Preterm Adolescents Exhibit Higher Blood Pressure and Sodium Retention with Higher Uric Acid and Differential Circulating Renin‐Angiotensin System Expression
Authors: South Andrew Michael , Nixon Patricia A. , Chappell Mark C. , Diz Debra I. , Jensen Elizabeth T. , Shaltout Hossam A. , Washburn Lisa K. 
Published: June 2021

Preterm birth increases the risk of developing early cardiovascular disease in the future, but the underlying mechanisms are poorly understood. We previously showed that adolescents born preterm have higher blood pressure (BP), blunted pressure natriuresis, higher angiotensin II (Ang II) but lower Ang‐(1–7), and higher uric acid. The influence of preterm birth on uric acid metabolism may foster an increased risk of cardiovascular disease in part through chronic alterations in the renin‐angiotensin system (RAS) and increased sodium retention. Thus, we hypothesize that the preterm birth‐induced increase in uric acid correlates with higher BP, attenuated sodium excretion, and differential RAS expression with higher Ang II and lower Ang‐(1–7) in adolescence.

A cohort of 175 adolescents born preterm was compared to 51 term controls. We recorded systolic and diastolic BP z‐scores. Circulating levels of Ang II and Ang‐(1–7) were quantified, their ratio calculated, and evaluated in relation to serum uric acid, spot urine sodium‐to‐creatinine ratios, and BP using Spearman correlation coefficients and generalized linear models by preterm birth status.

Compared to those born term, adolescents born preterm had higher mean systolic and diastolic BP z‐scores (−0.4 vs −0.86, p<0.001, and −0.26 vs −0.53, p=0.03, respectively) and a higher rate of hypertension (12% vs 2%, p=0.03). Higher SBP z‐score correlated with a higher Ang II:Ang‐(1–7) ratio (coefficient 0.18, p=0.02) and higher uric acid (β: 0.11 mg/dL, 95% CI 0.002 to 0.22 mg/dL). Higher serum uric acid correlated with lower Ang‐(1–7) (β: −0.02 pmol/L, 95% CI −0.04 to −0.001 pmol/L) and a higher Ang II:Ang‐(1–7) ratio (β: 0.04, 95% CI 0.008 to 0.08). Plasma Ang II correlated with a lower urine sodium:creatinine ratio (β: −0.01 pmol/L, 95% CI −0.02 to −0.004 pmol/L), a relationship that was stronger in adolescents born preterm compared to term (β: −0.01 pmol/L, 95% CI −0.02 to −0.001 pmol/L vs β: 0.001 pmol/L, 95% CI −0.009 to 0.01 pmol/L, interaction term p=0.04).

In summary, the present study finds that in adolescents born preterm who have higher uric acid, BP, plasma Ang II, and lower Ang‐(1–7), higher plasma Ang II relative to Ang‐(1–7) correlated with higher serum uric acid, lower urinary sodium excretion, and higher BP. We propose that prematurity may increase the risk of early cardiovascular disease in part through increased circulating levels of uric acid that may differentially influence the expression of Ang II and Ang‐(1–7), leading to increased sodium retention and elevated BP.

Support or Funding Information

Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01 HD047584; HD084227), the American Heart Association (AHA 14GRNT20480131), the Clinical Research Unit of Wake Forest Baptist Medical Center (MCRR/NIH M01‐RR07122), the Wake Forest Clinical and Translational Science Award (NIH UL1 TR001420), and Forsyth Medical Center and Wake Forest School of Medicine Department of Pediatrics.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.