Baseline Serum Uric Acid Levels Research Articles

The Additive Values of the Classification of Higher Serum Uric Acid Levels as a Diagnostic Criteria for Metabolic-Associated Fatty Liver Disease.

Serum uric acid (SUA) is regarded as an independent risk factor for nonalcoholic fatty liver disease (NAFLD). However, the role of SUA in the new diagnosis flowchart of metabolic-associated fatty liver disease (MAFLD) remains unclear. A cross-sectional study enrolled consecutive individuals with ultrasonography and magnetic resonance imaging–based proton density fat fraction (MRI-PDFF) measurements in the First Affiliated Hospital of Sun Yat-sen University from January 2015 to December 2021. All patients were divided into four groups according to their baseline SUA levels and sex. Of the 3537 ultrasound-diagnosed and 1017 MRI-PDFF-diagnosed MAFLD patients included, the prevalence of severe steatosis determined with ultrasound or MRI-PDFF increased across the serum SUA quartiles. The SUA cutoffs were identified as ≥478 µmol/L and ≥423.5 µmol/L for severe steatosis in male and female MAFLD, respectively. Furthermore, using these cutoff values, patients with higher SUA levels in the NAFLD–non-MAFLD group had higher liver fat contents than those without (16.0% vs. 9.7%, p < 0.001). The lean/normal-weight NAFLD–non-MAFLD patients with higher SUA levels are still at high risk of severe steatosis. This study supports the rationale for SUA being established as another risk factor for metabolic dysfunctions in lean/normal-weight MAFLD.

Baseline serum uric acid level is associated with progression-free survival, disease control rate, and safety in postoperative patients with colorectal cancer treated by FOLFOX, FOLFIRI, or XELOX.

BackgroundHigh serum uric acid (SUA) levels increase the risk of overall cancer morbidity and mortality, particularly for digestive malignancies. Nevertheless, the correlation between SUA level and clinical outcomes of the postoperative patients with colorectal cancer (CRC) treated by chemotherapy is unclear. This study aimed at exploring the relationship between baseline SUA level and progression-free survival (PFS), disease control rate (DCR), and safety in postoperative CRC patients receiving chemotherapy.Patients and MethodsWe conducted a retrospective study to evaluate the relationship between baseline SUA level and PFS, DCR, and incidence of serious adverse events of 736 postoperative CRC patients treated with FOLFOX, FOLFIRI or XELOX at our center.ResultsData from our center suggested that high baseline SUA level is linked to poor PFS in non-metastatic CRC patients using FOLFOX (HR=2.59, 95%CI: 1.29-11.31, p=0.018) and in male patients using FOLFIRI (HR=3.77, 95%CI: 1.57-39.49, p=0.012). In patients treated by FOLFIRI, a high SUA is also linked to a low DCR (p=0.035). In patients using FOLFOX, high baseline SUA level is also linked to a high incidence of neutropenia (p=0.0037). For patients using XELOX, there is no significant correlation between SUA level and PFS, effectiveness, or safety.ConclusionsThese findings imply that a high SUA level is a promising biomarker associated with poor PFS, DCR and safety of postoperative CRC patients when treated with FOLFOX or FOLFIRI.

Association of Uric Acid–Lowering Therapy With Incident Chronic Kidney Disease

Uric acid is a waste metabolite produced from the breakdown of purines, and elevated serum uric acid levels are associated with higher risk of hypertension, cardiovascular disease, and mortality and progression of chronic kidney disease (CKD). Treatment of hyperuricemia in patients with preexisting CKD has not been shown to improve kidney outcomes, but the associations of uric acid-lowering therapies with the development of new-onset kidney disease in patients with estimated glomerular filtration rate (eGFR) within reference range and no albuminuria is unclear. To examine the association of initiating uric acid-lowering therapy with the incidence of CKD. This cohort study included patients with eGFR of 60 mL/min/1.73 m2 or greater and no albuminuria treated at US Department of Veterans Affairs health care facilities from 2004 to 2019. Clinical trial emulation methods, including propensity score weighting, were used to minimize confounding. Data were analyzed from 2020 to 2022. Newly started uric acid-lowering therapy. The main outcomes were incidences of eGFR less than 60 mL/min/1.73 m2, new-onset albuminuria, and end-stage kidney disease. A total of 269 651 patients were assessed (mean [SD] age, 57.4 [12.5] years; 252 171 [94%] men). Among these, 29 501 patients (10.9%) started uric acid-lowering therapy, and 240 150 patients (89.1%) did not. Baseline characteristics, including serum uric acid level, were similar among treated and untreated patients after propensity score weighting. In the overall cohort, uric acid-lowering therapy was associated with higher risk of both incident eGFR less than 60 mL/min/1.73 m2 (weighted subhazard ratio [SHR], 1.15 [95% CI, 1.10-1.20; P < .001) and incident albuminuria (SHR, 1.05 [95% CI, 1.01-1.09; P < .001) but was not associated with the risk of end-stage kidney disease (SHR, 0.96 [95% CI, 0.62-1.50]; P = .87). In subgroup analyses, the association of uric acid-lowering therapy with worse kidney outcomes was limited to patients with baseline serum uric acid levels of 8 mg/dL or less. These findings suggest that in patients with kidney function within reference range, uric acid-lowering therapy was not associated with beneficial kidney outcomes and may be associated with potential harm in patients with less severely elevated serum uric acid levels.

