Effects of Uric Acid Lowering Therapy in Patients With Essential Arterial Hypertension

Effects of Uric Acid Lowering Therapy in Patients With Essential Arterial Hypertension | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effects of Uric Acid Lowering Therapy in Patients With Essential Arterial Hypertension Krystian Gruszka, Tomasz Drożdż, Wiktoria Wojciechowska, Piotr Jankowski, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-140202/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Jan, 2022 Read the published version in Blood Pressure Monitoring → Version 1 posted You are reading this latest preprint version Abstract Background Asymptomatic hyperuricemia (AHU) is defined as elevated serum uric acid (UA) concentration without symptoms. This study aimed to determine the effects of AHU treatment with allopurinol on selected hypertension mediated organ damage (HMOD) indices in patients with uncomplicated essential arterial hypertension (AH). Methods Patients aged 30-70 years with AHU and essential hypertension grade 1-2 with adequate blood pressure (BP) control, without previous urate lowering therapy (ULT) were divided into two groups: a) receiving allopurinol (ULT group) and b) age-and sex matched patients without ULT (control group). Both groups received UA-lowering diet. BP (office, 24 hour and central), echocardiographic parameters, pulse-wave velocity, carotid intima-media thickness (IMT) and lab tests (high-sensitivity C-reactive protein (hs-CRP) were measured at baseline and at 6 months follow-up. Results Out of 100 participants 87 completed the study (44 ULT patients and 43 controls). At 6 months follow-up, there was a significantly greater reduction in serum UA concentration in the ULT group than in the control group (464±68.8 µmol/l vs 314±55.6 µmol/l, p<0.0001). Patients receiving allopurinol had significant reductions in office systolic (137±11.8 mmHg vs 134±9.3 mmHg; p=0.025) and diastolic BP (83±9.9 mmHg vs 79±8.7 mmHg, p=0.017), central systolic BP (56±8.9 mmHg vs 51±12.9 mmHg, p=0.046), pulse pressure (43±10.4 mmHg vs 39±11.2 mmHg, p=0.017), IMT (0.773±0.121 mm vs 0.752±0.13 mm, p=0.044), left atrium volume index (40±13.5 ml/m 2 vs 38±12.3 ml/m 2 , p=0.044), and hs-CRP level (3.36±2.73 mg/l vs 2.74±1.91 mg/l, p=0.028) compared to controls. The decrease in UA concentration was significantly related to the reduction in IMT (R=0.37, p<0.001), central SBP (R=0.26, p=0.015) and hs-CRP concentration (R=0.30, p=0.004). Multivariate regression analysis revealed the independent relationship between reduction in IMT and UA lowering (R=0.3234, R2=0.0722, p<0.026). Conclusions In patients with AH and asymptomatic hyperuricemia treatment with allopurinol leads to further improvement in BP control and reduction in HMOD intensity, in particular IMT. The decrease in hs-CRP concentration associated with ULT may have a beneficial effect on patient long-term prognosis. Cardiac & Cardiovascular Systems asymptomatic hyperuricemia uric acid essential arterial hypertension hypertension mediated organ damage Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Asymptomatic hyperuricemia (AHU) is traditionally defined as elevated serum uric acid (UA) concentration but in which neither symptoms of monosodium urate crystal deposition disease, such as gout, nor uric acid renal disease have occurred [1]. The prevalence of AHU has increased over several decades and nowadays it affects 16.9% of the adult population [2]. AHU is more common in subjects with arterial hypertension (AH) than in the general population [3,4]. High UA concentration is one of the important factors associated with the development of AH and promotes vascular and renal organ damage [5]. Experimental and epidemiological data reveal associations between hyperuricemia and hypertension, cardiovascular risk, chronic kidney disease (CKD), and metabolic syndrome [6-8]. The risk of coronary artery disease mortality increases by 13% for each 1 mg/dl (60 μmol/L) increase in UA concentration [9]. However, it is still debatable whether hyperuricemia is an independent cardiovascular risk factor. Numerous clinical disorders associated with high UA serum level support the decision to treat AHU to reduce cardiovascular risk. Some results of previous studies showed beneficial effects of AHU pharmacological treatment such as: decreased concentration of inflammation markers (high-sensitivity C-reactive protein, hs-CRP), reduced carotid intima-media thickness (IMT) [10], reduced levels of oxidative stress markers, improved endothelial function [11], reduced serum creatinine and increased estimated glomerular filtration rate (eGFR) [12] as well as reduced blood pressure (BP) [13]. Allopurinol mainly is used to treat AHU, especially in patients at high cardiovascular risk, but there is no evidence for its effect on hard end-points, and this topic still needs further investigations [14-16]. Nevertheless, Borghi at al. [15] in the “Expert consensus for the diagnosis and treatment of patient with hyperuricemia and high cardiovascular risk” recommend considering treatment of AHU as a part of cardiovascular events prevention when serum UA concentration is ≥5 mg/dl (300 μmol/l) in patients with high cardiovascular risk and when serum UA concentration is ≥6 mg/dl (360 μmol/l) in other patients. Generally, treatment of AHU as a component of cardiovascular prevention is not a gold standard due to the lack of sufficient evidence from clinical studies. The aim of the study was to determine the effects of AHU treatment with allopurinol on selected Hypertension Mediated Organ Damage (HMOD) indices in patients with uncomplicated essential AH. Methods The study population consisted of 562 patients aged 30-70 years, both women and men consecutively admitted to the hypertension outpatient department between September 2017 and March 2018 with: diagnosed AHU defined as a serum UA ≥ 6 mg/dl (360 μmol/l) [15, 17] and with essential hypertension grade 1 or 2 (BP ≥140/90 and <180/110 mmHg) in accordance with the 2018 ESH/ESC guidelines [18] with previously confirmed adequate BP control on antihypertensive treatment (below 140/90 mmHg in office measurements). Patients, who received allopurinol (100-300 mg/day) according to Expert consensus [15] comprised urate lowering therapy (ULT) group (n=50). Then, within 5 days from recruitment of the ULT patient, a control patient with AHU and AH who did not receive allopurinol treatment, with age±3 years and preferably the same gender was recruited in a ratio of 1:1 (n=50 cases and n =50 controls). All patients were given the same dietary advice recommended for AH and AHU. All examinations were performed prior to treatment initiation and after 6 months of follow-up. The exclusion criteria included: any symptoms of monosodium urate crystal deposition disease, especially gout; coronary heart disease (previous myocardial infarction, coronary angioplasty procedure or coronary artery bypass surgery); symptomatic heart failure more than New York Heart Association (NYHA) class I or reduced ejection fraction < 50%; kidney or liver failure; inflammatory diseases; history of allergy to allopurinol or other serious drug reactions (e.g. Lyell’s syndrome); or treatment change during follow-up. Study flowchart is presented in Figure 1. The study was performed in accordance with the 1975 Declaration of Helsinki for Human Research and approved by the Jagiellonian University Bioethical Committee (No. 122.6120.94.2017 of April 27th, 2017). A written informed consent was obtained from all patients. Measurement of peripheral blood pressure All participants underwent physical examination and office BP measurements (mean of three measurements at one-minute intervals) in standard conditions, after 10 minutes rest, in sitting position on the non-dominant arm with the use of the validated Omron M5-I oscillometric device (Omron Healthcare Co., Japan). 24-hour ambulatory BP monitoring (ABPM) was performed using a SpaceLabs 90207 recorder (SpaceLabs Inc, Richmond, Washington, USA) to confirm BP control. Measurements were taken every 15 minutes during daily activity (06:00–22:00h) and every 20 minutes at night-time (22:00– 06:00 h). For further analyses the mean values of the 24-hour, daytime, and night-time systolic (SBP) and diastolic blood pressure (DBP), and heart rate were calculated. BP measurements were performed according to the ESH/ESC guidelines for the management of hypertension [18]. Echocardiographic measurements Echocardiographic examination using the Vivid®E95 (GE-Healthcare Chicago, IL, USA) device and 2,7-3,6 MHz transducer was performed. Left ventricular mass (LVM) was calculated according to the ASE formula [19, 20]. Left ventricular mass index (LVMI) was calculated LVM/height 2.7 [21]. Left atrium volume (LAV) was assessed using the modified Simpson’s method [22]. Left atrium volume index (LAVI) was calculated as LAV/body surface area. Global longitudinal strain (GLS) by speckle tracking echocardiography was measured as the average value of 18 segments, based on three apical imaging planes [23]. Central blood pressure, pulse wave velocity and intima-media thickness measurements SphygmoCor (AtCor Medical, Sydney, Australia) device was used to examine arterial stiffness. Carotid-femoral pulse wave velocity (PWV) and central BP in the aorta were measured according to the recommendations of ESH experts [24, 25]. Intima-media thickness (IMT) measurement of common carotid artery was carried out in accordance with the Mannheim consensus with the use of the Vivid®E95 (GE-Healthcare Chicago, IL, USA) and a 10 MHz linear transducer. After at least 10 minutes of patient rest in supine position, good-quality B-mode ultrasound images of left and right common carotid arteries were recorded during five consecutive heart cycles. The intima - media thickness (IMT) of the far wall was measured offline using EchoPAC workstation software. Automatic IMT measurement was based on tracing of 1 cm (starting about 1 cm proximally from bifurcation) of the leading edge of the intima surface and the leading edge of the adventitia surface followed by multiple measurements between pairs of pixels located on both traces. Mean IMT was calculated as the average of the left and right IMT [26]. Other measurements In all patients medical history was collected including concomitant diseases, smoking and drinking habits and the use of medications. Laboratory tests: serum concentrations of uric acid, creatinine, total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and hs-CRP were also obtained at the initial visit. All performed examinations and laboratory tests were then repeated after 6 months of follow-up. Statistical analyses Data are presented as means and standard deviations (SD) and medians and interquartile ranges in cases where nonparametric tests were used. To determine the study sample, we chose as optimal parameter the IMT because of the association with atherosclerosis, BP and potential reversibility during ULT. The analysis showed that to determine a 0.1 mm difference in IMT with mean value of 0.9 and SD of 0.16 mm [27, 28] with a power of 80% and with a significance of p=0.05, using the two-tailed test, the population of 42 people in each group is required. Normality of variables distribution was tested and, if confirmed, parametric tests were used. When studied variables did not have normal distribution nonparametric tests were used. Between group differences were evaluated using Student’s t-test, Mann-Whitney U test or chi-squared test, as appropriate. To assess the effects of the therapy the repeated-measures t-test, Wilcoxon signed-rank test, ANCOVA and the association between variables using the Spearman rank correlation were used. Univariate and multivariate regression analyses were used to determine the influence of independent factors on IMT. P-values <0.05 were considered statistically significant for all tests. Statistical analyses were performed using STATISTICA software (StatSoft, Poland), version 13.1. Results The flow of participants in the study is presented in Figure 1. The final analysis included 87 patients: 44 in the ULT group (20 females and 24 males) and 43 in the control group (23 females, 20 males). During the study follow-up, 13 patients (n=6 in the ULT group, n=7 in the control group) were withdrawn from the study due to the need of antihypertensive therapy modification or lack of follow-up appointment There were no significant differences in studied parameters at baseline visit between patients who dropped out and those who completed the study. Baseline characteristics Baseline characteristics of the study patients are presented in Table 1. There were no significant differences between the ULT group and the control group in age, sex distribution, and baseline serum UA concentration (p=0.054). However, they did differ in BMI and total cholesterol (see Tables 1 and 2). The effects of uric acid lowering therapy In this study, ULT was safe and no treatment-related adverse effects were observed. Biochemistry Changes in laboratory parameters from baseline to 6 months follow-up in both groups are summarized in Table 2. Urate-lowering therapy with the use of allopurinol 100-300 mg daily (mean 184 ± 91.3 mg, median 150 (100; 300) mg) in the ULT group was associated with a significant reduction in serum uric acid concentration level (464 ± 68.8 vs. 314 ± 55.6 µmol/l; p<0.001). In the control group a small albeit statistically significant reduction in serum UA concentration