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1.
Hyperuricemia: a novel old disorder-relationship and potential mechanisms in heart failure.
Borghi, C, Palazzuoli, A, Landolfo, M, Cosentino, E
Heart failure reviews. 2020;(1):43-51
Abstract
Uric acid, the metabolic mediator of gout and urate renal stones, is associated with increased cardiovascular risk burden. Hyperuricemia is an old emerging metabolic disorder, and interaction among uric acid and cardiovascular diseases has been clearly described. Several illness including hypertension, myocardial infarction, metabolic syndrome, and heart failure, are related with uric acid levels increase. In this review, we will discuss the pathophysiology of hyperuricemia and describe the biological plausibility for this metabolite to participate in the pathogenesis of cardiovascular disorders. In particular, we will focus on the implications of hyperuricemia in the onset and progression of heart failure, paying special attention to the pathophysiology and the possible clinical implications. We will conclude by discussing the effects of lowering plasma uric acid concentration on the prognosis of heart failure by reviewing most of available data on the different classes of drugs directly or indirectly involved in the hyperuricemia management.
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2.
A novel mutation in gene of PRPS1 in a young Chinese woman with X-linked gout: a case report and review of the literature.
Yang, BY, Yu, HX, Min, J, Song, XX
Clinical rheumatology. 2020;(3):949-956
Abstract
Pyrophosphate synthetase-1(PRS-1) is a crucial enzyme that catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) with substrate: adenosine triphosphate (ATP) and ribose-5-phophate(R5P) in the de novo pathways of purine and pyrimidine nucleotide synthesis. Mutation in PRPS1 can result in a series of diseases of purine metabolism, which includes PRS-1 superactivity. The common clinical phenotypes are hyperuricemia and hyperuricosuria. We identified a novel missense mutation in X-chromosomal gene PRPS1 in a young Chinese woman while her mother has heterogeneous genotype and phenotype. A 24-year-old Chinese female patient suffered hyperuricemia, gout, and recurrent hyperpyrexia for more than 6 years, and then was diagnosed with hyperandrogenism, insulin resistance (IR), and polycystic ovary syndrome (PCOS). A novel missense mutation, c.521(exon)G>T, p.(Gly174Val) was detected by next-generation sequencing (NGS) and confirmed by Sanger sequencing in the patient and her parents. Interestingly, her mother has the same heterozygous missense mutation but without uric acid overproduction which can be explained by the phenomenon of the skewed X-chromosome inactivation. The substituted amino acid Val for Gly174 is positioned in the pyrophosphate (PPi) binding loop, and this mutation impacts the binding rate of Mg2+-ATP complex to PRS-1, thus the assembling of homodimer is affected by changed Val174 leading to the instability of the allosteric site. Our report highlights the X-linked inheritance of gout in females caused by mutation in PRPS1 accompanied with severe metabolic disorders and recurrent hyperpyrexia.
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3.
Association between serum vitamin D and uric acid in the eastern Chinese population: a population-based cross-sectional study.
Chen, Y, Cheng, J, Chen, Y, Wang, N, Xia, F, Chen, C, Han, B, Lu, Y
BMC endocrine disorders. 2020;(1):79
Abstract
BACKGROUND Uric acid (UA) is the end product of purine metabolism, which is thought to be related to many human diseases, such as nephrolithiasis, gout, cardiovascular disease (CVD), type 2 diabetes mellitus, metabolic syndrome. However, the relationship between serum UA (SUA) and 25(OH) D is still unclear in the eastern Chinese population. METHODS We did a population-based observational investigation, which included 12,770 residents living in eastern China. Ultimately, data from 9220 subjects were analyzed. Serum 25(OH) D, SUA, fasting plasma glucose (FPG), fasting insulin, HbA1c and other metabolic parameters were tested. Waist circumference (WC), weight and height were also measured. Questionnaires were collected from these subjects for information on smoking and drinking status. RESULTS We enrolled 9220 Chinese adults, including 3681 males (age 55.57 ± 13.23 years) and 5539 females (age 54.31 ± 12.83 years). The levels of SUA were 352.07 ± 79.25 nmol/L and 269.29 ± 64.68 nmol/L in males and females, respectively. The proportion of adults with hyperuricemia (HUA) was 12.26% in the total population. Levels of SUA were positively associated with 25(OH) D, and the incidence of HUA increased 9.4% for every 10 nmol/L increase in 25(OH) D (P < 0.001). CONCLUSIONS SUA was positively associated with 25(OH) D in the eastern Chinese population. Higher levels of serum 25(OH) D may be a potential predictor of HUA.