The Association between Baseline, Changes in Uric Acid, and Renal Failure in the Elderly Chinese Individuals: A Prospective Study with a 3-Year Follow-Up.

Objective The objective is to find whether serum uric acid (SUA) levels are associated with the progression of chronic kidney disease (CKD) remains uncertain, and follow-up data among the elderly population are relatively lacking, especially in China. The aim of the present study was to reveal the association between baseline SUA levels, changes in SUA levels, and renal failure in Chinese elderly adults. Methods In this retrospective cohort study, 425 subjects (age range 71–100 years) were analyzed and divided into quartiles based on baseline SUA levels (Q1: <4.8; Q2: <5.7; Q3: <6.5; and Q4: ≥6.5 mg/dl). CKD was defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. We used multiple linear and logistic regressions to compare the risk of renal dysfunction among the different SUA level groups. Results The prevalence of hyperuricemia was 24.24% in the elderly subjects. In the multivariable analysis, the odds ratio (OR) for the development of CKD increased with the increase in SUA quartiles at baseline (1.00 vs. 1.79 (95% CI, 1.00–3.22), 3.4 (95% CI, 1.79–6.47), and 6.79 (95% CI, 3.45–13.75), respectively; P for linear trend <0.001), and a per unit increase in baseline SUA levels gave an OR of 1.76 (95% CI, 1.45–2.14) for renal failure. At the same time, a change in SUA levels had a stronger inverse correlation with a change in eGFR in females (r = −0.318, P < 0.001) than in males (r = −0.187, P < 0.01). In a linear regression analysis, a 1 mg/dl increase in SUA levels was associated with an additional 1.25 (95% CI, −1.83 to −0.67) ml/min/1.73 m2 decrease in eGFR over a 3-year period. Conclusion Elevated baseline SUA levels and changes in SUA levels were associated with a decline in eGFR and an increased risk of CKD in an elderly Chinese population.

Serum uric acid levels on admission and prognosis of acute coronary syndrome: a bi-institutional report

Objective: This study aimed to determine the association between the baseline serum uric acid (SUA) level and the short-term outcomes of patients with acute coronary syndrome (ACS). Methods: In this retrospective, bi-institutional study, patients with a diagnosis of ACS were recruited and followed-up for 30 days regarding the development of major adverse cardiovascular and cerebrovascular events (MACCEs). The associations between the SUA level upon admission and cardiovascular morbidities and patient prognosis were examined using univariate and multivariate analyses. Results: A total of 145 patients with ACS, with a mean age of 67.5±12.2 years, were recruited in this study. The rates of cardiovascular risk factors were higher in patients with elevated SUA levels. A cumulative MACCE was reported in 42 (29%) patients (19.5% in normal individuals and 39.7% in patients with elevated SUA levels, respectively; P=0.007). Based on the receiver operating characteristic (ROC) curve analysis, an on-admission SUA level above 6.9 mg/dL could discriminate patients with MACCE from those without MACCE during 30 days of follow-up (AUC=0.637; 95% CI: 0.553–0.715), with 64.3% sensitivity and 66% specificity. Based on multivariate logistic regression analysis, an elevated SUA level was associated with an increased risk of MACCE (odds ratio, 15.353; 95% CI: 2.026–116.328). Conclusion: In patients with ACS, an elevated baseline SUA level was associated with a higher prevalence of cardiovascular risk factors and morbidities, as well as an increased risk of MACCE in a short-term follow-up.

