Search

Background: We aimed to probe the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA)., Methods: The study included 1169 gout patients and 7029 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and 2001-2018, respectively. The association between serum 25(OH)D and mortality was evaluated by Cox proportional hazard and restricted cubic spline models., Results: Among participants with gout and HUA, the weighted mean concentrations of serum 25(OH)D were 71.49 ± 30.09 nmol/L and 64.81 ± 26.92 nmol/L, respectively. Vitamin D deficiency occurred in 29.68% of gout patients and 37.83% of HUA patients. During 6783 person-years of follow-up among gout patients, 248 all-cause deaths occurred, among which 76 died from cardiovascular disease (CVD) and 49 died from cancer. 1375 HUA patients were recorded for all-cause mortality during 59,859 person-years of follow-up, including 427 CVD deaths and 232 cancer deaths. After multifactorial adjustment, per one-unit increment in natural log-transformed 25(OH)D was associated with lower risk of 55% all-cause mortality and 61% CVD mortality among gout patients, and a 45% reduced risk of cancer mortality among HUA patients. Restricted cubic splines showed a U-shaped relationship with all-cause and CVD mortality among HUA patients, with inflection points of 72.7 nmol/L and 38.0 nmol/L, respectively. The results were robust in subgroup and sensitivity analyses., Conclusions: Serum 25(OH)D was negatively linearly correlated with mortality among gout patients, whereas U-shaped correlated with mortality in HUA patients. These results indicate that adequate vitamin D status could prevent premature death., (© 2024. The Author(s).)

Background: Asymptomatic hyperuricemia (HUA) and normouricemic gout are common in clinic but recommendations for them in hypertension management are absent. The present study aims to simultaneously evaluate the effect of HUA and gout on long-term mortality in hypertension., Methods: Individuals from 2007-2018 National Health and Nutrition Examination Survey were enrolled. Hazard ratios and 95% confidence intervals (CIs) were calculated with the aid of the Cox proportional-hazards model. The restricted cubic spline (RCS) analysis was made to show the dose-response relationship between uric acid and mortality. All-cause mortality and cardiovascular mortality were compared using the Kaplan-Meier curve with a log-rank test., Results: Thirty thousand eight hundred and nineteen eligible individuals were included, of which 5841 suffered from HUA and 1476 suffered from gout. During a median follow-up of 7.25 (95% CI 7.18-7.32) years, 2924 (6.8%) patients died, including 722 (1.6%) cases of cardiovascular death. Hypertensive patients with HUA and gout showed 1.34 and 1.29 times higher all-cause mortality compared with those without HUA or gout. For hypertensive patients without gout, HUA was significantly associated with higher risk of all-cause [1.27 (1.13, 1.43)] and cardiovascular [1.80 (1.44, 2.24)] mortality compared with normouricemia. However, for hypertensive patients without HUA, gout was associated with a higher mortality but not statistically significant. A J-shaped relationship was found between serum uric acid and mortality., Conclusion: HUA and gout are additive risk factors for all-cause and cardiovascular mortality in hypertension. Furthermore, asymptomatic HUA is significantly associated with poor long-term prognosis but normouricemic gout is not., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: To test the association of C-reactive protein (CRP) with all-cause and cause-specific mortality in people with gout., Methods: This cohort study included 502 participants with gout from the National Health and Nutrition Examination Survey. Multivariate Cox regression analysis, subgroup analysis, and restricted cubic spline (RCS) analyses were utilized to examine the association of CRP levels with all-cause, cardiovascular, and cancer mortality., Results: After adjusting for multiple variables, Cox regression analysis showed that compared with individuals in the lowest tertile of CRP levels, those in the middle and highest tertiles experienced increases in all-cause mortality risk of 74.2% and 149.7%, respectively. Similarly, the cancer mortality risk for individuals in the highest tertile of CRP levels increased by 283.9%. In addition, for each standard deviation increase in CRP, the risks of all-cause and cancer mortality increased by 25.9% and 35.4%, respectively (P < 0.05). Subgroup analyses demonstrated that the association between CRP levels and all-cause mortality remained significant across subgroups of age (≤ 60 and > 60 years), gender (male), presence or absence of hypertension, non-diabetes, cardiovascular disease, non-cardiovascular disease and non-cancer. Furthermore, the association with cancer mortality was significant in subgroups including males, those without hypertension and cancer, and those with or without diabetes. However, the association with cardiovascular mortality was only significant in the non-hypertension subgroup (P < 0.05). Nonlinear association of CRP with all-cause mortality and linear association with cancer mortality were also confirmed (P for nonlinearity = 0.008 and 0.135, respectively)., Conclusions: CRP levels were associated with increased all-cause and cancer mortality among individuals with gout., (© 2024. The Author(s).)

