Baseline Uric Acid Research Articles

Effects of ertugliflozin on uric acid and gout-related outcomes in persons with type 2 diabetes and cardiovascular disease: Post hoc analyses from VERTIS CV.

To conduct post hoc analyses of the VERTIS CV (NCT01986881) trial to explore the effects of ertugliflozin on serum uric acid (UA) and gout-related outcomes. Participants with type 2 diabetes and atherosclerotic cardiovascular disease were randomised (1:1:1) to placebo, ertugliflozin 5 mg or ertugliflozin 15 mg. Mean UA over time (260 weeks) was evaluated for pooled ertugliflozin versus placebo overall, and by baseline quintile of UA (≤4.3 mg/dL [≤255.8 µmol/L], >4.3-5.1 mg/dL [>255.8-303.4 µmol/L], >5.1-5.8 mg/dL [>303.4-345.0 µmol/L], >5.8-6.9 mg/dL [>345.0-410.4 µmol/L] and >6.9 mg/dL [>410.4 µmol/L]), glycated haemoglobin level, albuminuria status, estimated glomerular filtration rate and KDIGO (Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease) risk category. The effect of ertugliflozin on a composite of gout onset or initiation of anti-gout medication was assessed. The mean UA levels at baseline were 5.67 and 5.62 mg/dL in the placebo and ertugliflozin groups, respectively. Ertugliflozin reduced UA over Weeks 6-260 compared with placebo, with least squares mean (LSM) changes (95% confidence interval [CI]) from baseline at Week 260 of 0.07 mg/dL (-0.02, 0.15) and -0.19 mg/dL (-0.25, -0.13) in the placebo and pooled ertugliflozin groups, respectively. At Week 260, placebo-adjusted LSM change (95% CI) from baseline in UA was -0.26 mg/dL (-0.36, -0.16) with ertugliflozin. Ertugliflozin was associated with reductions in UA across baseline UA quintiles compared with placebo. The incidence of the composite of gout-related outcomes was 84/2539 (3.3%) for placebo and 133/5091 (2.6%) for ertugliflozin (hazard ratio for the composite 0.76 [95% CI 0.580, 1.002]). Ertugliflozin was generally associated with lowering UA overall and across subgroups compared with placebo, and numerically reduced rates of gout-related outcome events.

The use of allopurinol in prophylaxis against contrast-induced nephropathy in patients undergoing percutaneous coronary intervention

Abstract Background Contrast-induced nephropathy (CIN) is a serious complication after percutaneous coronary intervention (PCI). Inflammation and development of reactive oxygen species are among the postulated mechanisms of CIN. Allopurinol with anti-inflammatory action could be a preventive method of CI-AKI. Aim of the work To determine the effect of adding allopurinol to hydration in the prevention of CIN in patients undergoing PCI, with or without hyperuricemia. Methods One hundred and seven patients with moderate to high Mehran score undergoing elective PCI were randomly allocated to the allopurinol (n=52) or the control group (n=55). Those in the allopurinol group (hyperuricemic n=25, and normouricemic n= 27) received allopurinol 300 mg one day and one hour before PCI beside intravenous hydration (1 ml/kg/hour) normal saline, a maximum of 100 ml/hour for 12 hours pre and post coronary angiography. Patients in the control group (hyperuricemic n=26 and normouricemic n=29), received the same intravenous hydration only. Serum creatinine and urea were measured before and 48 hours after the procedure while the uric acid level was measured before the procedure only. CIN was defined by a percentage increase in serum creatinine of ≥25% or absolute serum creatinine ≥0.5 mg/dl, 48 hours after PCI. Results The mean age of the studied patients was 59.6 ± 9.1 years old, 59% were male. No difference between both groups regarding baseline characteristics or medications. Average Mehran score was 9.0 ± 1.2. CIN was observed in 5 patients in the allopurinol group (9.6%) and 15 patients in the control group (27.3%) (P = 0.017). There was no significant difference between both groups regarding the contrast volume (179.8 ± 68.1 vs. 153.8 ± 57.9 ml, p: 0.052). Hyperuricemia had no significant effect on increasing the incidence of CI-AKI either in patients with or without CKD (p=0.964). Conclusion Allopurinol on the top of hydration was found to decrease the incidence of CIN following PCI in patients with moderate to high Mehran score for CIN. The anti-inflammatory action of allopurinol could be the mechanism of this favorable effect, as baseline uric acid didn't affect the results. Further multi-center study with a larger sample size is needed to offer more definite results.

