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Junk E, Tzivian L, Folkmane I, Folkmanis K, Jushinskis J, Strazda G, Folkmanis V, Kuzema V, Petersons A. Major adverse cardiovascular events and hyperuricemia as an effect-modifying factor in kidney transplant recipients. World J Transplant 2025; 15:102287. [DOI: 10.5500/wjt.v15.i3.102287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 01/31/2025] [Accepted: 02/20/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND Major adverse cardiovascular (CV) events (MACEs) are the primary cause of morbidity and mortality in kidney transplantation (KT) recipients. The risk for MACEs is impacted by an array of traditional and transplant-related non-traditional CV risk factors.
AIM To investigate the association between potential CV risk factors related to KT and MACEs, and their potential modification by hyperuricemia (HU).
METHODS The relationship between CV risk factors related to KT and MACEs was examined in a cohort of 545 patients who underwent transplantation between 2008 and 2019. The mean age of patients at KT was 55.0 years ± 14.2 years (range 15.0–89.0 years). Univariate and multivariate logistic regression models were constructed to identify risk factors influencing MACEs. To explore the potential effect modification by uric acid (UA), patients were categorized into groups based on UA levels: (1) Low (< 356 μmol/L); (2) Normal (356–416 μmol/L); (3) High (416–475 μmol/L); and (4) Very high (> 475 μmol/L).
RESULTS MACEs occurred in 145 of 545 (26.6%) KT recipients. The most prevalent comorbidities were hypertension (87%), dyslipidemia (78%), secondary hyperparathyroidism (68%), HU (63%) and anemia (33%). In the multivariate logistic regression model, the most significant factors associated with MACEs were previous CV events [odds ratio (OR) = 70.6, 95%CI: 24.9–200.1], left ventricular hypertrophy (LVH) (OR = 12.6, 95%CI: 2.7– 58.3), HU treatment (OR = 4.3, 95%CI: 2.4–7.6), and anemia (OR = 5.3, 95%CI: 2.9–9.8). Effect modification by the presence of HU revealed that independent factors associated with MACEs were age (OR = 1.03, 95%CI: 1.0–1.1), previous CV events (OR = 41.7, 95%CI: 13.6–127.6), LVH (OR = 15.3, 95%CI: 2.0–116.6), HU treatment (OR = 2.5, 95%CI: 1.3–4.6) and anemia (OR = 5.4, 95%CI: 2.8–10.5). Effect modification by UA levels dichotomized at 475 μmol/L (very high level of UA) revealed that HU treatment was not associated with MACEs in groups with or without very high UA levels.
CONCLUSION A very high level of UA was observed to act as an effect-modifying factor for MACEs, especially when combined with other risk factors such as age, previous CV events, LVH, and anemia.
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Affiliation(s)
- Elizabete Junk
- Department of Internal Diseases, St. Bonifatius Hospital Lingen, Lingen 49808, Germany
- Faculty of Medicine and Life Sciences, University of Latvia, Riga LV-1004, Latvia
| | - Lilian Tzivian
- Faculty of Medicine and Life Sciences, University of Latvia, Riga LV-1004, Latvia
- Institute of Occupational, Social and Environmental Medicine, Centre for Health and Society, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University of Dusseldorf, Düsseldorf 40225, Germany
| | - Inese Folkmane
- Faculty of Medicine and Life Sciences, University of Latvia, Riga LV-1004, Latvia
- Centre of Nephrology, Pauls Stradiņš Clinical University Hospital, Riga LV-1002, Latvia
| | - Kristofs Folkmanis
- Faculty of Medicine and Life Sciences, University of Latvia, Riga LV-1004, Latvia
- International Center for Robotic Urology, Kreisklinikum Siegen, Siegen 57076, North Rhine-Westphalia, Germany
| | - Janis Jushinskis
- Centre of Transplantation, Pauls Stradiņš Clinical University Hospital, Riga LV-1002, Latvia
- Faculty of Medicine, Riga Stradins University, Riga LV-1007, Latvia
| | - Gunta Strazda
- Faculty of Medicine and Life Sciences, University of Latvia, Riga LV-1004, Latvia
| | - Valdis Folkmanis
- Faculty of Medicine and Life Sciences, University of Latvia, Riga LV-1004, Latvia
| | - Viktorija Kuzema
- Centre of Nephrology, Pauls Stradiņš Clinical University Hospital, Riga LV-1002, Latvia
- Faculty of Medicine, Riga Stradins University, Riga LV-1007, Latvia
| | - Aivars Petersons
- Faculty of Medicine, Riga Stradins University, Riga LV-1007, Latvia
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Han Y, Yao M, Zhao H, Han X, Di H, Xie T, Wu J, Wang Y, Zhang Y, Zeng X. Exploration of the Interrelationship Between Serum Uric Acid, Gout, and Cardiac, Renal, and Metabolic Conditions in Middle Aged and Older People. J Am Heart Assoc 2025; 14:e038723. [PMID: 40145269 DOI: 10.1161/jaha.124.038723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 02/11/2025] [Indexed: 03/28/2025]
Abstract
BACKGROUND Cardiac, renal, and metabolic (CRM) conditions are major causes of morbidity and mortality globally. This study aims to explore the relationship between serum uric acid (SUA), hyperuricemia, gout, and CRM conditions in middle-aged and elderly populations. METHODS Sample 1 included participants from CHARLS (China Health and Retirement Longitudinal Study, n=9341), and Sample 2 from NHANES (National Health and Nutrition Examination Survey, unweighted n=17 913; weighted n=115 646 390). Ordinal logistic regression, Cox regression, and restricted cubic spline analyses were used to assess the relationship between SUA, hyperuricemia, gout, and CRM conditions. A 2-sample Mendelian randomization analysis was conducted to explore causal associations between SUA and CRM conditions. RESULTS In both samples, SUA, hyperuricemia, and gout were positively correlated with the risk of CRM conditions. Among participants with 3 or ≥1 CRM condition(s), SUA, asymptomatic hyperuricemia, and gout with poorly controlled hyperuricemia showed significant positive associations with all-cause mortality, whereas these associations were not observed in patients with gout with normal SUA levels. The restricted cubic spline analysis revealed a positive relationship between SUA levels and the risk of all-cause mortality in participants with ≥1 CRM condition(s), demonstrating a nonlinear dose-response relationship across both samples (P for nonlinearity <0.05). Mendelian randomization analysis indicated that SUA was causally associated with cardiovascular disease, chronic kidney disease, and diabetes. CONCLUSIONS Hyperuricemia and gout are strong predictors of increased prevalence and mortality of CRM conditions, emphasizing the importance of managing hyperuricemia and gout in these patients.
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Affiliation(s)
- Yingdong Han
- Department of family medicine & Division of General Internal Medicine, Department of internal medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital) Beijing China
| | - Menghui Yao
- Department of family medicine & Division of General Internal Medicine, Department of internal medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital) Beijing China
| | - He Zhao
- Department of family medicine & Division of General Internal Medicine, Department of internal medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital) Beijing China
| | - Xinxin Han
- Department of family medicine & Division of General Internal Medicine, Department of internal medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital) Beijing China
| | - Hong Di
- Department of family medicine & Division of General Internal Medicine, Department of internal medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital) Beijing China
| | - Tiange Xie
- Department of family medicine & Division of General Internal Medicine, Department of internal medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital) Beijing China
| | - Juan Wu
- Department of family medicine & Division of General Internal Medicine, Department of internal medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital) Beijing China
| | - Yibo Wang
- Department of family medicine & Division of General Internal Medicine, Department of internal medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital) Beijing China
| | - Yun Zhang
- Department of family medicine & Division of General Internal Medicine, Department of internal medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital) Beijing China
| | - Xuejun Zeng
- Department of family medicine & Division of General Internal Medicine, Department of internal medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital) Beijing China
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Hua T, Zheng S, Ding J, Geng Z, Zhang W, Qi T, Li Y, Wang X. Cross-sectional study on the association between serum uric acid levels and the risk of benign prostatic hyperplasia. BMJ Open 2025; 15:e092844. [PMID: 40107683 PMCID: PMC11927409 DOI: 10.1136/bmjopen-2024-092844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Accepted: 03/05/2025] [Indexed: 03/22/2025] Open
Abstract
OBJECTIVE Serum uric acid (SUA), a non-protein antioxidant, exerts anti-inflammatory and antioxidative stress effects. This study aimed to investigate the association between SUA levels and the risk of benign prostatic hyperplasia (BPH). METHODS This cross-sectional study included 48 653 adult men who underwent health checkups at the Health Examination Center of the Affiliated Hospital of Yangzhou University in 2022. Data on demographics, clinical history and laboratory parameters were collected. Multivariable logistic regression models were used to analyse the relationship between SUA levels and BPH risk, with further exploration in different subgroups. RESULTS Logistic regression analysis revealed a significantly decreased risk of BPH among participants in the highest SUA quartile (Q4) compared with those in the lowest quartile (Q1) (fully adjusted OR=0.83, 95% CI: 0.78 to 0.90, p<0.0001). Subgroup analyses demonstrated that this inverse association was more pronounced in subgroups of age>60 years (Q4: OR=0.77, 95% CI: 0.68 to 0.87, p<0.0001), non-obesity (Q4: OR=0.81, 95% CI: 0.75 to 0.87, p<0.0001), without non-alcoholic fatty liver disease (NAFLD) (Q4: OR=0.81, 95% CI: 0.73 to 0.89, p<0.0001), hypertension (Q4: OR=0.81, 95% CI: 0.74 to 0.89, p<0.0001) and without diabetes (Q4: OR=0.84, 95% CI: 0.78 to 0.90, p<0.0001). Curve fitting revealed that higher SUA levels were associated with a lower risk of BPH even in the presence of increased BPH risk factors such as diabetes and hypertension. CONCLUSIONS This study demonstrates a significant inverse association between SUA levels and BPH risk, particularly in subgroups of older age, non-obesity, absence of NAFLD, hypertension and absence of diabetes. This suggests a potential protective role of SUA in BPH development, highlighting the potential value of maintaining SUA levels within a reasonable range for BPH prevention.
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Affiliation(s)
- Tianchi Hua
- Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China
| | - Shengqi Zheng
- Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China
| | - Jiawen Ding
- Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China
| | - Zhaoyong Geng
- Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China
| | - Wei Zhang
- Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China
| | - Tingyue Qi
- Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China
| | - Yifan Li
- Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China
| | - Xiaoxiang Wang
- Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China
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Yu L, Sun J, Liu X. A retrospective study of the association between serum uric acid and risk of coronary heart disease complicated with different types of chronic heart failure. Eur J Med Res 2025; 30:146. [PMID: 40022200 PMCID: PMC11871693 DOI: 10.1186/s40001-025-02403-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 02/23/2025] [Indexed: 03/03/2025] Open
Abstract
Heart failure (HF) is a terminal stage of cardiovascular diseases, classified based on ejection fraction. Serum uric acid (SUA) has been implicated in the pathogenesis and progression of coronary artery disease (CAD) with HF, yet its predictive value remains unclear. This study aimed to evaluate the predictive role of SUA in the progression of HF in CAD patients and its potential to differentiate HF types. A retrospective analysis was conducted on 342 CAD patients, including 29 with CAD alone and 313 with CAD complicated by varied HF types. Biochemical parameters and HF severity were assessed, and logistic regression analyses were performed to identify independent predictors of HF progression. Significant differences were observed in biochemical parameters, including glutamic-pyruvic transaminase (ALT), glutamic oxalacetic transaminase (AST), alkaline phosphatase (ALP), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), creatine kinase-MB (CK-MB), SUA, lactate dehydrogenase (LDH), myoglobin (MTO), between groups. SUA levels were significantly higher in CAD patients with HF, particularly in those with reduced ejection fraction. Univariate and multivariate logistic regression analyses identified history of hypertension, AST, and SUA as independent predictors of HF progression, with SUA showing the highest odds ratio. In addition, SUA levels were positively correlated with Gensini scores, indicating its association with CAD severity. SUA is a strong predictor of HF progression in CAD patients, especially for patients with HFrEF, which can serve as a diagnostic and prognostic marker for HF progression in CAD patients.
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Affiliation(s)
- Lei Yu
- Department of Clinical Laboratory, Wuhan City No.3 Hospital, No. 216, Guanshan Avenue, Hongshan District, Wuhan, 430060, China.
- Guangdong Medical University, No.1, Xincheng Road, Songshan Lake Science and Technology Park, Dongguan, 523808, Guangdong, China.
| | - Jianbin Sun
- Department of Clinical Laboratory, Wuhan City No.3 Hospital, No. 216, Guanshan Avenue, Hongshan District, Wuhan, 430060, China
| | - Xinguang Liu
- Guangdong Medical University, No.1, Xincheng Road, Songshan Lake Science and Technology Park, Dongguan, 523808, Guangdong, China.
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Lunzer R, Delle-Karth G, Zeitlinger M, Prager M, Pracher LM. [Colchicine-Phoenix from the ashes]. Wien Klin Wochenschr 2025; 137:1-33. [PMID: 39912853 PMCID: PMC11802715 DOI: 10.1007/s00508-024-02490-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/29/2024] [Indexed: 02/07/2025]
Abstract
Colchicine is an anti-inflammatory herbal medicine with a history stretching back thousands of years. It is a cornerstone in the acute and prophylactic treatment of gout and has secured a permanent place in the standard pharmacological repertoire for familial Mediterranean fever, pericarditis, neutrophilic dermatoses, Behçet's disease and severe aphthous ulcers refractory to oral treatment. The US Food and Drug Administration (FDA) has recently approved colchicine to reduce the risk of myocardial infarction, stroke, coronary revascularization and cardiovascular death in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular diseases. The recommendation level for cardiovascular prophylaxis was raised from IIb to IIa in the current European Society of Cardiology (ESC) guidelines from 2024. Clinical studies in recent years also demonstrated an effect for acute coronary syndrome and atrial fibrillation. This review article highlights the efficacy and safety profile of colchicine and provides insights into recent and potential future evidence-based fields of application.
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Affiliation(s)
- Raimund Lunzer
- Abteilung für Innere Medizin II, Krankenhaus der Barmherzigen Brüder, Marschallgasse 12, 8020, Graz, Österreich.
| | | | - Markus Zeitlinger
- Universitätsklinik für Klinische Pharmakologie, Medizinische Universität Wien, Wien, Österreich
| | - Marlene Prager
- Universitätsklinik für Klinische Pharmakologie, Medizinische Universität Wien, Wien, Österreich
| | - Lena Maria Pracher
- Universitätsklinik für Klinische Pharmakologie, Medizinische Universität Wien, Wien, Österreich
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Zhou X, Wang Z, Zhu Y, Feng S, Wu H, Zhu D, Wu Z, Kao Q. Effect of serum uric acid to creatinine ratio on cognitive function decline in middle-aged adults: Longitudinal evidence from CHARLS. J Alzheimers Dis 2025; 103:582-592. [PMID: 39791192 DOI: 10.1177/13872877241303789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
Abstract
BACKGROUND Serum uric acid (SUA) was a predictor of cognitive function. The association of SUA/serum creatinine ratio (Scr), which represents renal function-normalized SUA and cognitive function is unknown. OBJECTIVE This study investigated the association of the SUA/Scr with cognitive function and the potential mediation effect of inflammation in the above relationship. METHODS This study used 1-5 waves of data from the China Health and Retirement Longitudinal Study. 3302 participants aged 45-60 years at baseline were included. Among them, 1129 who attended subsequent 2-3 waves were further included for cumulative exposure calculation to the SUA/Scr ratio. The Cox models were used to evaluate the impact of baseline SUA/Scr ratio and its cumulative exposure on cognitive function decline. RESULTS During a median follow-up of 8.6 years, there were 1512 (45.8%) cognitive function declined. After adjustment, the highest quartile of the SUA/SCr ratio was associated with the highest risk of cognitive function decline (Hazard ratio, 1.175; 95% confidence interval, 1.015-1.360). Restricted cubic spline showed a linear association between the SUA/Scr ratio and the risk of cognitive function decline (pnon-linear = 0.514). There were a stronger association of cumulative SUA/Scr ratio and its exposure burden with cognitive function decline [the highest versus lowest quartile: 1.635 (1.006-2.656), the high versus low group: 1.729 (1.212-2.466), respectively]. No significant mediating effect through white blood cell count or C-reactive protein in SUA/Scr ratio-cognitive function decline was found. CONCLUSIONS The SUA/Scr ratio was associated with a higher risk of cognitive decline, whereas the mechanism mediated by inflammation indicators was not found.