Baseline uric acid levels and steady-state favipiravir concentrations are associated with occurrence of hyperuricemia among COVID-19 patients

ObjectivesFavipiravir is an antiviral that is being evaluated for the treatment of COVID-19. Use of favipiravir is associated with elevation of serum uric acid levels. Risk factors for the occurrence of hyperuricemia are unclear. MethodsSpecimens from COVID-19 patients who received 10 days of favipiravir in a previous clinical trial (jRCTs041190120) were used. Serum favipiravir concentrations were measured by LC-MS. Factors associated with the development of hyperuricemia were investigated using logistic regression analysis. Optimal cut-off values for the baseline serum uric acid levels and steady-state serum favipiravir concentrations in predicting the occurrence of hyperuricemia were determined by ROC curve analysis. ResultsAmong the 66 COVID-19 patients who were treated with favipiravir for 10 days, the steady-state serum favipiravir concentrations were significantly correlated with serum uric acid levels. High baseline serum uric acid levels and steady-state serum favipiravir concentrations during therapy were factors associated with the development of hyperuricemia. The cut‑off baseline serum uric acid level and steady-state serum favipiravir concentration during favipiravir administration determined to predict hyperuricemia were 3.7 mg/dL and 46.14 μg/mL, respectively. ConclusionsPatients with high baseline serum uric acid levels or who achieved high steady-state serum favipiravir concentrations during therapy were susceptible to hyperuricemia.

Hyperuricemia is a risk factor for the progression to end-stage renal disease in minimal change disease.

BackgroundMinimal change disease (MCD) is one of the most common causes of nephrotic syndrome worldwide. Hyperuricemia increases the end-stage renal disease (ESRD) risk in glomerulonephritis. In this study, we aimed to determine the effect of high serum uric acid levels on the progression to ESRD in MCD.MethodsA total of 800 patients diagnosed with MCD by kidney biopsy were retrospectively analyzed. We determined the relationship of hyperuricemia with the progression to ESRD in MCD using the Cox proportional hazard model and Kaplan-Meier survival analysis. The primary outcome was defined as the initiation of dialysis or kidney transplantation.ResultsA total of 42 patients (5.3%) progressed to ESRD during the follow-up period. In the restricted cubic spline curve, serum uric acid levels exhibited a positive correlation with ESRD progression in patients with MCD. In the fully adjusted model, the risk of MCD progression increased by 29% for every 1 mg/dL increase in the baseline serum uric acid level (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.09–1.54; p = 0.004). Falling into the high uric acid group (serum uric acid level > 7 mg/dL in men and > 6 mg/dL in women) was also a risk factor for progression of MCD to ESRD (HR, 3.40; 95% CI, 1.59–7.31; p < 0.001).ConclusionOur study shows that hyperuricemia is an independent risk factor for the progression to ESRD in patients with MCD.

Association between higher serum uric acid levels within the normal physiological range and changes of lumbar spine bone mineral density in healthy Chinese postmenopausal women: a longitudinal follow-up study.

The aim of this study was to investigate whether higher serum uric acid (SUA) levels within the physiological range were associated with changes in lumbar spine bone mineral density (LBMD) in postmenopausal women without existing lumbar spine osteoporosis after a longitudinal follow-up of 3.09 years, and to further confirm the relationship between SUA and bone mineral density (BMD) in other sites such as femoral neck, total hip, and trochanter at follow-up. A longitudinal study of 175 healthy postmenopausal women without osteoporosis was conducted in Shenyang, China. BMD of the lumbar spine, femoral neck, total hip, and trochanter were measured using dual-energy x-ray absorptiometry at each visit. Pearson's correlation analysis and regression analyses were performed to determine any associations. There were positive correlations between baseline SUA and BMD of the lumbar spine (P = 0.03), total hip (P = 0.04), and trochanter (P = 0.04). Moreover, higher baseline SUA levels were independently associated with LBMD decline and the odds ratio of the baseline SUA of the third quartile group was 0.12 (95% confidence interval, 0.02-0.70, P < 0.05), with P = 0.23 for the trend in baseline SUA when compared with participants in the lowest, first quartile group after adjustment for many potential confounding variables. Higher SUA levels within the normal physiological range were independently associated with decreased LBMD, and SUA levels were positively related to the BMD of the lumbar spine, total hip, and trochanter in healthy Chinese postmenopausal women.