was observed (437 ± 61.1 vs. 426 ± 56.9 µmol/l, p=0.044). Compared to controls, there was a significant reduction in hs-CRP levels in the ULT group at 6 months follow-up. Blood pressure . Baseline office and central BPs were higher in the ULT group than in the control group, however the unadjusted decline in DBP at 6 months follow-up in the ULT group was significantly higher compared to controls (Figure 2). The ANCOVA analysis corrected for baseline BP values showed no differences between study groups in observed BP decrease after 6 months observation. HMOD Among the assessed echocardiographic parameters, significant reductions in LAV and LAVI were noticed in the ULT group at 6 months follow-up (Table 4). There were no comparable changes in the echocardiographic parameters in the control group at follow-up. Compared to the control group, there was a significant reduction in carotid IMT in the ULT group at 6 months follow-up (Figure 3, Table 4). In our study, UA lowering therapy had no effect on the change in arterial stiffness determined by PWV (Table 4). The magnitude of reduction in IMT, CRP, LAVI, and UA was greater in the ULT group than in the control group (Figure 2). In all patients, the amount of reduction in serum UA concentration was related to the reduction in IMT (R=0.37, p<0.001) (Figure 4), central SBP (R=0.26, p=0.015), TG (R=0.31, p=0.003), hs-CRP concentration (R=0.30, p=0.004), LAV (R=0.35, p<0.001), LAVI (R=0.35, p<0.001), and with an increase in E wave (R=-0.27, p=0.012), and E wave deceleration time (R=-0.26, p=0.017). The multivariate regression analyses showed a significant association between UA lowering and IMT reduction in the entire study group after adjustment for changes in LDL and PP values (the known pathophysiological factors influencing IMT) (R=0.3234, R2=0.0722, p<0.026). Discussion The 2018 ESC/ESH Guidelines for the management of arterial hypertension recommend routine measurement of serum UA as part of the screening in hypertensive patients, because elevated UA level is independently associated with increased cardiovascular risk in both hypertensive patients and general population [18]. Reduction in serum UA concentration with ULT may have an impact on the reduction in parameters related to cardiovascular risk such as IMT, LAVI or serum hs-CRP level. In a three-year randomized parallel-controlled study in patients with type 2 diabetes and AHU, Liu et al. found that effective control of the serum UA level with allopurinol therapy decreases the serum hs-CRP level and carotid IMT [10]. Our study demonstrates that UA lowering therapy is associated with a significant reduction in hs-CRP and IMT in patients with hypertension, however in a substantially shorter duration (i.e. 6 months). Based on these results, the reduction in hs-CRP indicates that ULT has an anti-inflammatory effect likely to explain the accompanying reduction in carotid IMT which is a surrogate marker for atherosclerosis, commonly known as a chronic inflammatory disease. In a study by Higgins et al. one-year treatment with allopurinol at a dose of 300 mg daily resulted in a decrease in central SBP and augmentation index, and prevented progression in IMT in patients following ischemic stroke or transient ischemic attack (TIA) [27]. Carotid IMT has been shown to predict cardiovascular risk in multiple large studies [29], however its reproducibility and usefulness in daily practice is limited [18]. In our study we used an automatic IMT measuring technique (using multiple measurement points) to increase the accuracy and repeatability of measurements according to the Mannheim consensus [26]. Our study found a significant reduction in office (SBP, DBP, PP) and central (SBP, PP) BP values but not in ambulatory BP values in the ULT group. Our findings suggest that treatment with allopurinol is safe and despite the minor impact on ambulatory BP levels (Table 3), UA lowering therapy significantly improves HMOD even after a relatively short time of treatment. Limited office BP changes following allopurinol therapy in our study may result from adequate BP control at baseline and short study duration in the ULT group (6 months) compared to a longer (3 years) study by Liu et al. [10]. While most available data indicate that allopurinol reduces BP regardless of antihypertensive drugs, the underlying mechanism is not clear [13]. In the meta-analysis of 15 randomized controlled trials performed in patients with hyperuricemia, with length of follow-up from 2 to 23 months, allopurinol decreased BP and creatinine level [30]. A sub-analysis revealed that allopurinol significantly decreased SBP irrespective of antihypertensive drug therapy, however a decrease in DBP was only observed in patients receiving antihypertensive drugs. In patients receiving combination of antihypertensive drugs and allopurinol in a dose ≤300 mg/day the reduction in SBP was larger compared to patients receiving allopurinol at higher dose (>300 mg/day) [30]. A further interesting finding derived from our study is a significant reduction in left atrium volume index, likely as a result of the decrease in central BP (afterload) following ULT. The noticeable decrease in UA concentration in the ULT group is comparable to previous studies [10], confirming the adherence to drug therapy. Interestingly, a slight, but significant decrease in UA concentration was also present in the control group indicating that patients follow a dietary advice which previously has proven its efficacy. In the study by Rai et al. the Dietary Approaches to Stop Hypertension (DASH) diet resulted in up to 32% reduction in the incidence of gout over the 26-year follow-up (HR 0.68, 95% CI 0.57-0.80, p value for trend <0.001) [31]. Previous studies found a strong relationship with systemic inflammation even in the absence of gout [32]. Moreover, serum urate was found to independently predict changes in circulating CRP [33]. Indeed, allopurinol treatment was associated with a decrease in hs-CRP and insulin resistance in patients with AHU [34]. Our findings support this observation documenting a reduction in hs-CRP in the ULT group and a significant association between changes in hs-CRP and serum UA level. Findings related to BP changes following allopurinol therapy are inconsistent. A study by Jalal et al. conducted in chronic kidney disease (CKD) patients found that a 3-month therapy with allopurinol had no effects on BP levels, inflammation and oxidative stress markers compared to placebo [35]. In contrast, a study by Kanbay et al. has shown that a 4-month treatment with allopurinol led to a decrease in SBP and an increase in flow-mediated dilation and eGFR in patients without CKD [36]. Different results in both studies on BP changes during allopurinol treatment are likely to be explained by advanced and irreversible atherosclerotic changes in the arteries in high risk CKD patients. In line with this observation, our study population was limited to patients with essential hypertension grade 1 or 2 without previous history of coronary heart disease, CKD or symptomatic heart failure. In our opinion patients with potentially reversible cardiovascular changes are most likely to receive the greatest benefits from intensive ULT used in parallel with the modification of other cardiovascular risk factors as part of primary prevention of ischemic heart disease. We have previously shown that a higher UA concentration via higher serum matrix metalloproteinase (MMP) 3 enhances selected HMOD, especially carotid IMT in patients with AH [37]. Extracellular MMPs are part of inflammation leading to the degradation of collagen, vessel remodelling and atherosclerotic plaque rupture [38,39]. It is still the matter of controversy whether hyperuricemia is only a biomarker of cardiovascular risk or a direct factor attributable to the harmful effects on cardiovascular system [40]. The study limitations A small sample size could be viewed as a study limitation. However, all patients enrolled in this study were comprehensively phenotyped concerning BP levels and associated HMOD to determine the true effects of allopurinol therapy. Secondly, the short length of follow-up may limit our findings, however the study duration was planned based on available data and allopurinol efficacy. Conclusions Allopurinol in patients with arterial hypertension and hyperuricemia decreases blood pressure and, in a relatively short time, seems to favourably influence hypertension-mediated organ damage, in particular intima-media thickness. Our findings indicate that the beneficial effects of urate lowering therapy with allopurinol on blood pressure and organ damage may result from anti-inflammatory and anti-atherosclerotic actions, with a potential impact on long-term patient outcomes Further prospective studies in larger patient groups are required to support our findings. Declarations Ethics approval and consent to participate The study was performed in accordance with the 1975 Declaration of Helsinki for Human Research and approved by the Jagiellonian University Bioethical Committee (No. 122.6120.94.2017 of April 27th, 2017). A written informed consent was obtained from all patients. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request. Competing interests The authors declare that they have no conflict of interest. Funding Not applicable. Authors' contributions K.G. and M.R. designed the study. K.G., T.D., W.W., P.J., M.T., M.B., D.H., G.B. and MR wrote the main manuscript text. K.G., T.D. and M.R. recruited patients for the study. K.G., T.D., W.W., and M.T. and G.B. performed statistical analyses. M.T., M.B. and D.H. prepared figures 1 and 3. W.W. and P.J. prepared figures 2 and 4. All authors reviewed the manuscript. Acknowledgements Not applicable. List Of Abbreviations ABPM: ambulatory blood pressure monitoring; AH: arterial hypertension; AHU: asymptomatic hyperuricemia; ANOVA: analysis of variance; BP: blood pressure; CKD: chronic kidney disease; E: early ventricular filling velocity; E/e’: early diastolic mitral annulus velocity ratio; eGFR: estimated glomerular filtration rate; ESC: European Society of Cardiology; ESH: European Society of Hypertension; GLS: left ventricular global longitudinal strain; HDL: high-density lipoprotein cholesterol; HMOD: hypertension mediated organ damage; hs-CRP: high sensitivity C- reactive protein; IMT: carotid intima-media thickness; IVRT: isovolumic relaxation time; LAVI: left atrium volume index; LDL: low-density lipoprotein cholesterol; LVM: left ventricular mass; NHANES: National Health and Nutrition Examination Survey; NT-proBNP: N-terminal prohormone of brain natriuretic peptide; NYHA: New York Heart Association; PP: pulse pressure; PWV: carotid-femoral pulse wave velocity; SBP: systolic blood pressure; TG: triglycerides; UA: uric acid; ULT: urate-lowering therapy. 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Korean Circ J. 2017;47(1):1-8. doi:10.4070/kcj.2016.0232 Qu L, Jiang H, Chen J. Effect of uric acid-lowering therapy on blood pressure: systematic review and meta-analysis. Ann Med. 2017;49(2):142-156. doi:10.1080/07853890.2016.1243803 Rai SK, Fung TT, Lu N, et al. The Dietary Approaches to Stop Hypertension (DASH) diet, Western diet, and risk of gout in men: prospective cohort study. BMJ. 2017;357:j1794. doi:10.1136/bmj.j1794 Inaba S, Sautin Y, Garcia GE, et al. What can asymptomatic hyperuricaemia and systemic inflammation in the absence of gout tell us? Rheumatology (Oxford). 2013;52(6):963-965. doi:10.1093/rheumatology/ket001. Ruggiero C, Cherubini A, Miller E 3rd, et al. Usefulness of uric acid to predict changes in C-reactive protein and interleukin-6 in 3-year period in Italians aged 21 to 98 years. Am J Cardiol. 2007;100(1):115-121. doi:10.1016/j.amjcard.2007.02.065. Takir M, Kostek O, Ozkok A, et al. Lowering Uric Acid With Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia. J Investig Med. 2015;63(8):924-929. doi:10.1097/JIM.0000000000000242 Jalal DI, Decker E, Perrenoud L, et al. Vascular Function and Uric Acid-Lowering in Stage 3 CKD. J Am Soc Nephrol. 2017;28(3):943-952. doi:10.1681/ASN.2016050521 Kanbay M, Huddam B, Azak A, et al. A randomized study of allopurinol on endothelial function and estimated glomular filtration rate in asymptomatic hyperuricemic subjects with normal renal function. Clin J Am Soc Nephrol. 2011;6(8):1887-1894. doi:10.2215/CJN.11451210 Gruszka K, Rajzer M, Drożdż T, et al. Selected matrix metalloproteinases activity and hypertension-mediated organ damage in relation to uric acid serum level. Cardiol J. 2019;2019-03-26(48):1-9. doi:10.5603/CJ.a2019.0033 Johnson JL. Metalloproteinases in atherosclerosis. Eur J Pharmacol. 2017;816:93-106. doi:10.1016/j.ejphar.2017.09.007 Raffetto JD, Khalil RA. Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease. Biochem Pharmacol. 2008;75(2):346-359. doi:10.1016/j.bcp.2007.07.004 40. Stewart DJ, Langlois V, Noone D. Hyperuricemia and Hypertension: Links and Risks. Integr Blood Press Control. 