Mildly decreased egfr modifies the association between uric acid and risk of kidney function decline: a 5-year population-based cohort study

Abstract Background the role of uric acid (UA) in chronic kidney disease (CKD) remains controversial. In this study, the effects of UA levels on risk of kidney function (KF) decline in patients with normal or mildly decreased KF at baseline were investigated. Methods Data were extracted from the community-based Tongzhou Cohort Study. The cohort of 4246 patients was divided into the normal KF group (estimated glomerular filtration rate [eGFR] ≥ 90 mL/min/1.73 m2) or mildly decreased KF group (60 ≤ eGFR < 90 mL/min/1.73 m2). The primary endpoint was the risk of kidney function decline, which defined as a composite of a ≥ 30% decrease in eGFR from baseline or new onset of CKD diagnosed during the annual checkups. Results A total of 284 participants reached the primary endpoint during the 5-year follow-up period. There was a significant interaction between UA levels and baseline eGFR (p < 0.001). Restricted cubic spline analysis revealed a U-shaped association between baseline UA levels and the risk of decreased KF for participants with normal KF (cut-off value = 5.0 mg/dL; pnonlinear = 0.025) and a linear association for participants with mildly decreased KF (pnonlinear = 0.384). The odds ratio of an increase in UA levels by 1 mg/dL was 1.15 [95% confidence interval (CI) 1.02–1.31, p = 0.028] for the primary endpoint and 1.15 (95% CI = 1.01–1.31, p = 0.037) for new onset of CKD for participants with mildly decreased KF. Conclusion The association between uric acid and risk of KF decline was U-shaped in participants with normal KF while linear in participants with mildly decreased KF.

Identifying reliable obesity indices for hyperuricemia among middle-aged and elderly populations: a longitudinal study

BackgroundGiven the established link between obesity and hyperuricemia (HUA), the research want to investigate the relationship between different obesity indices and HUA, and further analyze which obesity index can better predict HUA.MethodsThe data were obtained from a longitudinal study involving middle-aged and elderly populations in Dalian, China. The research encompassed individuals who exhibited typical uric acid levels initially and tracked their progress over a three-year period. 8 obesity indices were evaluated retrospectively. Subgroup analyses were conducted to identify susceptible populations. Restricted cubic splines (RCS) were utilized to model the dose-response relationships between obesity indices and HUA. Receiver operating characteristic (ROC) curves were applied to visualize and compare the predictive value of both traditional and new obesity indices for HUA.ResultsAmong 4,112 individuals with normal baseline uric acid levels, 950 developed HUA. Significant associations with HUA were observed for body mass index (BMI), waist circumference (WC), body roundness index (BRI), cardiometabolic index (CMI), visceral adiposity index (VAI), Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), and abdominal volume index (AVI). Subgroup analysis indicated that all obesity indices proved more effective in assessing the onset of HUA in women without Metabolic Syndrome (MetS). Further analysis using RCS revealed non-linear dose-response relationships between LAP, CMI, VAI, and HUA in males, with similar non-linear relationships observed for all indices in females. The results from the ROC curves indicate that LAP may serve as a better predictor of HUA in males, and CVAI may serve as a better predictor in females.ConclusionHUA is closely associated with obesity indices. Among females, CVAI emerges as the preferred predictive index for HUA. In males, LAP emerges as the preferred predictive index for HUA.

HYPERTRIGLYCERIDEMIA IN PATIENTS WITH ACUTE AND CHRONIC CORONARY SYNDROME: PREVALENCE AND THEIR ASSOCIATION WITH EXTREME CARDIOVASCULAR RISK AND LEFT VENTRICULAR FUNCTION

Objective: Hypertriglyceridemia prevalence in Acute and Chronic Coronary Syndrome (ACS and CCS respectively) patients in the era of very low LDL target is still unknow. The objective of our study is to evaluate the prevalence of triglyceride levels above 150 or 200 mg/dL despite statin therapy and LDL cholesterol at targets in ACS and CCS subjects enrolled in a Cardiac Rehabiliatitation (CR) program Design and method: This cross-sectional observational study was conducted at the Niguarda Hospital (Milan, Italy). Patients undergoing CR after ACS/CCS from January 1, 2012, to March 28, 2023, were included. Data on demographic, clinical, laboratory, and instrumental variables were collected. Results: The study population consisted of 740 patients with a mean age of 64.3±10.7 years, predominantly male (81.7%). Triglyceride levels significantly decrease during the CR period (131.1±63.8 vs 116.9±75.9 mg/dL; p < 0.001) similarly to LDL cholesterol (107.9 ± 38.8 mg/dL vs 69.9 ± 25.9mg/dL, p<0.001). 50.8% of the subjects reach the LDL cholesterol target. The percentage of patients with triglycerides >150 mg/dL at CR ends was 17.8% (15.6% when considering only patients that reach the LDL target of 55 mg/dL) while it is only 6.8% for triglycerides >200 mg/dL (5.9% when considering only patients that reach LDL target). Patients with triglycerides >150 mg/dL had higher baseline BMI, LDL cholesterol and uric acid with lower ejection fraction at CR ends. Hypertriglyceridemia significantly correlates with extreme CV risk (R= 0.08, p= 0.025). At multivariate analysis, FE (dependent variable) was significantly associated with triglycerides (beta= - 0,145, p= 0,026) and systolic BP (beta= 0,137, p= 0,032). Conclusions: Despite high intensity statin therapy and lower LDL cholesterol targets, a substantial proportion of patients in cardiac rehabilitation still had elevated triglyceride levels. This study highlights the potential role of Icosapent Ethyl in managing hypertriglyceridemia in these patients.