Comparative study of a novel selective urate reabsorption inhibitor \u201cdotinurad\u201d among patient groups with different stages of renal dysfunction

BackgroundDotinurad is a selective urate reabsorption inhibitor (SURI), which selectively inhibits URAT1 to lower serum uric acid levels in patients with hyperuricemia. Herein, the effects of dotinurad were compared among patient groups with different stages of renal dysfunction.MethodsPatient data from four clinical trials were pooled and divided into four groups according to the stage of renal dysfunction to compare the effects of dotinurad at different stages. The grouping (stages G1–G3b) was based on the estimated glomerular filtration rate (eGFR) of the patients. In addition, patient data from a long-term study (34 or 58 weeks) were evaluated in the same manner.ResultsIn the pooled analysis, the percentage of patients achieving a serum uric acid level of ≤ 6.0 mg/dL was 64.7–100.0% at a dose of 2 or 4 mg. In the long-term analysis, the percentage of patients achieving a serum uric acid level of ≤ 6.0 mg/dL was 60.0–100.0% at a dose of 2 or 4 mg. Although the outcomes in stage G3b were worse due to higher baseline serum uric acid levels, satisfactory outcomes were observed in all stages. Even in stages G3a and G3b, when renal function declined, the eGFR remained constant throughout the dose period.ConclusionThe efficacy of dotinurad was confirmed in hyperuricemic patients with normal renal function (stage G1) and mild to moderate renal dysfunction (stage G2–G3b). Dotinurad was found to be effective in the treatment of hyperuricemia in patients with mild to moderate renal dysfunction.

Association between baseline and changes in serum uric acid and incident metabolic syndrome: a nation-wide cohort study and updated meta-analysis

BackgroundTo prospectively examine the associations of baseline serum uric acid (SUA) and SUA changes with incident metabolic syndrome (MetS) and update the evidence through a meta-analysis.MethodsOur analyses were based on the China Health and Retirement Longitudinal Study from 2011–2012 to 2015–2016. The exposures were baseline SUA and SUA changes, and the outcome was incident MetS assessed in 2015–2016. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A meta-analysis was conducted to synthesize evidence from all cohort studies on the same topic.ResultsOf 3779 participants (47.2% men; mean age: 59.5 years) without MetS, 452 participants developed MetS after a follow-up of 4 years. Compared to the lowest quartiles, the adjusted ORs (95% CIs) for MetS were 1.08 (0.77–1.50), 1.32 (0.95–1.82), and 1.55 (1.12–2.16) for three higher quartiles of baseline SUA, and 1.23 (0.89–1.71), 1.39 (1.00–1.93), and 1.89 (1.38–2.58) for three higher quartiles of SUA changes. Each increment of 1 mg/dL of baseline SUA level was associated with 19% higher odds of MetS (adjusted OR 1.19; 95% CI 1.07–1.33). In the meta-analysis of 24 cohort studies among 140,913 participants, the pooled relative risk (95% CI) was 1.32 (1.25–1.40) for the highest versus lowest SUA category, and 1.15 (1.09–1.21) for each 1 mg/dL increase in the SUA level.ConclusionsBoth baseline SUA and longitudinal SUA changes were positively associated with risk of MetS among middle-aged and elderly Chinese, which was supported by findings from a comprehensive meta-analysis across multiple populations. SUA levels might need to be monitored closely for subsequent risk of MetS in clinical practice.

Effects of baseline serum uric acid and apolipoprotein E4 on longitudinal cognition and cerebral metabolism

Serum uric acid, a natural antioxidant, may have a protective effect on the progression of Alzheimer's disease (AD). To investigate the effect of serum uric acid on longitudinal cognitive and brain metabolic changes, we utilized data on baseline serum uric acid levels, APOE genotyping, and longitudinal cognitive scores from the Alzheimer's Disease Neuroimaging Initiative for 1,343 participants with normal cognition (NC), mild cognitive impairment (MCI), or dementia. In 979 participants, brain metabolism was measured using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images. Higher serum uric acid levels exhibited a detrimental effect on NC, whereas a protective trend was observed in individuals with cognitive impairment. Interestingly, higher uric acid levels were associated with a slower decline in cognitive scores and brain metabolism in females with MCI, and this effect was found in APOE4 carriers, but not in non-carriers. Longitudinal AD-like patterns of brain metabolism on FDG-PET images also appeared to mediate the effects of baseline uric acid levels on longitudinal cognitive decline. In summary, higher serum uric acid may interact with APOE4 to alleviate longitudinal metabolic changes and cognitive decline in female MCI patients.

