Higher Uric Acid Levels Research Articles

Chronic Kidney Disease Observational Cohort Study And Assessment Of Baseline Characteristics And Their Relationship With Diabetes Status And Kidney Function

Background: Chronic kidney disease (CKD) may result in end-stage renal disease (ESRD), and undesirable outcomes such as death and dialysis. We carried out an observational cohort study to ascertain risk factors for the renal outcomes, all-cause mortality in patients with CKD. In this report, we studied the baseline demographic and laboratory characteristics of the cohort. Methods: A single-center, retrospective, observational cohort study was conducted at the outpatient Nephrology Clinic of Health Sciences University, Kayseri Medical Faculty, from January 1, 2010, to December 31, 2020. Age 18 to 70 years and eGFR 15 to 59 mL/min/1.73 m2 were inclusion criteria. Baseline demographic and laboratory data were documented. Results: One thousand seventy-three patients with CKD were enrolled in the study. Mean (SD) age was 55.87 (8.83) years, and 53.2% were men. %45.9 and %84.4 had diabetes mellitus and hypertension, respectively. The mean body mass index was 26.73 (3.95) kg/m2. Mean eGFR was 34.14 (10.45) mL/min/1.73 m2 using chronic kidney disease epidemiology collaboration. Median (p25-p75) urinary protein-creatinine ratio was 48.80 [22.40, 89.00] mg/mmol. Older patients had a lower eGFR, and the male gender was more common at stage 3 patients. Stage 4 patients had lower hemoglobin and serum calcium levels. Also, low eGFR was associated with high uric acid levels. Conclusion: This study along with future analysis may elucidate the natural history and clinical consequences of CKD. Controllable factors could be understood, and CKD progression and adverse outcomes may be prevented in this way.

Pengaruh Pemberian Jus Nanas Terhadap Penurunan Kadar Asam Urat pada Lansia di RT 05 RW 06 Kelurahan Rempoa Kecamatan Ciputat Timur Kota Tangerang Selatan

Gout purine metabolism disorder if it does not last normally, there will be a process of accumulation of crystals of uric acid in the joints and cause pain. This condition is commonly found in the elderly due to the slow rate of metabolism of the body. The prevalence of gout or gout based on diagnosis of health workers in Indonesia (7.3%) and based on the diagnosis or symptoms (24.7%). The purpose of this study was to determine the effect of pineapple juice on reducing uric acid levels in the elderly. This research design uses a quasi-experimental with one group pretest- posttest without control. The population in this study was 22 elderly with 18 samples who’s experienced with high level of uric acid. This study used sampling technique with was purposive sampling. The test results of this study found that the average before pineapple juice intervention was 8,244 mg/dl, after pineapple juice intervention was 6,628 mg/dl, and the final results of the paired T test showed that the p value was 0.000 (α≤ 0.05) so it could be concluded that there was an effect of giving pineapple juice on reducing uric acid levels in the elderly. This means that H0 is rejected and Ha is accepted. From the results of this study, it is hoped that it can be considered as one of the nursing care interventions by providing education in reducing uric acid levels as a source of useful information for the community

Ghrelin and Leptin among Patients with Urolithiasis with Concomitant Hyperuricemia and Metabolic Syndrome

Introduction: The study evaluated the selected appetite hormones (ghrelin, leptin) and inflammatory parameters (tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6)) in patients with urolithiasis, metabolic syndrome (MetS), and hyperuricemia. Materials: 57 patients with urolithiasis, MetS and hyperuricemia (UP group) and 29 healthy people as the control group (CG group) were recruited to the study. All persons were 22-60 age. Methods: After preliminary testing, the qualified participants were evaluated for fasting serum levels of ghrelin, leptin, IL-6, and TNF-α. Results: Our results revealed differences between average values of leptin (p = 0.045), ghrelin (p < 0.001), IL-6 (p < 0.001), and TNF-α (p < 0.001) in the studied groups. Moreover, in the UP group, significant correlations were found between ghrelin and leptin; between these hormones and IL-6, and between leptin and uric acid (UA). Besides, leptin concentration increased significantly along with the changes in the body mass index (BMI) categories in the UP group. Conclusions: This study showed that patients with urolithiasis, concomitant MetS, and high UA levels may have problems managing appetite hormones.

