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    Serum ros products, no radicals and ascorbate radicals in gout patients are not associated with diastolic dysfunction of the heart and treatment with allopurinol or febuxostat

    Background: Most gout patients (pts) have impaired heart function. Its etiopathogenesis involves hyperuricemia, activation of the renin-angiotensin system, oxidative stress and inflammation. Half of the cases of heart failure are due to diastolic dysfunction. There is not enough data on the level of oxidative stress and diastolic dysfunction in gout pts.

    Objective: To establish the association between serum levels of reactive oxygen species (ROS) products, nitric oxide (NO) radicals and ascorbate radicals with echocardiographic parameters, reflecting diastolic function of the heart.

    Methods: This was a cross-sectional study including 71 gout pts in a mean age 56.86±11.95 years, 61 males and 10 females (45 without tophi pts and 26 gouty tophi pts). The serum levels of ROS products, NO radicals and ascorbate radicals were determined by ex vivo electron paramagnetic resonance (EPR) study. All EPR measurements were performed on an X-band EMXmicro, spectrometer Bruker, Germany, equipped with Standard Resonator. Spectral processing was done by using Bruker WIN-EPR and Sinfonia software. Pts underwent two-dimensional echocardiography conducted with 2.5 MHz transducer phased array working with pulse Doppler frequency of 2.5 MHz. Parameters of the transmitral blood flow were measured: the ratio between maximal early and late flow velocities (E/A ratio) and deceleration time (DT). With tissue Doppler imaging, mitral annulus early diastolic velocity (Em) was recorded. Statistical analyses were done by One-Sample Kolmogorov-Smirnov, Chi-Square, Fisher’s exact test, Mann-Whitney, t-test and Pearson correlation.

    Results: Gouty arthritis without tophi and gouty tophi pts were age-matched, (p=0.309). The mean values
    of serum uric acid (p=0.569) and distribution of the subjects with gout attack (p=0.173), smoking (p=0.828), arterial hypertension (p=0.735), dyslipidemia (p=0.646), chronic renal failure (p=0.233) and obesity (p=0.623) was equal in the groups. In the tophi group, CRP and the number of pts who had suffered a cardiovascular event were higher (p=0.048; p=0.031). In the presence of gouty tophi E/A ratio was lower (p=0.001). We did not observe a difference in the mean values of DT and Em between gouty arthritis without tophi and gouty tophi pts (mean±SD; 243.27±29.39 msec vs 253.42±39.78 msec, p=0.429; 0.43±1.79 m/sec vs 0.33±0.99 m/sec, p=0.181). No correlation existed between serum ROS products with E/A ratio, DT and Em (r= -0.020, p=0.869; r= -0.124, p=0.314; r=0.086, p=0.481). We did not find a correlation between serum NO radicals with E/A ratio, DT and Em (r= -0.019, p=0.881; r=0.070, p=0.572; r=0.226, p=0.060). The same applies to ascorbate radicals, which did not correlate with E/A ratio, DT and Em (r=0.006, p=0.961; r=0.001, p=0.996; r=0.203, p=0.093). Among treated and untreated with Allopurinol pts the mean values of ROS products (p=0.169), NO radicals (p=0.167), ascorbate radicals (p=0.460), E/A ratio (p=0.282), DT (p=0.515) and Em (p=0.390) were comparable. Among treated and untreated with febuxostat pts no difference was estimated in the mean values of ROS products (p=0.546), NO radicals (p=0.076), ascorbate radicals (p=0.309), E/A ratio (p=0.805), DT (p=0.282) and Em (p=0.946).

    Conclusions: We suppose that the maintenance of chronic inflammatory process in tophi pts has a more important role for the development of diastolic dysfunction than the level of oxidative stress.
    Keywords: oxidative stress; gout; diastolic dysfunction