Importance: Recurrent flares are the hallmark of clinical manifestation of gout. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been associated with a lower risk of incident gout; however, their association with recurrent flares is unknown., Objective: To examine the association of SGLT2i vs active comparators (ie, glucagonlike peptide-1 receptor agonists [GLP-1 RA] or dipeptidyl peptidase-4 inhibitors [DPP-4i]) with the risk of recurrent gout flares and all-cause mortality among patients with gout and type 2 diabetes., Design, Setting, and Participants: This population-based retrospective cohort study was performed from January 1, 2013, to March 31, 2022, using a UK primary care database. Participants included patients with gout and type 2 diabetes with visits to their general practitioners., Exposures: Initiation of treatment with SGLT2i or active comparators., Main Outcomes and Measures: The primary outcome was the number of recurrent gout flares ascertained using recorded codes and prescription records. Secondary outcomes were the first recurrent gout flare and all-cause mortality. The association of SGLT2i compared with active comparators for the risk of recurrent flares, the first recurrent flare, and all-cause mortality was assessed using Poisson regression or the Cox proportional hazards model with propensity score overlap weighting., Results: Of a total of 5931 patients included in the analysis (mean [SD] age, 66.0 [11.6] years; 4604 [77.6%] men), 1548 initiated SGLT2i treatment and 4383 initiated treatment with active comparators during the study period. The relative rate of the recurrent flares with SGLT2i vs active comparators was 0.79 (95% CI, 0.65-0.97). Similar results were observed in the association of SGLT2i with the rate of recurrent flares when compared with DPP-4i or GLP-1 RA. For the first recurrent flare for SGLT2i vs active comparators, rate difference was -8.8 (95% CI, -17.2 to -0.4) per 1000 person-years and the hazard ratio was 0.81 (95% CI, 0.65-0.98). All-cause mortality per 1000 person-years was 18.8 for SGLT2i and 24.9 for active comparators, with rate difference of -6.1 (95% CI, -10.6 to -1.6) per 1000 person-years and hazard ratio of 0.71 (95% CI, 0.52-0.97)., Conclusions and Relevance: The findings of this cohort study suggest that SGLT2i were associated with a lower risk of recurrent gout flares and mortality than their active comparators in patients with gout and type 2 diabetes. These findings further suggest that SGLT2i could help reduce the burden of recurrent gout flares and could also narrow the mortality gap between patients with gout and the general population.

Background: Two recent randomized clinical trials of escalating doses of allopurinol for the progression of chronic kidney disease (CKD) reported no benefits but potentially increased risk for death. Whether the risk could occur in patients with gout and concurrent CKD remains unknown., Objective: To examine the relation of allopurinol initiation, allopurinol dose escalation, and achieving target serum urate (SU) level after allopurinol initiation to all-cause mortality in patients with both gout and CKD., Design: Cohort study., Setting: The Health Improvement Network U.K. primary care database (2000 to 2019)., Participants: Patients aged 40 years or older who had gout and concurrent moderate-to-severe CKD., Measurements: The association between allopurinol initiation and all-cause mortality over 5-year follow-up in propensity score (PS)-matched cohorts was examined. Analysis of hypothetical trials were emulated: achieving target SU level (<0.36 mmol/L) versus not achieving target SU level and dose escalation versus no dose escalation for mortality over 5-year follow-up in allopurinol initiators., Results: Mortality was 4.9 and 5.8 per 100 person-years in 5277 allopurinol initiators and 5277 PS-matched noninitiators, respectively (hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.93]). In the target trial emulation analysis, the HR of mortality for the achieving target SU level group compared with the not achieving target SU level group was 0.87 (CI, 0.75 to 1.01); the HR of mortality for allopurinol in the dose escalation group versus the no dose escalation group was 0.88 (CI, 0.73 to 1.07)., Limitation: Residual confounding cannot be ruled out., Conclusion: In this population-based data, neither allopurinol initiation, nor achieving target SU level with allopurinol, nor allopurinol dose escalation was associated with increased mortality in patients with gout and concurrent CKD., Primary Funding Source: Project Program of National Clinical Research Center for Geriatric Disorders.