Comparison of Clinical Features, Serum Lipid, and Uric Acid Levels in Patients with Unipolar Depression and Bipolar Depression.

The level of uric acid and serum lipids has been suggested as a possible biomarker of bipolar disorder. We aimed to investigate the differences in clinical features and serum levels of lipids and uric acid in patients with bipolar depression or unipolar depression in order to distinguish them. The clinical data of 53 patients with unipolar depression (unipolar group) and 61 patients with bipolar depression (bipolar group), who all met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders-IV of the American Psychiatric Association, were compared with each other retrospectively. The serum levels of uric acid and lipids (including total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides) were measured after hospital admission. The Statistical Package for the Social Science version 22.0 software was used for statistical analysis, and logistic regression was employed to identify the susceptible factors of bipolar depression. Taking into account confounding factors, logistic regression analysis revealed that the high levels of uric acid (odds ratio = 1.016, P = .001) and low levels of triglycerides (odds ratio = 0.457, P = .025) were significantly correlated with bipolar depression. It has been demonstrated from this study that individuals with bipolar depression have higher serum uric acid levels and lower triglyceride levels than unipolar depression ones. Therefore, serum levels of uric acid and triglycerides might have the potential to be the biomarkers for differential diagnosis between bipolar and unipolar depression.

Uric Acid and Risk of Cardiovascular Disease and Mortality: A Longitudinal Cohort Study.

This study aimed to examine the association of serum uric acid levels with incident cardiovascular disease and mortality in Korean adults without gout. This large longitudinal cohort study included adults aged > 19 years who had serum uric acid levels measured at least once at the National Health Insurance Service Ilsan Hospital from January 1, 2006 to December 31, 2015. Longitudinal data on person-level cardiovascular disease and cardiovascular mortality were linked to the National Health Insurance Service claims database and National Death Index. Among a total of 92,454 study participants with a median follow-up of 4.7 years, 7,670 (8.3%) composite events of cardiovascular disease or cardiovascular mortality were observed. Multivariable Cox proportional-hazards models revealed that each 1 mg/dL increment in uric acid level was associated with a 6% higher risk of composite outcomes. Compared with that for the uric acid level category of 4.0 to < 5.0 mg/dL, adjusted hazard ratios (95% confidence interval) for uric acid level categories of 5.0 to < 6.0, 6.0 to < 7.0, and ≥ 7.0 mg/dL were 1.10 (1.04-1.18), 1.20 (1.11-1.30), and 1.36 (1.25-1.47), respectively. In the secondary analyses for cardiovascular disease or cardiovascular mortality examined separately, a higher uric acid level was similarly associated with a higher risk of each adverse outcome. These associations were generally consistent across clinically relevant subgroups. A graded association was noted between serum uric acid levels and cardiovascular risk, suggesting that higher uric acid levels may adversely affect cardiovascular health and survival in individuals without gout.

The Effects of High Dietary Fructose Consumption on the Development of Gout

Fructose is frequently used as a food ingredient due to its low production costs, its significant sweetening power and its easy incorporation into a broad variety of foods and beverages. In recent years, it has been observed that people on a Western diet high in fructose often have high levels of uric acid in their blood. It was recognized that the metabolism of fructose in the body might cause increased production of uric acid, which then may impact the intensity of lipogenesis and the development of metabolic syndrome (MetS), insulin resistance, gout, cardiovascular diseases, leptin resistance, non-alcoholic fatty liver disease, or some combination of the above. To date, the treatment of hyperuricemia has been the recommendation of a low-purine diet characterized by limiting protein-containing products and certain alcoholic beverages, in addition to consumption of tart cherry or the widely prescribed purine analog and xanthine oxidase inhibitor allopurinol in an attempt to decrease endogenous uric acid production. However, these recommendations often contribute to an increased intake of carbohydrate-rich foods that may contain fructose or high fructose corn syrup (HFCS) constituents. Increased fructose consumption may then enhance the secretion of uric acid and, consequently, attenuate or negate any potential therapeutic effects from the prescribed therapeutic regimen. A better option instead of a low-purine diet for some would be to follow a healthy meal plan such as DASH or the Mediterranean diet, which can also benefit metabolic parameters. This article provides an overview of this approach, focusing on MetS and hyperuricemia among high-fructose dieters.