Dynamic LVEF Decline and Serum NT-proBNP and Uric Acid Levels before Heart Transplantation are Independent Predictors of Adverse Outcomes in Young Adult Patients with Dilated Cardiomyopathy.

The present study investigated the predictors of adverse outcomes in young adult patients with dilated cardiomyopathy (DCM) who underwent heart transplantation (HTx). Twenty-four young adult patients (aged 18-45 years) with DCM who underwent HTx in our hospital from January 2012 to December 2022 were included in this retrospective analysis. Pre- and post-HTx data were collected for echocardiography, N-terminal pro-brain natriuretic peptide (NT-proBNP), and uric acid (UA). Data collected at the time of DCM diagnosis were designated as baseline data. Post-HTx assessments were conducted at 1 week and 3, 6, 12, and 36 months post-HTx. The primary endpoint was defined as any adverse event, including left ventricular ejection fraction (LVEF) 50% (n = 3), 50% increase in right or left ventricular diameter (n = 12), or death (n = 2). Patients were categorized into a non-adverse-event group (n = 12) or an adverse-event group (n = 12). Baseline NT-proBNP (p = 0.014) and UA (p = 0.012) were significantly higher in the adverse-event group than in the non-adverse-event group. Baseline NT-proBNP 7390 pg/mL (relative risk (RR) = 7.412, p = 0.046), UA 542 µmol/L (RR = 8.838, 95% confidence interval (95% CI) = 1.541-50.694, p = 0.014), and sustained reduction in LVEF ( 3%) over a 2-year pharmacological treatment prior to HTx (RR = 3.252, p = 0.046) were significantly associated with an increased risk of adverse events post-HTx. In young adult DCM patients post-HTx, heightened baseline levels of NT-proBNP and UA levels and a sustained reduction in LVEF over time prior to undergoing an HTx are significantly associated with an increased risk of adverse events post-HTx. Future studies are needed to observe whether individualized monitoring strategies could reduce the incidence of adverse events following HTx in these patients.

Ensemble machine learning prediction of hyperuricemia based on a prospective health checkup population.

Objectives: An accurate prediction model for hyperuricemia (HUA) in adults remain unavailable. This study aimed to develop a stacking ensemble prediction model for HUA to identify high-risk groups and explore risk factors. Methods: A prospective health checkup cohort of 40899 subjects was examined and randomly divided into the training and validation sets with the ratio of 7:3. LASSO regression was employed to screen out important features and then the ROSE sampling was used to handle the imbalanced classes. An ensemble model using stacking strategy was constructed based on three individual models, including support vector machine, decision tree C5.0, and eXtreme gradient boosting. Model validations were conducted using the area under the receiver operating characteristic curve (AUC) and the calibration curve, as well as metrics including accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score. A model agnostic instance level variable attributions technique (iBreakdown) was used to illustrate the black-box nature of our ensemble model, and to identify contributing risk factors. Results: Fifteen important features were screened out of 23 clinical variables. Our stacking ensemble model with an AUC of 0.854, outperformed the other three models, support vector machine, decision tree C5.0, and eXtreme gradient boosting with AUCs of 0.848, 0.851 and 0.849 respectively. Calibration accuracy as well as other metrics including accuracy, specificity, negative predictive value, and F1 score were also proved our ensemble model's superiority. The contributing risk factors were estimated using six randomly selected subjects, which showed that being female and relatively younger, together with having higher baseline uric acid, body mass index, γ-glutamyl transpeptidase, total protein, triglycerides, creatinine, and fasting blood glucose can increase the risk of HUA. To further validate our model's applicability in the health checkup population, we used another cohort of 8559 subjects that also showed our ensemble prediction model had favorable performances with an AUC of 0.846. Conclusion: In this study, the stacking ensemble prediction model for HUA was developed, and it outperformed three individual models that compose it (support vector machine, decision tree C5.0, and eXtreme gradient boosting). The contributing risk factors were identified with insightful ideas.

