Uric Acid and the Developmental Origins of Hypertension

E ver since the first observations of an increased risk of cardiovascular disease among low birth weight subjects, numerous studies have sought the underlying mechanisms. Low birth weight can be caused by either preterm birth or poor intrauterine growth, and both entities lead to an increased risk of hypertension. Whereas persons born growth-restricted at term exhibit classical cardiovascular risk markers, such as intima–media thickening and endothelial dysfunction, the long-term cardiovascular consequences of preterm birth are less clear. In persons born very preterm, endothelial function is unaffected and there is no consistent evidence of premature loss of arterial elasticity or intima–media thickening.1 Lately, preterm birth has been associated with altered vascular structure (rather than function),1 sympatho-adrenal overactivity,2 and with insulin resistance, factors which are all related to arterial hypertension. In the current issue of American Journal of Hypertension, Park and coworkers highlight an interesting potential mechanism underlying the association between low birth weight and later hypertension. They report findings from a study investigating uric acid levels and blood pressure in relation to preand postnatal growth in a cohort of 136 3-year-old children.3 Serum uric acid levels were found to be higher in children born preterm, particularly in those who had higher weight gain from birth to 3 years of age. Although blood pressure (BP) did not differ between children born small and term controls with normal birth weight, both systolic and diastolic BP correlated to uric acid levels. Recently, uric acid has been reappraised as an independent risk factor for cardiovascular disease. In experimental models, hyperuricemia induces hypertension and in humans, it seems to predict the development of hypertension, at least in young subjects. The mechanisms by which hypertension is induced by hyperuricemia have not been fully elucidated, but endothelial dysfunction and alterations in renin expression have been demonstrated in response to hyperuricemia.4 Interestingly, in a small randomized controlled trial in adolescents with newly diagnosed essential hypertension allopurinol treatment alone leads to a substantial decrease in BP, as compared to placebo.5 In most studies of low birth weight and subsequent cardiovascular disease risk, it is difficult to control for genetic and environmental confounding. Hereditary and environmental factors which are associated with low birth weight, as well as with preterm birth, are possibly also the most important determinants of uric acid levels, postnatal weight gain, and BP. In future studies, it would be interesting to follow uric acid levels and BP in pregnant women and their offspring longitudinally to achieve better control of confounding factors. In conclusion, the study by Park et al. points out a new area of study within the field of developmental programming of cardiovascular disease. Further studies of the role of uric acid are warranted, especially in the growing population of children surviving very and extremely preterm birth into adulthood.