The influence of uric acid on the course of amyotrophic lateral sclerosis

Uric acid has antioxidant and neuroprotective properties. A number of studies show that high levels of uric acid may have a positive influence on the course of amyotrophic lateral sclerosis (ALS), especially in males. The frequency of ALS is lower in patients with gout than in the general population. We present a case of a patient with gout and slowly progressive ALS. More research is needed on the potential role of uric acid in ALS and other neurodegenerative disorders.

The inflammation process of gout arthritis and its treatment.

Gout arthritis is an inflammatory condition that occurs suddenly in joints affected by high uric acid levels (hyperuricemia). The uric acid levels in this disease fluctuate throughout its various phases, resulting in frequent or recurrent attacks. This study aims to review some aspects of gout arthritis, such as its pathophysiology, treatment goals, and adverse drug reactions. This study employs review literature using articles published between 2017 and 2022 as the research methodology. Furthermore, articles under 2017 are used as references if they are relevant to the study's subject matter. The findings showed the importance of the pathogenesis of inflammation in the treatment of gout arthritis. It is also recommended to use anti-inflammatories such as colchicine and uric acid-lowering medications starting at a specific time to prevent unintended risks. Hence, pharmacotherapy management's adverse effects include nausea, vomiting, myalgia, neuropathy, and stomach pain.

Nutritional Status as a Risk Factor for New-Onset Atrial Fibrillation in Acute Myocardial Infarction.

Our study aimed to identify new-onset atrial fibrillation (NOAF) risk factors in acute myocardial infarction (AMI) patients after treatment with percutaneous coronary intervention (PCI) and investigate whether their nutritional status can be a predicting factor of NOAF. We analyzed 662 AMI patients after PCI for NOAF occurrence during follow-up hospitalization and divided them into an NOAF and non-NOAF group. The patients' nutritional status was assessed using the controlling nutritional status (CONUT) score and geriatric nutritional risk index (GNRI). The Kaplan‒Meier analysis was used to assess NOAF-free survival in varying degrees of malnutrition. Cox proportional hazards models were used to identify the risk factors for NOAF. Eighty-four (12.7%) patients developed NOAF during hospitalization. There was a statistically significant difference in the occurrence of NOAF among different categories of nutritional status. The CONUT score and GNRI classifications were independent predictors of NOAF. NOAF occurrence was associated with older age, higher uric acid levels, higher N-terminal pro-B-type natriuretic peptide levels, greater left atrial size, and worse Killip class upon admission. The nutritional status can affect NOAF occurrence in AMI patients after PCI. The CONUT score and GNRI are ideal tools for evaluating the nutritional status of AMI patients, with an excellent predictive effect on NOAF.

Мочевая кислота и психические расстройства

Over the past 100 years, there has been a progressive increase in the level of serum uric acid (UA). Modern scientific data suggest that the impact of hyperuricemia (HU) goes beyond the classical gout manifestations. UA has both oxidant and antioxidant properties, which determines its multidirectional effect on the human body as a whole. High serum UA levels may be a sign of increased purine metabolism and decreased adenosine transmission. Currently, there is evidence concerning the impact of all purine metabolism components on the mental sphere. The article discusses the pathogenetic association of purine metabolism disorders with the mental disorders and the possibility of considering UA as one of the targets for drug therapy of mental disorders. The results of recent studies show that allopurinol can be an important drug therapy component in patients with mental disorders. Accessibility and a good safety profile can also be the basis for further drug studies regarding the prospects of its wide practical use in patients with mental disorders and HU. KEYWORDS: uric acid, mental disorders, depression, adenosine, xanthine oxidase, allopurinol. FOR CITATION: Zhelyabina O.V., Eliseev M.S., Sosin D.N., Levin M.E. Uric acid and mental disorders. Russian Medical Inquiry. 2023;7(7):460– 466 (in Russ.). DOI: 10.32364/2587-6821-2023-7-7-9.