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4.
Association between dairy product consumption and hyperuricemia in an elderly population with metabolic syndrome.
Mena-Sánchez, G, Babio, N, Becerra-Tomás, N, Martínez-González, MÁ, Díaz-López, A, Corella, D, Zomeño, MD, Romaguera, D, Vioque, J, Alonso-Gómez, ÁM, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2020;(2):214-222
Abstract
BACKGROUND AND AIMS The prevalence of hyperuricemia has increased substantially in recent decades. It has been suggested that it is an independent risk factor for weight gain, hypertension, hypertriglyceridemia, metabolic syndrome (MetS), and cardiovascular disease. Results from epidemiological studies conducted in different study populations have suggested that high consumption of dairy products is associated with a lower risk of developing hyperuricemia. However, this association is still unclear. The aim of the present study is to explore the association of the consumption of total dairy products and their subtypes with the risk of hyperuricemia in an elderly Mediterranean population with MetS. METHODS AND RESULTS Baseline cross-sectional analyses were conducted on 6329 men/women (mean age 65 years) with overweight/obesity and MetS from the PREDIMED-Plus cohort. Dairy consumption was assessed using a food frequency questionnaire. Multivariable-adjusted Cox regressions were fitted to analyze the association of quartiles of consumption of total dairy products and their subtypes with the prevalence of hyperuricemia. Participants in the upper quartile of the consumption of total dairy products (multiadjusted prevalence ratio (PR) = 0.84; 95% CI: 0.75-0.94; P-trend 0.02), low-fat dairy products (PR = 0.79; 95% CI: 0.70-0.89; P-trend <0.001), total milk (PR = 0.81; 95% CI: 0.73-0.90; P-trend<0.001), low-fat milk (PR = 0.80; 95% CI: 0.72-0.89; P-trend<0.001, respectively), low-fat yogurt (PR = 0.89; 95% CI: 0.80-0.98; P-trend 0.051), and cheese (PR = 0.86; 95% CI: 0.77-0.96; P-trend 0.003) presented a lower prevalence of hyperuricemia. Whole-fat dairy, fermented dairy, and yogurt consumption were not associated with hyperuricemia. CONCLUSIONS High consumption of total dairy products, total milk, low-fat dairy products, low-fat milk, low-fat yogurt, and cheese is associated with a lower risk of hyperuricemia.
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5.
Association of Uric Acid with Incident Metabolic Syndrome in a Japanese General Population.
Sumiyoshi, H, Ohyama, Y, Imai, K, Kurabayashi, M, Saito, Y, Nakamura, T
International heart journal. 2019;(4):830-835
Abstract
Uric acid is associated with cardiovascular disease (CVD) and its risk factors. Here, we examined the association between the serum uric acid level and incident metabolic syndrome in a Japanese general population. This retrospective, observational study was based on data obtained from an annual health checkup program in Gunma Prefecture, Japan. We evaluated 14,793 participants who did not use antihypertensive or antidiabetic medications and did not present with CVD or metabolic syndrome at the study baseline in 2009. Metabolic syndrome was defined as per the Japanese diagnostic criteria. A discrete proportional hazards regression model was used to evaluate the association between the serum uric acid level at baseline and the incident metabolic syndrome through 2012 and was adjusted for age, gender, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, high-density lipoprotein cholesterol, and triglyceride. At baseline, the average age of the participants was 48.9 years, who were comprised of 40% women. The mean serum uric acid level at baseline was 5.3 ± 1.4 mg/dL. During the three-year follow-up, 7% of the cohort (n = 1,031) developed metabolic syndrome. The uric acid level was strongly associated with incident metabolic syndrome in the multivariable model (adjusted hazard ratio: 1.10; 95% confidence interval, 1.04-1.17; P < 0.01 per 1 mg/dL increase for uric acid). Higher uric acid levels were independently associated with a greater risk of incident metabolic syndrome in a Japanese general population.
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6.
Higher levels of serum uric acid influences hepatic damage in patients with non-alcoholic fatty liver disease (NAFLD).
