Serum Uric Acid Levels Mediated Atrial Fibrillation in Patients with Hypertension

Background: Oxidative stress and inflammatory cytokines play an important role in the development of hypertension and Atrial Fibrillation (AF). Clinical studies have shown that serum Uric Acid (UA) levels are positively associated with hypertension and AF. Xanthine Oxidase (XO) is a key enzyme in UA metabolism. It can be a source of oxidative stress in AF. In this study, we investigated the role of XO in oxidative stress and inflammatory cytokines in UA-induced AF. Methods: According to the inclusion and exclusion criteria, 60 patients hospitalized in the Xinjiang Uygur Autonomous Region People's Hospital from June 2017 to June 2018 were selected as the research group. Thirty healthy subjects who completed physical examination in the same period comprised the healthy control group. All subjects underwent echocardiography. Fasting blood samples were collected, and clinical data, such as sex, age, course of disease, BMI, smoking, drinking, dyslipidemia, diabetes mellitus, and diuretics, were recorded in detail. ELISA method was used to analyze the circulatory levels of UA, XO, nicotinamide adenine dinucleotide phosphate oxidase-4 (Nox-4; a biomarker of oxidative stress), and inflammatory cytokines (high-sensitivity C-reactive protein [Hs-CRP], interleukin-1β [IL-1β], interleukin-8 [IL-8], and TNF-α). Results: According to the clinical manifestations, electrophysiological examination, and diagnostic criteria of hypertension, the patients were divided into hypertension with AF group (AF group), hypertension without AF group (non-AF group), and healthy control group. The average age, body mass index, course of hypertension, blood pressure, hyperlipidemia, and diabetes mellitus in the AF group were higher than in the non-AF and control groups (P<0.05). In comparison with the non-AF and control groups, the serum levels of high-density lipoprotein cholesterol, triglycerides, and creatinine in the AF group were significantly increased (P<0.05), whereas the estimated glomerular filtration rate was significantly reduced (P<0.05). In the AF group, the blood concentrations of UA, XO, and Nox-4 significantly increased compared with those in the non-AF and control groups (P<0.001). The circulatory levels of inflammatory cytokines (Hs-CRP, IL-1β, IL-8, and TNF-α) significantly increased in the AF group (P<0.001). Pearson correlation analysis showed that the serum levels of XO in the AF group have a significant positive correlation with the blood concentrations of Nox-4 and inflammatory cytokines (Hs-CRP, IL-1β, IL-8, and TNF-α) (P<0.01) with correlation coefficients of r=0.99, 0.91, 0.96, 0.95, 0.97. Conclusions: XO showed remarkable elevated ROS accumulation and inflammatory cytokines, there by resulting in induced AF formation in patients with hypertension.