Effective Health Screening Strategies for Overcoming Non-Communicable Diseases in Sambimulyo Village, Banyuwangi Regency

Non-communicable diseases (NCDs) are chronic conditions that cannot be transmitted from one person to another. These conditions do not usually cause symptoms at first, but over time they can progress and damage the affected organ, leading to complications or even death. A lack of public knowledge about NCDs is a major contributor to complications and deaths from these diseases. To address this issue, a series of activities have been organized as part of the Movement for the Control of Non-Communicable Diseases. These activities focus on understanding the definitions, risk factors, prevention methods, and symptoms of diabetes, hypertension, and hyperuricemia. This study used a descriptive observational method, collecting primary data from pre- and post-test responses and health test results. In the first intervention, information about NCDs was provided and participants’ knowledge was increased by 31.25%. The second intervention was a health screening, which included measuring blood pressure and blood sugar levels. Uric acid levels were also measured at five points in Sambimulyo Village, with 129 participants. The results showed that 41.1% had high blood pressure, 29.5% were classified as diabetic, and 18.8% had high uric acid levels. These activities increased public knowledge about NCDs, provided information about the community’s risk factors, and improved communication, education, and information about how to manage these conditions.

Optimal uric acid reduction to improve vascular endothelial function in patients with chronic heart failure complicated by hyperuricemia.

Although an association of serum uric acid levels with endothelial function has been shown in various clinical settings, the optimal treatment target that would benefit vascular endothelial function has not been established. We, therefore, conducted a post hoc analysis of the Excited-UA study to identify an optimal target. Patients (N = 133) with chronic heart failure and comorbid hyperuricemia who enrolled in the Excited-UA study were divided into three tertiles based on their serum uric acid level 24 weeks after initiating xanthine oxidase inhibitor treatment with topiroxostat or allopurinol (i.e., groups with low, moderate, and high uric acid levels). Flow-mediated dilation (FMD) and reactive hyperemia index (RHI) values measured by reactive hyperemia peripheral arterial tonometry (RH-PAT) were compared among groups. The change from baseline in the FMD value 24 weeks after treatment was comparable among the three groups. In contrast, the change from baseline in the RHI was significantly different among the three groups (-0.153 ± 0.073, 0.141 ± 0.081 and -0.103 ± 0.104 in the low, moderate, and high uric acid level groups, respectively, P = 0.032). After adjustment for age, body mass index, and concomitant use of diuretics, which differed among the three groups, the change in the RHI in the moderate uric acid level group tended to be higher than that in the high uric acid level group (P = 0.057) and was significantly higher than that in the low uric acid level group (P = 0.020). These results indicate that targeting excessively low uric acid levels by treatment with xanthine oxidase inhibitors might be less beneficial for improving microvascular endothelial function in patients with chronic heart failure. Comparisons of the changes from baseline in vascular endothelial function parameters at 24 weeks among the 3 groups of low, moderae and high uric acid levels achieved with xanthine oxidase inhibitors. After adjustment for confounding factors, such as age, body mass index and concomitant diuretic use, which showed differences among the 3 groups, the change in RHI in the moderate uric acid level group tended to be higher than that in the high uric acid level group and was significantly higher than that in the low uric acid level group.

Naringenin Ameliorates Hyperuricemia by Regulating Renal Uric Acid Excretion via the PI3K/AKT Signaling Pathway and Renal Inflammation through the NF-κB Signaling Pathway