Baseline Uric Acid Levels and Intravenous Thrombolysis Outcomes in Patients With Acute Ischemic Stroke: A Prospective Cohort Study.

The study aimed to investigate the relationship between uric acid (UA) levels and functional outcomes at 3 months in patients with acute ischemic stroke (AIS) who underwent intravenous thrombolysis (IVT). This prospective cohort study included 1001 consecutive patients with AIS who underwent IVT. The correlation between UA levels and post-IVT AIS outcomes was examined. Any nonlinear relationship was assessed using a restricted cubic spline function. The nonlinear P value for the association of UA levels with favorable (modified Rankin Scale [mRS] score ≤2) and excellent (mRS score ≤1) outcomes at 3 months post-IVT were <0.001 and 0.001, respectively. However, for patients with and without hyperuricemia, no evident nonlinear relationship was observed between UA levels and favorable 3-month post-IVT outcomes, with nonlinear P values of 0.299 and 0.207, respectively. The corresponding interaction analysis yielded a P value of 0.001, indicating significant heterogeneity. Similar results were obtained for excellent outcomes at 3 months post-IVT. In the hyperuricemia group, increased UA levels by 50 μmol/L reduced the odds of a favorable 3-month post-AIS outcome (odds ratio [OR], 0.75 [95% CI, 0.57-0.97]). Conversely, in the nonhyperuricemia group, a similar UA increase was linked to higher favorable outcome odds (OR, 1.31 [95% CI, 1.15-1.50]). An inverted U-shaped nonlinear relationship was observed between UA levels and favorable and excellent outcomes at 3 months in patients with AIS who underwent IVT. Higher UA levels predict favorable outcomes in patients without hyperuricemia but unfavorable outcomes in those with hyperuricemia.

Clinical significance of the m6A methyltransferase METTL3 in peripheral blood of patients with coronary heart disease.

This study aims to explore the association of methyltransferase-like protein 3 (METTL3) expression with severity of coronary artery stenosis in patients with coronary heart disease (CHD). A total of 100 patients administrated in the Fourth Affiliated Hospital of China Medical University between October 2022 and June 2023 with primary symptoms of chest pain or tightness, or cardiac discomfort, and who underwent coronary angiography for a definitive diagnosis, were included in the study. The baseline characteristics, including TG, TC, LDL-C, HDL-C, uric acid and past history were recorded. Peripheral blood samples were collected to assess the expression levels of METTL3, YT521-B homology domains 1 (YTHDF1), YT521-B homology domains 2 (YTHDF2), and YT521-B homology domains 3 (YTHDF3) using the PCR method. Relative expression levels of METTL3 protein were determined by Western blotting. Correlation analysis were conducted to evaluate the relationship between METTL3/YTHDF1 gene expression and clinical data. Receiver operating characteristic (ROC) curve analysis was employed to assess the predictive value of METTL3 and YTHDF1 for CHD. Binary logistic regression was used to determine whether the expression of METTL3 and YTHDF1 in peripheral blood were risk factors for CHD. The study found no significant differences in baseline characteristics between CHD patients and controls, except for length of stay, Lymphocytes, Neutrophils, AST, HDL-C and modified Gensini score. The gene expression levels of METTL3 and YTHDF1 were significantly higher in CHD patients compared to controls (p < 0.05). Furthermore, METTL3 protein expression was also significantly elevated in the CHD group compared to the control group (p < 0.05). METTL3 gene expression correlated with HDL-C and Gensini score, while YTHDF1 gene expression correlated with Age, WBC, Neutrophils, RDW-CV, modified Gensini score. ROC curve analysis demonstrated an AUC of 0.692 for METTL3 in CHD, with a sensitivity of 66.7% and a specificity of 69.8% at a cut-off value of >0.052. The AUC for YTHDF1 in CHD was 0.623, with a sensitivity of 47.4% and a specificity of 74.4% at a cut-off value of >0.027. Binary logistic regression revealed that only increased METTL3 expression in peripheral blood was an independent risk factor for CHD (p < 0.05). The increased expression of METTL3 in peripheral blood may serve as a potential biomarker and predictive factor for CHD.