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Affiliation(s)
- Xiangjun Zhou
- Hangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou, P. R. China
| | - Zhe Wang
- Hangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou, P. R. China
| | - Yi Zhu
- Hangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou, P. R. China
| | - Shuang Feng
- Hangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou, P. R. China
| | - Haijian Wu
- Hangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou, P. R. China
| | - Dongliang Zhu
- Hangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou, P. R. China
| | - Zheyuan Wu
- Hangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou, P. R. China
| | - Qingjun Kao
- Hangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou, P. R. China
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Lewandowska K, Lipski D, Uruski P, Narkiewicz K, Januszewicz A, Wolf J, Prejbisz A, Rajzer M, Więcek A, Tykarski A. Randomised, double-blind, placebo-controlled study evaluating the effect of allopurinol on the risk of cardiovascular events in patients with high and very high cardiovascular risk, including the presence of long-COVID-19 syndrome: the ALL-VASCOR study protocol. BMJ Open 2024; 14:e075741. [PMID: 39053954 PMCID: PMC11284933 DOI: 10.1136/bmjopen-2023-075741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 06/24/2024] [Indexed: 07/27/2024] Open
Abstract
INTRODUCTION Numerous studies, but not all, have suggested a positive effect of allopurinol on the cardiovascular system. The randomised, double-blind, placebo-controlled study evaluating the effect of allopurinol on the risk of cardiovascular events in patients with high and very high cardiovascular risk, including the presence of long-COVID-19 syndrome (ALL-VASCOR) study aims to evaluate the efficacy of allopurinol therapy for improving cardiovascular outcomes in patients at high and very high cardiovascular risk excluding ischaemic heart disease. This is particularly important due to the high cost of cardiovascular disease treatment and its status as one of the leading causes of mortality. METHODS AND ANALYSIS The ALL-VASCOR study is a randomised, double-blind, placebo-controlled, multicentre trial that examines the effect of allopurinol therapy (200-500 mg of allopurinol daily) versus an equivalent dose of placebo on the risk of cardiovascular events in 1116 patients aged 40-70 with serum uric acid levels above 5 mg/dL at high and very high risk of cardiovascular disease. The ALL-VASCOR study will also assess the occurrence of long-COVID-19 syndrome. The study will measure primary and secondary as well as additional endpoints and the planned intervention will end on 31 July 2028 unless advised otherwise by the Safe Monitoring Board or other applicable authorities. Participant recruitment is planned to begin in March 2024 in Poland. ETHICS AND DISSEMINATION The study was ethically approved by the Bioethics Committee of Poznan University of Medical Sciences (No 03/23, 12 January 2023). The results are expected after 2028 and will be disseminated in peer-reviewed journals and at international conferences. PROTOCOL VERSION NUMBER 01-15 November 2022. TRIAL REGISTRATION NUMBER EudraCT: 2022-003573-32, 27 October 2022, ClinicalTrials: NCT05943821, 13 July 2023.
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Affiliation(s)
- Katarzyna Lewandowska
- Department of Hypertensiology, Angiology and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland
| | - Dawid Lipski
- Department of Hypertensiology, Angiology and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland
| | - Paweł Uruski
- Department of Hypertensiology, Angiology and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland
| | - Krzysztof Narkiewicz
- Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland
| | - Andrzej Januszewicz
- Department of Hypertension, National Institute of Cardiology, Warsaw, Poland
| | - Jacek Wolf
- Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland
| | - Aleksander Prejbisz
- Department of Epidemiology, Cardiovascular Prevention and Health Promotion, National Institute of Cardiology, Warsaw, Poland
| | - Marek Rajzer
- First Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Jagiellonian University Medical College, Krakow, Poland
| | - Andrzej Więcek
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland
| | - Andrzej Tykarski
- Department of Hypertensiology, Angiology and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland
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Huang T, Huang X, Cui X, Dong Q. Predictive nomogram models for atrial fibrillation in COPD patients: A comprehensive analysis of risk factors and prognosis. Exp Ther Med 2024; 27:171. [PMID: 38476891 PMCID: PMC10928814 DOI: 10.3892/etm.2024.12459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 01/24/2024] [Indexed: 03/14/2024] Open
Abstract
The aim of the present study was to identify the independent risk factors and prognostic indicators for atrial fibrillation (AF) in patients with chronic obstructive pulmonary disease (COPD) and to develop predictive nomogram models. This retrospective study included a total of 286 patients with COPD who were admitted to the Second Affiliated Hospital of Guilin Medical College between January 2020 and May 2022. The average age of the patients was 77.11±8.67 years. Based on the presence or absence of AF, the patients were divided into two groups: The AF group (n=87) and the non-AF group (n=199). Logistic regression analysis was conducted to identify variables with significant differences between the two groups. Nomogram models were constructed to predict the occurrence of AF in COPD patients and to assess prognosis. Survival analysis was performed using the Kaplan-Meier method. The follow-up period for the present study extended until April 31, 2023. Survival time was defined as the duration from the date of the interview to the date the participant succumbed or the end of the follow-up period. In the present study, age, uric acid (UA) and left atrial diameter (LAD) were found to be independent risk factors for the development of AF in patients diagnosed with COPD. The stepwise logistic regression analysis revealed that age had an odds ratio (OR) of 1.072 [95% confidence interval (CI): 1.019-1.128; P=0.007], UA had an OR of 1.004 (95% CI: 1.001-1.008; P=0.010) and LAD had an OR of 1.195 (95% CI: 1.098-1.301; P<0.001). Univariate and multivariate Cox regression analysis revealed that LAD and UA were independent prognostic factors for long-term mortality in COPD patients with AF. LAD had a hazard ratio (HR) of 1.104 (95% CI: 1.046-1.165; P<0.001) and UA had an HR of 1.004 (95% CI: 1.000-1.008; P=0.042). Based on these findings, predictive nomogram models were developed for AF in COPD patients, which demonstrated good discrimination ability with an area under the curve of 0.886. The prognostic nomogram for COPD patients with AF also showed good predictive accuracy with a concordance index of 0.886 (95% CI: 0.842-0.930). These models can provide valuable information for risk assessment and prognosis evaluation in clinical practice. Age, UA and LAD are independent risk factors for AF in COPD patients. The developed nomogram models provide a reliable tool for predicting AF in COPD patients and for prognosis assessment.
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Affiliation(s)
- Tao Huang
- Department of Critical Care Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region 541100, P.R. China
| | - Xingjie Huang
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region 541100, P.R. China
| | - Xueying Cui
- Department of Reproductive Medical Center, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region 541004, P.R. China
| | - Qinghua Dong
- Department of Critical Care Medicine, Guilin Municipal Hospital of Traditional Chinese Medicine, Guilin, Guangxi Zhuang Autonomous Region 541000, P.R. China
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Tang X, Liu S, Qiu X, Su L, Huang D, Liang J, Yang Y, Juan Tan JH, Zeng X, Xie Y. High prevalence of hyperuricemia and the association with metabolic syndrome in the rural areas of Southwestern China: A structural equation modeling based on the Zhuang minority cohort. Nutr Metab Cardiovasc Dis 2024; 34:497-505. [PMID: 38161122 DOI: 10.1016/j.numecd.2023.06.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 04/27/2023] [Accepted: 06/25/2023] [Indexed: 01/03/2024]
Abstract
BACKGROUND AND AIMS The prevalence of hyperuricemia (HUA) and metabolic syndrome (MetS) in the Zhuang minority had not been examined. We aimed to determine the prevalence of HUA and MetS, and explore the interrelationship among the serum uric acid to creatinine (SUA/Cr) ratio, MetS, and its components. METHODS AND RESULTS A cross-sectional study was conducted with structured questionnaire and physical examination based on the Zhuang minority cohort. A Structural Equation Model was performed to examine the hypothesis link between the SUA/Cr ratio, MetS, and its components. 10,902 aged 35-74 years Zhuang minority adults were included. The total prevalence of HUA and MetS was 17.5% and 23.7%, respectively. The SUA/Cr ratio had a positive effect on MetS (the standardized coefficient βr was 0.311 in males and 0.401 in females). The SUA/Cr ratio was positively associated with obesity (βr = 0.215), dyslipidemia (βr = 0.177), and high blood pressure (βr = 0.034) in males and was positively associated with obesity (βr = 0.303), dyslipidemia (βr = 0.162), and hyperglycemia (βr = 0.036) in females. CONCLUSIONS The prevalence of HUA in the aged 35-74 years Zhuang minority adults was high while the prevalence of MetS was relatively low. As HUA is an earlier-onset metabolic disorder and the SUA/Cr ratio had a positive effect on MetS and its components, the prevention measures of MetS should be strengthened. And the SUA/Cr ratio can be used as an early warning sign to implement the intervention measures of MetS.
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Affiliation(s)
- Xiaofen Tang
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Shun Liu
- Department of Maternal, Child and Adolescent Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Xiaoqiang Qiu
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Li Su
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Dongping Huang
- Department of Sanitary Chemistry, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Jun Liang
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Yu Yang
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Jennifer Hui Juan Tan
- National University of Singapore, Yong Loo Lin School of Medicine 10 Medical Dr, 117597, Singapore
| | - Xiaoyun Zeng
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Key Laboratory of High-Incidence-Tumor Prevention and Treatment, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, China.
| | - Yihong Xie
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China.
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Bugajska J, Berska J, Wójcik M, Sztefko K. Amino acid profile in overweight and obese prepubertal children - can simple biochemical tests help in the early prevention of associated comorbidities? Front Endocrinol (Lausanne) 2023; 14:1274011. [PMID: 37964971 PMCID: PMC10641253 DOI: 10.3389/fendo.2023.1274011] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 09/27/2023] [Indexed: 11/16/2023] Open
Abstract
Background It is accepted that plasma branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) are closely related to metabolic risk. Arterial hypertension, metabolic syndrome, endothelial dysfunction, inflammation, and metabolic dysfunction-associated fatty liver disease (MAFLD) are frequently seen in obese patients. Many attempts have been made to find biochemical indicators for the early detection of metabolic complications in children. It is not known if different amino acid profiles and BCAA and AA concentrations in overweight and obese children correlate with chemerin, proinflammatory, and simple biochemical markers. Thus, the study aimed to find out the early markers of cardiovascular disease and MAFLD in overweight and obese children. Materials and methods The study included 20 overweight and obese children (M/F 12/8; mean age 7.7 ± 2.3 years; BMI 26.8 ± 5.0 kg/m2) and 12 non-obese children (control group) (M/F 4/8; mean age 6.5 ± 2.2 years; BMI 14.8 ± 1.5 kg/m2). The following plasma amino acids were measured: aspartic acid, glutamic acid, serine, asparagine, glycine, glutamine, taurine, histidine, citrulline, threonine, alanine, arginine, proline, tyrosine, methionine, valine, isoleucine, leucine, phenylalanine, tryptophan, ornithine, and lysine. Chemerin, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and basic biochemistry parameters were measured. Results The mean plasma levels of leucine, isoleucine, valine, phenylalanine, tyrosine, glutamic acid, and alanine were significantly higher in overweight and obese children than in the control group (p<0.03-p<0.0004). Conversely, the mean values of serine, asparagine, glutamine, and citrulline were significantly lower in overweight and obese children than in the control group (p<0.03-p<0.0007). Isoleucine, leucine, valine (BCAAs) tyrosine, and phenylalanine (AAAs) levels showed a positive correlation with uric acid, ALT, hs-CRP, and chemerin (r=0.80-0.36; p<0.05-p<0.00001), but not with IL-6. The mean values of glucose, IL-6, hs-CRP, chemerin, uric acid, and ALT were significantly higher in overweight and obese children than in the control group (p<0.03-p<0.00002). In contrast, the lipid profile did not differ between groups. Conclusion An abnormal amino acid profile in overweight and obese pre-pubertal children, accompanied by elevated ALT and UA observed in the studied cohort, may suggest early metabolic disturbances that can potentially lead to metabolic syndrome, or MAFLD, and increased cardiovascular risk.
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Affiliation(s)
- Jolanta Bugajska
- Department of Clinical Biochemistry, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland
| | - Joanna Berska
- Department of Clinical Biochemistry, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland
| | - Małgorzata Wójcik
- Department of Pediatric and Adolescent Endocrinology, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland
| | - Krystyna Sztefko
- Department of Clinical Biochemistry, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland
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11
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Shen L, Dong Y, Li M, Zhou Z, Zhang J, Liu Y, Zhao W. The relationship between leukocyte level and hypertension in elderly patients with hyperuricemia. Medicine (Baltimore) 2022; 101:e32327. [PMID: 36595776 PMCID: PMC9794235 DOI: 10.1097/md.0000000000032327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
To evaluate the change of leukocyte level caused by hyperuricemia, and to explore the relationship between leukocyte level and hypertension in elderly patients with hyperuricemia. A cross-sectional study of serum uric acid (UA) level was conducted in 1352 elderly people over 65 years old. The samples were divided into 3 categories according to the tertiles of leukocyte: Tertile 1, leukocyte ≤ 5.2 × 109/L; Tertile 2, leukocyte = 5.3-6.3 × 109/L; Tertile 3, leukocyte ≥ 6.4 × 109/L. Multiple logistic regression models were used for modeling relationships between leukocyte, hyperuricemia and hypertension. Human vascular endothelial cells were treated by different concentrations of UA. The levels of interleukin-1 beta, tumor necrosis factor-α, endothelial nitric oxide synthase, inducible nitric oxide synthase and reactive oxygen species were measured by Western Blot or fluorescence microscope. The levels of leukocyte were higher in elderly patients with hyperuricemia than without hyperuricemia. Hyperuricemia was an independent risk factor of leukocyte in Tertile 3 (odds ratio [OR] = 1.657, 95% confidence interval [CI]: 1.180-2.328). The prevalences of hypertension were higher in elderly patients with hyperuricemia than without hyperuricemia (77.0% vs 63.5%). In the Model 1, hyperuricemia was an independent risk factor of hypertension (OR = 1.536, 95% CI: 1.026-2.302). Leukocyte in Tertile 3 was an independent risk factor of hypertension (OR = 1.333, 95% CI: 1.031-1.724). Expression levels of interleukin-1 beta, inducible nitric oxide synthase and tumor necrosis factor-α were obviously higher in the UA group than the control group, along with the productions of reactive oxygen species. But the expression level of endothelial nitric oxide synthase was obviously lower in the UA group. Hyperuricemia was associated with an increased risk for hypertension. The chronic inflammation caused by hyperuricemia maybe one of important pathogenesis of incident hypertension in patients with hyperuricemia.