Hyperuricemia characterized by high serum levels of uric acid (UA, >6.8 mg/dL) is regarded as a common chronic metabolic disease. When used as a food supplement, naringenin might have various pharmacological activities, including antioxidant, free-radical-scavenging, and inflammation-suppressing activities. However, the effects of naringenin on hyperuricemia and renal inflammation and the underlying mechanisms remain to be elucidated. Here, we comprehensively examined the effects of naringenin on hyperuricemia and the attenuation of renal impairment. Mice were injected with 250 mg/kg of potassium oxonate (PO) and given 5% fructose water to induce hyperuricemia. The pharmacological effects of naringenin (10 and 50 mg/kg) and benzbromarone (positive control group, 20 mg/kg) on hyperuricemic mice were evaluated in vivo. The disordered expression of urate transporters in HK-2 cells was stimulated by 8 mg/dL UA, which was used to determine the mechanisms underlying the effects of naringenin in vitro. Naringenin markedly reduced the serum UA level in a dose-dependent manner and improved renal dysfunction. Moreover, the increased elimination of UA in urine showed that the effects of naringenin were associated with the regulation of renal excretion. Further examination indicated that naringenin reduced the expression of GLUT9 by inhibiting the PI3K/AKT signaling pathway and reinforced the expression of ABCG2 by increasing the abundance of PDZK1 in vivo and in vitro. Furthermore, sirius red staining and western blotting indicated that naringenin plays a protective role in renal injury by suppressing increases in the levels of pro-inflammatory cytokines, including IL-6 and TNF-α, which contribute to the inhibition of the TLR4/NF-κB signaling pathway in vivo and in vitro. Naringenin supplementation might be a potential therapeutic strategy to ameliorate hyperuricemia by promoting UA excretion in the kidney and attenuating the inflammatory response by decreasing the release of inflammatory cytokines. This study shows that naringenin could be used as a functional food or dietary supplement for hyperuricemia prevention and treatment.

Serum uric acid as a risk factor for rejection after deceased donor kidney transplantation: A mono-institutional analysis of paired kidneys.

Deceased donor kidney transplantation (DDKT) is a major therapeutic option for patients with end-stage renal diseases. Although medical techniques improved in recent years, acute or chronic rejection after DDKT is not uncommon and often results in poor graft survival. Therefore, the determination of risk factors is very important to stratify patients and to improve outcomes. This study aims to evaluate the risk factors for treated rejection (TR) of patients after DDKT. Clinical data of deceased donors and corresponding recipients were retrospectively collected. The primary outcome was TR defined as the treatment for rejection within 24 months after DDKT. Univariate comparisons of baseline characteristics were performed with Chi-square test, t-test, and Mann-Whitney U test. Logistic regression was constructed to analyze potential risk factors. Receiver operating characteristic (ROC) curve and Jordan index were generated to determine the optimal cutoff value. The association between continuous variables and TR was examined and visualized by using restricted cubic spline (RCS) models. Data of 123 deceased donors and 246 recipients were obtained and analyzed. The median age was 41 (4-62) years for recipients and 39 (1-65) years for donors. The recipients who died or suffered graft loss during the follow-up period were 8 (3.3%) and 12 (4.9%), respectively. After univariate analysis and subsequent multivariate analysis, the preoperative serum uric acid (OR, 2.242; 95% CI, 1.037-4.844; P = 0.040), platelet (OR, 2.163; 95% CI, 1.073-4.361, P = 0.031), absolute neutrophil count (OR, 2.183; 95% CI, 1.025-4.649; P = 0.043), and HLA-DQ mismatch (OR, 2.102; 95% CI, 1.093-4.043; P = 0.026) showed statistical significance. RCS models showed that patients with higher levels of uric acid had increased risk of TR. Serum uric acid and other three indicators were found to be the independent risk factors for TR, which may contribute to stratify patients and develop personalized regimen in perioperative period.

Association between uric acid level and contrast-induced acute kidney injury in patients with type 2 diabetes mellitus after coronary angiography: a retrospective cohort study

BackgroundThis study assessed the predictive value of uric acid (UA) for contrast-induced acute kidney injury (CI-AKI) in patients with type 2 diabetes mellitus (T2DM) who underwent coronary angiography (CAG). A nomogram to aid in the prediction of CI-AKI was also developed and validated, and the construction of a prognostic nomogram combined with clinical features was attempted.MethodsThis study retrospectively enrolled T2DM patients who underwent CAG between December 2019 and December 2020 at the Affiliated Zhongda Hospital of Southeast University. Multivariable logistic regression analysis was used for the analysis of clinical outcomes. Receiver operating characteristic (ROC) analyses were performed to determine the area under the ROC curve (AUC) and the cut-off points for continuous clinical data. The prediction accuracies of models for CI-AKI were estimated through Harrell’s concordance indices (C-index). Nomograms of the prognostic models were plotted for individualized evaluations of CI-AKI in T2DM patients after CAG.ResultsA total of 542 patients with T2DM who underwent CAG were included in this study. We found that a high UA level (≥ 425.5 µmol/L; OR = 6.303), BUN level (≥ 5.98 mmol/L; OR = 3.633), Scr level (≥ 88.5 µmol/L; OR = 2.926) and HbA1C level (≥ 7.05%; OR = 5.509) were independent factors for CI-AKI in T2DM patients after CAG. The nomogram model based on UA, BUN, Scr and HbA1C levels presented outstanding performance for CI-AKI prediction (C-index: 0.878). Decision curve analysis (DCA) showed good clinical applicability in predicting the incidence of CI-AKI in T2DM patients who underwent CAG.ConclusionHigh UA levels are associated with an increased incidence of CI-AKI in T2DM patients after CAG. The developed nomogram model has potential predictive value for CI-AKI and might serve as an economic and efficient prognostic tool in clinical practice.