Uric acid mediated the relationship between obesity and hypertension in children and adolescents: A population‑based cohort study

Background and aimObesity and hyperuricemia (HUA) often coexist and have been widely accepted as risk factors for hypertension, but the role of uric acid (UA) in the relationship between obesity and hypertension remains unknown in children and adolescents. Methods and resultsA total of 7525 subjects aged 6–16 years were from the School-based Cardiovascular and Bone Health Promotion Program (SCVBH) at baseline (2017) and followed up in 2019. Multivariable logistic regression with interaction terms, cross-lagged panel analysis, and causal mediation model were applied to delineate the joint impact of obesity and HUA on hypertension, including the interaction effect, the temporal association, and the mediating effect of UA in the relationship between obesity and hypertension. There were 10.8 % of the participants with normotension at baseline developed hypertension after two years of follow-up. Cross-lagged panel analysis showed that the two-time point association was significant only from baseline BMI to follow-up UA (β1 = 0.302, P < 0.001), but not from baseline UA to follow-up BMI (β2 = 0.002, P = 0.745). Multivariable logistic regression showed that both obesity and HUA increased the risk of hypertension, but no interaction effect between HUA and obesity. The causal mediation analysis found that UA partially mediated the association between BMI and SBP (mediate proportion: 20.3 %, 95 % CI: 17.4–22.9 %) or DBP (mediate proportion: 11.9 %, 95 % CI: 3.9–18.2 %). The results were consistent in the analysis of systolic hypertension rather than diastolic hypertension. ConclusionsIt is mediating effect that UA played in the progress from obesity to hypertension, particularly systolic hypertension in children and adolescents.

Serum Uric Acid Levels and Outcome of Acute Ischemic Stroke: a Dose-Response Meta-analysis.

Previous meta-analyses have reported conflicting results regarding the relationship between baseline uric acid (UA) levels and acute ischemic stroke (AIS) outcomes. Therefore, we conducted a dose-response meta-analysis to elucidate the association's strength and shape. Studies on the association between baseline UA levels and AIS outcomes in the PubMed and EMBASE databases were searched from their inception to April 17, 2023. Two researchers independently reviewed the studies for inclusion. A total of 23 articles involving 15,733 patients with AIS were included. The analysis revealed a significant inverse correlation between UA levels and AIS outcomes. The linear trend estimation indicated that a 50-μmol/L increment in UA level was associated with a 21.7% lower risk of hemorrhagic transformation (odds ratio [OR]: 0.783; 95% confidence interval [CI]: 0.743, 0.826; I2 = 43.4%; n = 4), 7.0% lower risk of 90-day unfavorable outcome [modified Rankin scale score ≥ 2] (OR: 0.930; 95% CI: 0.875, 0.990; I2 = 0%; n = 3), and 7.5% lower risk of 90-day poor outcome [modified Rankin scale score ≥ 3] (OR: 0.925; 95% CI: 0.863, 0.990; I2 = 74.4%; n = 3) in patients with AIS after accounting for relevant covariates. A linear dose-response relationship exists between baseline UA levels and the outcome of patients with AIS within a certain range, with higher baseline UA levels associated with better outcomes after AIS. Further dose-response meta-analyses, including a larger number of original articles, are required to validate our findings.

Association between serum uric acid and prostate cancer mortality in androgen deprivation therapy: A population-based cohort study.

This population-based study examined the association between baseline uric acid (UA) and prostate cancer (PCa)-related mortality amongst PCa patients receiving androgen deprivation therapy (ADT). Adults with PCa who received ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with missing baseline UA were excluded. Patients were followed up until September 2021. The outcome was PCa-related mortality. Altogether, 4126 patients (median follow-up 3.1[interquartile range 1.4-6.0] years) were included. A J-shaped association was observed between baseline UA level and PCa-related mortality risk, with a direct association in those with mean(0.401 mmol/L) or above-mean baseline UA levels (hazard ratio (HR) per standard deviation-increase 1.35 [95% confidence interval 1.21,1.51], p < 0.001), and an inverse association in those with below-mean baseline UA levels (HR 0.78[0.67,0.92], p = 0.003). The former remained significant on competing risk regression, but not the latter. A J-shaped relationship between baseline UA level and PCa-related mortality risk was identified. This study was mainly limited by potential unmeasured and residual confounders. Further validation studies are warranted.

#4916 A PILOT STUDY ON THE BENEFICIAL EFFECT OF RASBURICASE IN THE PREVENTION OF ACUTE RENAL FAILURE IN PATIENTS WITH CARDIORENAL SYNDROME