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Affiliation(s)
- Lijin Shen
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital &Metabolic Diseases Hospital, Tianjin Medical University, Tianjin, China
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12
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Liu T, Gao H, Zhang Y, Wang S, Lu M, Dai X, Liu Y, Shi H, Xu T, Yin J, Gao S, Wang L, Zhang D. Apigenin Ameliorates Hyperuricemia and Renal Injury through Regulation of Uric Acid Metabolism and JAK2/STAT3 Signaling Pathway. Pharmaceuticals (Basel) 2022; 15:1442. [PMID: 36422572 PMCID: PMC9697024 DOI: 10.3390/ph15111442] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 11/18/2022] [Indexed: 08/09/2023] Open
Abstract
Hyperuricemia (HUA) is a kind of metabolic disease with high incidence that still needs new countermeasures. Apigenin has uric-lowering and kidney-protective activities, but how apigenin attenuates HUA and renal injury remains largely unexploited. To this end, an acute HUA mouse model was established by intraperitoneal injection of potassium oxazinate and oral administration with hypoxanthine for 7 consecutive days. Apigenin intervention decreased serum uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), interleukin-18 (IL-18), liver xanthine oxidase (XOD), and urine protein levels, and increased serum interleukin-10 (IL-10) and urine UA and CRE levels in HUA mice. Moreover, administration of apigenin to HUA mice prevented renal injury, decreased renal glucose transporter 9 (GLUT9) and urate anion transporter 1 (URAT1) levels, and increased renal organic anion transporter 1 (OAT1). These alterations were associated with an inhibition of IL-6, phospho-janus kinase 2 (P-JAK2), phospho-signal transducer, and activator of transcription 3 (P-STAT3), and suppression of cytokine signaling 3 (SOCS3) expression in the kidneys. Additionally, the molecular docking results showed that apigenin had strong binding capacity with UA transporters and JAK2 proteins. In summary, apigenin could improve UA metabolism and attenuate renal injury through inhibiting UA production, promoting excretion, and suppressing the JAK2/STAT3 signaling pathway in HUA mice. The results suggest that apigenin may be a suitable drug candidate for management of HUA and its associated renal injury.
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Affiliation(s)
- Tianyuan Liu
- Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Huimin Gao
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Science, Beijing 100700, China
| | - Yueyi Zhang
- Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Shan Wang
- Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Meixi Lu
- Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Xuan Dai
- Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yage Liu
- Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Hanfen Shi
- Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Tianshu Xu
- Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Jiyuan Yin
- Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Sihua Gao
- Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Lili Wang
- Department of TCM Pharmacology, Chinese Material Medica School, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Dongwei Zhang
- Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China
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Zhong X, Jiao H, Zhao D, Teng J. A case-control study to investigate association between serum uric acid levels and paroxysmal atrial fibrillation. Sci Rep 2022; 12:10380. [PMID: 35726017 PMCID: PMC9209416 DOI: 10.1038/s41598-022-14622-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Accepted: 06/09/2022] [Indexed: 11/24/2022] Open
Abstract
The relationship between serum uric acid (SUA) levels and paroxysmal atrial fibrillation (AF) remains controversial. The objective of this case–control study was to investigate the association between serum SUA levels and paroxysmal AF by gender in 328 patients. This study included 328 hospitalized patients with newly diagnosed paroxysmal AF in China between January 2019 and September 2021. Controls with sinus rhythm were matched (2:1) to cases by age and gender. Baseline data were analyzed using ANOVA, T-test, and Chi-square test. Pearson correlation analyses were used to confirm the correlation between variables, and multivariate regression analyses were used to adjust for covariates. Elevated SUA levels in female patients were significantly associated with paroxysmal AF after adjusting for confounding factors (OR = 1.229, 95% CI 1.058–1.427, P = 0.007). Further results showed SUA levels were negatively correlated with high-density lipoprotein cholesterol (HDL-C) (r = − 0.182, p = 0.001) and apolipoprotein A1 (APOA1) (r = − 0.109, p = 0.049), were positively correlated with low-density lipoprotein cholesterol (LDL-C) (r = 0.169, p = 0.002) and prealbumin (PAB) (r = 0.161, p = 0.004) . Nevertheless, there was no significant complication difference between SUA levels and paroxysmal AF (P > 0.05). Increased SUA in female patients was significantly associated with paroxysmal AF in a Chinese population. This finding implies that it would be interesting to monitor and interfere with hyperuricemia in paroxysmal AF patients.
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Affiliation(s)
- Xia Zhong
- Department of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People's Republic of China
| | - Huachen Jiao
- Department of Cardiology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No. 16369, Jingshi Road, Lixia District, Jinan, Shandong, People's Republic of China.
| | - Dongsheng Zhao
- Department of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People's Republic of China
| | - Jing Teng
- Department of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People's Republic of China
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14
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Mantovani A, Bonapace S, Dugo C, Beatrice G, Petracca G, Cappelli D, Csermely A, Molon G, Targher G. Association between higher serum uric acid levels and plasma N-terminal pro-B-type natriuretic peptide concentrations in patients with coronary artery disease and without overt heart failure. Int J Cardiol 2022; 353:127-130. [DOI: 10.1016/j.ijcard.2022.02.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Revised: 02/07/2022] [Accepted: 02/10/2022] [Indexed: 11/30/2022]
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Mikuls TR, Soto Q, Petro A, Helget L, Roul P, Sayles H, Cope B, Neogi T, LaMoreaux B, O’Dell JR, England BR. Comparison of Rates of Lower Extremity Amputation in Patients With and Without Gout in the US Department of Veterans Affairs Health System. JAMA Netw Open 2022; 5:e2142347. [PMID: 34989795 PMCID: PMC8739736 DOI: 10.1001/jamanetworkopen.2021.42347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 11/11/2021] [Indexed: 11/28/2022] Open
Abstract
Importance Cardiometabolic and other risk factors could render patients with gout more likely to undergo lower extremity amputation (LEA). Objective To examine the rate of and factors associated with LEA in patients with gout. Design, Setting, and Participants In this matched cohort study using national administrative data, multivariable Cox proportional hazards regression models were used to examine the associations of gout with LEA. In analyses limited to patients with gout, attributes of serum urate control and treatment with urate-lowering therapy were examined as factors associated with LEA. This study included patients who used US Department of Veterans Affairs services from January 1, 2000, to July 31, 2015. Patients with gout were identified using diagnostic codes and matched with up to 10 controls by age, sex, and year of benefit enrollment. Data analysis was performed from January 26, 2021, to September 3, 2021. Exposures Gout classification served as the primary independent variable of interest. In analyses limited to patients with gout, factors associated with serum urate control and urate-lowering therapy were examined. Main Outcomes and Measures Overall LEA, as well as toe, transmetatarsal, below-the-knee, and above-the-knee amputation. Results This cohort study included 5 924 918 patients, 556 521 with gout (mean [SD] age, 67 [12] years; 550 963 (99.0%) male; 88 853 [16.0%] Black non-Hispanic; 16 981 [4.3%] Hispanic/Latinx; 345 818 [62.1%] White non-Hispanic; 80 929 [14.5%] with race and ethnicity data missing; and 23 940 [4.3%] classified as other) and 5 368 397 without gout (mean [SD] age, 67 [12] years; 5 314 344 [99.0%] male; 558 464 [10.4%] Black non-Hispanic; 204 291 [3.0%] Hispanic/Latinx; 3 188 504 [59.4%] White non-Hispanic; 1 257 739 [23.4%)] with race and ethnicity data missing; and 159 399 [3.0%] classified as other). Compared with patients without gout, patients with gout were more likely to undergo amputation, an increased rate that remained after adjustment (adjusted hazard ratio, 1.20; 95% CI, 1.16-1.24) and was highest for below-the-knee amputation (adjusted hazard ratio, 1.59; 95% CI, 1.39-1.81). In those with gout, poor serum urate control (mean >7 mg/dL during the preceding year) was associated with a 25% to 37% increase in the rate of amputation. In contrast, treatment with urate-lowering therapy was not associated with the LEA rate. Conclusions and Relevance In this matched cohort study, patients with gout were more likely to undergo LEA. This increase was independent of other comorbidities that have been associated with amputation, including diabetes and peripheral vascular disease. Serum urate control was independently associated with the LEA rate, suggesting the possibility that lower extremity amputation may be preventable in some patients.
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Affiliation(s)
- Ted R. Mikuls
- Veterans Affairs Nebraska–Western Iowa Health Care System, Omaha, Nebraska
- Division of Rheumatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha
| | - Quint Soto
- Veterans Affairs Nebraska–Western Iowa Health Care System, Omaha, Nebraska
- Division of Rheumatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha
| | - Alison Petro
- Veterans Affairs Nebraska–Western Iowa Health Care System, Omaha, Nebraska
- Division of Rheumatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha
| | - Lindsay Helget
- Veterans Affairs Nebraska–Western Iowa Health Care System, Omaha, Nebraska
- Division of Rheumatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha
| | - Punyasha Roul
- Veterans Affairs Nebraska–Western Iowa Health Care System, Omaha, Nebraska
- Division of Rheumatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha
| | - Harlan Sayles
- Division of Rheumatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha
- Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha
| | - Brendan Cope
- Division of Rheumatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha
| | - Tuhina Neogi
- Section of Rheumatology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
| | | | - James R. O’Dell
- Veterans Affairs Nebraska–Western Iowa Health Care System, Omaha, Nebraska
- Division of Rheumatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha
| | - Bryant R. England
- Veterans Affairs Nebraska–Western Iowa Health Care System, Omaha, Nebraska
- Division of Rheumatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha
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Feitosa RS, Martins BP, Almeida LM, de Oliveira MB, de Araújo RMS, de Oliveira KA. Serum uric acid is independently associated with metabolic syndrome and systemic hypertension in women from northeast Brazil. Women Health 2021; 62:68-74. [PMID: 34965850 DOI: 10.1080/03630242.2021.2019170] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Hyperuricemia (HU) has been associated with cardiovascular risk and metabolic syndrome (MS) worldwide. However, inconsistencies about this relation are still reported, and it is not clear whether hyperuricemia is an independent risk factor for MS. The aim of this study was to determine hyperuricemia associations with systemic hypertension and MS in women from northeast Brazil. The study included 301 women. Hyperuricemia was considered for serum uric acid (SUA) ≥6 mg/dL. Insulin resistance (IR) was measured by TyG index (TyG ≥ 4.55). Fisher test and Multivariate logistic regression analyses estimated the association between hyperuricemia (or SUA level) and systemic hypertension and MS. Hyperuricemia association with systemic hypertension was independent of age, body-mass index (BMI), smoking and alcoholism (OR: OR: 4.6050; p = .000256), and MS components (OR: 4.1296; IC95% 1.8330_9.3033; p = .000621). Hyperuricemia increased risk of systemic hypertension by 4,6 -fold. SUA level was associated with MS, independently of other classic component factors of the syndrome (OR:1.34, p = .0129). Hyperuricemia and high SUA levels were associated with MS and systemic hypertension. Effect of hyperuricemia in systemic hypertension is independent of age, BMI, lifestyle, and MS factors. SUA levels are independently associated with MS.
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Affiliation(s)
| | | | - Lucas Martins Almeida
- Medical School, Health Sciences Center, Federal University of Piauí, Teresina, Brazil
| | - Max Brandão de Oliveira
- Statistics Department, Nature Sciences Center, Federal University of Piauí, Teresina, Brazil
| | | | - Karla Andrade de Oliveira
- Biochemistry and Pharmacology Department, Health Sciences Center, Federal University of Piauí, Teresina, Brazil
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Lu J, Bai Z, Chen Y, Li Y, Tang M, Wang N, Zhu X, Dai H, Zhang W. Effects of bariatric surgery on serum uric acid in people with obesity with or without hyperuricaemia and gout: a retrospective analysis. Rheumatology (Oxford) 2021; 60:3628-3634. [PMID: 33394025 DOI: 10.1093/rheumatology/keaa822] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 11/04/2020] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVES Weight reduction may reduce serum uric acid (SUA). This study aimed to examine the changes of SUA before and after bariatric surgery in patients with obesity with or without hyperuricaemia and gout. METHODS This is a retrospective analysis of 147 routinely collected data on hospital patients with obesity who underwent bariatric surgery. The body weight and SUA were measured at baseline and after surgery at 1-7 days, 1, 3, 6 and 12 months. RESULTS The mean (95% CI) weight reduction of 147 patients was 30.7 (28.7, 32.7) kg 1 year after surgery (P < 0.001). SUA decreased rapidly from 419.0 (400.1, 437.8) µmol/l at baseline to 308.4 (289.6, 327.2) µmol/l at 1-7 days, flared up to 444.8 (423.9, 465.6) µmol/l at 1 month, then decreased again to 383.8 (361.5, 406.1) µmol/l at 3 months, 348.9 (326.3, 371.5) µmol/l at 6 months and 327.9 (305.3, 350.5) µmol/l at 12 months (P < 0.001). Similar trends but more rapid reductions were observed in 55 hyperuricaemia patients and 25 gout patients. All 25 gout patients had an elevated SUA above the therapeutic target (≥360µmmol/l) at baseline, but in 10 patients it was reduced below this target at 12 months. The mean reduction (95% CI) of SUA in all patients and gout patients was 84.3 (63.1-105.4) and 163.6 (103.9, 223.3) µmmol/l, respectively. CONCLUSION Bariatric surgery significantly reduces body weight and SUA for obese patients with hyperuricaemia and gout. Gout may be considered as an indicator for this surgical treatment in people with severe obesity.
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Affiliation(s)
- Jine Lu
- Medical Laboratory Department, Qujing City, Yunnan Province, China
| | - Zhiyao Bai
- Medical Laboratory Department, Qujing City, Yunnan Province, China
| | - Yunqing Chen
- Rheumatology Immunology Department, Qujing City, Yunnan Province, China
| | - Yingxu Li
- Department of Hepatobiliary Medicine, Second People's Hospital, Qujing City, Yunnan Province, China
| | - Min Tang
- Department of Hepatobiliary Medicine, Second People's Hospital, Qujing City, Yunnan Province, China
| | - Ning Wang
- Medical Laboratory Department, Qujing City, Yunnan Province, China
| | - Xingcheng Zhu
- Medical Laboratory Department, Qujing City, Yunnan Province, China
| | - Hongbin Dai
- Medical Laboratory Department, Qujing City, Yunnan Province, China
| | - Weiya Zhang
- Academic Rheumatology, Division of Rheumatology, Orthopedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK
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Pascart T, Carpentier P, Choi HK, Norberciak L, Ducoulombier V, Luraschi H, Houvenagel E, Legrand J, Verclytte S, Becce F, Budzik JF. Identification and characterization of peripheral vascular color-coded DECT lesions in gout and non-gout patients: The VASCURATE study. Semin Arthritis Rheum 2021; 51:895-902. [PMID: 34198148 DOI: 10.1016/j.semarthrit.2021.06.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 05/17/2021] [Accepted: 06/15/2021] [Indexed: 12/27/2022]
Abstract
OBJECTIVE To characterize peripheral vascular plaques color-coded as monosodium urate (MSU) deposition by dual-energy computed tomography (DECT) and assess their association with the overall soft-tissue MSU crystal burden. METHODS Patients with suspected crystal arthropathies were prospectively included in the CRYSTALILLE inception cohort to undergo baseline knees and ankles/feet DECT scans; treatment-naive gout patients initiating treat-to-target urate-lowering therapy (ULT) underwent repeated DECT scans with concomitant serum urate level measurements at 6 and 12 months. We determined the prevalence of DECT-based vascular MSU-coded plaques in knee arteries, and assessed their association with the overall DECT volumes of soft-tissue MSU crystal deposition and coexistence of arterial calcifications. DECT attenuation parameters of vascular MSU-coded plaques were compared with dense calcified plaques, control vessels, control soft tissues, and tophi. RESULTS We investigated 126 gout patients and 26 controls; 17 ULT-naive gout patients were included in the follow-up study. The prevalence of DECT-based vascular MSU-coded plaques was comparable in gout patients (24.6%) and controls (23.1%; p=0.87). Vascular MSU-coded plaques were strongly associated with coexisting arterial calcifications (p<0.001), but not with soft-tissue MSU deposition. Characterization of vascular MSU-coded plaques revealed specific differences in DECT parameters compared with control vessels, control soft tissues, and tophi. During follow-up, vascular MSU-coded plaques remained stable despite effective ULT (p=0.64), which decreased both serum urate levels and soft-tissue MSU volumes (p<0.001). CONCLUSION Our findings suggest that DECT-based MSU-coded plaques in peripheral arteries are strongly associated with calcifications and may not reflect genuine MSU crystal deposition. Such findings should therefore not be a primary target when managing gout patients.
