Uric Acid and Vascular Damage in Essential Hypertension: Role of Insulin Resistance.

Velia Cassano,Daniele Crescibene,Marcello Magurno,Giuseppe Armentaro,Giorgio Sesti,Raffaele Maio,Angela Sciacqua,Francesco Andreozzi,Marta Letizia Hribal,Francesco Perticone,Sofia Miceli,Maria Perticone,Corrado Pelaia,Alfredo Toscani

doi:10.3390/nu12092509

Velia Cassano, Daniele Crescibene + Show 12 more

Open Access

https://doi.org/10.3390/nu12092509

Copy DOI

Journal: Nutrients	Publication Date: Aug 19, 2020
Citations: 32	License type: CC BY 4.0

Affiliation: Magna Graecia University, Sapienza University of Rome

Abstract

Increased levels of uric acid (UA) have been shown to be correlated with many clinical conditions. Uric acid may adversely affect the insulin signalling pathway inducing insulin resistance (IR). Several studies report the association between arterial stiffness (AS), an early indicator of atherosclerosis, and UA. The purpose of the present study was to evaluate the association between UA and AS, considering the potential role of IR. We enrolled 1114 newly diagnosed, never-treated hypertensive patients. Insulin resistance was assessed by the homeostatic model assessment (HOMA) index. Arterial stiffness was evaluated as the measurement of the carotid–femoral pulse wave velocity (PWV). The study cohort was divided into subgroups, according to increasing tertiles of UA. The mean values of UA were 5.2 ± 1.6 mg/dL in the overall population. Pulse wave velocity was linearly correlated with UA (p < 0.0001), HOMA (p < 0.0001), high sensitivity C-reactive protein (p < 0.0001), systolic blood pressure (p < 0.0001) and LDL cholesterol (p = 0.005). Uric acid was the strongest predictor of PWV and was associated with the highest risk for increased AS. The interaction analysis showed that the joint effect of increased UA and HOMA was significantly higher than that expected in the absence of interaction under the additive model, indicating that the two biomarkers synergically interacted for promoting vascular damage. Our data showed that UA interacted with IR to increase AS in a large cohort of newly diagnosed, never-treated hypertensive patients.

Highlights

Uric acid (UA) is mainly synthesized by the hepatic tissue as the end product of purine catabolism and excreted by the kidney; it circulates predominantly in the form of a monovalent sodium salt [1]
There was a higher prevalence of males in the tertile with the highest uric acid (UA) levels and body mass index (BMI), fasting glucose and insulin levels, homeostatic model assessment (HOMA) index and high sensitivity C reactive protein (hs-CRP) concentration increased progressively from the first to the third tertile, while HDL and estimated glomerular filtration rate (e-GFR) values progressively decreased
Several previous studies have provided evidence suggesting a possible correlation between subclinical organ damage and increased serum UA [23,24,25,26,27]

Summary

Introduction

Uric acid (UA) is mainly synthesized by the hepatic tissue as the end product of purine catabolism and excreted by the kidney; it circulates predominantly in the form of a monovalent sodium salt (urate) [1]. Hyperuricemia (i.e., increased serum UA levels) is caused by either lower secretion, higher synthesis, or a combination of both these defects. Several mechanisms have been proposed to explain these associations. UA may directly affect the intracellular insulin signalling pathway, inducing insulin resistance (IR) [13]. All these mechanisms may, in turn, cause subclinical organ damage, and accumulating evidence indicates that higher

Objectives

Methods

Results

Conclusion