Angiotensin-converting enzyme gene (ACE) polymorphisms are associated with dysregulation of biochemical parameters in hypertensive patients.

The genetic component, including genes and their variants, plays a significant role in the pathophysiology of arterial hypertension (AH). Thus, clinical, epidemiological and genetic studies have been carried out to improve the understanding of disease mechanisms, improve diagnostic quality and contribute to prevention. To determine the association of risk factors, biochemical parameters and different ACE gene polymorphisms with AH. The case-control study was carried out in the population of Ouro Preto, Brazil. The subjects answered a questionnaire containing clinical and sociodemographic data. The ACE gene polymorphisms rs4291, rs4363 and rs4335 were evaluated by real time-polymerase chain reaction (real-time PCR) in 310 people (155 hypertensive and 155 normotensive patients), in addition to biochemical parameters. A multivariate logistic regression model was used to identify factors associated with AH. Analysis of continuous variables was performed using the Kruskal-Wallis test to assess significance between groups and Dunn's post-test for multiple comparisons. The results showed that AH was associated with age, education, smoking, obesity and high levels of triglycerides, sodium, glucose and uric acid. Regarding the biochemical parameters, in hypertensive patients, the rs4363 and rs4335 polymorphisms were associated with high levels of triglycerides, urea and glucose; the rs4291 polymorphism was associated with elevated urea and glucose levels. No association was detected between SNPs and HA. AH was associated with socioeconomic status, lifestyle habits and biochemical parameters. ACE polymorphisms may have influenced the levels of triglycerides, urea and glucose in hypertensive patients.

Effects of T-2 toxin on growth performance, feather quality, tibia development and blood parameters in Yangzhou goslings

T-2 toxin is a dangerous natural pollutant and widely exists in animal feed, often causing toxic damage to poultry, such as slow growth and development, immunosuppression, and death. Although geese are considered the most sensitive poultry to T-2 toxin, the exact damage caused by T-2 toxin to geese is elusive. In the present study, a total of forty two 1-day-old healthy Yangzhou male goslings were randomly allotted seven diets contaminated with 0, 0.2, 0.4, 0.6, 0.8, 1.0, or 2.0 mg/kg T-2 toxin for 21 d, and the effects of T-2 toxin exposure on growth performance, feather quality, tibia development, and blood parameters were investigated. The results showed that T-2 toxin exposure significantly inhibited feed intake, body weight gain, shank length growth, and organ development (e.g., ileum, cecum, liver, spleen, bursa, and tibia) in a dose-dependent manner. In addition, the more serious feathering abnormalities and feather damage were observed in goslings exposed to a high dose of T-2 toxin (0.8, 1.0, and 2.0 mg/kg), which were mainly sparsely covered with short, dry, rough, curly, and gloss-free feathers on the back. We also found that hypertrophic chondrocytes of the tibial growth plate exhibited abnormal morphology and nuclear consolidation or loss, accompanied by necrosis and excessive apoptosis under 2.0 mg/kg T-2 toxin exposure. Moreover, 2.0 mg/kg T-2 toxin exposure triggered erythropenia, thrombocytosis, alanine aminotransferase, and aspartate aminotransferase activity, as well as high blood urea nitrogen, uric acid, and lactic dehydrogenase levels. Collectively, these data indicate that T-2 toxin had an adverse effect on the growth performance, feather quality, and tibia development, and caused liver and kidney damage and abnormal blood parameters in Yangzhou goslings, providing crucial information toward the prevention and control of T-2 toxin contamination in poultry feed.

