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

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.

Keywords: arterial stiffness; atherosclerosis; hypertension; insulin resistance; uric acid.

Figure 1

Mean pulse wave velocity (PWV) values in four groups according to the median of HOMA and uric acid (UA). Group 1 = individuals with UA < median values and HOMA < median (n = 328, black column); Group 2 = UA > median, HOMA < median (n = 214, dark grey column); Group 3 = UA < median, HOMA > median (n = 230, light grey column); Group 4 = UA > median, HOMA > median (n = 342, white column). * p < 0.0001 for the fourth group as compared to the three other groups.

Figure 2

Graphic representation of the biological interaction analysis between serum uric acid (UA) and HOMA on increased arterial stiffness (AS) (PWV > 10 m/s). Group 1 (UA < median values and HOMA < median) represented the reference group (black column); observed values are reported for Group 2 (UA > median, HOMA < median, dark grey column) and Group 3 (UA < median, HOMA > median, light grey column). Observed actual values (white column) and expected values according to an additive (light blue column) or multiplicative (yellow column) model are reported for Group 4 (UA > median, HOMA > median).