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Affiliation(s)
- Tristan Pascart
- Department of Rheumatology, Lille Catholic Hospitals and Lille Catholic University, Lille, France.
| | - Paul Carpentier
- Department of Diagnostic and Interventional Radiology, Lille Catholic Hospitals and Lille Catholic University, Lille, France
| | - Hyon K Choi
- Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, USA
| | - Laurène Norberciak
- Department of Research, Biostatistics, Lille Catholic Hospitals and Lille Catholic University, Lille, France
| | - Vincent Ducoulombier
- Department of Rheumatology, Lille Catholic Hospitals and Lille Catholic University, Lille, France
| | - Hélène Luraschi
- Department of Rheumatology, Lille Catholic Hospitals and Lille Catholic University, Lille, France
| | - Eric Houvenagel
- Department of Rheumatology, Lille Catholic Hospitals and Lille Catholic University, Lille, France
| | - Julie Legrand
- Department of Diagnostic and Interventional Radiology, Lille Catholic Hospitals and Lille Catholic University, Lille, France
| | - Sébastien Verclytte
- Department of Diagnostic and Interventional Radiology, Lille Catholic Hospitals and Lille Catholic University, Lille, France
| | - Fabio Becce
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Jean-François Budzik
- Department of Diagnostic and Interventional Radiology, Lille Catholic Hospitals and Lille Catholic University, Lille, France
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Miranda-Aquino T, Pérez-Topete SE, González-Padilla C, Hernández-Del Río JE, Lomelí-Sánchez ÓS, Esturau-Santaló RM, Gutiérrez-Ureña SR, González-Díaz V. Asymptomatic hyperuricaemia and coronary artery disease. REUMATOLOGIA CLINICA 2021; 17:263-267. [PMID: 31707094 DOI: 10.1016/j.reuma.2019.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 07/16/2019] [Accepted: 08/19/2019] [Indexed: 06/10/2023]
Abstract
BACKGROUND Uric acid has been related to a tendency to precipitate to form crystals, presenting asymptomatically, until the formation of arthritis, tophi or renal lithiasis. Previously, the presence of asymptomatic hyperuricaemia has been associated with the presence of cardiovascular disease. OBJECTIVES To determine the association of complex coronary artery disease in patients with asymptomatic hyperuricaemia. MATERIAL AND METHODS An observational retrospective, transversal, unicentric study was conducted in a tertiary hospital in Mexico, in the period from June 2017 to March 2019. All patients admitted for coronary angiography were included; patients with gout, use of diuretics and chronic kidney disease were excluded. RESULTS During the study period, a total of 300 patients were collected, of which 40% presented hyperuricaemia. The patients with hyperuricaemia were older (59 vs. 63, P = .002). The group of patients with asymptomatic hyperuricaemia had a higher proportion of complex coronary lesions (64 vs. 35%, P ≤ .0001) as well as a higher SYNTAX I score (27 vs. 17, P ≤ .001). There was a higher probability of presenting complex coronary lesions in this group of patients (OR 3.4, P ≤ .0001). In addition, in the group division of uric acid levels, it was related to the presence of complex coronary lesions (Q1 = .5, P = .06), (Q2 = 2, P = .01) and (Q3 = 3, P ≤ .0001). CONCLUSION Asymptomatic hyperuricaemia has a higher prevalence and association of presenting complex coronary lesions.
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Affiliation(s)
- Tomás Miranda-Aquino
- Cardiología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México.
| | - Silvia Esmeralda Pérez-Topete
- Reumatología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México
| | - Christian González-Padilla
- Cardiología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México
| | - Jorge Eduardo Hernández-Del Río
- Cardiología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México
| | - Óscar Sergio Lomelí-Sánchez
- Cardiología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México
| | - Ramón Miguel Esturau-Santaló
- Cardiología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México
| | - Sergio Ramón Gutiérrez-Ureña
- Reumatología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México
| | - Verónica González-Díaz
- Reumatología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México
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20
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Tian Y, Lin L, Zhao M, Peng A, Zhao K. Xanthine oxidase inhibitory activity and antihyperuricemic effect of Moringa oleifera Lam. leaf hydrolysate rich in phenolics and peptides. JOURNAL OF ETHNOPHARMACOLOGY 2021; 270:113808. [PMID: 33450289 DOI: 10.1016/j.jep.2021.113808] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 11/17/2020] [Accepted: 01/06/2021] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Moringa oleifera Lam. leaf (MOL), a rich source of protein and phenolics, was traditionally used to treat various diseases including headaches, fevers, sore throat and dyslipidemia. Recently, MOL was reported to possess antioxidant, anti-dyslipidemia and hepato-renal protective activities, indicating that MOL could become a potential agent to improve metabolic disorders associated with hyperuricemia. The antihyperuricemic effect of MOL hydrolysate (MOLH) with high contents of phenolics and peptides remains unknown. AIM OF THE STUDY The aim of this study is to investigate xanthine oxidase (XO) inhibitory activity of MOLH, to clarify phenolic and peptide profiles of MOLH, and to evaluate possible mechanism underlying the antihyperuricemic effect of MOLH. MATERIALS AND METHODS MOLH was prepared by enzymatic hydrolysis using commercial trypsin. XO inhibitory activity was determined by XO reaction-UPLC-MS coupling method. The chemical profiles of the phenolic and peptide fractions of MOLH were determined by UPLC-QTOF-MS/MS. The antihyperuricemic effect of MOLH was evaluated in a potassium oxonate-induced hyperuricemic rat model at doses of 200 and 500 mg/kg. Serum uric acid (UA), urea nitrogen, creatinine (CRE), triglyceride (TG), total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels, serum XO activity, liver malondialdehyde (MDA) equivalent level, renal tumor necrosis factor-α and interleukin-1β levels, and protein expression of renal urate-anion transporter 1, glucose transporter 9 and ATP-binding cassette transporter G2 were determined. RESULTS The phenolic and peptide fractions played key roles in inhibiting XO activity and blocking uric acid production. Five flavonoids and sixteen polypeptides were identified in the phenolic and peptide fractions of MOLH, respectively. MOLH (200 and 500 mg/kg) could effectively reduce the serum UA level of hyperuricemic rats (p < 0.001) by regulation of serum XO activity (p < 0.05 at 200 mg/kg, p < 0.01 at 500 mg/kg) and renal urate transporters. Besides, MOLH could improve metabolic disorders associated with hyperuricemia by its multiple actions on liver MDA (p < 0.001), serum CRE (p < 0.05 at 500 mg/kg) and serum TG (p < 0.001). CONCLUSION The results provided scientific evidence that MOLH rich in phenolics and peptides ameliorated hyperuricemia and metabolic disorders. This study validated the potential use of MOLH for regulation of hyperuricemia.
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Affiliation(s)
- Yuchen Tian
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510641, China; Guangdong Food Green Processing and Nutrition Regulation Technologies Research Center, Guangzhou, 510641, China
| | - Lianzhu Lin
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510641, China; Guangdong Food Green Processing and Nutrition Regulation Technologies Research Center, Guangzhou, 510641, China.
| | - Mouming Zhao
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510641, China; Guangdong Food Green Processing and Nutrition Regulation Technologies Research Center, Guangzhou, 510641, China
| | - An Peng
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510641, China; Guangdong Food Green Processing and Nutrition Regulation Technologies Research Center, Guangzhou, 510641, China
| | - Kun Zhao
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510641, China; Guangdong Food Green Processing and Nutrition Regulation Technologies Research Center, Guangzhou, 510641, China
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Kurniasari MD, Karwur FF, Rayanti RE, Dharmana E, Rias YA, Chou KR, Tsai HT. Second-Hand Smoke and Its Synergistic Effect with a Body-Mass Index of >24.9 kg/m 2 Increase the Risk of Gout Arthritis in Indonesia. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:4324. [PMID: 33921811 PMCID: PMC8073587 DOI: 10.3390/ijerph18084324] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 04/11/2021] [Accepted: 04/15/2021] [Indexed: 12/16/2022]
Abstract
To analyze the association between smoking status (active smoking and exposure to Second-Hand Smoking (SHS)) and the synergistic effect of smoking status and BMI with gout risk, a community-based case-control design was undertaken among 385 participants, including 304 healthy controls and 81 gout patients from seven community health services. Adjusted Odd Ratios (AORs) and 95% Confidence Interval (CIs) of gout for active smoking and SHS were 3.26 (95% CI = 1.07~9.90) and 4.67 (95% CI = 2.18~10.00) compared to non-smokers. Time-dependent manner of active smoking and SHS significantly increased gout risk with AORs and 95% CIs of 5.95 (1.41~25.03) and 10.12 (3.51~29.14). Dose-dependency of active smokers and SHS showed AORs and 95% CIs of 5.15 (1.28~20.63) and 4.37 (1.33~14.28). Smoking 20 cigarettes (one pack) per day for one year is equivalent to one pack-year. Active smoking >20 pack-year and SHS > 26.5 pack-year increased gout risk with AORs and 95% CIs of 7.18 (1.53~33.67) and 9.95 (3.64~27.22). Participants who smoked (active smoking and SHS) and with Body Mass Index (BMI) of > 24.9 kg/m2 synergistically increased gout risk, with an AOR of 9.65 and 95% CI of 3.25~28.65, compared to BMI ≤ 24.9 kg/m2 and non-smoker. Smoking status (active smoking and SHS) and the synergistic effect of smoking status and BMI increased gout risk in Indonesia.
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Affiliation(s)
- Maria Dyah Kurniasari
- School of Nursing, College of Nursing, Taipei Medical University, Wu-Xing Street, No 250, Taipei City 11031, Taiwan; (M.D.K.); (K.R.C.)
- Department of Nursing, Faculty of Medicine and Health Sciences, Universitas Kristen Satya Wacana, Diponegoro Street, No 52-60, Salatiga City 50711, Indonesia;
| | - Ferry Fredy Karwur
- Department of Nutrition, Faculty of Medicine and Health Sciences, Universitas Kristen Satya Wacana, Diponegoro Street, No 52-60, Salatiga City 50711, Indonesia;
| | - Rosiana Eva Rayanti
- Department of Nursing, Faculty of Medicine and Health Sciences, Universitas Kristen Satya Wacana, Diponegoro Street, No 52-60, Salatiga City 50711, Indonesia;
| | - Edi Dharmana
- Faculty of Medicine, Universitas Diponegoro, Prof. Sudarto Street, No.13, Semarang City 50275, Indonesia;
| | - Yohanes Andy Rias
- Faculty of Health and Medicine, Institut Ilmu Kesehatan Bhakti Wiyata Kediri, College of Nursing, KH Wachid Hasyim Street, No.65, Kediri City 64114, Indonesia;
| | - Kuei Ru Chou
- School of Nursing, College of Nursing, Taipei Medical University, Wu-Xing Street, No 250, Taipei City 11031, Taiwan; (M.D.K.); (K.R.C.)
- Center for Nursing and Healthcare Research in Clinical Practice Application, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
- Department of Nursing, Taipei Medical University-Shuang Ho Hospital, Taipei 23561, Taiwan
- Psychiatric Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan
| | - Hsiu-Ting Tsai
- School of Nursing, College of Nursing, Taipei Medical University, Wu-Xing Street, No 250, Taipei City 11031, Taiwan; (M.D.K.); (K.R.C.)
- Post-Baccalaureate Program in Nursing, College of Nursing, Taipei Medical University, Wu-Xing Street, No 250, Taipei 11031, Taiwan
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22
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Haddadin F, Arevalo AB, Jabri A, Beydoun H, Fram F, Munoz Estrella A, Karim S, Virani S, Ali Y. The risk and severity of stroke in patients with atrial fibrillation and gout: A National Representative Database study. J Arrhythm 2021; 37:394-399. [PMID: 33850581 PMCID: PMC8021996 DOI: 10.1002/joa3.12505] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 12/27/2020] [Accepted: 12/31/2020] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND It has been shown that gout is associated with left atrium remodeling and a pro-inflammatory state leading to the development of atrial fibrillation (AF). There is limited evidence whether gout increases the risk of stroke in patients with AF. We assessed the incidence of gout and the risk of stroke in patients with AF. METHODS This is a retrospective cohort study using the 2016 US National Inpatient Sample (NIS) based on ICD-10 codes. The outcomes of the study were the risk and severity of new stroke in patients with pre-existing AF and gout. RESULTS In 2016, we identified 3 844 057 patients admitted to the hospitals in NIS with history of AF, of which 240 875 had history of gout. Patients with AF and gout have higher risk of new stroke (OR 2.07 [1.97-2.19], P < .001), and this risk remains significantly elevated after adjusting for CHADS2VASC score variables, chronic kidney disease, dyslipidemia, obesity, and race (OR 1.10 [1.01-1.11], P = .041). However, presence of gout in patients with AF was not associated with all-cause in-hospital mortality, need for mechanical ventilation, percutaneous gastrostomy tube insertion, or discharge to skilled nursing facility. CONCLUSION Subjects with AF and gout compared to AF alone had an increased risk of new stroke, but presence of gout was not associated with stroke severity. There is a potential role of gout as a risk factor or a risk marker for stroke in subjects with AF.