2019;12:43-62. doi:10.2147/IBPC.S184685 Tables Table 1 . Baseline clinical data in the i urate-lowering therapy (ULT) and control groups. Characteristics Study population N=87 ULT group N=44 Control group N=43 P Anthropometrics Age [years] median 62 (50.5; 68) 62 (48,5; 69) 62 (53; 67) 0.699* mean 57.8 ± 12.3 57.6 ± 12.9 57.9 ± 11.7 0.918 Female [ n (%)] 43 (50.59%) 20 (45.45%) 23 (53.49%) 0.454 # Body mass index [kg/m2] 27.9 ± 4.2 29.1 ± 4 26.7 ± 4.2 0.008 Risk factors [n (%)] Current smoking 15 (17.24%) 7 (15.91%) 8 (18.6%) 0.739 # Alcohol intake 20 (23%) 11 (25%) 9 (20.93%) 0.651 # Regular physical activity 31 (35.63%) 12 (27.27%) 19 (44.19%) 0.099 # Hypercholesterolemia 57 (65.52%) 29 (65.91%) 28 (65.12%) 0.938 # Diabetes 16 (18.39%) 9 (20.45%) 7 (16.28%) 0.615 # Hypertension treatment Antihypertensive medication use [ n (%)] 87 (100%) 44 (100%) 43 (100%) 1.000 # Number of antihypertensive drugs 2 (1;3) 2.5 ± 1.2 3 (1;3) 2.5 ± 1.2 3 (1;3) 2.5 ± 1.2 0.972* Time of hypertension treatment [years] 13.6 ± 8.4 15 ± 8.2 13 ± 8.1 0.147 Values presented as mean ± standard deviation or median (25 th ; 75 th percentile). * Mann-Whitney U test # chi-squared test Table 2. Longitudinal changes in laboratory parameters in the urate-lowering therapy (ULT) and control groups. ULT group N=44 Control group N=43 Baseline Follow-up P Baseline Follow-up P Uric acid [µmol/l] 464 ± 68.8 314 ± 55.6 <0.0001 437 ± 61.1 426 ± 56.9 0.044 eGRF [ml/min/1,75m2] 80 ± 18.6 80 ± 18.1 0.935 87 ± 20.1 89 ± 20.7 0.125 Lipids Total cholesterol [mmol/l] 4.3 ± 0.77 4.3 ± 0.97 0.829 4.7 ± 0.86 # 4.7 ±0.77 0.841 LDL cholesterol [mmol/l] 2.2 ± 0.62 2.2 ± 0.79 0.703 2.4 ± 0.74 2.5 ± 0.69 0.450 HDL cholesterol [mmol/l] 1.43 (1.18; 1.77) 1.46 ± 0.4 1.47 (1.2; 1.76) 1.46 ± 0.38 0.163* 1.38 (1.11; 1.64) 1.43 ± 0.46 1.36 (1.12; 1.6) 1.42 ± 0.41 0.888* Triglycerides [mmol/l] 1.36 ± 0.54 1.31 ± 0.56 0.374 1.7 ± 1.04 1.76 ± 0.91 0.048 NT-proBNP [pg/ml] 88 (46; 221) 165 ± 180.1 128 (40; 212) 154 ± 173 0.548* 67 (38; 131) 95 ± 67.3 73 (40; 153) 92 ± 60 0.845* hs-CRP [mg/l] 2.65 (1.4; 5) 3.36 ± 2.73 2.16 (1.45; 3.58) 2.74 ± 1.91 0.028* 1.23 (1; 3.2) 1.92 ± 1.28 # 1.31 (0.9; 3.41) 2 ± 1.44 0.682* Values presented as mean ± standard deviation or median (25 th ; 75 th percentile). # differences between ULT group and control group at baseline (p<0,05) * Mann-Whitney U test eGFR – estimated glomerular filtration rate, LDL – low density lipoprotein, HDL – high density lipoprotein, NT-proBNP – N-terminal pro hormone B-type natriuretic peptide, hs-CRP – high-sensitivity C-reactive protein Table 3 . Longitudinal changes in blood pressure in the urate-lowering therapy (ULT) and control groups. ULT group N=44 Control group N=43 mmHg Baseline Follow-up P Baseline Follow-up P Peripheral haemodynamics Office SBP [mmHg] 137 ± 11.8 134 ± 9.3 0.025 133 ± 11.5 131 ± 11.3 0.383 Office DBP [mmHg] 83 ± 9.9 79 ± 8.7 0.017 79 ± 8.6 # 78 ± 8.9 0.665 Office PP [mmHg] 56 ± 8.9 51 ± 12.9 0.046 55 ± 14.9 54 ± 14.4 0.626 Central haemodynamics Central SBP [mmHg] 129 ± 12 123 ± 11.8 0.004 123 ± 10.2 # 122 ± 9.6 0.787 Central DBP [mmHg] 87 ± 10 85 ± 9.4 0.217 82 ± 8.3 # 82 ± 9.2 0.913 Central PP [mmHg] 43 ± 10.4 39 ± 11.2 0.017 42 ± 11.5 41 ± 10.7 0.723 ABPM 24 hours 24 h SBP [mmHg] 119 ± 9.6 120 ± 9.7 0.368 115 ± 9.3 116 ± 8.9 0.399 24 h DBP [mmHg] 72 ± 7.4 72 ± 6.6 0.555 71 ± 7 71 ± 7.4 0.766 24 h PP [mmHg] 46 ± 7.2 48 ± 8.0 0.099 44 ± 6.5 45 ± 7.4 0.574 ABPM daytime Day SBP [mmHg] 125 ± 8.2 125 ± 8.8 0.984 120 ± 9.7 120 ± 10.1 0.431 Day DBP [mmHg] 76 ± 7.8 76 ± 6.2 0.725 75 ± 6.7 75 ± 7.8 0.868 Day PP [mmHg] 48 ± 7.7 48 ± 7.3 0.925 45 ± 7.2 45 ± 7.9 0.442 ABPM nighttime Night SBP [mmHg] 111 ± 10.7 112 ± 10.4 0.410 106 ± 9.1 # 106 ± 9.1 0.541 Night DBP [mmHg] 65 ± 8.6 65 ± 7.5 1.000 62 ± 7.1 63 ± 7.1 0.477 Night PP [mmHg] 47 ± 8.8 48 ± 7.8 0.321 43 ± 7.3 43 ± 7.7 0.951 Values presented as mean ± standard deviation. # differences between ULT group and control group at baseline (p<0.05) ABPM - ambulatory blood pressure monitoring, PP – pulse pressure. 24 h – 24 hour Table 4. Longitudinal changes in echocardiographic parameters, pulse wave velocity (PWV) and carotid intima-media thickness (IMT) in the urate-lowering therapy (ULT) and control groups. ULT group N=44 Control group N=43 Baseline Follow-up P Baseline Follow-up P Echocardiography LVMI [g/m 2 ] * 109 (94.9; 121.3) 112 ± 31.5 105 (93.4; 117.5) 108 ± 24.8 0.069 95 (81.5; 117.3) 99 ± 24.7 96 (76.1; 111.4) 98 ± 25.9 0.648 LVMI [g/m 2.7 ] * 48 (44.2; 57.8) 53 ± 17.0 48 (41.7; 55.5) 51 ± 14.3 0.056 42 (33.6; 57.0) 45 ± 13.7 42 (34.2; 53.4) 45 ± 14.2 0.682 LVM [g] * # 206 (179.1; 234.8) 216 ± 66.2 200 (177.9; 227.1) 209 ± 52.4 0.053 176 (151.8; 213.2) 184 ± 49.9 181.4 (148.1; 206.4) 184 ± 52.2 0.756 LAVI [ml/m 2 ] # 40 ± 13.5 38 ± 12.3 0.044 34 ± 8.9 36 ± 8.6 0.009 LAV [ml] 77 ± 26.8 74 ± 23.2 0.044 65 ± 19.5 67 ± 19.2 0.009 IVRT [ms] * 91 (82.5; 106.5) 96.6 ± 23.1 103 (87; 122) 103 ± 24 0.016 91 (75; 103) 85 ± 27 98 (86; 111) 97 ± 20.2 0.003 EF [%] 62 ± 5.1 62 ± 5.5 0.311 62 ± 5.9 62 ± 4.9 0.229 GLS [%]* -19.2 (-18.1; -19.9) -19.3 ± 2.2 -18.9 (-18.3; -20.5) -19.2 ± 2.2 0.769 -20 (-18.7; -21) -20 ± -1.7 -20 (-19; -20.2) -20 ± 1.3 0.885 Arterial stiffness PWV [m/s] * 7.8 (7; 10) 8.6 ± 2 7.8 (7.1; 9.6) 8.3 ± 1.7 0.109 7.6 (6.8; 9.1) 8 ± 1.5 8.1 (7.1; 8.9) 8.1 ± 1.3 0.691 Carotid ultrasound IMT [mm] 0.773 ± 0.121 0.752 ± 0.130 0.044 0.729 ± 0.133 0.734 ± 0.130 0.330 Values presented as mean ± standard deviation or median (25 th ; 75 th percentile). * Mann-Whitney U test # differences between ULT group and control group at baseline (p<0,05) LVMI – left ventricular mass index, LVM – left ventricular mass, LAVI – left atrium volume index, LAV – left atrium volume, IVRT – isovolumic relaxation time, EF – left ventricular ejection fraction, GLS – left ventricular global longitudinal strain, PWV – carotid-femoral pulse wave velocity, IMT – intima-media thickness Cite Share Download PDF Status: Published Journal Publication published 31 Jan, 2022 Read the published version in Blood Pressure Monitoring → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-140202","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":8447092,"identity":"60c8dd0a-8356-4aaf-8595-a3a10ddbd0a5","order_by":0,"name":"Krystian Gruszka","email":"","orcid":"","institution":"Jagiellonian University Medical College, 1st Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Krakow, Poland","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Krystian","middleName":"","lastName":"Gruszka","suffix":""},{"id":8447093,"identity":"21e624a1-6b14-4d6e-8526-b148d2cdea05","order_by":1,"name":"Tomasz Drożdż","email":"","orcid":"","institution":"Jagiellonian University Medical College, 1st Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Krakow, Poland","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tomasz","middleName":"","lastName":"Drożdż","suffix":""},{"id":8447094,"identity":"ff53fe07-af54-4bae-9998-24feabc7bca2","order_by":2,"name":"Wiktoria Wojciechowska","email":"","orcid":"","institution":"Jagiellonian University Medical College, 1st Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Krakow, Poland","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wiktoria","middleName":"","lastName":"Wojciechowska","suffix":""},{"id":8447095,"identity":"ce90e609-efaf-4506-a9d8-283f52cd2200","order_by":3,"name":"Piotr Jankowski","email":"","orcid":"","institution":"Jagiellonian University Medical College, 1st Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Krakow, Poland","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Piotr","middleName":"","lastName":"Jankowski","suffix":""},{"id":8447096,"identity":"5641175a-22a4-4409-994c-8a3cddf59513","order_by":4,"name":"Michał Terlecki","email":"","orcid":"","institution":"Jagiellonian University Medical College, 1st Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Krakow, Poland","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Michał","middleName":"","lastName":"Terlecki","suffix":""},{"id":8447097,"identity":"13a2473f-d1fb-4457-be5d-27186ae5e31e","order_by":5,"name":"Magdalena Bijak","email":"","orcid":"","institution":"Jagiellonian University Medical College, 1st Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Krakow, Poland","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Magdalena","middleName":"","lastName":"Bijak","suffix":""},{"id":8447098,"identity":"71f6c8e1-f163-4219-9288-64603829fe90","order_by":6,"name":"Dagmara Hering","email":"","orcid":"","institution":"Department of Hypertension and Diabetology, Medical University of Gdansk, Poland","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dagmara","middleName":"","lastName":"Hering","suffix":""},{"id":8447099,"identity":"de8402e5-4e38-408a-944e-9b60cfefec25","order_by":7,"name":"Grzegorz Bilo","email":"","orcid":"","institution":"Istituto Auxologico Italiano, IRCCS, Department of Cardiovascular, Neural and Metabolic Sciences, Milan, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Grzegorz","middleName":"","lastName":"Bilo","suffix":""},{"id":8447100,"identity":"5382f419-33d5-4ebb-bfad-8d8c67fb50cc","order_by":8,"name":"Marek Rajzer","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIie3PMQrCMBSA4RcCdYl2fWDBK7QU1EW8yitdPYJoJaCL0FVv4QEcnhR08RAFwVk3BwejgqBD4yiYHx4kkC8kAC7Xb0ZmhuNcPjZoRmbfkK1YahDZkwgruSfFil9HLaQz48PpvPZkvKvvyvO624LmpJoEe6JocQy8dtFIJosjRlmwqSYIRKliT7ULFWnFKDJMLMQvqbiyxFgbcmXs2wlSooFlGEpDgM15OylTMectoXnYcs6YTq1/8Qfp6cJD8vN9aBajXt7UXEkAFL3vPbQAgNrnnXbicrlcf9YN6CdHhLKC7IcAAAAASUVORK5CYII=","orcid":"","institution":"Jagiellonian University Medical College, 1st Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Krakow, Poland","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Marek","middleName":"","lastName":"Rajzer","suffix":""}],"badges":[],"createdAt":"2021-01-04 07:14:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-140202/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-140202/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1097/MBP.0000000000000578","type":"published","date":"2022-01-31T13:26:38+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":5157598,"identity":"63095c7c-a3f9-42d0-b1d5-bb250b56bc63","added_by":"auto","created_at":"2021-01-21 15:53:02","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":73435,"visible":true,"origin":"","legend":"Study flowchart\nULT – urate lowering therapy\n","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-140202/v1/e80e1f3d45723bc53ab58d34.jpg"},{"id":5157773,"identity":"25db85ed-4e49-4203-9054-faf0ac1a0e88","added_by":"auto","created_at":"2021-01-21 15:56:02","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":42457,"visible":true,"origin":"","legend":"Relative to baseline level changes (presented as percentage) in selected parameters in the urate-lowering therapy (ULT) and control groups.\noSBP – office systolic blood pressure, oDBP – office diastolic blood pressure, cPP – central pulse pressure, PWV – carotid-femoral pulse wave velocity, IMT – carotid intima-media thickness, LAVI – left atrium volume index, hs-CRP – high sensitivity C- reactive protein\n","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-140202/v1/7f4590418359102f5ed89ded.jpg"},{"id":5157435,"identity":"b4ccc5ef-dcb9-46ee-b096-90baff88dd2a","added_by":"auto","created_at":"2021-01-21 15:50:02","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":278157,"visible":true,"origin":"","legend":"Intima-media thickness (IMT) changes in the urate-lowering therapy (ULT) group [1] and in the control group [0] at 6 months follow-up.","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-140202/v1/fd493ebc6c0935a32446e4e4.jpg"},{"id":5157432,"identity":"222e8084-586e-4901-be5f-686018e895e1","added_by":"auto","created_at":"2021-01-21 15:50:02","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":38810,"visible":true,"origin":"","legend":"Correlation between reduction in uric acid (UA) concentration and reduction in intima-media thickness (IMT) in the whole study group at follow up. \nReduction = day 0 value – after 6 months value\n","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-140202/v1/2fd4b50c76f9790a2bacc171.jpg"},{"id":18161268,"identity":"23ebbea5-5421-4ad9-beeb-b7f8ac81d4e6","added_by":"auto","created_at":"2022-02-12 13:27:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":688732,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-140202/v1/b601a1be-3533-4da0-a843-c690fef789f0.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eEffects of Uric Acid Lowering Therapy in Patients With Essential Arterial Hypertension\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eAsymptomatic hyperuricemia (AHU) is traditionally defined as elevated serum uric acid (UA) concentration but in which neither symptoms of monosodium urate crystal deposition disease, such as gout, nor uric acid renal disease have occurred [1]. The prevalence of AHU has increased over several decades and nowadays it affects 16.9% of the adult population [2]. AHU is more common in subjects with arterial hypertension (AH) than in the general population [3,4]. High UA concentration is one of the important factors associated with the development of AH and promotes vascular and renal organ damage [5]. Experimental and epidemiological data reveal associations between hyperuricemia and hypertension, cardiovascular risk, chronic kidney disease (CKD), and metabolic syndrome [6-8]. The risk of coronary artery disease mortality increases by 13% for each 1 mg/dl (60 \u0026mu;mol/L) increase in UA concentration [9]. However, it is still debatable whether hyperuricemia is an independent cardiovascular risk factor. Numerous clinical disorders associated with high UA serum level support the decision to treat AHU to reduce cardiovascular risk. Some results of previous studies showed beneficial effects of AHU pharmacological treatment such as: decreased concentration of inflammation markers (high-sensitivity C-reactive protein, hs-CRP), reduced carotid intima-media thickness (IMT) [10], reduced levels of oxidative stress markers, improved endothelial function [11], reduced serum creatinine and increased estimated glomerular filtration rate (eGFR) [12] as well as reduced blood pressure (BP) [13]. Allopurinol mainly is used to treat AHU, especially in patients at high cardiovascular risk, but there is no evidence for its effect on hard end-points, and this topic still needs further investigations [14-16]. Nevertheless, Borghi at al. [15] in the \u0026ldquo;Expert consensus for the diagnosis and treatment of patient with hyperuricemia and high cardiovascular risk\u0026rdquo; recommend considering treatment of AHU as a part of cardiovascular events prevention when serum UA concentration is \u0026ge;5 mg/dl (300 \u0026mu;mol/l) in patients with high cardiovascular risk and when serum UA concentration is \u0026ge;6 mg/dl (360 \u0026mu;mol/l) in other patients. Generally, treatment of AHU as a component of cardiovascular prevention is not a gold standard due to the lack of sufficient evidence from clinical studies.