Fernández Rodríguez, CM, Aller, R, Gutiérrez García, ML, Ampuero, J, Gómez-Camarero, J, Martín-Mateos, RMª, Burgos-Santamaría, D, Rosales, JM, Aspichueta, P, Buque, X, et al
Revista espanola de enfermedades digestivas. 2019;(4):264-269
Abstract
BACKGROUND recent evidence suggests a causal link between serum uric acid and the metabolic syndrome, diabetes mellitus, arterial hypertension, and renal and cardiac disease. Uric acid is an endogenous danger signal and activator of the inflammasome, and has been independently associated with an increased risk of cirrhosis. AIM AND METHODS six hundred and thirty-four patients from the nation-wide HEPAMET registry with biopsy-proven NAFLD (53% NASH) were analyzed to determine whether hyperuricemia is related with advanced liver damage in patients with non-alcoholic fatty liver disease (NAFLD). Patients were divided into three groups according to the tertile levels of serum uric acid and gender. RESULTS the cohort was composed of 50% females, with a mean age of 49 years (range 19-80). Patients in the top third of serum uric acid levels were older (p = 0.017); they had a higher body mass index (p < 0.01), arterial blood pressure (p = 0.05), triglyceridemia (p = 0.012), serum creatinine (p < 0.001) and total cholesterol (p = 0.016) and lower HDL-cholesterol (p = 0.004). According to the univariate analysis, the variables associated with patients in the top third were more advanced steatosis (p = 0.02), liver fibrosis (F2-F4 vs F0-1; p = 0.011), NASH (p = 0.002) and NAS score (p = 0.05). According to the multivariate logistic regression analysis, the top third of uric acid level was independently associated with steatosis (adjusted hazard ratio 1.7; CI 95%: 1.05-2.8) and NASH (adjusted hazard ratio 1.8; CI 95%: 1.08-3.0) but not with advanced fibrosis (F2-F4) (adjusted hazard ratio 1.09; CI 95%: 0.63-1.87). CONCLUSION higher levels of serum uric acid were independently associated with hepatocellular steatosis and NASH in a cohort of patients with NAFLD. Serum uric acid levels warrants further evaluation as a component of the current non-invasive NAFLD scores of histopathological damage.
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7.
An evidence-based review on urate-lowering treatments: implications for optimal treatment of chronic hyperuricemia.
Bove, M, Cicero, AF, Veronesi, M, Borghi, C
Vascular health and risk management. 2017;:23-28
Abstract
Several studies suggest that chronic hyperuricemia, the main precursor of gout, is involved in the pathogenesis of different systemic disorders that affect cardiovascular and renal systems, such as hypertension, obesity, hypercholesterolemia, atherosclerosis, metabolic syndrome, chronic heart failure, and chronic kidney disease. Recent epidemiological evidence has shown an increasing trend in the prevalence of hyperuricemia and gout in the Western world: a number of population-based studies estimate a prevalence of up to 21% for hyperuricemia and 1%-4% for gout. As such, early detection and careful management of this pathological condition is required, starting from lifestyle changes (mainly based on a diet low in red meat, sugars, and alcoholic beverages, with increased intake of vegetables, water, and vitamin C sources), adding specific drugs to lead serum uric acid (SUA) levels under the target value of 7 mg/dL. In particular, nonselective and selective XO inhibitors (allopurinol, oxypurinol, febuxostat) reduce SUA levels and the overproduction of reactive oxygen species, mainly related to XO overactivity that often causes inflammatory damage to the vascular endothelium. The effect of lowering SUA levels via XO inhibition includes an attenuation of oxidative stress and related endothelial dysfunction that largely contribute to the pathophysiology of metabolic syndrome and cardiovascular diseases. Therefore, the inhibition of XO overactivation seems to be an excellent therapeutic option to limit the harmful effects of excess UA and reactive oxygen species. In conclusion, rapid diagnosis and correct therapy for hyperuricemia may also improve the prevention and/or treatment of serious and multifactorial diseases. The available evidence supports the importance of promoting new experimental clinical trials to confirm the emerging antioxidant role of XO inhibitors, which could effectively contribute to cardiovascular and chronic kidney disease prevention.
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8.
[Metabolic syndrome and concentrations of uric acid and ultrasensitive C-reactive protein].