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Urate-lowering therapy (predominantly allopurinol) is highly effective as a treatment for gout, but its wider long-term effects remain unclear. This systematic review and meta-analysis aimed to ascertain the association between mortality and the use of allopurinol in patients with gout., Method: Medline, Embase, CINAHL, and the Cochrane Library were searched from inception to August 2018. Articles eligible for inclusion used a cohort design and examined cardiovascular or all-cause mortality in patients diagnosed with gout and prescribed allopurinol. Information on study characteristics, design, sample size, and mortality risk estimates were extracted. Article quality was assessed using the Newcastle-Ottawa Scale. Included articles were described in a narrative synthesis and, where possible, risk estimate data were pooled., Results: Four articles reported a hazard ratio (HR) risk estimate for all-cause mortality in patients with gout using allopurinol, and 2 of these also reported cardiovascular mortality. Two articles found allopurinol to be protective in patients with gout, 1 found no statistically significant association, and 1 found no statistically significant effect of escalation of allopurinol dosage on all-cause or cardiovascular-related mortality. Data pooling was possible for all-cause mortality and found no association between allopurinol use in patients with gout and all-cause mortality compared to patients with gout not using allopurinol (adjusted HR 0.80 [95% confidence interval 0.60-1.05])., Conclusion: There was no significant association between all-cause mortality and allopurinol use in people with gout. However, the number of included studies was small, suggesting that further studies are needed., (© 2020 The Authors. Arthritis Care & Research published by Wiley Periodicals Inc. on behalf of American College of Rheumatology.)

To analyze the epidemiology, clinical features and costs of hospitalized patients with gout during the last decade in Spain. Retrospective observational study based on data from the Minimum Basic Data Set (MBDS) from the Spanish National Health Service database. Patients ≥ 18 years with any gout diagnosis at discharge who had been admitted to public or private hospitals between 2005 and 2015 were included. Patients were divided in two periods: p1 (2005-2010) and p2 (2011-2015) to compare the number of hospitalizations, mean costs and mortality rates. Data from 192,037 patients with gout was analyzed. There was an increase in the number of hospitalized patients with gout (p < 0.001). The more frequent comorbidities were diabetes (27.6% of patients), kidney disease (26.6%) and heart failure (19.3%). Liver disease (OR 2.61), dementia (OR 2.13), cerebrovascular diseases (OR 1.57), heart failure (OR 1.41), and kidney disease (OR 1.34) were associated with a higher mortality risk. Women had a lower risk of mortality than men (OR 0.85). General mortality rates in these hospitalized patients progressively increased over the years (p < 0.001). In addition, costs gradually rose, presenting a significant increase in p2 even after adjusting for inflation (p = 0.001). A progressive increase in hospitalizations, mortality rates and cost in hospitalized patients with gout was observed. This harmful trend in a preventable illness highlights the need for change and the search for new healthcare strategies.

BACKGROUND Kidney transplantation is associated with increased prevalence of gout. However, evidence of the effect of gout on long-term kidney transplantation outcomes is mixed. This study examined mortality risk among patients with a history of kidney transplantation with vs. without gout. MATERIAL AND METHODS A retrospective study was conducted using Medicare Fee-for-Service administrative claims of patients with a history of kidney transplantation. Cox proportional hazards models determined the effect of gout on all-cause mortality, controlling for confounders, including comorbid mortality risk, via the Charlson Comorbidity Index. Because the relationships between gout and components of the Charlson Comorbidity Index are also debated, 3 different model assumptions were used: 1) gout shares a common cause with these comorbidities, 2) gout is upstream of these comorbidities, 3) the effect of gout on mortality is modified by these comorbidities. RESULTS Gout increased the risk of all-cause mortality in the unadjusted model (hazard ratio: 1.44, 95% CI 1.27-1.63) and after adjustment for demographics and transplant vintage (hazard ratio: 1.16, 95% CI 1.02-1.32). Gout was not a significant risk after adjustment for baseline Charlson Comorbidity Index (hazard ratio: 1.03, 95% CI 0.90-1.17). Gout was associated with greater mortality among patients without baseline comorbidities (Charlson Comorbidity Index=0; hazard ratio: 3.48, 95% CI 1.27-9.57) in the stratified model. CONCLUSIONS Among patients with a history of kidney transplantation, gout did not have an independent effect on all-cause mortality. However, gout was a predictor of mortality among patients with no comorbidities, suggesting that gout is an early warning sign of poor health in kidney transplantation patients.