\u003c/p\u003e\n\u003cp\u003eThe aim of the study was to determine the effects of AHU treatment with allopurinol on selected Hypertension Mediated Organ Damage (HMOD) indices in patients with uncomplicated essential AH.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe study population consisted of 562 patients aged 30-70 years, both women and men consecutively admitted to the hypertension outpatient department between September 2017 and March 2018 with: diagnosed AHU defined as a serum UA \u0026ge; 6 mg/dl (360 \u0026mu;mol/l) [15, 17] and with essential hypertension grade 1 or 2 (BP \u0026ge;140/90 and \u0026lt;180/110 mmHg) in accordance with the 2018 ESH/ESC guidelines [18] with previously confirmed adequate BP control on antihypertensive treatment (below 140/90 mmHg in office measurements). Patients, who received allopurinol (100-300 mg/day) according to Expert consensus [15] comprised urate lowering therapy (ULT) group (n=50). Then, within 5 days from recruitment of the ULT patient, a control patient with AHU and AH who did not receive allopurinol treatment, with age\u0026plusmn;3 years and preferably the same gender was recruited in a ratio of 1:1 (n=50 cases and n =50 controls). All patients were given the same dietary advice recommended for AH and AHU. All examinations were performed prior to treatment initiation and after 6 months of follow-up.\u003c/p\u003e\n\u003cp\u003eThe exclusion criteria included: any symptoms of monosodium urate crystal deposition disease, especially gout; coronary heart disease (previous myocardial infarction, coronary angioplasty procedure or coronary artery bypass surgery); symptomatic heart failure more than New York Heart Association (NYHA) class I or reduced ejection fraction \u0026lt; 50%; kidney or liver failure; inflammatory diseases; history of allergy to allopurinol or other serious drug reactions (e.g. Lyell\u0026rsquo;s syndrome); or treatment change during follow-up. Study flowchart is presented in Figure 1.\u003c/p\u003e\n\u003cp\u003eThe study was performed in accordance with the 1975 Declaration of Helsinki for Human Research and approved by the Jagiellonian University Bioethical Committee (No. 122.6120.94.2017 of April 27th, 2017). A written informed consent was obtained from all patients.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMeasurement of peripheral blood pressure \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll participants underwent physical examination and office BP measurements (mean of three measurements at one-minute intervals) in standard conditions, after 10 minutes rest, in sitting position on the non-dominant arm with the use of the validated Omron M5-I oscillometric device (Omron Healthcare Co., Japan).\u003c/p\u003e\n\u003cp\u003e24-hour ambulatory BP monitoring (ABPM) was performed using a SpaceLabs 90207 recorder (SpaceLabs Inc, Richmond, Washington, USA) to confirm BP control. Measurements were taken every 15 minutes during daily activity (06:00\u0026ndash;22:00h) and every 20 minutes at night-time (22:00\u0026ndash; 06:00 h). For further analyses the mean values of the 24-hour, daytime, and night-time systolic (SBP) and diastolic blood pressure (DBP), and heart rate were calculated. BP measurements were performed according to the ESH/ESC guidelines for the management of hypertension [18].\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEchocardiographic measurements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eEchocardiographic examination using the Vivid\u0026reg;E95 (GE-Healthcare Chicago, IL, USA) device and 2,7-3,6 MHz transducer was performed. Left ventricular mass (LVM) was calculated according to the ASE formula [19, 20]. Left ventricular mass index (LVMI) was calculated LVM/height\u003csup\u003e2.7\u003c/sup\u003e [21]. Left atrium volume (LAV) was assessed using the modified Simpson\u0026rsquo;s method [22]. Left atrium volume index (LAVI) was calculated as LAV/body surface area. Global longitudinal strain (GLS) by speckle tracking echocardiography was measured as the average value of 18 segments, based on three apical imaging planes [23].\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCentral blood pressure, pulse wave velocity and intima-media thickness measurements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSphygmoCor (AtCor Medical, Sydney, Australia) device was used to examine arterial stiffness. Carotid-femoral pulse wave velocity (PWV) and central BP in the aorta were measured according to the recommendations of ESH experts [24, 25].\u003c/p\u003e\n\u003cp\u003eIntima-media thickness (IMT) measurement of common carotid artery was carried out in accordance with the Mannheim consensus with the use of the Vivid\u0026reg;E95 (GE-Healthcare Chicago, IL, USA) and a 10 MHz linear transducer. After at least 10 minutes of patient rest in supine position, good-quality B-mode ultrasound images of left and right common carotid arteries were recorded during five consecutive heart cycles. The intima - media thickness (IMT) of the far wall was measured offline using EchoPAC workstation software. Automatic IMT measurement was based on tracing of 1 cm (starting about 1 cm proximally from bifurcation) of the leading edge of the intima surface and the leading edge of the adventitia surface followed by multiple measurements between pairs of pixels located on both traces. Mean IMT was calculated as the average of the left and right IMT [26].\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOther measurements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn all patients medical history was collected including concomitant diseases, smoking and drinking habits and the use of medications. Laboratory tests: serum concentrations of uric acid, creatinine, total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and hs-CRP were also obtained at the initial visit.\u003c/p\u003e\n\u003cp\u003eAll performed examinations and laboratory tests were then repeated after 6 months of follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are presented as means and standard deviations (SD) and medians and interquartile ranges in cases where nonparametric tests were used. To determine the study sample, we chose as optimal parameter the IMT because of the association with atherosclerosis, BP and potential reversibility during ULT. The analysis showed that to determine a 0.1 mm difference in IMT with mean value of 0.9 and SD of 0.16 mm [27, 28] with a power of 80% and with a significance of p=0.05, using the two-tailed test, the population of 42 people in each group is required. Normality of variables distribution was tested and, if confirmed, parametric tests were used. When studied variables did not have normal distribution nonparametric tests were used. Between group differences were evaluated using Student\u0026rsquo;s t-test, Mann-Whitney U test or chi-squared test, as appropriate. To assess the effects of the therapy the repeated-measures t-test, Wilcoxon signed-rank test, ANCOVA and the association between variables using the Spearman rank correlation were used. Univariate and multivariate regression analyses were used to determine the influence of independent factors on IMT. P-values \u0026lt;0.05 were considered statistically significant for all tests. Statistical analyses were performed using STATISTICA software (StatSoft, Poland), version 13.1.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe flow of participants in the study is presented in Figure 1.\u003c/p\u003e\n\u003cp\u003eThe final analysis included 87 patients: 44 in the ULT group (20 females and 24 males) and 43 in the control group (23 females, 20 males). During the study follow-up, 13 patients (n=6 in the ULT group, n=7 in the control group) were withdrawn from the study due to the need of antihypertensive therapy modification or lack of follow-up appointment There were no significant differences in studied parameters at baseline visit between patients who dropped out and those who completed the study.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eBaseline characteristics\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eBaseline characteristics of the study patients are presented in Table 1.\u003c/p\u003e\n\u003cp\u003eThere were no significant differences between the ULT group and the control group in age, sex distribution, and baseline serum UA concentration (p=0.054). However, they did differ in BMI and total cholesterol (see Tables 1 and 2).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe effects of uric acid lowering therapy\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, ULT was safe and no treatment-related adverse effects were observed.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eBiochemistry\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eChanges in laboratory parameters from baseline to 6 months follow-up in both groups are summarized in Table 2. Urate-lowering therapy with the use of allopurinol 100-300 mg daily (mean 184 \u0026plusmn; 91.3 mg, median 150 (100; 300) mg) in the ULT group was associated with a significant reduction in serum uric acid concentration level (464 \u0026plusmn; 68.8 vs. 314 \u0026plusmn; 55.6 \u0026micro;mol/l; p\u0026lt;0.001). In the control group a small albeit statistically significant reduction in serum UA concentration was observed (437 \u0026plusmn; 61.1 vs. 426 \u0026plusmn; 56.9 \u0026micro;mol/l, p=0.044). Compared to controls, there was a significant reduction in hs-CRP levels in the ULT group at 6 months follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eBlood pressure\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e.\u003c/p\u003e\n\u003cp\u003eBaseline office and central BPs were higher in the ULT group than in the control group, however the unadjusted decline in DBP at 6 months follow-up in the ULT group was significantly higher compared to controls (Figure 2).\u003c/p\u003e\n\u003cp\u003eThe ANCOVA analysis corrected for baseline BP values showed no differences between study groups in observed BP decrease after 6 months observation.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eHMOD\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAmong the assessed echocardiographic parameters, significant reductions in LAV and LAVI were noticed in the ULT group at 6 months follow-up (Table 4). There were no comparable changes in the echocardiographic parameters in the control group at follow-up.\u003c/p\u003e\n\u003cp\u003eCompared to the control group, there was a significant reduction in carotid IMT in the ULT group at 6 months follow-up (Figure 3, Table 4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn our study, UA lowering therapy had no effect on the change in arterial stiffness determined by PWV (Table 4).\u003c/p\u003e\n\u003cp\u003eThe magnitude of reduction in IMT, CRP, LAVI, and UA was greater in the ULT group than in the control group (Figure 2).\u003c/p\u003e\n\u003cp\u003eIn all patients, the amount of reduction in serum UA concentration was related to the reduction in IMT (R=0.37, p\u0026lt;0.001) (Figure 4), central SBP (R=0.26, p=0.015), TG (R=0.31, p=0.003), hs-CRP concentration (R=0.30, p=0.004), LAV (R=0.35, p\u0026lt;0.001), LAVI (R=0.35, p\u0026lt;0.001), and with an increase in E wave (R=-0.27, p=0.012), and E wave deceleration time (R=-0.26, p=0.017).\u003c/p\u003e\n\u003cp\u003eThe multivariate regression analyses showed a significant association between UA lowering and IMT reduction in the entire study group after adjustment for changes in LDL and PP values (the known pathophysiological factors influencing IMT) (R=0.3234, R2=0.0722, p\u0026lt;0.026).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe 2018 ESC/ESH Guidelines for the management of arterial hypertension recommend routine measurement of serum UA as part of the screening in hypertensive patients, because elevated UA level is independently associated with increased cardiovascular risk in both hypertensive patients and general population [18]. Reduction in serum UA concentration with ULT may have an impact on the reduction in parameters related to cardiovascular risk such as IMT, LAVI or serum hs-CRP level. In a three-year randomized parallel-controlled study in patients with type 2 diabetes and AHU, Liu et al. found that effective control of the serum UA level with allopurinol therapy decreases the serum hs-CRP level and carotid IMT [10]. Our study demonstrates that UA lowering therapy is associated with a significant reduction in hs-CRP and IMT in patients with hypertension, however in a substantially shorter duration (i.e. 6 months). Based on these results, the reduction in hs-CRP indicates that ULT has an anti-inflammatory effect likely to explain the accompanying reduction in carotid IMT which is a surrogate marker for atherosclerosis, commonly known as a chronic inflammatory disease.