Roldán-Menco, C, Díaz-Perez, A, Barrios-Puerta, Z, Pinto-Aragón, EE
Revista de salud publica (Bogota, Colombia). 2017;(5):603-608
Abstract
OBJECTIVE To establish the prevalence of metabolic syndrome (MS) according to ATP III and its correlation with the concentration of uric acid and C-reactive protein (CRP) in people aged between 45 and 60, living in the Getsemaní neighborhood of Cartagena. MATERIALS AND METHODS Observational, descriptive-correlational study on a population of 802 inhabitants of the Getsemaní neighborhood of Cartagena, Colombia. A random sample of 302 inhabitants was analyzed with a 95% confidence interval and 5% margin of error. ATP III diagnostic criteria were applied, and the instrument used included basic data about the general context of the patient (social, demographic and economic aspects, family history, work activity and physical characteristics such as weight, waist circumference, blood pressure, and BMI), as well as diagnostic tests such as glycemia, total cholesterol, triglycerides, HDLc, LDLc, uric acid and ultra-sensitive C-reactive protein. RESULTS The prevalence of metabolic syndrome in the susceptible population is 18 %. The most common metabolic syndrome factor is abdominal obesity with 85 %, followed by increase of triglycerides by 76 %. CONCLUSION The prevalence of metabolic syndrome was considered high when applying ATP III criteria. No significant association was observed regarding CRP values and the chances of developing metabolic syndrome in both men and women. However, uric acid levels were correlated to the disease in the group of women susceptible to suffering from MS with a value of p=0.0022.
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9.
Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders: A Critical Review.
Caliceti, C, Calabria, D, Roda, A, Cicero, AFG
Nutrients. 2017;(4)
Abstract
There is a direct relationship between fructose intake and serum levels of uric acid (UA), which is the final product of purine metabolism. Recent preclinical and clinical evidence suggests that chronic hyperuricemia is an independent risk factor for hypertension, metabolic syndrome, and cardiovascular disease. It is probably also an independent risk factor for chronic kidney disease, Type 2 diabetes, and cognitive decline. These relationships have been observed for high serum UA levels (>5.5 mg/dL in women and >6 mg/dL in men), but also for normal to high serum UA levels (5-6 mg/dL). In this regard, blood UA levels are much higher in industrialized countries than in the rest of the world. Xanthine-oxidase inhibitors can reduce UA and seem to minimize its negative effects on vascular health. Other dietary and pathophysiological factors are also related to UA production. However, the role of fructose-derived UA in the pathogenesis of cardiometabolic disorders has not yet been fully clarified. Here, we critically review recent research on the biochemistry of UA production, the relationship between fructose intake and UA production, and how this relationship is linked to cardiometabolic disorders.
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10.
Effect of allopurinol and uric acid normalization on serum lipids hyperuricemic subjects: A systematic review with meta-analysis.
Castro, VMF, Melo, AC, Belo, VS, Chaves, VE
Clinical biochemistry. 2017;(18):1289-1297
Abstract
Although uric acid is not part of any definition of metabolic syndrome, a number of studies have shown strong associations between the concentration of uric acid and metabolic syndrome or its components. The purpose of this systematic review with meta-analysis was to evaluate, using prospective interventional studies, the effects of allopurinol therapy and uric acid normalization on serum concentrations of triacylglycerol, total-cholesterol, LDL-cholesterol and HDL-cholesterol in hyperuricemic subjects. A systematic search of the PubMed and Scopus databases was performed following the guidelines described in the PRISMA statement. Seven studies were included in the meta-analysis, including six randomized controlled trials and one controlled before-and-after study. Despite differences in the follow-up periods (4, 12 and 24weeks) and allopurinol dose (100-300mg/day), all the studies showed decreases in the mean serum uric acid level (95% confidence interval: -2.61 to -1.55 (4weeks), -2.94 to -1.09 (12weeks) and -2.59 to -1.22 (24weeks); p<0.05). However, no effect was observed based on differences in mean serum triacylglycerol and total- and LDL-cholesterol concentrations, independent of the follow-up period. Allopurinol therapy during weeks 4 and 12 induced a decrease in the mean HDL-cholesterol level (95% confidence interval: -7.22 to -0.47 (4weeks) and -7.18 to -0.32 (12weeks); p<0.05). This review suggests that allopurinol and uric acid normalization does not improve serum lipid levels, although larger and longer trials of higher quality are needed to confirm this.