To provide recent statistics on worldwide gout epidemiology. Current and prediction data on gout epidemiology were retrieved from the Global Health Data Exchange (GHDx) registry and from the World Health Organization (WHO) database on projected mortality. Overall, 7.44 million cases of gout have been estimated around the world in 2017 (incidence, 0.097%), with a prevalence of 41.22 million cases (0.54%), and causing 1.28 million DALYs (0.051% of all DALYs). Gout incidence, prevalence, and health loss considerably increased during the last 25 years and are all higher in men than in women. The burden of gout increases linearly with aging, until the age of 64 years, and is correlated with socio-demographic index (SDI), with incident risk of gout > 3-fold higher in high than in low SDI regions. Projections suggest that gout mortality may increase by 55% in 2060. The epidemiologic burden of gout remains high around the world, especially in men and in high SDI countries, with a trend that is unlikely to reverse soon.Key Points• A significant association can be found between gout and socioeconomic status.• Projections suggest that gout mortality may increase by 55% in 2060.• The epidemiologic burden of gout remains high around the world.

Background: Cardiovascular guidelines do not give firm recommendations on statin therapy in patients with gout because evidence is lacking., Aim: To analyze the effectiveness of statin therapy in primary prevention of coronary heart disease (CHD), ischemic stroke (IS), and all-cause mortality in a population with gout., Methods: A retrospective cohort study (July 2006 to December 2017) based on Information System for the Development of Research in Primary Care (SIDIAP Q ), a research-quality database of electronic medical records, included primary care patients (aged 35-85 years) without previous cardiovascular disease (CVD). Participants were categorized as nonusers or new users of statins (defined as receiving statins for the first time during the study period). Index date was first statin invoicing for new users and randomly assigned to nonusers. The groups were compared for the incidence of CHD, IS, and all-cause mortality, using Cox proportional hazards modeling adjusted for propensity score., Results: Between July 2006 and December 2008, 8018 individuals were included; 736 (9.1%) were new users of statins. Median follow-up was 9.8 years. Crude incidence of CHD was 8.16 (95% confidence interval [CI]: 6.25-10.65) and 6.56 (95% CI: 5.85-7.36) events per 1000 person-years in new users and nonusers, respectively. Hazard ratios were 0.84 (95% CI: 0.60-1.19) for CHD, 0.68 (0.44-1.05) for IS, and 0.87 (0.67-1.12) for all-cause mortality. Hazard for diabetes was 1.27 (0.99-1.63)., Conclusions: Statin therapy was not associated with a clinically significant decrease in CHD. Despite higher risk of CVD in gout populations compared to general population, patients with gout from a primary prevention population with a low-to-intermediate incidence of CHD should be evaluated according to their cardiovascular risk assessment, lifestyle recommendations, and preferences, in line with recent European League Against Rheumatism recommendations.