\u003c/p\u003e\n\u003cp\u003eIn a study by Higgins et al. one-year treatment with allopurinol at a dose of 300 mg daily resulted in a decrease in central SBP and augmentation index, and prevented progression in IMT in patients following ischemic stroke or transient ischemic attack (TIA) [27].\u003c/p\u003e\n\u003cp\u003eCarotid IMT has been shown to predict cardiovascular risk in multiple large studies [29], however its reproducibility and usefulness in daily practice is limited [18]. In our study we used an automatic IMT measuring technique (using multiple measurement points) to increase the accuracy and repeatability of measurements according to the Mannheim consensus [26].\u003c/p\u003e\n\u003cp\u003eOur study found a significant reduction in office (SBP, DBP, PP) and central (SBP, PP) BP values but not in ambulatory BP values in the ULT group. Our findings suggest that treatment with allopurinol is safe and despite the minor impact on ambulatory BP levels (Table 3), UA lowering therapy significantly improves HMOD even after a relatively short time of treatment. Limited office BP changes following allopurinol therapy in our study may result from adequate BP control at baseline and short study duration in the ULT group (6 months) compared to a longer (3 years) study by Liu et al. [10].\u003c/p\u003e\n\u003cp\u003eWhile most available data indicate that allopurinol reduces BP regardless of antihypertensive drugs, the underlying mechanism is not clear [13]. In the meta-analysis of 15 randomized controlled trials performed in patients with hyperuricemia, with length of follow-up from 2 to 23 months, allopurinol decreased BP and creatinine level [30]. A sub-analysis revealed that allopurinol significantly decreased SBP irrespective of antihypertensive drug therapy, however a decrease in DBP was only observed in patients receiving antihypertensive drugs. In patients receiving combination of antihypertensive drugs and allopurinol in a dose \u0026le;300 mg/day the reduction in SBP was larger compared to patients receiving allopurinol at higher dose (\u0026gt;300 mg/day) [30].\u003c/p\u003e\n\u003cp\u003eA further interesting finding derived from our study is a significant reduction in left atrium volume index, likely as a result of the decrease in central BP (afterload) following ULT.\u003c/p\u003e\n\u003cp\u003eThe noticeable decrease in UA concentration in the ULT group is comparable to previous studies [10], confirming the adherence to drug therapy. Interestingly, a slight, but significant decrease in UA concentration was also present in the control group indicating that patients follow a dietary advice which previously has proven its efficacy. In the study by Rai et al. the Dietary Approaches to Stop Hypertension (DASH) diet resulted in up to 32% reduction in the incidence of gout over the 26-year follow-up (HR 0.68, 95% CI 0.57-0.80, p value for trend \u0026lt;0.001) [31].\u003c/p\u003e\n\u003cp\u003ePrevious studies found a strong relationship with systemic inflammation even in the absence of gout [32]. Moreover, serum urate was found to independently predict changes in circulating CRP [33]. Indeed, allopurinol treatment was associated with a decrease in hs-CRP and insulin resistance in patients with AHU [34]. Our findings support this observation documenting a reduction in hs-CRP in the ULT group and a significant association between changes in hs-CRP and serum UA level.\u003c/p\u003e\n\u003cp\u003eFindings related to BP changes following allopurinol therapy are inconsistent. A study by Jalal et al. conducted in chronic kidney disease (CKD) patients found that a 3-month therapy with allopurinol had no effects on BP levels, inflammation and oxidative stress markers compared to placebo [35]. In contrast, a study by Kanbay et al. has shown that a 4-month treatment with allopurinol led to a decrease in SBP and an increase in flow-mediated dilation and eGFR in patients without CKD [36]. Different results in both studies on BP changes during allopurinol treatment are likely to be explained by advanced and irreversible atherosclerotic changes in the arteries in high risk CKD patients. In line with this observation, our study population was limited to patients with essential hypertension grade 1 or 2 without previous history of coronary heart disease, CKD or symptomatic heart failure. In our opinion patients with potentially reversible cardiovascular changes are most likely to receive the greatest benefits from intensive ULT used in parallel with the modification of other cardiovascular risk factors as part of primary prevention of ischemic heart disease. We have previously shown that a higher UA concentration via higher serum matrix metalloproteinase (MMP) 3 enhances selected HMOD, especially carotid IMT in patients with AH [37]. Extracellular MMPs are part of inflammation leading to the degradation of collagen, vessel remodelling and atherosclerotic plaque rupture [38,39]. It is still the matter of controversy whether hyperuricemia is only a biomarker of cardiovascular risk or a direct factor attributable to the harmful effects on cardiovascular system [40].\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe study limitations\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA small sample size could be viewed as a study limitation. However, all patients enrolled in this study were comprehensively phenotyped concerning BP levels and associated HMOD to determine the true effects of allopurinol therapy. Secondly, the short length of follow-up may limit our findings, however the study duration was planned based on available data and allopurinol efficacy.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eAllopurinol in patients with arterial hypertension and hyperuricemia decreases blood pressure and, in a relatively short time, seems to favourably influence hypertension-mediated organ damage, in particular intima-media thickness. Our findings indicate that the beneficial effects of urate lowering therapy with allopurinol on blood pressure and organ damage may result from anti-inflammatory and anti-atherosclerotic actions, with a potential impact on long-term patient outcomes Further prospective studies in larger patient groups are required to support our findings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was performed in accordance with the 1975 Declaration of Helsinki for Human Research and approved by the Jagiellonian University Bioethical Committee (No. 122.6120.94.2017 of April 27th, 2017). A written informed consent was obtained from all patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eK.G. and M.R. designed the study. K.G., T.D., W.W., P.J., M.T., M.B., D.H., G.B. and MR wrote the main manuscript text. K.G., T.D. and M.R. recruited patients for the study. K.G., T.D., W.W., and M.T. and G.B. performed statistical analyses. M.T., M.B. and D.H. prepared figures 1 and 3. W.W. and P.J. prepared figures 2 and 4. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cp\u003eABPM: ambulatory blood pressure monitoring; AH: arterial hypertension; AHU: asymptomatic hyperuricemia; ANOVA: analysis of variance; BP: blood pressure; CKD: chronic kidney disease; E: early ventricular filling velocity; E/e\u0026rsquo;: early diastolic mitral annulus velocity ratio; eGFR: estimated glomerular filtration rate; ESC: European Society of Cardiology; ESH: European Society of Hypertension; GLS: left ventricular global longitudinal strain; HDL: high-density lipoprotein cholesterol; HMOD: hypertension mediated organ damage; hs-CRP: high sensitivity C- reactive protein; IMT: carotid intima-media thickness; IVRT: isovolumic relaxation time; LAVI: left atrium volume index; LDL: low-density lipoprotein cholesterol; LVM: left ventricular mass; NHANES: National Health and Nutrition Examination Survey; NT-proBNP: N-terminal prohormone of brain natriuretic peptide; NYHA: New York Heart Association; PP: pulse pressure; PWV: carotid-femoral pulse wave velocity; SBP: systolic blood pressure; TG: triglycerides; UA: uric acid; ULT: urate-lowering therapy.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCampion EW, Glynn RJ, Delabry LO. Asymptomatic hyperuricemia. Risks and consequences in the normative aging study. Am J Med. 1987;82(3):421-426. doi:10.1016/0002-9343(87)90441-4\u003c/li\u003e\n\u003cli\u003eChen-Xu M, Yokose C, Rai SK, et al. Contemporary Prevalence of Gout and Hyperuricemia in the United States and Decadal Trends: The National Health and Nutrition Examination Survey, 2007\u0026ndash;2016. Arthritis Rheumatol. 2019;71(6):991-999. doi:10.1002/art.40807\u003c/li\u003e\n\u003cli\u003eSong P, Wang H, Xia W, et al. Prevalence and correlates of hyperuricemia in the middle-aged and older adults in China. Sci Rep. 2018;8(1):4314. doi: 10.1038/s41598-018-22570-9.\u003c/li\u003e\n\u003cli\u003eYokokawa H, Fukuda H, Suzuki A, et al. Association Between Serum Uric Acid Levels/Hyperuricemia and Hypertension Among 85,286 Japanese Workers. J Clin Hypertens (Greenwich). 2016;18(1):53-59. doi:10.1111/jch.12627\u003c/li\u003e\n\u003cli\u003eKanbay M, Girerd N, Machu J-L, et al. Impact of Uric Acid on Hypertension Occurrence and Target Organ Damage: Insights From the STANISLAS Cohort With a 20-Year Follow-up. Am J Hypertens. 2020:hpaa030. doi:10.1093/ajh/hpaa030\u003c/li\u003e\n\u003cli\u003eRaja S, Kumar A, Aahooja RD, et al. Frequency of Hyperuricemia and its Risk Factors in the Adult Population. Cureus. 2019;11(3):e4198. doi:10.7759/cureus.4198\u003c/li\u003e\n\u003cli\u003eQin T, Zhou X, Wang J, et al. Hyperuricemia and the Prognosis of Hypertensive Patients: A Systematic Review and Meta-Analysis. J Clin Hypertens (Greenwich). 2016;18(12):1268-1278. doi:10.1111/jch.12855\u003c/li\u003e\n\u003cli\u003eAbeles AM. Hyperuricemia, Gout, and Cardiovascular Disease: An Update. Curr Rheumatol Rep. 2015;17(3):1-5. doi:10.1007/s11926-015-0495-2\u003c/li\u003e\n\u003cli\u003eLi M, Hu X, Fan Y, et al. Hyperuricemia and the risk for coronary heart disease morbidity and mortality a systematic review and dose-response meta-analysis. Sci Rep. 2016;6:19520. doi:10.1038/srep19520\u003c/li\u003e\n\u003cli\u003eLiu P, Wang H, Zhang F, et al. The Effects of Allopurinol on the Carotid Intima-media Thickness in Patients with Type 2 Diabetes and Asymptomatic Hyperuricemia : A Three-year Randomized Parallel-controlled Study. Intern Med. 2015;54(17)(13497235):2129-2137. doi:10.2169/internalmedicine.54.4310\u003c/li\u003e\n\u003cli\u003eHiggins P, Dawson J, Lees KR, et al. Xanthine Oxidase Inhibition For The Treatment Of Cardiovascular Disease : A Systematic Review and Meta-Analysis. Cardiovasc Ther. 2011;30(4):217\u0026ndash;226. doi:10.1111/j.1755-5922.2011.00277.x\u003c/li\u003e\n\u003cli\u003eAl S, Rf S, Gd W. Uric acid lowering therapies for preventing or delaying the progression of chronic kidney disease ( Review ). Cochrane Database Syst Rev. 2017;10(10). doi:10.1002/14651858.CD009460.pub2.www.cochranelibrary.com\u003c/li\u003e\n\u003cli\u003eAgarwal V, Hans N, Messerli FH. Effect of Allopurinol on Blood Pressure : A Systematic Review and. J Clin Hypertens. 2013;15(6):435-442. doi:10.1111/j.1751-7176.2012.00701.x\u003c/li\u003e\n\u003cli\u003eBrucato A, Cianci F, Carnovale C. Management of hyperuricemia in asymptomatic patients: A critical appraisal. Eur J Intern Med. 2020;74(October 2019):8-17. doi:10.1016/j.ejim.2020.01.001\u003c/li\u003e\n\u003cli\u003eBorghi C, Tykarski A, Widecka K, et al. Expert consensus for the diagnosis and treatment of patient with hyperuricemia and high cardiovascular risk. Cardiol J. 2018;25(5):545-564. doi:10.5603/CJ.2018.0116\u003c/li\u003e\n\u003cli\u003eLiu CW, Chang WC, Lee CC, et al. The net clinical benefits of febuxostat versus allopurinol in patients with gout or asymptomatic hyperuricemia \u0026ndash; A systematic review and meta-analysis. Nutr Metab Cardiovasc Dis. 2019;29(10):1011-1022. doi:10.1016/j.numecd.2019.06.016\u003c/li\u003e\n\u003cli\u003eRichette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017;76(1):29-42. doi:10.1136/annrheumdis-2016-209707\u003c/li\u003e\n\u003cli\u003eWilliams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-3104. doi:10.1093/eurheartj/ehy339\u003c/li\u003e\n\u003cli\u003eHammond IW, Devereux RB, Alderman MH, et al. The prevalence and correlates of echocardiographic left ventricular hypertrophy among employed patients with uncomplicated hypertension. J Am Coll Cardiol. 1986;7(3):639-650. doi:10.1016/s0735-1097(86)80476-4\u003c/li\u003e\n\u003cli\u003ePerrone-Filardi P, Coca A, Galderisi M, et al. Noninvasive cardiovascular imaging for evaluating subclinical target organ damage in hypertensive patients: a consensus article from the European Association of Cardiovascular Imaging, the European Society of Cardiology Council on Hypertension and the European Society of Hypertension. J Hypertens. 2017;35(9):1727-1741. doi:10.1097/HJH.0000000000001396\u003c/li\u003e\n\u003cli\u003eCuspidi, C., Meani, S., Negri, F. et al. Indexation of left ventricular mass to body surface area and height to allometric power of 2.7: is the difference limited to obese hypertensives?. J Hum Hypertens 23, 728\u0026ndash;734 (2009). doi.org/10.1038/jhh.2009.16\u003c/li\u003e\n\u003cli\u003eIwataki M, Takeuchi M, Otani K, et al. Measurement of left atrial volume from transthoracic three-dimensional echocardiographic datasets using the biplane Simpson's technique. J Am Soc Echocardiogr. 