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Affiliation(s)
- Faris Haddadin
- Section of CardiologyBaylor College of MedicineHoustonTXUSA
| | - Ana B. Arevalo
- Department of MedicineIcahn School of Medicine at Mount Sinai MorningsideNew YorkNYUSA
| | - Ahmad Jabri
- Heart and Vascular CenterMetrohealth Medical CenterCase Western Reserve UniversityClevelandOHUSA
| | - Hassan Beydoun
- Department of CardiologyUniversity of Arizona COM‐PhoenixPhoenixAZUSA
| | - Farah Fram
- Faculty of MedicineUniversity of JordanAmmanJordan
| | | | - Saima Karim
- Heart and Vascular CenterMetrohealth Medical CenterCase Western Reserve UniversityClevelandOHUSA
| | - Salim Virani
- Section of CardiologyMichael E. DeBakey Veterans Affairs Medical CenterSection of Cardiovascular ResearchDepartment of MedicineBaylor College of MedicineHoustonTXUSA
| | - Yousaf Ali
- Department of RheumatologyThe Mount Sinai HospitalNew YorkNYUSA
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23
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Hu Y, Chan Z, Li C, Shi Y, She X, Gu C, Wang Y, Zhou C, Zhao S, Zheng Z, Chen H. Higher Serum Uric Acid Levels Are Associated With an Increased Risk of Vision-Threatening Diabetic Retinopathy in Type 2 Diabetes Patients. Invest Ophthalmol Vis Sci 2021; 62:23. [PMID: 33861320 PMCID: PMC8083112 DOI: 10.1167/iovs.62.4.23] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Purpose To investigate the association between serum uric acid (SUA) levels and vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes. Methods This cross-sectional study evaluated 3481 patients with type 2 diabetes from four communities in China between 2016 and 2019. VTDR was defined as severe nonproliferative, proliferative diabetic retinopathy, or clinically significant macular edema evaluated by fundus photography and optical coherence tomography. Potential association between SUA and VTDR was examined using multivariable logistic regression. Sub-group analyses based on sex were constructed. Results A total of 305 participants had VTDR. Both higher SUA (odds ratio [OR], 1.22 per 100 µmol/L; 95% confidence interval [CI], 1.04–1.44; P = 0.013) and hyperuricemia (OR, 1.47; 95% CI, 1.07–2.04; P = 0.019) were positively associated with VTDR after adjustment for relevant covariates. Compared with those in the lowest SUA quartile, participants in the third (OR, 1.60; 95% CI, 1.07–2.39; P = 0.022) and fourth (OR, 2.05; 95% CI, 1.37–3.08; P = 0.001) sex-specific SUA quartiles showed a significantly increased risk of VTDR after adjustment. No sex-related difference was observed. Conclusions Higher SUA levels were associated with an increased risk of VTDR in patients with type 2 diabetes in both sexes, although females seemed to be more sensitive to high SUA than males. Prospective cohort studies are needed to verify SUA as a biomarker for predicting the risk of VTDR. Whether decreased SUA levels could decrease the risk of VTDR also requires further investigation.
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Affiliation(s)
- Yanan Hu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhulin Chan
- Department of Ophthalmology, the PLA Navy Anqing Hospital, Anhui, China
| | - Chunxia Li
- Department of Ophthalmology, Shanghai TCM-INTEGRATED Hospital, Shanghai University of Tradition Chinese Medicine, Shanghai, China
| | - Ya Shi
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xinping She
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chufeng Gu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yujie Wang
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chuandi Zhou
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shuzhi Zhao
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhi Zheng
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Haibing Chen
- Department of Endocrinology and Metabolism, Shanghai 10th People's Hospital, Tongji University, Shanghai, China
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Marty-Ané A, Norberciak L, Andrès M, Houvenagel E, Ducoulombier V, Legrand J, Budzik JF, Pascart T. Crystal deposition measured with dual-energy computed tomography: association with mortality and cardiovascular risks in gout. Rheumatology (Oxford) 2021; 60:4855-4860. [DOI: 10.1093/rheumatology/keaa920] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 11/26/2020] [Indexed: 12/27/2022] Open
Abstract
Abstract
Objectives
To determine whether the volume of monosodium urate (MSU) crystal deposition measured with dual-energy CT (DECT) is predictive of short-term mortality and development of cardiovascular comorbidities and diabetes mellitus.
Methods
Patients with a diagnosis of gout having had baseline DECT scans of their knees and feet to measure the volume of MSU crystal deposition were included to undergo a follow-up visit. Risk factors for mortality and a composite variable (onset of any cardio-metabolic event) were examined using multivariable Cox models.
Results
A total of 128 patients aged 66.1 (14.0) years with gout durations of 11.4 (10.4) years were included; most were naïve of urate lowering therapy (61.7%), with a follow-up visit at 24 (12, 36) months. Baseline serum urate (SU) level was 7.44 (2.29) mg/dl and DECT volume of MSU crystals was 0.2 (0, 0.9) cm3. A total of 14 patients died during follow-up, 6/14 from a cardiovascular cause, and 17 patients presented a new cardio-metabolic comorbidity. Factors associated with mortality risk were baseline DECT volume of MSU crystals [hazard ratio (HR) 1.02, 95% CI: 1.002, 1.03] and baseline SU level (HR 1.04, 95% CI: 1.003, 1.06). DECT volume of MSU crystals was the only factor associated with the onset of cardio-metabolic comorbidities with a HR of 1.014 (95% CI: 1.001, 1.03).
Conclusions
Volume of MSU crystals measured with DECT is a biomarker for the risk of developing new cardio-metabolic diseases and for all-cause mortality.
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Affiliation(s)
- Anne Marty-Ané
- Rheumatology Department, Lille Catholic Hospitals, Lille Catholic University
| | - Laurène Norberciak
- Research Department, Biostatistics, Lille Catholic Hospitals, Lille, France
| | - Mariano Andrès
- Rheumatology Department, Alicante General University Hospital-ISABIAL
- Clinical Medicine Department, Miguel Hernandez University, Alicante, Spain
| | - Eric Houvenagel
- Rheumatology Department, Lille Catholic Hospitals, Lille Catholic University
| | | | - Julie Legrand
- Department of Musculoskeletal Imaging, Lille Catholic Hospitals, Lille Catholic University
| | - Jean-François Budzik
- Department of Musculoskeletal Imaging, Lille Catholic Hospitals, Lille Catholic University
- MABLab, ULR 4490, Lille University, Lille, France
| | - Tristan Pascart
- Rheumatology Department, Lille Catholic Hospitals, Lille Catholic University
- MABLab, ULR 4490, Lille University, Lille, France
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Excess serum uric acid is associated with metabolic syndrome in obese adolescent patients. J Diabetes Metab Disord 2020; 19:535-543. [PMID: 32548073 PMCID: PMC7270295 DOI: 10.1007/s40200-020-00507-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Accepted: 02/06/2020] [Indexed: 01/09/2023]
Abstract
Purpose Obesity is a significant cause of morbidity in adolescents. Excess serum uric acid (SUA) has been associated with metabolic syndrome (MS) among adults. We evaluated the relationship among SUA and markers of insulin resistance (IR) and low-grade inflammation in obese adolescents with and without MS. Methods The study was a retrospective chart review of obese patients seen in the LeBonheur Endocrine clinic seen in clinic between September 2016 and December 2017. MS was defined as according to the International Diabetes Federation. Body mass index standard deviation score (BMI SDS), systolic blood pressure (SBP), diastolic blood pressure (DBP), body composition, fasting lipids, glucose, high sensitivity c-reactive protein (hs-CRP), serum uric acid (SUA), HbA1c, alanine transferase (ALT), aspartate transferase (AST), insulin and homeostatic model assessment for insulin resistance (HOMA-IR) were extracted from the charts of the 100 obese adolescents (57% female). Results Hyperuricemia (SUA >357 umol/L) was present in 41.8% of entire cohort without significant ethnic/racial and/or gender differences. Adolescents with HUA had higher FM, SBP, HbA1c, insulin and HOMA-IR (p < 0.05). While SUA was positively correlated with FM, SBP, HOMA-IR and HbA1c, and triglyceride:HDL-C ratio (TG:HDL-C) (p < 0.05). MS was identified in 32.8% of cohort. MS showed significantly higher FM, SBP, DBP, SUA, ALT, insulin, HOMA-IR, and TG:HDL-c ratio than non-MS subgroup (p < 0.05). FM was positively correlated with SUA, HOMA-IR and hsCRP (p < 0.01). Conclusions In our study, those with hyperuricemia (HUA) showed elevated markers of metabolic syndrome including BP, serum glucoses, IR and triglycerides. In our cohort, SUA appears to correlate with MS comorbidities.
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Piepoli MF, Salvioni E, Corrà U, Doni F, Bonomi A, La Gioia R, Limongelli G, Paolillo S, Sinagra G, Scardovi AB, Raimondo R, Emdin M, Re F, Cicoira M, Correale M, Badagliacca R, Clemenza F, Lombardi C, Agostoni P. Increased serum uric acid level predicts poor prognosis in mildly severe chronic heart failure with reduced ejection fraction. An analysis from the MECKI score research group. Eur J Intern Med 2020; 72:47-52. [PMID: 31787490 DOI: 10.1016/j.ejim.2019.11.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 10/21/2019] [Accepted: 11/07/2019] [Indexed: 10/25/2022]
Abstract
BACKGROUND Hyperuricemia prognostic impact on clinical outcomes in chronic heart failure (HF) patients has been investigated with inconclusive results. OBJECTIVES Aim of the study was to evaluate the prognostic impact of serum uric acid (SUA) on long-term clinical outcomes in HF. METHODS An analysis of MECKI (Metabolic Exercise Cardiac Kidney Index) database, with median follow-up of 3.4 years. RESULTS Relation between SUA and all-cause/ cardiovascular (CV) deaths have been analysed in 4,577 patients (3,688 males, age 62.7 ± 12.9 years), with reduced ejection fraction HF (35 ± 11%), peakVO2 1151 ± 440 ml/min; NYHA class I-II (72.6%), III-IV (27.4%). SUA was associated with increased total and CV mortality (HR 1.120 and HR 1.128, respectively p < 0.0001), also after adjustment for peakVO2, VE/VCO2 slope, diuretic use and MECKI score. SUA was significantly associated with CV mortality only in NYHA class I-II (HR 1.17, p < 0.0001) while there was no association in class III-IV (HR 1.03, p = NS). No prognostic added values of SUA with respect to the MECKI score was observed at the ROC analysis. CONCLUSIONS SUA is confirmed to be associated with increased mortality, but in less severe HF only. However SUA did not show additional prognostic power to the MECKI score.
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Affiliation(s)
- Massimo Francesco Piepoli
- UOC Cardiologia, G da Saliceto Hospital, Piacenza, Italy; Department of Cardiology, University of Foggia, Foggia, Italy
| | | | - Ugo Corrà
- Cardiology Department, Istituti Clinici Scientifici Maugeri, Veruno Institute, Veruno, Italy
| | - Francesco Doni
- Cardiology Department, Istituti Clinici Scientifici Maugeri, Veruno Institute, Veruno, Italy
| | - Alice Bonomi
- Centro Cardiologico Monzino, IRCCS, Milano, Italy
| | - Rocco La Gioia
- Division of Cardiology, "S. Maugeri" Foundation, IRCCS, Institute of Cassano Murge, Bari, Italy
| | - Giuseppe Limongelli
- Cardiologia SUN, Ospedale Monaldi (Azienda dei Colli), Seconda Università di Napoli, Napoli, Italy
| | - Stefania Paolillo
- Department of Advanced Biomedical Sciences, Federico II University of Naples, Italy
| | - Gianfranco Sinagra
- Cardiovascular Department, Ospedali Riuniti and University of Trieste, Trieste, Italy
| | | | - Rosa Raimondo
- Fondazione Salvatore Maugeri, IRCCS, Istituto Scientifico di Tradate, Italy
| | - Michele Emdin
- Fondazione Gabriele Monasterio, CNR-Regione Toscana, Pisa, Italy; Life Science Institute, Scuola Superiore Sant'Anna, Pisa, Italy
| | - Federica Re
- Cardiology Division, Cardiac Arrhythmia Center and Cardiomyopathies Unit, San Camillo-Forlanini Hospital, Roma, Italy
| | | | | | - Roberto Badagliacca
- Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche, Anestesiologiche e Geriatriche, "Sapienza", Rome University, Rome, Italy
| | - Francesco Clemenza
- Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation IRCCS - ISMETT, Palermo, Italy
| | - Carlo Lombardi
- Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy
| | - Piergiuseppe Agostoni
- Centro Cardiologico Monzino, IRCCS, Milano, Italy; Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milano, Milano, Italy.
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Chau YT, Chen HY, Lin PH, Hsia SM. Preventive Effects of Fucoidan and Fucoxanthin on Hyperuricemic Rats Induced by Potassium Oxonate. Mar Drugs 2019; 17:md17060343. [PMID: 31185695 PMCID: PMC6627326 DOI: 10.3390/md17060343] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 05/27/2019] [Accepted: 06/06/2019] [Indexed: 02/06/2023] Open
Abstract
The purpose of this study was to investigate the preventive effects of fucoidan (Fc) and fucoxanthin (Fx) on hyperuricemic rats. Sprague Dawley (SD) rats were randomly assigned to seven groups: a control group, a hyperuricemia (HUA) group, low- and high-dose Fx groups, a Fc group, a combination Fc and Fx group, and a positive control group. Three weeks after the interventions, each group was given potassium oxonate (PO) and hypoxanthine (HX) to induce HUA in all groups except for the control group, and the rats were then sacrificed. Blood and urine were analyzed for biochemical properties, and differences in urine volume were determined. Livers and kidneys were collected to analyze xanthine oxidase (XO) activity and the expression of uric acid (UA) transporter-related proteins (GLUT9, ABCG2, OAT1, URAT1). The results show that HUA was successfully induced by PO/HX after 4 h of administration. The activity of XO was significantly reduced by a combination of Fc and Fx. In the combination group, both ABCG2 and OAT1 increased significantly, whereas GLUT9 and URAT1 decreased significantly. In summary, the combination of Fc and Fx can inhibit the activity of XO in the liver and regulate the expression of proteins related to UA transporter in the kidney to reduce the UA level in serum.
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Affiliation(s)
- Yung-Tsung Chau
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.
| | - Hsin-Yuan Chen
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.
| | - Po-Han Lin
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.
| | - Shih-Min Hsia
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.
- Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.
- School of Food and Safety, Taipei Medical University, Taipei 11031, Taiwan.
- Nutrition Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan.
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28
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In vitro and in vivo evidence of hypouricemic and anti-inflammatory activities of Maclura cochinchinensis (Lour.) Corner heartwood extract. J Tradit Complement Med 2019; 10:85-94. [PMID: 31956562 PMCID: PMC6957808 DOI: 10.1016/j.jtcme.2019.03.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2018] [Revised: 03/03/2019] [Accepted: 03/08/2019] [Indexed: 11/20/2022] Open
Abstract
Maclura cochinchinensis (Lour.) Corner (MC) heartwood extracts have been used for the treatment of gout, hyperuricemia, and inflammation in Thai traditional medicine. Despite their traditional use, their mechanisms of action remain unknown. The aim of this study was to determine the mechanisms of MC heartwood extract activity using both in vitro and in vivo models . The extraction methods were optimized to yield the highest contents of biochemical compounds and antioxidant activities. The effects of MC heartwood extract on xanthine oxidase and its enzyme kinetics were determined in vitro and the antihyperuricemic effect was evaluated in potassium oxonate (PO)-induced hyperuricemic mice. The anti-inflammatory effect of MC heartwood extract was also tested against lipopolysaccharide-induced proinflammatory mRNA upregulation in RAW 264.7 mouse macrophage cells. Soxhlet extraction of MC heartwood with 70% ethanol produced stronger antioxidant activity, and higher total phenolic and flavonoid contents than conventional methods did (maceration or decoction). By using HPLC, we found that MC contains morin as a major constituent, which may account for its pharmacological activities. Moreover, administration of MC heartwood extract (500 mg/kg) markedly decreased uric acid levels in PO-induced hyperuricemic mice (p < 0.05). MC heartwood extract inhibited the hepatic activity of xanthine oxidase ex vivo by approximately 53%. In addition, MC heartwood extract markedly downregulated mRNA expression of inflammatory mediators (TNF-α, TGF-β, iNOS, and COX-2) and this inhibition was comparable with that of dexamethasone. Therefore, MC heartwood extract is a promising candidate as a natural treatment for inflammation and the hyperuricemia that causes gout.