Background: Gout is the most common inflammatory arthritis with a rising prevalence around the globe. While educational inequalities in incidence and prevalence of gout have been reported, no previous study investigated educational inequality in mortality among people with gout. The aim of this study was to assess absolute and relative educational inequalities in all-cause and cause-specific mortality among people with gout in comparison with an age- and sex-matched cohort free of gout in southern Sweden., Methods: We identified all residents aged ≥30 years of Skåne region with doctor-diagnosed gout (ICD-10 code M10, n = 24,877) during 1998-2013 and up to 4 randomly selected age- and sex-matched comparators free of gout (reference cohort, n = 99,504). These were followed until death, emigration, or end of 2014. We used additive hazards models and Cox regression adjusted for age, sex, marital status, and country of birth to estimate slope and relative indices of inequality (SII/RII). Three cause-of-death attribution approaches were considered for RII estimation: "underlying cause", "any mention", and "weighted multiple-cause"., Results: Gout patients with the lowest education had 1547 (95% CI: 1001, 2092) more deaths per 100,000 person-years compared with those with the highest education. These absolute inequalities were larger than in the reference population (1255, 95% CI: 1038, 1472). While the contribution of cardiovascular (cancer) mortality to these absolute inequalities was greater (smaller) in men with gout than those without, the opposite was seen among women. Relative inequality in all-cause mortality was smaller in gout (RII 1.29 [1.18, 1.41]) than in the reference population (1.46 [1.38, 1.53]). The weighted multiple-cause approach generally led to larger RIIs than the underlying cause approach., Conclusions: Our register-based matched cohort study showed that low level of education was associated with increased mortality among gout patients. Although the magnitude of relative inequality was smaller in people with gout compared with those without, the absolute inequalities were greater reflecting a major mortality burden among those with lower education.

Background and Aims: Systemic reviews and meta-analyses suggest hyperuricemia is a cardiovascular risk factor. The effects of xanthine oxidase inhibitors on cardiac outcomes remain unclear. We assessed the effects of febuxostat and allopurinol on mortality and adverse reactions in adult patients with hyperuricemia., Methods and Results: PubMed and EMBASE were searched to retrieve randomized controlled trials of febuxostat and allopurinol from January 2005 to July 2018. The meta-analysis consisted of 13 randomized controlled trials with a combined sample size of 13,539 patients. Febuxostat vs. allopurinol was not associated with an increased risk of cardiac-related mortality in the overall population (OR: 0.72, 95% CI: 0.24-2.13, P = 0.55). Regarding adverse skin reactions, the patients receiving febuxostat had significantly fewer adverse skin reactions than those receiving allopurinol treatment (OR: 0.50, 95% CI: 0.30-085, P = 0.01). Compared with allopurinol, febuxostat was associated with an improved safety outcome of cardiac-related mortality and adverse skin reactions (OR: 0.72, 95% CI: 0.55-0.96, P = 0.02). The net clinical outcome, composite of incident gout and the safety outcome, was not different significantly in the patients receiving febuxostat or allopurinol (OR: 1.04, 95% CI: 0.76-0.1.42, P = 0.79). In sensitivity analyses, a borderline significance was found in the patients randomized to febuxostat vs. allopurinol regarding cardiac-related mortality (OR: 1.29, 95% CI: 1.00-1.67, P = 0.05) after the CARES study was included., Conclusion: Febuxostat vs. allopurinol was associated with the improved safety outcome and have comparable mortality and net clinical outcome in patients with hyperuricemia., Registration Number: PROSPERO(CRD42018091657)., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

The association between hyperuricemia or gout and cancer risk has been investigated in various published studies, but their results are conflicting. We conducted a meta-analysis to investigate whether hyperuricemia or gout was associated with the cancer incidence and mortality. Linear and nonlinear trend analyses were conducted to explore the dose-response association between them. The pooled relative risk (RR) and 95% confidence interval (CI) were used to evaluate cancer risk. A total of 24 articles (33 independent studies) were eligible for inclusion. When compared participants with the highest SUA (hyperuricemia) levels and those with the lowest SUA levels, the pooled RR was 1.08 (95% CI, 1.04-1.12), it was significantly associated among males but not among females (males, RR = 1.07; 95% CI, 1.03-1.11; females, RR = 1.06; 95% CI, 0.96-1.17). Hyperuricemia increased total cancer mortality (RR = 1.15; 95% CI, 1.05-1.26), but a significant association was observed in females rather than in males (females: RR = 1.26; 95% CI, 1.09-1.45; males, RR = 1.02; 95% CI, 0.80-1.30). Linear relationships of SUA levels with overall cancer incidence (p for nonlinearity = 0.238) and overall cancer mortality (p for nonlinearity = 0.263) were identified. However, 1 mg/dL increment in SUA levels was weakly significant in overall cancer incidence (RR = 1.01; 95% CI, 1.01-1.01) but not associated with overall cancer mortality (RR = 1.01; 95% CI, 0.99-1.03). Gout was significantly associated with increased cancer incidence (RR = 1.19; 95% CI, 1.12-1.25). In conclusion, Hyperuricemia or gout was associated with higher cancer incidence and mortality. Though a potential linear relationship between them was found, we'd better treat this result with caution., (© 2019 Wiley Periodicals, Inc.)