2012;25(12):1319-1326. doi:10.1016/j.echo.2012.08.017\u003c/li\u003e\n\u003cli\u003eKusunose K, Yamada H, Nishio S, et al. Index-beat assessment of left ventricular systolic and diastolic function during atrial fibrillation using myocardial strain and strain rate. J Am Soc Echocardiogr. 2012;25(9):953-959. doi:10.1016/j.echo.2012.06.009\u003c/li\u003e\n\u003cli\u003eLaurent S, Cockcroft J, Van Bortel L, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27(21):2588-2605. doi:10.1093/eurheartj/ehl254\u003c/li\u003e\n\u003cli\u003eVan Bortel LM, Laurent S, Boutouyrie P, et al. Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens. 2012;30(3):445-448. doi:10.1097/HJH.0b013e32834fa8b0\u003c/li\u003e\n\u003cli\u003eTouboul PJ, Hennerici MG, Meairs S, et al. Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011. Cerebrovasc Dis. 2012;34(4):290-296. doi:10.1159/000343145\u003c/li\u003e\n\u003cli\u003eHiggins P, Walters MR, Murray HM, et al. Allopurinol reduces brachial and central blood pressure, and carotid intima-media thickness progression after ischaemic stroke and transient ischaemic attack: a randomised controlled trial. Heart. 2014;100(14):1085-1092. doi:10.1136/heartjnl-2014-305683\u003c/li\u003e\n\u003cli\u003eGluszewska A, Gryglewska B, Rewiuk K, at al. Arterial structure and function and its short- and long-term changes after bariatric surgery. J Physiol Pharmacol. 2019 Dec;70(6). doi: 10.26402/jpp.2019.6.09.\u003c/li\u003e\n\u003cli\u003eKim GH, Youn HJ. Is Carotid Artery Ultrasound Still Useful Method for Evaluation of Atherosclerosis?. Korean Circ J. 2017;47(1):1-8. doi:10.4070/kcj.2016.0232\u003c/li\u003e\n\u003cli\u003eQu L, Jiang H, Chen J. Effect of uric acid-lowering therapy on blood pressure: systematic review and meta-analysis. Ann Med. 2017;49(2):142-156. doi:10.1080/07853890.2016.1243803\u003c/li\u003e\n\u003cli\u003eRai SK, Fung TT, Lu N, et al. The Dietary Approaches to Stop Hypertension (DASH) diet, Western diet, and risk of gout in men: prospective cohort study. BMJ. 2017;357:j1794. doi:10.1136/bmj.j1794\u003c/li\u003e\n\u003cli\u003eInaba S, Sautin Y, Garcia GE, et al. What can asymptomatic hyperuricaemia and systemic inflammation in the absence of gout tell us? Rheumatology (Oxford). 2013;52(6):963-965. doi:10.1093/rheumatology/ket001.\u003c/li\u003e\n\u003cli\u003eRuggiero C, Cherubini A, Miller E 3rd, et al. Usefulness of uric acid to predict changes in C-reactive protein and interleukin-6 in 3-year period in Italians aged 21 to 98 years. Am J Cardiol. 2007;100(1):115-121. doi:10.1016/j.amjcard.2007.02.065.\u003c/li\u003e\n\u003cli\u003eTakir M, Kostek O, Ozkok A, et al. Lowering Uric Acid With Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia. J Investig Med. 2015;63(8):924-929. doi:10.1097/JIM.0000000000000242\u003c/li\u003e\n\u003cli\u003eJalal DI, Decker E, Perrenoud L, et al. Vascular Function and Uric Acid-Lowering in Stage 3 CKD. J Am Soc Nephrol. 2017;28(3):943-952. doi:10.1681/ASN.2016050521\u003c/li\u003e\n\u003cli\u003eKanbay M, Huddam B, Azak A, et al. A randomized study of allopurinol on endothelial function and estimated glomular filtration rate in asymptomatic hyperuricemic subjects with normal renal function. Clin J Am Soc Nephrol. 2011;6(8):1887-1894. doi:10.2215/CJN.11451210\u003c/li\u003e\n\u003cli\u003eGruszka K, Rajzer M, Drożdż T, et al. Selected matrix metalloproteinases activity and hypertension-mediated organ damage in relation to uric acid serum level. Cardiol J. 2019;2019-03-26(48):1-9. doi:10.5603/CJ.a2019.0033\u003c/li\u003e\n\u003cli\u003eJohnson JL. Metalloproteinases in atherosclerosis. Eur J Pharmacol. 2017;816:93-106. doi:10.1016/j.ejphar.2017.09.007\u003c/li\u003e\n\u003cli\u003eRaffetto JD, Khalil RA. Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease. Biochem Pharmacol. 2008;75(2):346-359. doi:10.1016/j.bcp.2007.07.004\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e40. Stewart DJ, Langlois V, Noone D. Hyperuricemia and Hypertension: Links and Risks. Integr Blood Press Control. 2019;12:43-62. doi:10.2147/IBPC.S184685\u003c/p\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Baseline clinical data in the i urate-lowering therapy (ULT) and control groups.\u003c/p\u003e\n\u003ctable border=\"1\" width=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003cp\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eN=87\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003cp\u003e\u003cstrong\u003eULT group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eN=44\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e\u003cstrong\u003eControl group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eN=43\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eAnthropometrics\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eAge [years]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003emedian\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003cp\u003e62 (50.5; 68)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003cp\u003e62 (48,5; 69)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e62 (53; 67)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e0.699*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003emean\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003ch4\u003e57.8 \u0026plusmn; 12.3\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003ch4\u003e57.6 \u0026plusmn; 12.9\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e57.9 \u0026plusmn; 11.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e0.918\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eFemale [\u003cem\u003en \u003c/em\u003e(%)]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003ch4\u003e43 (50.59%)\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003ch4\u003e20 (45.45%)\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e23 (53.49%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e0.454\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eBody mass index [kg/m2]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003cp\u003e27.9 \u0026plusmn; 4.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003cp\u003e29.1 \u0026plusmn; 4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e26.7 \u0026plusmn; 4.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e0.008\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eRisk factors [n (%)]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eCurrent smoking\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003cp\u003e15 (17.24%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003cp\u003e7 (15.91%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e8 (18.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e0.739\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eAlcohol intake\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003cp\u003e20 (23%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003cp\u003e11 (25%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e9 (20.93%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e0.651\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eRegular physical activity\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003cp\u003e31 (35.63%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003cp\u003e12 (27.27%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e19 (44.19%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e0.099\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eHypercholesterolemia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003cp\u003e57 (65.52%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003cp\u003e29 (65.91%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e28 (65.12%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e0.938\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eDiabetes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003cp\u003e16 (18.39%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003cp\u003e9 (20.45%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e7 (16.28%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e0.615\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eHypertension treatment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eAntihypertensive medication use [\u003cem\u003en (%)]\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003cp\u003e87 (100%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003cp\u003e44 (100%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e43 (100%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e1.000\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eNumber of antihypertensive drugs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003cp\u003e2 (1;3)\u003c/p\u003e\n\u003cp\u003e2.5 \u0026plusmn; 1.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003cp\u003e3 (1;3)\u003c/p\u003e\n\u003cp\u003e2.5 \u0026plusmn; 1.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e3 (1;3)\u003c/p\u003e\n\u003cp\u003e2.5 \u0026plusmn; 1.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e0.972*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"189\"\u003e\n\u003cp\u003eTime of hypertension treatment [years]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"35\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"116\"\u003e\n\u003cp\u003e13.6 \u0026plusmn; 8.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"112\"\u003e\n\u003cp\u003e15 \u0026plusmn; 8.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"106\"\u003e\n\u003cp\u003e13 \u0026plusmn; 8.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"56\"\u003e\n\u003cp\u003e0.147\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eValues presented as mean \u0026plusmn; standard deviation or median (25\u003csup\u003eth\u003c/sup\u003e; 75\u003csup\u003eth\u003c/sup\u003e percentile).\u003c/p\u003e\n\u003cp\u003e* Mann-Whitney U test\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e#\u003c/sup\u003e chi-squared test\u003cstrong\u003e\u003cbr /\u003e \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Longitudinal changes in laboratory parameters in the urate-lowering therapy (ULT) and control groups.\u003c/p\u003e\n\u003ctable border=\"1\" width=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" width=\"227\"\u003e\n\u003cp\u003e\u003cstrong\u003eULT group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eN=44\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"18\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" width=\"219\"\u003e\n\u003cp\u003e\u003cstrong\u003eControl group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eN=43\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003ch4\u003eBaseline\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003eFollow-up\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"18\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"82\"\u003e\n\u003ch4\u003eBaseline\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"79\"\u003e\n\u003cp\u003eFollow-up\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"18\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"82\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"79\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eUric acid [\u0026micro;mol/l]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003ch4\u003e\u003cstrong\u003e464 \u003c/strong\u003e\u003cstrong\u003e\u0026plusmn; 68.8\u003c/strong\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e\u003cstrong\u003e314 \u0026plusmn; 55.6\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;0.0001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"18\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"82\"\u003e\n\u003ch4\u003e\u003cstrong\u003e437 \u0026plusmn; 61.1\u003c/strong\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"79\"\u003e\n\u003cp\u003e\u003cstrong\u003e426 \u0026plusmn; 56.9\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.044\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eeGRF [ml/min/1,75m2]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003ch4\u003e80 \u0026plusmn; 18.6\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e80 \u0026plusmn; 18.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e0.935\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"18\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"82\"\u003e\n\u003ch4\u003e87 \u0026plusmn; 20.1\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"79\"\u003e\n\u003cp\u003e89 \u0026plusmn; 20.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e0.125\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eLipids\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"18\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"82\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"79\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eTotal cholesterol \u0026nbsp;[mmol/l]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e4.3 \u0026plusmn; 0.77\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e4.3 \u0026plusmn; 0.97\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e0.829\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"18\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"82\"\u003e\n\u003ch4\u003e4.7 \u0026plusmn; 0.86\u003csup\u003e#\u003c/sup\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"79\"\u003e\n\u003ch4\u003e4.7 \u0026plusmn;0.77\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003ch4\u003e0.841\u003c/h4\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eLDL cholesterol [mmol/l]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e2.2 \u0026plusmn; 0.62\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e2.2 \u0026plusmn; 0.79\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e0.703\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"18\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"82\"\u003e\n\u003ch4\u003e2.4 \u0026plusmn; 0.74\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"79\"\u003e\n\u003ch4\u003e2.5 \u0026plusmn; 0.69\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003ch4\u003e0.450\u003c/h4\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eHDL cholesterol [mmol/l]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e1.43 (1.18; 1.77)\u003c/p\u003e\n\u003cp\u003e1.46 \u0026plusmn; 0.