Serum Uric Acid Concentrations and Risk of Adverse Outcomes in Patients With COVID-19.

BackgroundAlthough hyperuricemia frequently associates with respiratory diseases, patients with severe coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) can show marked hypouricemia. Previous studies on the association of serum uric acid with risk of adverse outcomes related to COVID-19 have produced contradictory results. The precise relationship between admission serum uric acid and adverse outcomes in hospitalized patients is unknown.MethodsData of patients affected by laboratory-confirmed COVID-19 and admitted to Leishenshan Hospital were retrospectively analyzed. The primary outcome was composite and comprised events, such as intensive care unit (ICU) admission, mechanical ventilation, or mortality. Logistic regression analysis was performed to explore the association between serum concentrations of uric acid and the composite outcome, as well as each of its components. To determine the association between serum uric acid and in-hospital adverse outcomes, serum uric acid was also categorized by restricted cubic spline, and the 95% confidence interval (CI) was used to estimate odds ratios (OR).ResultsThe study cohort included 1854 patients (mean age, 58 years; 52% women). The overall mean ± SD of serum levels of uric acid was 308 ± 96 µmol/L. Among them, 95 patients were admitted to ICU, 75 patients received mechanical ventilation, and 38 died. In total, 114 patients reached composite end-points (have either ICU admission, mechanical ventilation or death) during hospitalization. Compared with a reference group with estimated baseline serum uric acid of 279-422 µmol/L, serum uric acid values ≥ 423 µmol/L were associated with an increased risk of composite outcome (OR, 2.60; 95% CI, 1.07- 6.29) and mechanical ventilation (OR, 3.01; 95% CI, 1.06- 8.51). Serum uric acid ≤ 278 µmol/L was associated with an increased risk of the composite outcome (OR, 2.07; 95% CI, 1.18- 3.65), ICU admission (OR, 2.18; 95% CI, 1.17- 4.05]), and mechanical ventilation (OR, 2.13; 95% CI, 1.06- 4.28), as assessed by multivariate analysis.ConclusionsThis study shows that the association between admission serum uric acid and composite outcome of COVID-19 patients was U-shaped. In particular, we found that compared with baseline serum uric acid levels of 279-422 µmol/L, values ≥ 423 µmol/L were associated with an increased risk of composite outcome and mechanical ventilation, whereas levels ≤ 278 µmol/L associated with increased risk of composite outcome, ICU admission and mechanical ventilation.

Association between serum uric acid levels and cardiovascular events in hospitalized patients with type 2 diabetes

AimsThis study aimed to determine the association between serum uric acid (UA) levels and cardiovascular events in hospitalized patients with type 2 diabetes mellitus (T2DM). MethodsA retrospective cohort study was conducted in 2227 hospitalized patients with T2DM. Cox proportional hazards regression was used to assess the association between serum UA and cardiovascular events, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, heart failure, unstable angina, and arrhythmias requiring hospitalization. ResultsAmong 1314 men, 143 (10.9%) experienced cardiovascular events. Serum UA level was not associated with the risk of cardiovascular events (hazard ratio [HR] per 100 μmol/L increase in serum UA: 1.12, 95% confidence interval [CI]: 0.90–1.40). Among 913 women, 96 (10.5%) experienced cardiovascular events. For every 100 μmol/L increase in serum UA level, the risk of experiencing a cardiovascular event increased by 27% (HR: 1.27, 95% CI: 1.02–1.57). ConclusionsIn hospitalized patients with T2DM, baseline serum UA levels were positively associated with cardiovascular events in women, but not in men. Serum UA levels may be a significant independent risk factor for cardiovascular events in women with T2DM.