Abstract Background and Aims Uricase metabolizes uric acid into allantoin, a soluble compound that is easily excreted in the urine. Acute hyperuricemia is associated with endothelial injury and vasoconstriction, favoring acute renal failure. Preliminary studies show the protective role of lowering uric acid in cardiac patients. Method Pilot study conducted in patients with cardiorenal syndrome and hyperuricemia (&amp;gt;9 mg/dl). All received a single dose of rasburicase (0.20 mg/kg/day in the first 9 patients or a fixed dose of 6 mg in 14 patients) evaluating its effect on renal function and the need for renal replacement therapy. Results Twenty-three patients aged 68 ± 14 years were included, 14 men and 9 women, 87% hypertensive, 35% diabetic, 17% with liver disease, and 26% with cancer. Baseline: mean LVEF 40±14.1% (13-63), pro-BNP 19880±14000ng/l, basal Cr 1.55±0.58 mg/dl, uric acid 14.1±2.26, phosphorus 5 .3±1.6 mg/dl and CRP 7±8 mg/l. The evolution of renal function after treatment is shown in Table 1. In all patients, uric acid after rasburicase decreased to 0.5 mg/dl. There were no differences in renal function, RRT, and hospitalization between patients who received a dose of 0.20 mg/kg/day or 6 mg iv. Only 3 patients required RRT for 21±23 hours, with recovery from acute renal failure. Comparing the patients who required RRT versus those who did not, these presented higher baseline uric acid levels: 16.5±2.5 vs 13.7±1.1 mg/dl, P = .049, and there were no differences in LVEF. pro-BNP and previous renal function. One patient died during the hospital stay due to terminal CHF and sepsis, but having recovered kidney function. Conclusion Rasburicase administration may prevent established renal failure in patients with cardiorenal syndrome and hyperuricemia. Early treatment, avoiding very high levels of hyperuricemia, could be more effective in reducing the need for renal replacement therapy.

FACTOR ASSOCIATED WITH HYPERURICEMIA DEVELOPMENT DURING A 25 YEARS FOLLOW-UP: THE PAMELA STUDY

Objective: HyperUricemia (HU) has been associated with future fatal and non fatal CV events as well as with hypertension and metabolic syndrome development. However, only few data exist regarding the change in Uric Acid (UA) and the development of HU during a population follow-up. In particular, no study analyzed the variations during a very long follow-up. The present study was aimed at evaluating the factors associated with UA changes and HU development during a 25-years follow-up in the PAMELA study. Both the classic cut-off for hyperuricemia and the newly one identified by the Uric Acid Right for Heart Health (URRAH) study were used to define HU. Design and method: We analyzed data collected in 561 subjects of the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study with available SUA who complete the 3rd wave study (mean follow-up time 25.2 ± 0.5 years). The classic cut-off of 6/7 mg/dL (females and males respectively) and URRAH one (5.1/5.6 mg/dL for females and males) were used for HU definitions. Results: Mean UA value during follow-up increase from 4.7 ± 1.1 to 5.0 ± 1.2 mg/dL (p &lt; 0.001) with a mean increase of 0.3 ± 1.1 mg/dL. UA changes significanlty correlated with baseline UA (r = -0.39, p &lt; 0.001) and creatinine (r = -0 - 21, p &lt; 0.001). With the classic cut-off (6/7 mg/dL) 9.1% of the subjects develop HU and this was associated at the multivariate model with age, sex (male), baseline diastolic Blood Pressure (BP) (OR 1.038, p = 0.02) and UA (OR 2.62, p &lt; 0.001). With the new URRAH cut-off 19.1% of the subjects develop HU. At the multivariate model variables associated were gender (male) and baseline 24h systolic BP (OR 1.05, p &lt; 0.001), tryglicerides (OR 1.01, p = 0.01) and UA (4.99, p &lt; 0.001). Conclusions: The present study provide evidence that in the PAMELA study during the 25 year follow-up there is a progressive increase in UA. Baseline UA is the most important factor associated with HU development. However, also age, gender, triglycerides and BP could help to identify subjects that most probably will develop HU.

Incidence, clinical characteristics and prognosis of tumor lysis syndrome following B-cell maturation antigen-targeted chimeric antigen receptor-T cell therapy in relapsed/refractory multiple myeloma.

B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T cell (CAR-T) therapy is used for refractory or relapsed multiple myeloma (r/r MM). However, CAR-T-related tumor lysis syndrome (TLS) has been observed. We aimed to elucidate the incidence, clinical and laboratory characteristics, and prognosis of CAR-T cell-related TLS. Patients (n=105) with r/r MM treated with BCMA-targeted CAR-T cell therapy were included. Patient characteristics, laboratory parameters, and clinical outcomes were assessed. Eighteen (17.1%) patients developed TLS after BCMA-targeted CAR-T cell therapy. The median time till TLS onset was 8 days. Patients with TLS had steep rise in uric acid (UA), creatinine, and lactate dehydrogenase (LDH) within 6 days following CAR-T cell infusion and presented earlier and persistent escalation of cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-γ [IFN-γ], and ferritin levels). All 18 patients had cytokine release syndrome (CRS), of which 13 (72.2%) developed grade 3-4 CRS. Three of 18 patients (16.7%) developed immune effector cell-associated neurotoxicity syndrome (ICANS): two patients with grade 1 ICANS and one with grade 2 ICANS. TLS development had a negative effect on the objective response rate (77.8% in the TLS group vs. 95.4% in the non-TLS group, p<0.01). During the median follow-up of 15.1 months, the median PFS was poorer of patients with TLS (median: 3.4 months in the TLS group vs. 14.7 months in the non-TLS group, p<0.001, hazard ratio [HR]=3.5 [95% confidence interval [CI] 1.5-8.5]). Also, TLS development exhibited significant effects on OS (median: 5.0 months in the TLS group vs. 39.8 months in the non-TLS group, p<0.001, hazard ratio [HR]=3.7 [95% CI 1.3-10.3]). TLS was associated with a higher tumor burden, elevated baseline creatinine and UA levels, severe CRS, pronounced CAR-T cell expansion, and corticosteroid use. TLS is a frequently observed CAR-T therapy complication and negatively influences clinical response and prognosis. Close monitoring for TLS should be implemented during CAR-T cell therapy, especially for those at high TLS risk.