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29
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Singh JA, Cleveland JD. Gout and the risk of Parkinson's disease in older adults: a study of U.S. Medicare data. BMC Neurol 2019; 19:4. [PMID: 30611222 PMCID: PMC6321725 DOI: 10.1186/s12883-018-1234-x] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 12/26/2018] [Indexed: 01/21/2023] Open
Abstract
Background In the presence of limited available data, our objective was to assess the association of gout with the risk of incident Parkinson’s disease (PD) in adults 65 years or older. Methods We used the 5% random sample of Medicare claims data from 2006 to 2012 to examine the association of gout with incident PD. The multivariable Cox regression model adjusted for demographics, comorbidity, and common cardiovascular disease and gout medications. We calculated hazard ratios (HR) and 95% confidence interval (CI). Sensitivity analyses adjusted for comorbidity categorically, or individually and for additional cardiovascular comorbidities. Results In a cohort study, 1.72 million Medicare beneficiaries were eligible. The mean age was 75 years (standard deviation [SD], 7.6), 58% were female, 86% were White and 37% had Charlson-Romano comorbidity index score of ≥2. We found that 22,636 people developed incident PD, 1129 with gout and 21,507 without gout. The respective crude incidence rates of incident PD were 3.7 vs. 2.2 per 1000 person-years. We found that gout was associated with 1.14-times higher hazard ratio (95% CI, 1.07, 1.21) of PD in the main analysis; findings were confirmed in sensitivity analyses. We noted that the risk differed slightly by age; ages 65–75, 75–85 and > 85 had hazard ratios of incident PD with gout of 1.27 (95% CI, 1.16, 1.39), 1.07 (95% CI, 0.97, 1.16) and 0.97 (95% CI, 0.79, 1.20), respectively, but no gender or race differences were noted. Conclusions Gout was associated with a higher risk of incident PD in older adults, with the risk being significant in the age group 65–75 years. Future studies need to assess the mechanisms of this increased risk. Electronic supplementary material The online version of this article (10.1186/s12883-018-1234-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Jasvinder A Singh
- Medicine Service, VA Medical Center, 700 19th St S, Birmingham, Birmingham, AL, 35233, USA. .,Department of Medicine at School of Medicine, University of Alabama at Birmingham, Faculty Office Tower 805B, 510 20th Street S, Birmingham, AL, 35294-0022, USA. .,Division of Epidemiology at School of Public Health, University of Alabama at Birmingham, 1720 Second Ave. South, Birmingham, AL, 35294-0022, USA.
| | - John D Cleveland
- Department of Medicine at School of Medicine, University of Alabama at Birmingham, Faculty Office Tower 805B, 510 20th Street S, Birmingham, AL, 35294-0022, USA
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30
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Parfenov VA, Ostroumova OD, Ostroumova TM, Kochetkov AI, Fateeva VV, Khacheva KK, Khakimova GR, Epstein OI. Vascular cognitive impairment: pathophysiological mechanisms, insights into structural basis, and perspectives in specific treatments. Neuropsychiatr Dis Treat 2019; 15:1381-1402. [PMID: 31190841 PMCID: PMC6535085 DOI: 10.2147/ndt.s197032] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 02/14/2019] [Indexed: 01/19/2023] Open
Abstract
Vascular cognitive impairment (VCI) and vascular dementia are the most common forms of cognitive disorder associated with cerebrovascular disease and related to increased morbidity and mortality among the older population. Growing evidence suggests the contribution of blood-pressure variability, cardiac arrhythmia, hyperactivation of the renin-angiotensin-aldosterone system, endothelial dysfunction, vascular remodeling and stiffness, different angiopathies, neural tissue homeostasis, and systemic metabolic disorders to the pathophysiology of VCI. In this review, we focus on factors contributing to cerebrovascular disease, neurovascular unit alterations, and novel approaches to cognitive improvement in patients with cognitive decline. One of the important factors associated with the neuronal causes of VCI is the S100B protein, which can affect the expression of cytokines in the brain, support homeostasis, and regulate processes of differentiation, repair, and apoptosis of the nervous tissue. Since the pathological basis of VCI is complex and diverse, treatment affecting the mechanisms of cognitive disorders should be developed. The prospective role of a novel complex drug consisting of released-active antibodies to S100 and to endothelial NO synthase in VCI treatment is highlighted.
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Affiliation(s)
- Vladimir A Parfenov
- Department of Neurology, Federal State Autonomous Educational Institution of Higher Education, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russian Federation
| | - Olga D Ostroumova
- Laboratory of Clinical Pharmacology and therapy, Federal State Budgetary Educational Institution of Higher Education "N.I. Pirogov Russian National Research Medical University" of the Ministry of Health of the Russian Federation, Russian Clinical and Research Center of Gerontology, Moscow, Russia.,Department of Clinical Pharmacology, Internal Medicine and Propaedeutics I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Tatiana M Ostroumova
- Department of Neurology, Federal State Autonomous Educational Institution of Higher Education, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russian Federation
| | - Alexey I Kochetkov
- Laboratory of Clinical Pharmacology and therapy, Federal State Budgetary Educational Institution of Higher Education "N.I. Pirogov Russian National Research Medical University" of the Ministry of Health of the Russian Federation, Russian Clinical and Research Center of Gerontology, Moscow, Russia
| | - Victoria V Fateeva
- Medical Information Department, OOO NPF Materia Medica Holding, Moscow, Russian Federation
| | - Kristina K Khacheva
- Medical Information Department, OOO NPF Materia Medica Holding, Moscow, Russian Federation
| | - Gulnara R Khakimova
- Research and Analytical Division of Scientific Research and Development Department, Moscow, Russian Federation
| | - Oleg I Epstein
- Laboratory of Physiologicaly Active Substances, Department of Molecular and Cellular Pathophysiology, Research Institute of General Pathology and Pathophysiology, Moscow, Russian Federation
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31
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Yoshizawa T, Niwano S, Niwano H, Tamaki H, Nakamura H, Igarashi T, Oikawa J, Satoh A, Kishihara J, Murakami M, Fukaya H, Ako J. Antiremodeling Effect of Xanthine Oxidase Inhibition in a Canine Model of Atrial Fibrillation. Int Heart J 2018; 59:1077-1085. [PMID: 30158379 DOI: 10.1536/ihj.17-391] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
In a canine rapid atrial stimulation model of atrial fibrillation (AF), we have demonstrated an increased production of reactive oxygen species (ROS) along with electrical and structural remodeling. In the present study, we hypothesized that antioxidants can suppress atrial remodeling canines with AF. We therefore evaluated the effect of febuxostat, a xanthine oxidase (XO) inhibitor and a pure antioxidant, on atrial remodeling.AF was produced by performing a 3-week rapid atrial pacing (400 bpm) in 13 dogs divided into three groups: pacing + febuxostat group (n = 5; atrial pacing with 50 mg/day of febuxostat (administration); pacing control group (n = 5; atrial pacing without any drug administration); and non-pacing group (n = 3). Electrophysiological studies were conducted in the first 2 groups every week. Atrial tissue fibrosis was evaluated by Azan and immunofluorescent staining of fibronectin. Oxidative stress was evaluated by DHE and FCF-DA staining.Shortening of the refractory period and increase in AF inducibility appeared gradually in the pacing control group, but such changes were suppressed in the pacing + febuxostat group (P = 0.05). The pacing control group showed increase in fibrosis, which was suppressed in the febuxostat group. In DHE and DCF-DA staining, the pacing control group showed an increase in oxidative stress, which was suppressed in the pacing + febuxostat group. The pacing control group exhibited fibronectin expression, which was suppressed in the pacing + febuxostat group.The antioxidant effect of febuxostat may achieve an inhibition of new-onset AF in canines.
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Affiliation(s)
- Tomoharu Yoshizawa
- Department of Cardiovascular Medicine, Kitasato University School of Medicine.,Department of Cardiology, Yamato Municipal Hospital
| | - Shinichi Niwano
- Department of Cardiovascular Medicine, Kitasato University School of Medicine
| | - Hiroe Niwano
- Department of Education, Tamagawa University, Collage of Education
| | - Hideaki Tamaki
- Department of Anatomy, Kitasato University School of Medicine
| | - Hironori Nakamura
- Department of Cardiovascular Medicine, Kitasato University School of Medicine
| | - Tazuru Igarashi
- Department of Cardiovascular Medicine, Kitasato University School of Medicine
| | - Jun Oikawa
- Department of Cardiovascular Medicine, Kitasato University School of Medicine
| | - Akira Satoh
- Department of Cardiovascular Medicine, Kitasato University School of Medicine
| | - Jun Kishihara
- Department of Cardiovascular Medicine, Kitasato University School of Medicine
| | - Masami Murakami
- Department of Cardiovascular Medicine, Kitasato University School of Medicine
| | - Hidehira Fukaya
- Department of Cardiovascular Medicine, Kitasato University School of Medicine
| | - Junya Ako
- Department of Cardiovascular Medicine, Kitasato University School of Medicine
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32
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Tana C, Ticinesi A, Prati B, Nouvenne A, Meschi T. Uric Acid and Cognitive Function in Older Individuals. Nutrients 2018; 10:nu10080975. [PMID: 30060474 PMCID: PMC6115794 DOI: 10.3390/nu10080975] [Citation(s) in RCA: 104] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 07/23/2018] [Accepted: 07/26/2018] [Indexed: 01/08/2023] Open
Abstract
Hyperuricemia has been recognized as an independent cardiovascular risk factor in epidemiological studies. However, uric acid can also exert beneficial functions due to its antioxidant properties, which may be particularly relevant in the context of neurodegenerative diseases. In this paper, we critically revise the evidence on the relationship between serum uric acid levels and cognitive function in older individuals, focusing on the etiology of cognitive impairment (Alzheimer’s disease, Parkinson’s dementia, and vascular dementia) and on the interactive connections between uric acid, dementia, and diet. Despite high heterogeneity in the existing studies, due to different characteristics of studied populations and methods of cognitive dysfunction assessment, we conclude that serum uric acid may modulate cognitive function in a different way according to the etiology of dementia. Current studies indeed demonstrate that uric acid may exert neuroprotective actions in Alzheimer’s disease and Parkinson’s dementia, with hypouricemia representing a risk factor for a quicker disease progression and a possible marker of malnutrition. Conversely, high serum uric acid may negatively influence the disease course in vascular dementia. Further studies are needed to clarify the physio-pathological role of uric acid in different dementia types, and its clinical-prognostic significance.
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Affiliation(s)
- Claudio Tana
- Internal Medicine and Critical Subacute Care Unit, Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, 43125 Parma, Italy.
| | - Andrea Ticinesi
- Internal Medicine and Critical Subacute Care Unit, Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, 43125 Parma, Italy.
- Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.
| | - Beatrice Prati
- Internal Medicine and Critical Subacute Care Unit, Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, 43125 Parma, Italy.
| | - Antonio Nouvenne
- Internal Medicine and Critical Subacute Care Unit, Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, 43125 Parma, Italy.
| | - Tiziana Meschi
- Internal Medicine and Critical Subacute Care Unit, Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, 43125 Parma, Italy.
- Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.
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Singh JA, Cleveland JD. The risk of polymyalgia rheumatica in older adults with gout: a Medicare claims study. Rheumatol Adv Pract 2018; 2:rky024. [PMID: 31431970 DOI: 10.1093/rap/rky024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Revised: 05/29/2018] [Indexed: 11/14/2022] Open
Abstract
Objective In the absence of previous studies, the objective was to assess whether gout is associated with a lower risk of PMR. Methods We used the 5% Medicare sample to assess whether gout in adults 65 years or older increases the risk of incident PMR. The main multivariable-adjusted model included age, gender, race, Charlson-Romano co-morbidity score, the use of medications for cardiovascular diseases (statins, β-blockers, diuretics, angiotensin-converting enzyme inhibitors) and gout (allopurinol, febuxostat). Hazard ratios and 95% CI were calculated. Results There were 11 744 cases of incident PMR, with crude incidence rates of PMR of 289/100 000 person-years in patients with gout and 109/100 000 person-years in patients without gout. People with incident PMR had a mean duration of gout of 2.2 years before PMR diagnosis (s.d., 1.6; median, 1.8; interquartile range, 0.8, 3.2). Multivariable-adjusted analyses showed that gout was associated with PMR with a hazard ratio of 2.45 (95% CI, 2.28, 2.64; P < 0.0001). Older age, female gender, White race and higher co-morbidity index were associated with a higher hazard of PMR. Sensitivity analyses that substituted continuous Charlson-Romano co-morbidity score with categorized score or individual co-morbidities (plus hypertension, hyperlipidaemia and coronary artery disease) confirmed the main findings with minimal attenuation of hazard ratio, 2.39 (95% CI, 2.22, 2.57; P < 0.0001) and 2.13 (95% CI, 1.98, 2.29; P < 0.0001), respectively. Conclusion Contrary to our hypothesis, gout was associated with >2-fold higher risk of incident PMR in older adults. Studies should explore whether inflammation or hyperuricaemia is the underlying mechanism for this association.
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Affiliation(s)
- Jasvinder A Singh
- Medicine Service, VA Medical Center, Birmingham.,Department of Medicine at School of Medicine.,Division of Epidemiology at School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA
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Mantovani A, Targher G, Temporelli PL, Lucci D, Gonzini L, Nicolosi GL, Marchioli R, Tognoni G, Latini R, Cosmi F, Tavazzi L, Maggioni AP. Prognostic impact of elevated serum uric acid levels on long-term outcomes in patients with chronic heart failure: A post-hoc analysis of the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) trial. Metabolism 2018; 83:205-215. [PMID: 29477817 DOI: 10.1016/j.metabol.2018.02.007] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Revised: 02/07/2018] [Accepted: 02/19/2018] [Indexed: 11/27/2022]
Abstract
BACKGROUND The prognostic impact of hyperuricemia on long-term clinical outcomes in patients with chronic heart failure (HF) has been investigated in observational registries and clinical trials, but the results have been often inconclusive. We examined the prognostic impact of elevated serum uric acid levels on long-term clinical outcomes in the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) trial. CLINICAL TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER NCT00336336. METHODS We assessed the rates of all-cause death, cardiovascular death, cardiovascular hospitalization and the composite of all-cause death or cardiovascular hospitalization over a median follow-up of 3.9 years among 6683 ambulatory patients with chronic HF. RESULTS Patients in the 3rd serum uric acid tertile (>7.2 mg/dl) had a nearly 1.8-fold increased risk of both all-cause death and cardiovascular death, and a nearly 1.5-fold increased risk of cardiovascular hospitalization and of the composite endpoint compared to those in the 1st uric acid tertile (<5.7 mg/dl). Beyond serum uric acid ≥ 7 mg/dl the risk of outcomes increased sharply and linearly. The significant association between elevated serum uric acid levels and adverse outcomes persisted after adjustment for multiple established cardiovascular risk factors, HF etiology, left ventricular ejection fraction, medication use and other potential confounders, with an adjusted hazard ratio of 1.37 (95% CI 1.22-1.55) for all-cause death, 1.48 (1.29-1.69) for cardiovascular death, 1.19 (1.09-1.30) for cardiovascular hospitalization and 1.21 (1.11-1.31) for the composite endpoint, respectively. CONCLUSIONS Elevated serum uric acid levels are independently associated with poor long-term survival and increased risk of cardiovascular hospitalization in patients with chronic HF.