Long-term impact of baseline serum uric acid levels on living kidney donors: a retrospective study

BackgroundPreoperative characteristics of living kidney donors are commonly considered during donor selection and postoperative follow-up. However, the impact of preoperative uric acid (UA) levels is poorly documented. The aim of this study was to evaluate the association between preoperative serum UA levels and post-donation long-term events and renal function.MethodsThis was a single-center retrospective analysis of 183 living kidney donors. The donors were divided into high (≥5.5 mg/dl) and low (< 5.5 mg/dl) UA groups. We analyzed the relationship between preoperative UA levels and postoperative estimated glomerular filtration rate (eGFR), as well as adverse events (cardiovascular events and additional prescriptions for hypertension, gout, dyslipidemia, and diabetes mellitus), over 5 years after donation.ResultsIn total, 44 donors experienced 52 adverse events over 5 years. The incidence of adverse events within 5 years was significantly higher in the high UA group than in the low UA group (50% vs. 24%, p = 0.003); this was true even after the exclusion of hyperuricemia-related events (p = 0.047). UA emerged as an independent risk factor for adverse events (p = 0.012). Donors with higher UA levels had lower eGFRs after donation, whereas body mass index, hemoglobin A1c, blood pressure, and low-density lipoprotein cholesterol did not have any impact on the eGFR.ConclusionsThe findings suggest that preoperative UA levels should be considered during donor selection and postoperative follow-up.

Serum Uric Acid Levels Predict Mortality Risk in Male Amyotrophic Lateral Sclerosis Patients.

Objective: To explore the associations between serum uric acid levels with survival in male and female ALS patients.Methods: A longitudinal cohort study was carried out including 313 sporadic and 16 familial ALS patients with repeated serum uric acid measurements. Multivariate Cox regression models were used to evaluate the survival-related factors.Results: There were 207 male and 122 female, and the mean age of onset was 55.7 ± 11.2 years old. The male patients had significantly higher baseline uric acid levels than that in female patients (342.4 ± 91.4 vs. 279.3 ± 71.4 μmol/L; p < 0.0001). The uric acid levels were inversely associated with the decline rate of ALSFRS-R per month (ΔALSFRS-R). After multivariate Cox regression analysis, a survival advantage was found in male, but not female, with higher serum uric acid levels. In males, a shorter diagnostic delay (≤10 m), lower BMI at baseline (≤18.70 kg/m2), faster disease progression (ΔALSFRS-R > 0.63), and lower baseline uric acid levels (≤292 μmol/L, HR: 1.936; 95% CI: 1.334–2.810) were associated with a shorter survival. During follow-up, the serum uric acid levels were not significantly altered over time.Conclusion: There is an inverse correlation between baseline serum uric acid levels and risk of death, prominently in male ALS patients.

The variation of serum uric acid levels among patients with myocardial infarction treated with ticagrelor and the association between serum uric acid and platelet reactivity

Objectives: To compare the impact of ticagrelor or clopidogrel on serum uric acid levels among patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) and further evaluate the effects of variation of serum uric acid levels on platelet reactivity. Methods: STEMI patients who admitted to Fuwai Hospital from April 2017 to January 2020, and underwent primary PCI and discharged alive with aspirin and ticagrelor or clopidogrel were included in this study. Patients were divided into ticagrelor group and clopidogrel group. The baseline clinical data were collected. Serum uric acid and creatinine levels at baseline and 30 days post-PCI were measured. Light transmittance aggregometry was used to assess maximum aggregation rate induced by adenosine diphosphate and arachidonic acid. The changes of serum uric acid and creatinine were compared between the two groups. Multivariate logistic regression was performed to evaluate independent related factors for rise in the uric acid levels, and the effect of variation of serum uric acid level on platelet reactivity was analyzed. Results: A total of 967 patients were included, the age was (59.4±12.1) years, and 163 case were female. There were 550 cases in ticagrelor group (56.9%) and 417 cases in clopidogrel group (43.1%). Baseline serum uric acid and creatinine levels were similar between the 2 groups. At 30 days, the serum uric acid level [(347.2±96.5) mmol/L vs. (341.2±105.3) mmol/L, P=0.009] and absolute [46.4 (-2.4, 88.1) mmol/L vs. 25.0 (-21.9, 73.0) mmol/L, P=0.001] and percentage [13.2 (-0.01, 29.0) % vs. 7.9 (-5.7, 25.0) %, P=0.007] increase in the serum uric acid levels were significantly higher in ticagrelor group than in clopidogrel group. The level of serum creatinine at 30 days was significantly lower in ticagrelor group than in clopidogrel group [(89.7±21.3) μmol/L vs. (94.4±43.9) μmol/L, P<0.05], whereas there were no differences in absolute [8.0 (-1.4, 16.6) μmol/L vs. 7.8 (-2.0, 16.6) μmol/L] and percentage [10.5 (-1.7%, 22.6%) vs. 9.8 (-2.4%, 22.1%)] change in the serum creatinine between the 2 groups (all P>0.05). Logistic regression analysis showed that, after adjusting for confounding factors, ticagrelor therapy was an independent related factor of serum uric acid elevation (OR=1.582, 95% CI:1.023-2.447, P=0.039). The variation of the serum uric acid levels did not affect platelet aggregation and the percentage of high platelet reactivity in both groups. Conclusions: Ticagrelor use is related to a significant increase in the serum uric acid levels at 30 days post-PCI in this patient cohort. The variations in the uric acid levels do not increase the percentage of high platelet reactivity in STEMI patients treated with ticagrelor or clopidogrel.