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e1.47 (1.2; 1.76)\u003c/p\u003e\n\u003cp\u003e1.46 \u0026plusmn; 0.38\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e0.163*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"18\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"82\"\u003e\n\u003cp\u003e1.38 (1.11; 1.64)\u003c/p\u003e\n\u003ch4\u003e1.43 \u0026plusmn; 0.46\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"79\"\u003e\n\u003cp\u003e1.36 (1.12; 1.6)\u003c/p\u003e\n\u003ch4\u003e1.42 \u0026plusmn; 0.41\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003ch4\u003e0.888*\u003c/h4\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eTriglycerides [mmol/l]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e1.36 \u0026plusmn; 0.54\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e1.31 \u0026plusmn; 0.56\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e0.374\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"18\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"82\"\u003e\n\u003ch4\u003e\u003cstrong\u003e1.7 \u0026plusmn; 1.04\u003c/strong\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"79\"\u003e\n\u003ch4\u003e\u003cstrong\u003e1.76 \u0026plusmn; 0.91\u003c/strong\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003ch4\u003e\u003cstrong\u003e0.048\u003c/strong\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eNT-proBNP [pg/ml]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e88 (46; 221)\u003c/p\u003e\n\u003cp\u003e165 \u0026plusmn; 180.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e128 (40; 212)\u003c/p\u003e\n\u003cp\u003e154 \u0026plusmn; 173\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e0.548*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"18\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"82\"\u003e\n\u003cp\u003e67 (38; 131)\u003c/p\u003e\n\u003ch4\u003e95 \u0026plusmn; 67.3\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"79\"\u003e\n\u003cp\u003e73 (40; 153)\u003c/p\u003e\n\u003ch4\u003e92 \u0026plusmn; 60\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003ch4\u003e0.845*\u003c/h4\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003ehs-CRP [mg/l]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e\u003cstrong\u003e2.65 (1.4; 5) \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.36 \u0026plusmn; 2.73\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e\u003cstrong\u003e2.16 (1.45; 3.58)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.74 \u0026plusmn; 1.91\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"76\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.028*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"18\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"82\"\u003e\n\u003cp\u003e1.23 (1; 3.2)\u003c/p\u003e\n\u003ch4\u003e1.92 \u0026plusmn; 1.28\u003csup\u003e#\u003c/sup\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"79\"\u003e\n\u003cp\u003e1.31 (0.9; 3.41)\u003c/p\u003e\n\u003ch4\u003e2 \u0026plusmn; 1.44\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003ch4\u003e0.682*\u003c/h4\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eValues presented as mean \u0026plusmn; standard deviation or median (25\u003csup\u003eth\u003c/sup\u003e; 75\u003csup\u003eth\u003c/sup\u003e percentile).\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e#\u003c/sup\u003e differences between ULT group and control group at baseline (p\u0026lt;0,05) * Mann-Whitney U test\u003c/p\u003e\n\u003cp\u003eeGFR \u0026ndash; estimated glomerular filtration rate, LDL \u0026ndash; low density lipoprotein, HDL \u0026ndash; high density lipoprotein, NT-proBNP \u0026ndash; N-terminal pro hormone B-type natriuretic peptide, hs-CRP \u0026ndash; high-sensitivity C-reactive protein\u003cstrong\u003e\u003cbr /\u003e \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e. Longitudinal changes in blood pressure in the urate-lowering therapy (ULT) and control groups.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" width=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" width=\"218\"\u003e\n\u003cp\u003e\u003cstrong\u003eULT group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eN=44\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" width=\"229\"\u003e\n\u003cp\u003e\u003cstrong\u003eControl group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eN=43\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003emmHg\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003ch4\u003eBaseline\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003eFollow-up\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003ch4\u003eBaseline\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003eFollow-up\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003ePeripheral haemodynamics\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003eOffice SBP [mmHg]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u003cstrong\u003e137 \u0026plusmn; 11.8\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u003cstrong\u003e134 \u0026plusmn; 9.3\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.025\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003ch4\u003e133 \u0026plusmn; 11.5\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e131 \u0026plusmn; 11.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.383\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003eOffice DBP [mmHg]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u003cstrong\u003e83 \u0026plusmn; 9.9\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u003cstrong\u003e79 \u0026plusmn; 8.7\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.017\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003ch4\u003e79 \u0026plusmn; 8.6\u003csup\u003e#\u003c/sup\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003ch4\u003e78 \u0026plusmn; 8.9\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003ch4\u003e0.665\u003c/h4\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003eOffice PP [mmHg]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u003cstrong\u003e56 \u0026plusmn; 8.9\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u003cstrong\u003e51 \u0026plusmn; 12.9\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.046\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003ch4\u003e55 \u0026plusmn; 14.9\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003ch4\u003e54 \u0026plusmn; 14.4\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003ch4\u003e0.626\u003c/h4\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003eCentral haemodynamics\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003eCentral SBP [mmHg]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u003cstrong\u003e129 \u003c/strong\u003e\u0026plusmn;\u003cstrong\u003e 12\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u003cstrong\u003e123 \u003c/strong\u003e\u0026plusmn;\u003cstrong\u003e 11.8\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003cp\u003e123 \u0026plusmn; 10.2\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e122 \u0026plusmn; 9.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.787\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003eCentral DBP [mmHg]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e87 \u0026plusmn; 10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e85 \u0026plusmn; 9.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e0.217\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003cp\u003e82 \u0026plusmn; 8.3\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e82 \u0026plusmn; 9.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.913\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003eCentral PP [mmHg]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u003cstrong\u003e43 \u0026plusmn; 10.4\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u003cstrong\u003e39 \u0026plusmn; 11.2\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.017\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003cp\u003e42 \u0026plusmn; 11.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e41 \u0026plusmn; 10.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.723\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003eABPM 24 hours\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003e24 h SBP [mmHg]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e119 \u0026plusmn; 9.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e120 \u0026plusmn; 9.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e0.368\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003cp\u003e115 \u0026plusmn; 9.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e116 \u0026plusmn; 8.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.399\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003e24 h DBP [mmHg]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e72 \u0026plusmn; 7.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e72 \u0026plusmn; 6.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e0.555\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003cp\u003e71 \u0026plusmn; 7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e71 \u0026plusmn; 7.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.766\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003e24 h PP [mmHg]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e46 \u0026plusmn; 7.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e48 \u0026plusmn; 8.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e0.099\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003cp\u003e44 \u0026plusmn; 6.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e45 \u0026plusmn; 7.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.574\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003eABPM daytime\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003eDay SBP [mmHg]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e125 \u0026plusmn; 8.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e125 \u0026plusmn; 8.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e0.984\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003cp\u003e120 \u0026plusmn; 9.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e120 \u0026plusmn; 10.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.431\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003eDay DBP [mmHg]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e76 \u0026plusmn; 7.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e76 \u0026plusmn; 6.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e0.725\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003cp\u003e75 \u0026plusmn; 6.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e75 \u0026plusmn; 7.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.868\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003eDay PP [mmHg]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e48 \u0026plusmn; 7.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e48 \u0026plusmn; 7.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e0.925\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003cp\u003e45 \u0026plusmn; 7.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e45 \u0026plusmn; 7.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.442\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003eABPM nighttime\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003eNight SBP [mmHg]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e111 \u0026plusmn; 10.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e112 \u0026plusmn; 10.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e0.410\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003cp\u003e106 \u0026plusmn; 9.1\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e106 \u0026plusmn; 9.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.541\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003eNight DBP [mmHg]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e65 \u0026plusmn; 8.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e65 \u0026plusmn; 7.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003cp\u003e62 \u0026plusmn; 7.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e63 \u0026plusmn; 7.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.477\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"181\"\u003e\n\u003cp\u003eNight PP [mmHg]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e47 \u0026plusmn; 8.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"83\"\u003e\n\u003cp\u003e48 \u0026plusmn; 7.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"53\"\u003e\n\u003cp\u003e0.321\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"90\"\u003e\n\u003cp\u003e43 \u0026plusmn; 7.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"87\"\u003e\n\u003cp\u003e43 \u0026plusmn; 7.