Objective: To determine and compare the risk of cardiovascular events and mortality of febuxostat and allopurinol use., Patients and Methods: We conducted a cohort study using the Taiwan National Health Insurance Research Database. New users of febuxostat and allopurinol between April 1, 2012 and December 31, 2015 were identified, and the two groups were 1:1 matched by propensity score, benzbromarone use history, renal impairment, and time of drug initiation. The risk of major adverse cardiovascular events (MACEs), venous thromboembolism (VTE), heart failure (HF) hospitalization, atrial fibrillation hospitalization, cardiovascular (CV) death, and all-cause mortality was assessed using Cox proportional hazards models. The dose-response relationship between xanthine oxidase inhibitor use and adverse CV outcomes were also determined., Results: A total of 44,111 patients were included for each group, and all baseline covariates were well matched. Febuxostat users were at a significantly higher risk for HF hospitalization (hazard ratio [HR], 1.22; 95% CI, 1.13-1.33), atrial fibrillation hospitalization (HR, 1.19; 95% CI, 1.05-1.36), and CV death (HR, 1.19; 95% CI, 1.03-1.36) than allopurinol users, whereas no difference was found for the major adverse cardiac events composite endpoint, venous thromboembolism, myocardial infarction, ischemic stroke, and all-cause mortality. The elevated risk of HF hospitalization was consistent throughout the primary and sensitivity analyses. In addition, febuxostat increased the risk of adverse CV outcomes in a dose-dependent manner., Conclusion: The use of febuxostat, compared with allopurinol, was associated with a significantly increased risk of adverse CV events. Higher febuxostat doses had a greater impact. Further studies are needed to investigate the mechanisms linking febuxostat to adverse CV outcomes., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the cause-specific mortality and the possible involved clinical characteristics with increased mortality in a cohort of 700 patients with crystal-proven gout. The cause-specific mortality of gout was compared to the mortality of the general population., Methods: Patients with arthritis referred for diagnosis were consecutively included in the Gout Arnhem-Liemers Cohort (GOAL). Joint fluid analysis was performed in all patients and only crystal-proven gout patients were included in this study. At inclusion clinical characteristics and laboratory values were collected. At follow-up patients who died were identified. Standardized mortality ratios (SMRs) were calculated for all-causes, cardiovascular diseases, cancer, and infectious diseases using indirect standardization methods for mortality outcomes and compared with the general population. The clinical characteristics of the patients who died were compared with those of the survivors and were analyzed by a logistic regression analysis to identify any associations with mortality., Results: The study population at inclusion contained 573 (81.9%) men and 127 (18.1%) females with an average age of 62.0 (SD 13.4). During 3500 person-years from inclusion visit till 31 May 2016, in 700 gout patients, 66 deaths (27 cardiovascular deaths, 15 cancer-related deaths, 8 infectious deaths, 16 various other causes) occurred in this cohort. The all-cause standardized mortality ratio in gout patients was 2.21 (95% CI 1.68-2.74). In this cohort, gout patients had a higher SMR for death attributed to cardiovascular diseases (6.75; 95% CI 4.64-8.86), infectious diseases (4.66; 95% CI 1.51-7.82) and cancer (3.58; 95% CI 1.77-5.39). Corrected for confounders high serum uric acid levels (SUA; > 0,56 mmol/L), tophaceous gout, a history of peripheral vascular disease, myocardial infarction, and heart failure at the inclusion visit were associated with increased mortality during follow-up., Conclusion: Compared to the general population, gout patients have an increased association with all-cause disease mortality, especially attributed to cardiovascular diseases, cancer, and infectious diseases. This association is strongest in hyperuricemic (uric acid levels > 0,56 mmol/l) and tophaceous patients and in those with a history of peripheral vascular disease, myocardial infarction, and heart failure. Preventive measures like treatment of high SUA levels and treatment of cardiovascular risk factors need to be considered and evaluated.

