Increased Serum Uric Acid Levels Blunt the Antihypertensive Efficacy of Lifestyle Modifications in Children at Cardiovascular Risk

Abstract

P rimary hypertension is a growing concern in children and adolescents in western countries largely because of its association with the ongoing obesity epidemic. Elevated serum uric acid (SUA) levels are frequently found in children with hypertension and obesity.1 Although primary hypertension in children was initially thought to reflect the underlying presence of subtle renal damage and insulin resistance, recent epidemiological and experimental data support the hypothesis that SUA may play an independent pathogenetic role in the early stages of vascular damage and the subsequent development of hypertension.2 Moreover, hyperuricemia has been associated with increased risk of hypertension development in adults in a large number of studies published to date. [3][4][5] Among participants in the Bogalusa Heart Study, SUA levels measured during childhood and greater changes in SUA from youth to adulthood were significant predictors of adult blood pressure (BP) values.6 Accordingly, recent meta-analyses indicate that high SUA levels entail an increased risk of hypertension incidence 7 with a consistent dose-response relationship, which supports causal disease-exposure association. have consistently been demonstrated to induce significant increases in SUA levels. In this context, SUA is emerging as a potentially modifiable risk factor for the prevention and treatment of hypertension. In fact, a reduction in SUA levels has been shown to prevent the development of hypertension in animal models, 10,11 and preliminary clinical trials indicate a BP-lowering effect of SUA reduction by either xanthine See Editorial Commentary, pp 845-847Abstract-Primary hypertension is a growing concern in children because of the obesity epidemic largely attributable to western lifestyles. Serum uric acid is known to be influenced by dietary habits, correlates with obesity, and could represent a risk factor for hypertension. Preliminary studies in children highlighted uric acid as a potentially modifiable risk factor for the prevention and treatment of hypertension. The effect of lifestyle changes (increase of physical activity and dietary modifications) on blood pressure values, weight status, and serum uric acid levels in a cohort of 248 children referred for cardiovascular risk assessment were evaluated over a mean 1.5-year follow-up. At baseline, 48% of children were obese and 50% showed blood pressure values >90th percentile. At follow-up, a significant improvement in weight class (24% obese; P<0.0001) and blood pressure category (22% >90th percentile; P<0.0001) was found. Systolic blood pressure z-score (P<0.0001), uric acid value (P=0.0056), and puberty at baseline (P=0.0048) were independently associated with higher systolic blood pressure z-score at follow-up, whereas a negative association was observed with body mass index z-score decrease during follow-up (P=0.0033). The risk of hypertension at followup was associated with body mass index (P=0.0025) and systolic blood pressure (P<0.0001) z-score at baseline and inversely related t...

Longitudinal Association Between Serum Uric Acid and Arterial Stiffness

“…In addition, this finding suggests that it is likely the long-term exposure to high levels of SUA that matters, even in the absence of symptoms. Accordingly, the 2-step process proposed by Feig 26 seems to fit well with recently reported findings in children 27 , which suggest that time exposure to elevated SUA may lead to vascular remodeling and persistent hypertension as a long time consequence of functional and transient vasoconstriction.…”

Serum uric acid levels are associated with obesity but not cardio-cerebrovascular events in Chinese inpatients with type 2 diabetes

“…Our recent studies also support this view192033, in which both SUA and UUAE are closely associated with cardiovascular risk factors including HTN, metabolic syndrome, diabetic retinopathy and chronic kidney disease, but not with atherosclerosis in T2DM. Also, Viazzi et al 41. reported uric acid is a reliable predictor of blood pressure over time in Children at Cardiovascular Risk.…”

Impact of comorbidities on gout and hyperuricaemia: an update on prevalence and treatment options

“…Recently, a cross-sectional study suggested that coronary heart disease could be more severe in hyperuricaemic patients with asymptomatic MSU crystal deposition than normouricaemic or hyperuricaemic patients with no crystal deposits [47]. Prospective cohorts have shown that hyperuricaemia leads to hypertension [48], which was recently found to be more refractory when associated with hyperuricaemia [49, 50], renal failure [23], type 2 diabetes mellitus [51] and metabolic syndrome [52]. However, these impressive results did not prove causality because the observed associations could be explained by confounding factors, reverse causality or the intervention of a common causal factor.…”