.07),P = 0.002)和血浆Ang II/Ang-(1-7)降低(-0.48(-0.91,-0.06),P = 0.03)相关。
这些改变表明尿RAAS失衡,以Ang-(1-7)为代价促进Ang II的作用,随着时间的推移,这可能会增加肾炎症和纤维化的风险,并最终导致高血压和肾脏疾病。