The relationship between serum uric acid levels and development of obesity in living kidney donors after donor nephrectomy.

Hyperuricaemia plays a role in the pathogenesis of obesity and related metabolic disorders. The aim of this study to investigate the relationship between pre-donation serum uric acid (SUA) level and obesity development after nephrectomy in living kidney donors. Living donors of kidney transplants between 1998 and 2019 were evaluated. Donors with less than 1year of follow-up were excluded from the study. The participants were divided into two groups according to last control body mass index (BMI) (obese; ≥30kg/m2 and nonobese; <30kg/m2 ) and median baseline SUA level (<4.6mg/dL and ≥4.6mg/dL). In the included 240 donors, the mean follow-up was 50±44 (12-216) months. The mean age was 47±11 (19-82) years, and 46.6% of donors were male. At last control, the percentage of obese donors had increased significantly compared to pre-donation time (22.5% vs 33.8%; P<.001) and last control obese donors had both higher baseline SUA (5.1±1.4 vs 4.5±1.2; P<.01) and BMI (30.7±2.6 vs 24.8±3.0; P<.001). Cox regression analysis showed that there is an independent relationship between the baseline SUA level and development of obesity (odds ratio: 1.30 [CI; 1.12-1.50]; P<.001). In Kaplan-Meier analysis, the development of obesity was significantly higher in kidney donors with high SUA level. Living kidney donors (LKD) have a tendency to obesity after nephrectomy. Preoperative serum uric acid level gives important information in LKDs that it could foresee the development of obesity after donation.

Prognostic impacts of serum uric acid levels in patients with chronic heart failure: insights from the CHART-2 study.

AimsPrognostic impacts of serum uric acid (UA) levels in patients with chronic heart failure (CHF) remain inconclusive, especially for the whole range of serum UA levels.Methods and resultsIn the Chronic Heart Failure Registry and Analysis in the Tohoku District‐2 (CHART‐2) study, we enrolled 4652 consecutive patients with CHF and classified them into four groups based on baseline serum UA levels by the Classification and Regression Tree: G1 (<3.8 mg/dL, N = 313), G2 (3.8–7.1 mg/dL, N = 3070), G3 (7.2–9.2 mg/dL, N = 1018), and G4 (>9.2 mg/dL, N = 251). Mean age was 71 ± 12, 69 ± 12, 68 ± 13, and 69 ± 15 years in G1, G2, G3, and G4, respectively (P < 0.001). During the median follow‐up of 6.3 years, in G1, G2, G3, and G4, 111 (35%), 905 (29%), 370 (36%), and 139 (55%) patients died and 79 (25%), 729 (24%), 300 (29%), and 115 (46%) experienced heart failure hospitalization, respectively (both P < 0.001). G1 was characterized by a significantly high prevalence of women as compared with G2, G3, and G4 (59%, 32%, 24%, and 23%, respectively). Serum creatinine levels (0.8 ± 0.4, 0.9 ± 0.4, 1.2 ± 0.6, and 1.4 ± 0.8 mg/dL, respectively), prevalence of atrial fibrillation (34%, 39%, 45%, and 50%, respectively), and diuretics use (36%, 45%, 67%, and 89%, respectively) increased from G1, G2, G3 to G4 (all P < 0.001), while left ventricular ejection fraction decreased from G1, G2, G3 to G4 (59 ± 15, 58 ± 15, 54 ± 15, and 52 ± 17%, respectively, P < 0.001). Multivariable Cox proportional hazards models showed that, as compared with G2, both G1 and G4 had increased incidence of all‐cause death [adjusted hazard ratio (aHR) 1.34, 95% confidence interval (CI) 1.08–1.67, P = 0.009; aHR 1.28, 95% CI 1.02–1.61, P = 0.037, respectively] and heart failure admission (aHR 1.39, 95% CI 1.09–1.78, P = 0.008 and aHR 1.35, 95% CI, 1.06–1.71, P = 0.014, respectively). This U‐shaped relationship was evident in the elderly patients. Furthermore, abnormal transitions to either higher or lower levels of serum UA from G2 were associated with increased mortality (aHR 1.29, 95% CI 1.06–1.57, P = 0.012; aHR 1.57, 95% CI 1.12–2.20, P = 0.009).ConclusionsThese results demonstrate that serum UA levels have the U‐shaped prognostic effects and abnormal transitions to either higher or lower levels are associated with poor prognosis in the elderly patients with CHF.