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Affiliation(s)
- Alessandro Mantovani
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giovanni Targher
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | | | | | | | - Gian Luigi Nicolosi
- Department of Cardiology, Santa Maria degli Angeli Hospital, Pordenone, Italy
| | | | - Gianni Tognoni
- Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Famacologiche Mario Negri, Milan, Italy
| | - Roberto Latini
- Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Famacologiche Mario Negri, Milan, Italy
| | - Franco Cosmi
- Division of Cardiology, Ospedale Valdichiana Santa Margherita, Cortona, Italy
| | - Luigi Tavazzi
- Maria Cecilia Hospital, GVM Care & Research, Ettore Sansavini Health Science Foundation, Cotignola, Italy
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Battelli MG, Bortolotti M, Polito L, Bolognesi A. The role of xanthine oxidoreductase and uric acid in metabolic syndrome. Biochim Biophys Acta Mol Basis Dis 2018; 1864:2557-2565. [PMID: 29733945 DOI: 10.1016/j.bbadis.2018.05.003] [Citation(s) in RCA: 126] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 04/20/2018] [Accepted: 05/03/2018] [Indexed: 12/15/2022]
Abstract
Xanthine oxidoreductase (XOR) could contribute to the pathogenesis of metabolic syndrome through the oxidative stress and the inflammatory response induced by XOR-derived reactive oxygen species and uric acid. Hyperuricemia is strongly linked to hypertension, insulin resistance, obesity and hypertriglyceridemia. The serum level of XOR is correlated to triglyceride/high density lipoprotein cholesterol ratio, fasting glycemia, fasting insulinemia and insulin resistance index. Increased activity of endothelium-linked XOR may promote hypertension. In addition, XOR is implicated in pre-adipocyte differentiation and adipogenesis. XOR and uric acid play a role in cell transformation and proliferation as well as in the progression and metastatic process. Collected evidences confirm the contribution of XOR and uric acid in metabolic syndrome. However, in some circumstances XOR and uric acid may have anti-oxidant protective outcomes. The dual-face role of both XOR and uric acid explains the contradictory results obtained with XOR inhibitors and suggests caution in their therapeutic use.
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Affiliation(s)
- Maria Giulia Battelli
- Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Alma Mater Studiorum - University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy.
| | - Massimo Bortolotti
- Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Alma Mater Studiorum - University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy.
| | - Letizia Polito
- Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Alma Mater Studiorum - University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy.
| | - Andrea Bolognesi
- Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Alma Mater Studiorum - University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy.
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Latourte A, Soumaré A, Bardin T, Perez-Ruiz F, Debette S, Richette P. Uric acid and incident dementia over 12 years of follow-up: a population-based cohort study. Ann Rheum Dis 2018; 77:328-335. [PMID: 28754803 DOI: 10.1136/annrheumdis-2016-210767] [Citation(s) in RCA: 100] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Revised: 06/23/2017] [Accepted: 06/26/2017] [Indexed: 12/15/2022]
Abstract
OBJECTIVES In patients with gout, maintaining too low serum uric acid (SUA) level with urate-lowering therapy is a concern because uric acid is thought to be neuroprotective. However, the relation between SUA and dementia remains debated. This study aimed to investigate the impact of SUA level on the incidence of dementia. METHODS We assessed the longitudinal association between SUA level and incident dementia (Diagnostic and Statistical Manual of Mental Disorders Version IV (DSM-IV) criteria) in a large cohort of healthy older people from the community (Three-City Dijon cohort). Additionally, we investigated the relation between SUA level and MRI markers of brain ageing (white matter hyperintensity volume (WMHV), lacunes and hippocampal volume). RESULTS The study sample comprised 1598 people (mean (SD) age 72.4(4.1) years, 38.3% male). During the 13,357 person-years of follow-up (median duration: 10.1 years), dementia developed in 110 participants (crude incidence rate: 8.2/1000 person-years). After multiple adjustments, the multivariate HR with the highest (≥75th percentile) versus lowest SUA level was 1.79 (95% CI 1.17 to 2.73; p=0.007). The association was stronger with vascular or mixed dementia (HR=3.66 (95% CI 1.29 to 10.41), p=0.015) than Alzheimer's disease (HR=1.55 (95% CI 0.92 to 2.61), p=0.10). There was a non-significant trend towards an association between high SUA level and extensive WMHV (p=0.10), a biomarker of small vessel disease, but not hippocampal volume (p=0.94) or lacunes (p=0.86). The association between SUA level and vascular or mixed dementia might be affected by interim strokes. CONCLUSIONS Risk of dementia, especially vascular or mixed dementia, may be increased with high SUA levels in elderly people.
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Affiliation(s)
- Augustin Latourte
- Université Paris Diderot, UFR médicale, Paris, France
- Hôpital Lariboisière, Service de Rhumatologie, Paris, Cedex, France
- INSERM 1132, Université Paris-Diderot, Hôpital Lariboisière, Paris, France
| | - Aicha Soumaré
- Inserm Centre Bordeaux Population Health (U1219), Bordeaux, France
| | - Thomas Bardin
- Université Paris Diderot, UFR médicale, Paris, France
- Hôpital Lariboisière, Service de Rhumatologie, Paris, Cedex, France
- INSERM 1132, Université Paris-Diderot, Hôpital Lariboisière, Paris, France
| | - Fernando Perez-Ruiz
- Division of Rheumatology, Hospital Universitario Cruces, Biocruces Health Research Institute, and Basque Country University, Biscay, Spain
| | - Stéphanie Debette
- Inserm Centre Bordeaux Population Health (U1219), Bordeaux, France
- University of Bordeaux, Bordeaux, France
- Department of Neurology, Memory Clinic, Bordeaux, France
- Department of Neurology, Framingham Heart Study, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Pascal Richette
- Université Paris Diderot, UFR médicale, Paris, France
- Hôpital Lariboisière, Service de Rhumatologie, Paris, Cedex, France
- INSERM 1132, Université Paris-Diderot, Hôpital Lariboisière, Paris, France
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Impaired arterial responsiveness in untreated gout patients compared with healthy non-gout controls: association with serum urate and C-reactive protein. Clin Rheumatol 2018; 37:1903-1911. [PMID: 29450849 DOI: 10.1007/s10067-018-4029-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 02/01/2018] [Accepted: 02/06/2018] [Indexed: 12/13/2022]
Abstract
To determine whether arterial responsiveness is impaired among patients with gout, and whether arterial responsiveness inversely correlates with serum urate and inflammatory measures. This is a cross-sectional study of untreated gout subjects (n = 34) and non-gout healthy controls (n = 64). High-resolution dynamic ultrasound-measured flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent arterial responsiveness respectively. Serum urate (sUA) and high-sensitivity C-reactive protein (hsCRP) were measured in the gout group, and correlated with FMD and NMD responses. Both FMD (2.20 ± 0.53 vs 3.56 ± 0.31, p = 0.021) and NMD (16.69 ± 1.54 vs 24.51 ± 0.90, p = 0.00002) were impaired in the gout versus control group. Stratification for individual comorbidities suggested that no single risk factor accounted for impaired FMD/NMD in the gout subjects. However, the degree of association between gout and FMD, but not NMD impairment, was dampened after multivariable adjustment (FMD unadjusted beta = - 1.36 (SE 0.58), p = 0.02; adjusted beta = - 1.16 (SE 0.78), p = 0.14 and NMD unadjusted beta = - 7.68 (SE 1.78), p < 0.0001; adjusted beta = - 5.33 (SE 2.46), p = 0.03). Within the gout group, there was an inverse correlation between FMD and sUA (R = - 0.5, p = 0.003), and between FMD and hsCRP (R = - 0.42, p = 0.017), but not between NMD and sUA or hsCRP. Compared with healthy controls, subjects with gout have reduced arterial function. Individual comorbidities are insufficient to account for differences between gout and control groups, but multiple comorbidities may collectively contribute to impairment in endothelium-dependent arterial responsiveness. Endothelial impairment is also related to sUA and hsCRP, markers of gout severity and inflammation respectively. Studies to determine whether gout therapy may improve arterial responsiveness are warranted.
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Yamanaka H, Tamaki S, Ide Y, Kim H, Inoue K, Sugimoto M, Hidaka Y, Taniguchi A, Fujimori S, Yamamoto T. Stepwise dose increase of febuxostat is comparable with colchicine prophylaxis for the prevention of gout flares during the initial phase of urate-lowering therapy: results from FORTUNE-1, a prospective, multicentre randomised study. Ann Rheum Dis 2018; 77:270-276. [PMID: 29102957 PMCID: PMC5867413 DOI: 10.1136/annrheumdis-2017-211574] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Revised: 10/02/2017] [Accepted: 10/22/2017] [Indexed: 11/05/2022]
Abstract
OBJECTIVES To determine whether febuxostat with stepwise dose increase is as useful as colchicine prophylaxis in reducing gout flares during the initial introduction of urate-lowering therapy in patients with gout in comparison with febuxostat with no dose titration. METHODS In this prospective, multicentre, randomised open-label comparative study, patients were randomised to group A (stepwise dose increase of febuxostat from 10 to 40 mg/day), group B (fixed-dose febuxostat 40 mg/day plus colchicine 0.5 mg/day) or group C (fixed-dose febuxostat 40 mg/day) and observed for 12 weeks. Gout flare was defined as non-steroidal anti-inflammatory drug use for gout symptoms. RESULTS A total of 255 patients were randomised, and 241 patients were treated. Among the treated patients, gout flares were experienced by 20/96 (20.8%) in group A, 18/95 (18.9%) in group B and 18/50 (36.0%) in group C. The incidence of flare was significantly lower in groups A and B than that in group C (P=0.047 and P=0.024, respectively), although the differences were not significant after correction for multiple comparisons. No significant difference was noted between the incidence of gout flare in groups A and B. CONCLUSIONS Our data suggested that stepwise dose increase of febuxostat and low-dose colchicine prophylaxis effectively reduced gout flares in comparison with fixed-dose febuxostat alone. Stepwise dose increase of febuxostat may be an effective alternative to low-dose colchicine prophylaxis during the introduction of urate-lowering therapy. TRIAL REGISTRATION NUMBER UMIN 000008414.
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Affiliation(s)
- Hisashi Yamanaka
- Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan
| | | | | | | | | | - Masayuki Sugimoto
- Shoi-kai Medical Association, Koganeibashi Sakura Clinic, Tokyo, Japan
| | - Yuji Hidaka
- Taizan-kai Medical Association, Akasaka Central Clinic, Tokyo, Japan
| | - Atsuo Taniguchi
- Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan
| | | | - Tetsuya Yamamoto
- Department of Diabetes, Endocrinology and Metabolism, Hyogo College of Medicine, Hyogo, Japan
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Mantovani A, Rigolon R, Civettini A, Bolzan B, Morani G, Bonapace S, Dugo C, Zoppini G, Bonora E, Targher G. Hyperuricemia is associated with an increased prevalence of paroxysmal atrial fibrillation in patients with type 2 diabetes referred for clinically indicated 24-h Holter monitoring. J Endocrinol Invest 2018; 41:223-231. [PMID: 28711969 DOI: 10.1007/s40618-017-0729-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Accepted: 07/09/2017] [Indexed: 12/12/2022]
Abstract
PURPOSE Several studies have reported an association between hyperuricemia and increased risk of permanent atrial fibrillation (AF) in patients with and without type 2 diabetes mellitus (T2DM). Currently, no published data are available on the relationship between hyperuricemia and risk of paroxysmal AF. METHODS We retrospectively evaluated 245 T2DM outpatients without pre-existing AF, cancer, cirrhosis and end-stage renal disease, who underwent a 24-h ECG-Holter monitoring for various clinical indications. Hyperuricemia was defined as a serum uric acid level >7 mg/dl for men and >6 mg/dl for women or allopurinol use. The diagnosis of paroxysmal AF was confirmed in affected individuals on the basis of 24-h ECG-Holter monitoring by experienced cardiologists. RESULTS Hyperuricemia was observed in 59 (24.1%) patients, whereas paroxysmal AF was found in 11 (4.5%) patients. The prevalence of paroxysmal AF was higher in patients with hyperuricemia than in those without hyperuricemia (10.2 vs. 2.7%, p = 0.026). Logistic regression analysis showed that hyperuricemia was associated with an increased risk of prevalent paroxysmal AF. This association remained significant even after adjustment for age, metabolic syndrome and chronic kidney disease (adjusted-odds ratio 4.01, 95% CI 1.08-14.9; p = 0.039). Similar results were found when we used serum uric acid levels as a continuous measure. CONCLUSIONS This study shows for the first time that hyperuricemia is independently associated with an approximately fourfold increased risk of prevalent paroxysmal AF in patients with T2DM. These findings may partly explain the increased risk of permanent atrial fibrillation and cardiovascular death observed among patients with hyperuricemia.
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Affiliation(s)
- A Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale A. Stefani, 1, 37126, Verona, Italy.
| | - R Rigolon
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale A. Stefani, 1, 37126, Verona, Italy
| | - A Civettini
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale A. Stefani, 1, 37126, Verona, Italy
| | - B Bolzan
- Section of Cardiology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - G Morani
- Section of Cardiology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - S Bonapace
- Division of Cardiology, "Sacro Cuore" Hospital, Negrar, VR, Italy
| | - C Dugo
- Division of Cardiology, "Sacro Cuore" Hospital, Negrar, VR, Italy
| | - G Zoppini
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale A. Stefani, 1, 37126, Verona, Italy
| | - E Bonora
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale A. Stefani, 1, 37126, Verona, Italy
| | - G Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale A. Stefani, 1, 37126, Verona, Italy
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40
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Mantovani A, Rigolon R, Pichiri I, Morani G, Bonapace S, Dugo C, Zoppini G, Bonora E, Targher G. Relation of elevated serum uric acid levels to first-degree heart block and other cardiac conduction defects in hospitalized patients with type 2 diabetes. J Diabetes Complications 2017; 31:1691-1697. [PMID: 29033310 DOI: 10.1016/j.jdiacomp.2017.09.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Revised: 08/21/2017] [Accepted: 09/17/2017] [Indexed: 11/29/2022]
Abstract
AIMS Several studies have reported that moderately elevated serum uric acid levels are associated with an increased risk of tachyarrhythmias (mainly atrial fibrillation) in patients with and without type 2 diabetes mellitus (T2DM). It is currently unknown whether an association also exists between elevated serum uric acid levels and cardiac conduction defects in patients with T2DM. METHODS We retrospectively analyzed a hospital-based sample of 967 patients with T2DM discharged from our Division of Endocrinology over the years 2007-2014. Standard electrocardiograms were performed on all patients and were interpreted by expert cardiologists. RESULTS Overall, 267 (27.6%) patients had some type of conduction defects on electrocardiograms (defined as at least one block among first-degree atrio-ventricular block, second-degree block, third-degree block, left bundle branch block, right bundle branch block, left anterior hemi-block or left posterior hemi-block). Patients in the 3rd serum uric acid tertile had a higher prevalence of any cardiac conduction defects than those belonging to 2nd or 1st tertile, respectively (35.8% vs. 25.0% vs. 22.6%; p<0.0001). Elevated serum uric acid levels were associated with a nearly twofold increased risk of cardiac conduction defects after adjustment for age, sex, hemoglobin A1c, diabetes duration, metabolic syndrome, chronic kidney disease, chronic obstructive pulmonary disease, ischemic heart disease, valvular heart disease and medication use (adjusted-odds ratio 1.84, 95% confidence intervals 1.2-2.9; p=0.009). CONCLUSIONS Moderately elevated serum uric acid levels are associated with an increased prevalence of any cardiac conduction defects in hospitalized patients with T2DM, independent of multiple risk factors and potential confounding variables.