Association between vegetarian diet and gouty arthritis: A retrospective cohort study

Background and aimsA vegetarian diet is rich in vegetables, fruits, and soy products. Although vegetarian diet is beneficial for improving the health outcomes such as body mass index, metabolic syndrome, cardiovascular disease, and mortality rate, the association between a vegetarian diet and gout incidence is not well known. Methods and resultsWe linked the MJ Health Survey Data and MJ Biodata 2000 with the National Health Insurance Research Database (NHIRD) and the National Registration of Death (2000–2018). Information on the diet was collected from the MJ Health Survey Data, and the incidence of gouty arthritis was confirmed using the NHIRD. The Kaplan–Meier survival curve and log-rank test were used to compare the differences between vegetarian and non-vegetarian participants. Cox regression models were used to estimate the risk of the incidence of gouty arthritis. Among 76,972 participants, 37,297 (48.46%) were men, 2488 (3.23%) were vegetarians and the mean age was 41.65 ± 14.13 years. The mean baseline uric acid level was 6.14 ± 1.65 mg/dL. A total of 16,897 participants developed gouty arthritis, including 16,447 (22.08%) non-vegetarians and 450 (18.9%) vegetarians over a mean follow-up of 19 years. Significant differences were observed in the Kaplan–Meier survival curves between vegetarians and non-vegetarians (log-rank p < 0.001). Vegetarians had a significantly decreased incidence of gouty arthritis compared with non-vegetarians (hazard ratio = 0.87, 95% confidence interval = 0.78–0.98, p = 0.02) after adjusting for potential confounders. ConclusionPeople with a vegetarian diet had a significantly decreased risk of developing gouty arthritis compared with non-vegetarians in Taiwan.

Asociación del nivel de ácido úrico en suero con los beneficios del control intensivo de la presión arterial

Introduction and objectivesIntensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether the serum uric acid concentration at baseline alters the benefits of intensive SBP control is unknown. MethodsThe STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to<130mmHg) and standard (SBP target of 130 to <150mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. This post hoc analysis was performed to examine whether the effects of intensive SBP intervention differed by the baseline uric acid concentration using 2 models: restricted cubic spline curves and subgroup analyses, both based on the Fine-Gray subdistribution hazard model in the analysis of the primary outcome and secondary outcomes (excluding all-cause death). In the analysis of all-cause death, the Cox regression model was used. We also examined the change in the follow-up uric acid concentrations. ResultsOverall, the risk of the primary outcome rose as the cumulative uric acid concentration increased in both the intensive and standard treatment groups. Patients with intensive treatment had a lower multivariable-adjusted subdistribution hazard ratio for the primary outcome, but with a wide overlap of 95%CI. Next, we stratified patients according to their baseline uric acid concentration (tertile 1 [T1], <303.0μmol/L; tertile 2 [T2], 303.0 to <375.8μmol/L; and tertile 3 [T3], ≥375.8μmol/L). Subgroup analyses using tertiles provided HRs and 95%CI in T1 (HR, 0.55; 95%CI, 0.36–0.86; P=.008), T2 (HR, 0.80; 95%CI, 0.56–1.14; P=.22) and T3 (HR, 0.86; 95%CI, 0.60–1.21; P=.39), with an interaction P value of .29. The results for most of the secondary outcomes followed the same trends. ConclusionsThere was no evidence that the benefit of the intensive SBP control differed by baseline uric acid concentrations. This trial was registered at ClinicalTrial.gov (Identifier: NCT03015311).

Serum uric acid: A risk factor for right ventricular dysfunction and prognosis in heart failure with preserved ejection fraction.