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.951\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eValues presented as mean \u0026plusmn; standard deviation.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e#\u003c/sup\u003e differences between ULT group and control group at baseline (p\u0026lt;0.05)\u003c/p\u003e\n\u003cp\u003eABPM - ambulatory blood pressure monitoring, PP \u0026ndash; pulse pressure. 24 h \u0026ndash; 24 hour\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4.\u003c/strong\u003e Longitudinal changes in echocardiographic parameters, pulse wave velocity (PWV) and carotid intima-media thickness (IMT) in the urate-lowering therapy (ULT) and control groups.\u003c/p\u003e\n\u003ctable border=\"1\" width=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" width=\"262\"\u003e\n\u003cp\u003e\u003cstrong\u003eULT group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eN=44\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" width=\"224\"\u003e\n\u003cp\u003e\u003cstrong\u003eControl group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eN=43\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003ch4\u003eBaseline\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eFollow-up\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003ch4\u003eBaseline\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003eFollow-up\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eEchocardiography\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eLVMI [g/m\u003csup\u003e2\u003c/sup\u003e] *\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003ch4\u003e109 (94.9; 121.3)\u003c/h4\u003e\n\u003ch4\u003e112 \u0026plusmn; 31.5\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e105 (93.4; 117.5)\u003c/p\u003e\n\u003cp\u003e108 \u0026plusmn; 24.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003e0.069\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003ch4\u003e95 (81.5; 117.3)\u003c/h4\u003e\n\u003ch4\u003e99 \u0026plusmn; 24.7\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e96 (76.1; 111.4)\u003c/p\u003e\n\u003cp\u003e98 \u0026plusmn; 25.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.648\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eLVMI [g/m\u003csup\u003e2.7\u003c/sup\u003e] *\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003ch4\u003e48 (44.2; 57.8)\u003c/h4\u003e\n\u003ch4\u003e53 \u0026plusmn; 17.0\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e48 (41.7; 55.5)\u003c/p\u003e\n\u003cp\u003e51 \u0026plusmn; 14.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003e0.056\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003ch4\u003e42 (33.6; 57.0)\u003c/h4\u003e\n\u003ch4\u003e45 \u0026plusmn; 13.7\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e42 (34.2; 53.4)\u003c/p\u003e\n\u003cp\u003e45 \u0026plusmn; 14.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.682\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003ch4\u003e\u0026nbsp;\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eLVM [g] *\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003e206 (179.1; 234.8)\u003c/p\u003e\n\u003cp\u003e216 \u0026plusmn; 66.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e200 (177.9; 227.1)\u003c/p\u003e\n\u003cp\u003e209 \u0026plusmn; 52.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003e0.053\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003ch4\u003e176 (151.8; 213.2)\u003c/h4\u003e\n\u003ch4\u003e184 \u0026plusmn; 49.9\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003ch4\u003e181.4 (148.1; 206.4)\u003c/h4\u003e\n\u003ch4\u003e184 \u0026plusmn; 52.2\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003ch4\u003e0.756\u003c/h4\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eLAVI [ml/m\u003csup\u003e2\u003c/sup\u003e]\u003csup\u003e #\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003e\u003cstrong\u003e40 \u003c/strong\u003e\u003cstrong\u003e\u0026plusmn; 13.5\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u003cstrong\u003e38 \u0026plusmn; 12.3\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.044\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003ch4\u003e\u003cstrong\u003e34 \u0026plusmn; 8.9\u003c/strong\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003ch4\u003e\u003cstrong\u003e36 \u0026plusmn; 8.6\u003c/strong\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003ch4\u003e\u003cstrong\u003e0.009\u003c/strong\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eLAV [ml]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003e\u003cstrong\u003e77 \u003c/strong\u003e\u0026plusmn;\u003cstrong\u003e 26.8\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u003cstrong\u003e74 \u0026plusmn; 23.2\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.044\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003ch4\u003e\u003cstrong\u003e65 \u0026plusmn; 19.5\u003c/strong\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003ch4\u003e\u003cstrong\u003e67 \u0026plusmn; 19.2\u003c/strong\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003ch4\u003e\u003cstrong\u003e0.009\u003c/strong\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eIVRT [ms] *\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003e\u003cstrong\u003e91 (82.5; 106.5)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e96.6 \u0026plusmn; 23.1\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u003cstrong\u003e103 (87; 122)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e103 \u0026plusmn; 24\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.016\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003ch4\u003e\u003cstrong\u003e91 (75; 103) 85 \u0026plusmn; 27\u003c/strong\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003ch4\u003e\u003cstrong\u003e98 (86; 111) 97 \u0026plusmn; 20.2\u003c/strong\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003ch4\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/h4\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eEF [%]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003e62 \u0026plusmn; 5.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e62 \u0026plusmn; 5.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003e0.311\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003ch4\u003e62 \u0026plusmn; 5.9\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003ch4\u003e62 \u0026plusmn; 4.9\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003ch4\u003e0.229\u003c/h4\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eGLS [%]*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003e-19.2 (-18.1; -19.9)\u003c/p\u003e\n\u003cp\u003e-19.3 \u0026plusmn; 2.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e-18.9 (-18.3; -20.5)\u003c/p\u003e\n\u003cp\u003e-19.2 \u0026plusmn; 2.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003e0.769\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003ch4\u003e-20 (-18.7; -21)\u003c/h4\u003e\n\u003ch4\u003e-20 \u0026plusmn; -1.7\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003ch4\u003e-20 (-19; -20.2)\u003c/h4\u003e\n\u003ch4\u003e-20 \u0026plusmn; 1.3\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003ch4\u003e0.885\u003c/h4\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eArterial stiffness\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003ePWV [m/s] *\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003e7.8 (7; 10)\u003c/p\u003e\n\u003cp\u003e8.6 \u0026plusmn; 2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e7.8 (7.1; 9.6)\u003c/p\u003e\n\u003cp\u003e8.3 \u0026plusmn; 1.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003e0.109\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003cp\u003e7.6 (6.8; 9.1)\u003c/p\u003e\n\u003cp\u003e8 \u0026plusmn; 1.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e8.1 (7.1; 8.9)\u003c/p\u003e\n\u003cp\u003e8.1 \u0026plusmn; 1.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.691\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eCarotid ultrasound\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eIMT [mm]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"19\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.773 \u0026plusmn; 0.121\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.752 \u0026plusmn; 0.130\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.044\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003cp\u003e0.729 \u0026plusmn; 0.133\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"89\"\u003e\n\u003cp\u003e0.734 \u0026plusmn; 0.130\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"51\"\u003e\n\u003cp\u003e0.330\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eValues presented as mean \u0026plusmn; standard deviation or median (25\u003csup\u003eth\u003c/sup\u003e; 75\u003csup\u003eth\u003c/sup\u003e percentile).\u003c/p\u003e\n\u003cp\u003e* Mann-Whitney U test\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e#\u003c/sup\u003e differences between ULT group and control group at baseline (p\u0026lt;0,05)\u003c/p\u003e\n\u003cp\u003eLVMI \u0026ndash; left ventricular mass index, LVM \u0026ndash; left ventricular mass, LAVI \u0026ndash; left atrium volume index, LAV \u0026ndash; left atrium volume, IVRT \u0026ndash; isovolumic relaxation time, EF \u0026ndash; left ventricular ejection fraction, GLS \u0026ndash; left ventricular global longitudinal strain, PWV \u0026ndash; carotid-femoral pulse wave velocity, IMT \u0026ndash; intima-media thickness\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"asymptomatic hyperuricemia, uric acid, essential arterial hypertension, hypertension mediated organ damage ","lastPublishedDoi":"10.21203/rs.3.rs-140202/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-140202/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u003c/strong\u003e\u003c/p\u003e\u003cp\u003eAsymptomatic hyperuricemia (AHU) is defined as elevated serum uric acid (UA) concentration without symptoms. This study aimed to determine the effects of AHU treatment with allopurinol on selected hypertension mediated organ damage (HMOD) indices in patients with uncomplicated essential arterial hypertension (AH).\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\u003cp\u003ePatients aged 30-70 years with AHU and essential hypertension grade 1-2 with adequate blood pressure (BP) control, without previous urate lowering therapy (ULT) were divided into two groups: a) receiving allopurinol (ULT group) and b) age-and sex matched patients without ULT (control group). Both groups received UA-lowering diet. BP (office, 24 hour and central), echocardiographic parameters, pulse-wave velocity, carotid intima-media thickness (IMT) and lab tests (high-sensitivity C-reactive protein (hs-CRP) were measured at baseline and at 6 months follow-up.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eOut of 100 participants 87 completed the study (44 ULT patients and 43 controls). At 6 months follow-up, there was a significantly greater reduction in serum UA concentration in the ULT group than in the control group (464±68.8 µmol/l vs 314±55.6 µmol/l, p\u0026lt;0.0001). Patients receiving allopurinol had significant reductions in office systolic (137±11.8 mmHg vs 134±9.3 mmHg; p=0.025) and diastolic BP (83±9.9 mmHg vs 79±8.7 mmHg, p=0.017), central systolic BP (56±8.9 mmHg vs 51±12.9 mmHg, p=0.046), pulse pressure (43±10.4 mmHg vs 39±11.2 mmHg, p=0.017), IMT (0.773±0.121 mm vs 0.752±0.13 mm, p=0.044), left atrium volume index (40±13.5 ml/m\u003csup\u003e2\u003c/sup\u003e vs 38±12.3 ml/m\u003csup\u003e2\u003c/sup\u003e, p=0.044), and hs-CRP level (3.36±2.73 mg/l vs 2.74±1.91 mg/l, p=0.028) compared to controls. The decrease in UA concentration was significantly related to the reduction in IMT (R=0.37, p\u0026lt;0.001), central SBP (R=0.26, p=0.015) and hs-CRP concentration (R=0.30, p=0.004). Multivariate regression analysis revealed the independent relationship between reduction in IMT and UA lowering (R=0.3234, R2=0.0722, p\u0026lt;0.026).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eIn patients with AH and asymptomatic hyperuricemia treatment with allopurinol leads to further improvement in BP control and reduction in HMOD intensity, in particular IMT. The decrease in hs-CRP concentration associated with ULT may have a beneficial effect on patient long-term prognosis.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Effects of Uric Acid Lowering Therapy in Patients With Essential Arterial Hypertension","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-01-21 15:50:00","doi":"10.21203/rs.3.rs-140202/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ae5dad96-534b-4d7a-a6e7-958421053643","owner":[],"postedDate":"January 21st, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":1999828,"name":"Cardiac \u0026 Cardiovascular Systems"}],"tags":[],"updatedAt":"2022-02-12T13:26:38+00:00","versionOfRecord":{"articleIdentity":"rs-140202","link":"https://doi.org/10.1097/MBP.0000000000000578","journal":{"identity":"blood-pressure-monitoring","isVorOnly":true,"title":"Blood Pressure Monitoring"},"publishedOn":"2022-01-31 13:26:38","publishedOnDateReadable":"January 31st, 2022"},"versionCreatedAt":"2021-01-21 15:50:00","video":"","vorDoi":"10.1097/MBP.0000000000000578","vorDoiUrl":"https://doi.org/10.1097/MBP.0000000000000578","workflowStages":[]},"version":"v1","identity":"rs-140202","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-140202","identity":"rs-140202","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}