Age and sex dependent association of uric acid and incident hypertension

Background and aimsA previous meta-analysis suggested that the relationship between hyperuricemia and hypertension may be stronger in younger individuals and women. We aimed to investigate the age and sex dependent association of uric acid (UA) and incident hypertension. Methods and resultsWe analyzed data from the Health Examinees Study, a community-based prospective cohort study conducted in Korea from 2004 to 2013. It included 29,088 non-hypertensive subjects aged 40–79 (age, 52.5 ± 7.8 years; men, 31.4%) who had serum UA measurement and participated in the follow-up survey. The risk factors of hypertension were assessed using Cox regression. Over a mean 3.8 years of follow-up, 1388 men (15.2%) and 1942 women (9.7%) were newly diagnosed with hypertension. Upon age- and sex-based stratification, the risk of hypertension was highest in hyperuricemic subjects aged 40–49 years (HR: women, 2.16; men, 1.30). Across the entire cohort, the risk of incident hypertension was higher in groups with higher serum UA levels, and highest in women aged 40–49 years (HR, 1.44; P < 0.001). On multivariable linear regression analysis, the higher the baseline serum UA level, the greater the increase in blood pressure during follow-up, and this effect was strongest in women aged 40–49 years (β = 0.87 and P < 0.01 for systolic blood pressure). ConclusionsThe relationship between uric acid and incident hypertension tended to be dependent on age and sex. Younger women are at highest risk of UA-related incident hypertension.

Increased Susceptibility of Atrial Fibrillation Induced by Hyperuricemia in Rats: Mechanisms and Implications.

High levels of serum uric acid is closely associated with atrial fibrillation (AF); nonetheless, the detailed mechanisms remain unknown. Therefore, this work examined the intricate mechanisms of AF triggered by hyperuricemia and the impact of the uricosuric agent benzbromarone on atrial remodeling in hyperuricemic rats. After adjusting baseline serum uric acid levels, a total of 28 healthy male adult Sprague Dawley rats were randomly divided into 4 groups, namely, control (CTR), hyperuricemia (oxonic acid potassium salt, OXO) and benzbromarone (+ BBR), and OXO withdrawal groups. Primary rat cardiomyocytes were cultured with uric acid for 24h to investigate the direct influence of uric acid on cardiomyocytes. Results revealed that AF vulnerability and AF duration were dramatically greater in hyperuricemic rats (OXO group), while the atrial effective refractory periods (AERPs) were significantly shorter. Meanwhile, BBR treatment and withdrawal of 2% OXO administration remarkably reduced AF inducibility and shortened AF duration. Moreover, abnormal morphology of atrial myocytes, atrial fibrosis, apoptosis, and substantial sympathetic nerve sprouting were observed in hyperuricemic rats. Apoptosis and fibrosis of atria were partly mediated by caspase-3, BAX, TGF-β1, and α-smooth muscle actin. Uric acid significantly induced primary rat cardiomyocyte apoptosis and fibrosis in vitro. Also, we found that sympathetic nerve sprouting was markedly upregulated in the atria of hyperuricemia rats, and was restored by BRB or absence of OXO administration. In summary, our study confirmed that AF induced by hyperuricemic rats occurred primarily via induction of atrial remodeling, thereby providing a novel potential treatment approach for hyperuricemia-related AF.