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Affiliation(s)
- Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
| | - Riccardo Rigolon
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Isabella Pichiri
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giovanni Morani
- Section of Cardiology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Stefano Bonapace
- Division of Cardiology, "Sacro Cuore" Hospital, Negrar (VR), Italy
| | - Clementina Dugo
- Division of Cardiology, "Sacro Cuore" Hospital, Negrar (VR), Italy
| | - Giacomo Zoppini
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Enzo Bonora
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
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Abstract
BACKGROUND Atrial fibrillation (AF) represents a significant health concern, due to the increased prevalence, morbidity, and mortality. METHODS AND RESULTS There is a growing body of evidence correlating serum uric acid (SUA) with cardiovascular diseases such as arterial hypertension and AF. CONCLUSION Thus, a question arises as to whether SUA levels have a role in the pathophysiology of AF development.
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42
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Xu L, Shi Y, Zhuang S, Liu N. Recent advances on uric acid transporters. Oncotarget 2017; 8:100852-100862. [PMID: 29246027 PMCID: PMC5725069 DOI: 10.18632/oncotarget.20135] [Citation(s) in RCA: 112] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Accepted: 07/29/2017] [Indexed: 02/07/2023] Open
Abstract
Uric acid is the product of purine metabolism and its increased levels result in hyperuricemia. A number of epidemiological reports link hyperuricemia with multiple disorders, such as kidney diseases, cardiovascular diseases and diabetes. Recent studies also showed that expression and functional changes of urate transporters are associated with hyperuricemia. Uric acid transporters are divided into two categories: urate reabsorption transporters, including urate anion transporter 1 (URAT1), organic anion transporter 4 (OAT4) and glucose transporter 9 (GLUT9), and urate excretion transporetrs, including OAT1, OAT3, urate transporter (UAT), multidrug resistance protein 4 (MRP4/ABCC4), ABCG-2 and sodium-dependent phosphate transport protein. In the kidney, uric acid transporters decrease the reabsorption of urate and increase its secretion. These transporters’ dysfunction would lead to hyperuricemia. As the function of urate transporters is important to control the level of serum uric acid, studies on the functional role of uric acid transporter may provide a new strategy to treat hyperuricemia associated diseases, such as gout, chronic kidney disease, hyperlipidemia, hypertension, coronary heart disease, diabetes and other disorders. This review article summarizes the physiology of urate reabsorption and excretion transporters and highlights the recent advances on their roles in hyperuricemia and various diseases.
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Affiliation(s)
- Liuqing Xu
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Yingfeng Shi
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Shougang Zhuang
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.,Department of Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, RI 02903, USA
| | - Na Liu
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
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Zhou H, Wang Y, Cui L, Chen Y, Li C, Zhao J. The ongoing role of serum uric acid in blood pressure. Clin Exp Hypertens 2017; 39:601-605. [PMID: 28678545 DOI: 10.1080/10641963.2017.1299750] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Affiliation(s)
- Hui Zhou
- Shandong Gout Clinical Medical Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yangang Wang
- Shandong Gout Clinical Medical Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Lingling Cui
- Shandong Gout Clinical Medical Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ying Chen
- Shandong Gout Clinical Medical Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Changgui Li
- Shandong Gout Clinical Medical Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jinjiao Zhao
- Shandong Gout Clinical Medical Center, The Affiliated Hospital of Qingdao University, Qingdao, China
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Andrés M, Bernal JA, Sivera F, Quilis N, Carmona L, Vela P, Pascual E. Cardiovascular risk of patients with gout seen at rheumatology clinics following a structured assessment. Ann Rheum Dis 2017; 76:1263-1268. [PMID: 28093417 DOI: 10.1136/annrheumdis-2016-210357] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 11/29/2016] [Accepted: 12/26/2016] [Indexed: 11/03/2022]
Abstract
OBJECTIVES Gout-associated cardiovascular (CV) risk relates to comorbidities and crystal-led inflammation. The aim was to estimate the CV risk by prediction tools in new patients with gout and to assess whether ultrasonographic carotid changes are present in patients without high CV risk. METHODS Cross-sectional study. Consecutive new patients with crystal-proven gout underwent a structured CV consultation, including CV events, risk factors and two risk prediction tools-the Systematic COronary Evaluation (SCORE) and the Framingham Heart Study (FHS). CV risk was stratified according to current European guidelines. Carotid ultrasound (cUS) was performed in patients with less than very high CV risk. The presence of carotid plaques was studied depending on the SCORE and FHS by the area under the curve (AUC) of receiver operating curves. RESULTS 237 new patients with gout were recruited. CV stratification by scores showed a predominance of very high (95 patients, 40.1%) and moderate (72 patients, 30.5%) risk levels. cUS was performed in 142 patients, finding atheroma plaques in 66 (46.5%, 95% CI 37.8 to 54.2). Following cUS findings, patients classified as very high risk increased from 40.1% up to 67.9% (161/237 patients). SCORE and FHS predicted moderately (AUC 0.711 and 0.683, respectively) the presence of atheroma plaques at cUS. CONCLUSIONS The majority of patients presenting with gout may be at very high CV risk, indicating the need for initiating optimal prevention strategies at this stage. Risk prediction tools appear to underestimate the presence of carotid plaque in patients with gout.
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Affiliation(s)
- Mariano Andrés
- Sección de Reumatología, Hospital General Universitario de Alicante, Alicante, Spain
- Departamento de Medicina Clínica, Universidad Miguel Hernández, Alicante, Spain
| | - José Antonio Bernal
- Sección de Reumatología, Hospital General Universitario de Alicante, Alicante, Spain
| | - Francisca Sivera
- Sección de Reumatología, Hospital General Universitario de Elda, Alicante, Spain
| | - Neus Quilis
- Sección de Reumatología, Hospital General Universitario de Elda, Alicante, Spain
| | | | - Paloma Vela
- Sección de Reumatología, Hospital General Universitario de Alicante, Alicante, Spain
- Departamento de Medicina Clínica, Universidad Miguel Hernández, Alicante, Spain
| | - Eliseo Pascual
- Sección de Reumatología, Hospital General Universitario de Alicante, Alicante, Spain
- Departamento de Medicina Clínica, Universidad Miguel Hernández, Alicante, Spain
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Zhang R. Ghrelin suppresses inflammation in HUVECs by inhibiting ubiquitin-mediated uncoupling protein 2 degradation. Int J Mol Med 2017; 39:1421-1427. [PMID: 28487946 PMCID: PMC5428956 DOI: 10.3892/ijmm.2017.2977] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Accepted: 01/17/2017] [Indexed: 12/31/2022] Open
Abstract
Atherosclerosis is considered the major cause of heart attack, stroke and gangrene of the extremities, which is responsible for 50% of all mortality in Western countries. The pathogenesis and causes of atherosclerosis remain elusive. Recent studies highlight inflammation as a contributing factor for atherosclerosis in all stages of the disease process. In this study, we demonstrate that the treatment of human umbilical vein endothelial cells (HUVECs) with ghrelin inhibits the oxidized low-density lipoprotein (oxLDL)-induced inflammatory response, In addition, treatment with ghrelin led to the accumulation of uncoupling protein 2 (UCP2) in the cells, thus decreasing reactive oxygen species (ROS) generation. Moreover, the siRNA-mediated knockdown of UCP2 expression suggested that the inhibitory effects of ghrelin on the inflammatory response relied on its ability to induce the accumulation of cellular UCP2 levels. Further analysis indicated that the accumulation of UCP2 in the ghrelin-treated cells was due to the ability of ghrelin to inhibit the ubiquitination of UCP2 and prevent UCP2 degradation, resulting in the extended protein half-life of UCP2. On the whole, our data indicate that ghrelin inhibits the oxLDL-induced inflammatory response in HUVECs, and may thus have potential for use as an anti-atherosclerotic agent. Our data may also provide valuable insight into the pathogenesis of atherosclerosis.
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Affiliation(s)
- Ruolan Zhang
- Department of Cardiology, Harrison International Peace Hospital, Hengshui, Hebei 053000, P.R. China
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Al-Mohanna F. The Cardiokines. ENDOCRINOLOGY OF THE HEART IN HEALTH AND DISEASE 2017:87-114. [DOI: 10.1016/b978-0-12-803111-7.00004-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Huang CF, Liu JC, Huang HC, Chuang SY, Chen CI, Lin KC. Longitudinal transition trajectory of gouty arthritis and its comorbidities: a population-based study. Rheumatol Int 2016; 37:313-322. [PMID: 28004164 DOI: 10.1007/s00296-016-3634-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 12/09/2016] [Indexed: 10/20/2022]
Abstract
The aim of the study was to investigate the longitudinal transition trajectory of gout and its comorbidities in male patients with gout in different age groups. A total of 3973 male patients who received a new diagnosis of gouty arthritis were identified from the Taiwan Longitudinal Health Insurance Database and divided into two age cohorts (<50 and ≥50 years). Each patient was individually followed from 2000 to 2009 to identify associated comorbidities, namely hypertension, hypercholesterolemia, diabetes mellitus, cardiovascular diseases, and chronic kidney disease. Two outcome measurements of stroke and all-cause cancer were further identified until 2010. The transition trajectory was divided into the following five phenotype groups: persistent hypertension combined with a high prevalence of various gout-related comorbidities, persistent hypercholesterolemia combined with a moderate prevalence of various gout-related comorbidities, persistent low prevalence of various gout-related comorbidities, moderate to high prevalence of various gout-related comorbidities, and low to high prevalence of various gout-related comorbidities. Although the younger and older patients had a similar longitudinal transition trajectory of gout-related comorbidities, the older patients had a higher 10-year likelihood of transition from a low or moderate to a high prevalence of various gout-related comorbidities. In addition, the incidences of stroke and all-cause cancer were higher in the groups with high and moderate to high prevalences of various gout-related comorbidities than in the other groups. The occurrence of gouty arthritis in different life stages can cause cluster effects involving varying degrees of comorbidities over time. The findings of the current study can provide additional knowledge and increase clinical awareness regarding the early assessment and management of gout-related comorbidities in clinical practice.
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Affiliation(s)
- Chien-Fang Huang
- Division of Quality Improvement, Joint Commission of Taiwan, 5F No. 31, Sec. 2, Sanmin Road, Banqiao District, New Taipei City, Taiwan, ROC
| | - Ju-Chi Liu
- Division of Cardiovascular Medicine, Department of Internal Medicine, Taipei Medical University - Shuang Ho Hospital, No. 291, Zhongzheng Road, Zhonghe District, New Taipei City, Taiwan, ROC.,Department of Internal Medicine, School of Medicine, Medical College, Taipei Medical University, No. 252, Wu-Hsing Street, Taipei City, Taiwan, ROC
| | - Hui-Chuan Huang
- Accelerated Bachelor of Science in Nursing, College of Nursing, Taipei Medical University, No. 250 Wu-Hsing Street, Taipei City, Taiwan, ROC.,School of Nursing, College of Nursing, Taipei Medical University, No. 250 Wu-Hsing Street, Taipei City, Taiwan, ROC
| | - Shao-Yuan Chuang
- Division of Preventive Medicine and Health Services Research, Institute of Population Health Sciences, National Health Research Institutes, No. 35, Keyan Road, Miaoli County, Taiwan, ROC
| | - Chang-I Chen
- Taipei Cancer Center, Taipei Medical University, No. 252, Wu-Hsing Street, Taipei City, Taiwan, ROC.,Department of Healthcare Administration, School of Management, Taipei Medical University, No. 250 Wu-Hsing Street, Taipei City, Taiwan, ROC
| | - Kuan-Chia Lin
- Institute of Hospital and Health Care Administration, Community Research Center, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Beitou District, Taipei City, 11221, Taiwan, ROC.
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Meng J, Li Y, Yuan X, Lu Y. Effects of febuxostat on insulin resistance and expression of high-sensitivity C-reactive protein in patients with primary gout. Rheumatol Int 2016; 37:299-303. [PMID: 27878622 DOI: 10.1007/s00296-016-3612-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Accepted: 11/17/2016] [Indexed: 12/15/2022]
Abstract
We aimed to investigate the effects of febuxostat on IR and the expression of high-sensitivity C-reactive protein (hs-CRP) in patients with primary gout. Forty-two cases of primary gout patients without uric acid-lowering therapy were included in this study. After a physical examination, 20 age- and sex-matched patients were included as normal controls. The levels of fasting insulin (INS), fasting blood glucose (FBG), and hs-CRP were determined. IR was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Gout patients had higher levels of UA, INS, HOMA-IR, and hs-CRP than normal controls (P < 0.05). After 4-, 12-, and 24-week febuxostat treatments, UA and hs-CRP concentrations were significantly lower than baseline (P < 0.05). INS and HOM-IR decreased slightly after a 4-week treatment with febuxostat but declined significantly after 12 and 24 weeks of treatment. Importantly, hs-CRP values positively correlated with those of HOMA-IR (r = 0.353, P = 0.018) and INS (r = 0.426, P = 0.034). Our findings confirm that IR exists in gout patients and implicate that febuxostat can effectively control the level of serum UA and increase insulin sensitivity in primary gout patients.
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Affiliation(s)
- Juan Meng
- Department of Rheumatology and Immunology, Beijing Chao-Yang Hospital, Capital Medical University, 8 GongrenTiyuchangNanlu, Chaoyang District, Beijing, 100020, China
| | - Yanchun Li
- Department of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Chaoyang District, Beijing, China
| | - Xiaoxu Yuan
- Department of Rheumatology and Immunology, Beijing Chao-Yang Hospital, Capital Medical University, 8 GongrenTiyuchangNanlu, Chaoyang District, Beijing, 100020, China
| | - Yuewu Lu
- Department of Rheumatology and Immunology, Beijing Chao-Yang Hospital, Capital Medical University, 8 GongrenTiyuchangNanlu, Chaoyang District, Beijing, 100020, China.
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"TRP inflammation" relationship in cardiovascular system. Semin Immunopathol 2015; 38:339-56. [PMID: 26482920 PMCID: PMC4851701 DOI: 10.1007/s00281-015-0536-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Accepted: 10/08/2015] [Indexed: 02/07/2023]
Abstract
Despite considerable advances in the research and treatment, the precise relationship between inflammation and cardiovascular (CV) disease remains incompletely understood. Therefore, understanding the immunoinflammatory processes underlying the initiation, progression, and exacerbation of many cardiovascular diseases is of prime importance. The innate immune system has an ancient origin and is well conserved across species. Its activation occurs in response to pathogens or tissue injury. Recent studies suggest that altered ionic balance, and production of noxious gaseous mediators link to immune and inflammatory responses with altered ion channel expression and function. Among plausible candidates for this are transient receptor potential (TRP) channels that function as polymodal sensors and scaffolding proteins involved in many physiological and pathological processes. In this review, we will first focus on the relevance of TRP channel to both exogenous and endogenous factors related to innate immune response and transcription factors related to sustained inflammatory status. The emerging role of inflammasome to regulate innate immunity and its possible connection to TRP channels will also be discussed. Secondly, we will discuss about the linkage of TRP channels to inflammatory CV diseases, from a viewpoint of inflammation in a general sense which is not restricted to the innate immunity. These knowledge may serve to provide new insights into the pathogenesis of various inflammatory CV diseases and their novel therapeutic strategies.
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