The Importance of HDL-Cholesterol and Fat-Free Percentage as Protective Markers in Risk Factor Hierarchy for Patients with Metabolic Syndrome.

This research focused on establishing a hierarchy concerning the influence of various biological markers and body composition parameters on preventing, diagnosing and managing Metabolic Syndrome (MetS). Our cross-sectional cohort study included 104 subjects without any atherosclerotic antecedent pathology, organized in two groups (with and without MetS). All participants underwent clinical and anthropometric measurements, DEXA investigation and blood tests for all MetS criteria, together with adiponectin, leptin, insulin, uric acid and CRP. Based on mathematical logic, we calculated a normalized sensitivity score to compare the predictive power of biomarkers and parameters associated with MetS, upon the prevalence of MetS. Patients with MetS report higher levels of uric acid (p = 0.02), CRP (p = 0.012) and lower levels of adiponectin (p = 0.025) than patients without MetS. The top three biological markers with the highest predictive power of the prevalence of the disease are HDL, insulin, and adiponectin:leptin ratio, and the top three body composition parameters are trunk fat-free percentage, waist-height ratio and trunk fat percentage. Their high sensitivity scores differentiate them from all the other markers analysed in the study. Our findings report relevant scores for estimating the importance of cardiometabolic risks in the prevalence of MetS. The high rank of protective markers, HDL and trunk fat-free percentage, suggest that positive effects have a stronger association with the prevalence of MetS, than negative ones do. Therefore, this risk stratification study provides important support for prevention and management programs regarding MetS.

Uric Acid Induces a Proatherothrombotic Phenotype in Human Endothelial Cells by Imbalancing the Tissue Factor/Tissue Factor Pathway Inhibitor Pathway.

Several evidence show that elevated plasma levels of uric acid (UA) are associated with the increased risk of developing atherothrombotic cardiovascular events. Hyperuricemia is a risk factor for endothelial dysfunction (ED). ED is involved in the pathophysiology of atherothrombosis since dysfunctional cells lose their physiological, antithrombotic properties. We have investigated whether UA might promote ED by modulating the tissue factor (TF)/TF pathway inhibitor (TFPI) balance by finally changing the antithrombotic characteristics of endothelial cells. Human umbilical vein endothelial cells were incubated with increasing doses of UA (up to 9 mg/dL). TF gene and protein expressions were evaluated by real-time polymerase chain reaction (PCR) and Western blot. Surface expression and procoagulant activity were assessed by FACS (fluorescence activated cell sorting) analysis and coagulation assay. The mRNA and protein levels of TFPI were measured by real-time PCR and Western blot. The roles of inflammasome and nuclear factor-κB (NF-κB) as possible mechanism(s) of action of the UA on TF/TFPI balance were also investigated. UA significantly increased TF gene and protein levels, surface expression, and procoagulant activity. In parallel, TFPI levels were significantly reduced. The NF-κB pathways appeared to be involved in modulating these phenomena. Additionally, inflammasome might also play a role. The present in vitro study shows that one of the mechanisms by which high levels of UA contribute to ED might be the imbalance between TF/TFPI levels in endothelial cells, shifting them to a nonphysiological, prothrombotic phenotype. These UA effects might hypothetically explain, at least in part, the relationship observed between elevated plasma levels of UA and cardiovascular events.

Potential role of uric acid to activate NLRP3 inflammasome triggering endothelial dysfunction in preeclampsia

Preeclampsia (PE) is a pregnancy-related disorder associated with increasing maternal death rates and affecting 2–8% of pregnant women worldwide. Arterial hypertension and proteinuria, followed by other maternal dysfunctions are classic clinical parameters to identify this disease. Furthermore, hyperuricemia is strictly related to PE, and high plasmatic levels of uric acid have been associated with disease severity. The inflammation in the endothelium caused by danger signals, such as uric acid crystals, is persistent and stimulates the release of inflammatory cytokines, and activates the NLRP3 inflammasome. The mechanisms underlying endothelial dysfunction induced by the metabolism of uric acid, and consequently increased levels of inflammation and oxidative stress in women with PE could be ameliorated with interventions related to inhibition of the NLRP3 activation MSU-mediated and may improve the prognostics of this disease.