Hyperuricemia and right ventricular dysfunction (RVD) are both widespread in heart failure with preserved ejection fraction (HFpEF) patients. RVD is associated with a poor prognosis in HFpEF. The correlation between serum uric acid (UA) levels and right ventricular function is unclear. The prognostic performance of UA in patients with HFpEF needs further validation. A total of 210 patients with HFpEF were included in the study and divided into two groups according to UA level: the normal UA group (≤7 mg/dl) and the high UA group (>7 mg/dl). The variables examined included clinical characteristics, echocardiography, and serum biochemical parameters. Right ventricular function was assessed by tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular peak systolic velocity (TAPSV). Baseline characteristics were compared between the two groups, and the correlation between baseline UA and RVD was assessed using multifactorial binary logistic regression. Kaplan-Meier curves were used to describe all-cause mortality and heart failure readmission. Results showed that right ventricular function parameters were worse in the high UA group. After adjusting for UA, left ventricular posterior wall thickness (LVPWT), N-terminal B-type natriuretic peptide (NT-proBNP), atrial fibrillation (AF), and low-density lipoprotein cholesterol (LDL-C), UA (odds ratio = 2.028; p < 0.001) was independently associated with RVD, and UA >7 mg/dl (HR = 2.98; p < 0.001) was associated with heart failure readmission in patients with HFpEF. Elevated serum UA is closely associated with RVD and significantly associated with the heart failure readmission rate in patients with HFpEF.

Metabolic Syndrome and Its Components Are Associated with New-Onset Hyperuricemia in a Large Taiwanese Population Follow-Up Study.

The prevalence rate of hyperuricemia remains high in Taiwan, at 21.6% in men and 9.57% in women. Both metabolic syndrome (MetS) and hyperuricemia can cause many complications; however, few studies have evaluated the correlation between MetS and hyperuricemia. Therefore, in this observational cohort study, we explored associations between metabolic syndrome (MetS) and its components and new-onset hyperuricemia. Of 27,033 individuals in the Taiwan Biobank who had complete follow-up data, we excluded those with hyperuricemia at baseline (n = 4871), those with gout at baseline (n = 1043), those with no data on baseline uric acid (n = 18), and those with no data on follow-up uric acid (n = 71). The remaining 21,030 participants (mean age 50.8 ± 10.3 years) were enrolled. We found a significant association between new-onset hyperuricemia with MetS and the components of MetS (hypertriglyceridemia, abdominal obesity, low high-density lipoprotein cholesterol, hyperglycemia, and high blood pressure). Furthermore, compared to those without any MetS components, those with one MetS component (OR = 1.816), two MetS components (OR = 2.727), three MetS components (OR = 3.208), four MetS components (OR = 4.256), and five MetS components (OR = 5.282) were significantly associated with new-onset hyperuricemia (all p < 0.001). MetS and its five components were associated with new-onset hyperuricemia in the enrolled participants. Further, an increase in the number of MetS components was associated with an increase in the incidence rate of new-onset hyperuricemia.

Association of serum uric acid with benefits of intensive blood pressure control

Introduction and objectivesIntensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether the serum uric acid concentration at baseline alters the benefits of intensive SBP control is unknown. MethodsThe STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to<130mmHg) and standard (SBP target of 130 to <150mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. This post hoc analysis was performed to examine whether the effects of intensive SBP intervention differed by the baseline uric acid concentration using 2 models: restricted cubic spline curves and subgroup analyses, both based on the Fine-Gray subdistribution hazard model in the analysis of the primary outcome and secondary outcomes (excluding all-cause death). In the analysis of all-cause death, the Cox regression model was used. We also examined the change in the follow-up uric acid concentrations. ResultsOverall, the risk of the primary outcome rose as the cumulative uric acid concentration increased in both the intensive and standard treatment groups. Patients with intensive treatment had a lower multivariable-adjusted subdistribution hazard ratio for the primary outcome, but with a wide overlap of 95%CI. Next, we stratified patients according to their baseline uric acid concentration (tertile 1 [T1], <303.0μmol/L; tertile 2 [T2], 303.0 to <375.8μmol/L; and tertile 3 [T3], ≥375.8μmol/L). Subgroup analyses using tertiles provided HRs and 95%CI in T1 (HR, 0.55; 95%CI, 0.36–0.86; P=.008), T2 (HR, 0.80; 95%CI, 0.56–1.14; P=.22) and T3 (HR, 0.86; 95%CI, 0.60–1.21; P=.39), with an interaction P value of .29. The results for most of the secondary outcomes followed the same trends. ConclusionsThere was no evidence that the benefit of the intensive SBP control differed by baseline uric acid concentrations. This trial was registered at ClinicalTrial.gov (Identifier: NCT03015311).