Objectives: Gout is associated with a higher risk of cardiovascular disease and premature mortality. We examined the potential survival benefit of statin use among gout patients in the general population., Methods: We performed an incident user cohort study with time-stratified propensity score matching using a database representative of the UK general population between January 1999 and December 2014. To account for potential confounders, we compared propensity score-matched cohorts of statin initiators and non-initiators within 1-year cohort accrual blocks. We estimated the hazard ratio (HR) for mortality using a Cox proportional hazard model and the mortality rate difference using an additive hazard model. We examined potential subgroup effects stratified by key factors, including circulatory disease history., Results: Among 17,018 statin initiators, 2025 deaths occurred during the follow-up (mean = 5.0 years) with a mortality rate of 24.0/1000 person-years (PY). The number of deaths and all-cause mortality rate among matched comparators during the follow-up (mean = 4.6 years) were 2503 and 31.7/1000 PY respectively. Compared with non-initiators, statin initiators experienced a 16% lower relative risk of all-cause mortality (HR = 0.84, 95% CI: 0.79-0.89) and 7.7 (95% CI: 6.1-9.3) fewer deaths per 1000 PY. This protective association was stronger among those without prior circulatory disease (HRs = 0.65 vs. 0.85; p for interaction = 0.02)., Conclusion: In this general population-based cohort study, statin initiation was associated with a lower risk of mortality in gout, potentially with greater benefits among those without prior circulatory disease. The proper use of statins may help to substantially improve the premature mortality in gout., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Hyperuricemia and gout are associated with an increased risk of cardiovascular disease. Xanthine oxidase inhibitors, allopurinol and febuxostat, are the mainstay of urate-lowering treatment for gout and may have different effects on cardiovascular risk in patients with gout., Methods: Using US Medicare claims data (2008-2013), we conducted a cohort study for comparative cardiovascular safety of initiating febuxostat versus allopurinol among patients with gout ≥65 years of age. The primary outcome was a composite end point of hospitalization for myocardial infarction or stroke. Secondary outcomes were individual end points of hospitalization for myocardial infarction, stroke, coronary revascularization, new and recurrent heart failure, and all-cause mortality. We used propensity score matching with a ratio of 1:3 to control for confounding. We estimated incidence rates and hazard ratios for primary and secondary outcomes in the propensity score-matched cohorts of febuxostat and allopurinol initiators., Results: We included 24 936 febuxostat initiators propensity score-matched to 74 808 allopurinol initiators. The median age was 76 years, 52% were male, and 12% had cardiovascular disease at baseline. The incidence rate per 100 person-years for the primary outcome was 3.43 in febuxostat and 3.36 in allopurinol initiators. The hazard ratio for the primary outcome was 1.01 (95% CI, 0.94-1.08) in the febuxostat group compared with the allopurinol group. Risk of secondary outcomes including all-cause mortality was similar in both groups, except for a modestly decreased risk of heart failure exacerbation (hazard ratio, 0.94; 95% CI, 0.91-0.99) in febuxostat initiators. The hazard ratio for all-cause mortality associated with long-term use of febuxostat (>3 years) was 1.25 (95% CI, 0.56-2.80) versus allopurinol. Subgroup and sensitivity analyses consistently showed similar cardiovascular risk in both groups., Conclusions: Among a cohort of 99 744 older Medicare patients with gout, overall there was no difference in the risk of myocardial infarction, stroke, new-onset heart failure, coronary revascularization, or all-cause mortality between patients initiating febuxostat compared with allopurinol. However, there seemed to be a trend toward an increased, albeit not statistically significant, risk for all-cause mortality in patients who used febuxostat for >3 years versus allopurinol for >3 years. The risk of heart failure exacerbation was slightly lower in febuxostat initiators.

Objective: Observational data suggest that hyperuricemia and gout are associated with increased mortality, while allopurinol use is associated with reduced mortality. In addition, the protective effect of allopurinol may be dose dependent. The aim of the current study was to determine whether allopurinol dose escalation is associated with cause-specific mortality in patients with gout., Methods: In this 10-year observational, active-comparator study of US Veterans with gout who initiated treatment with allopurinol, propensity score matching, Cox proportional hazards models, and competing risks regression analyses were used to assess differences in cause-specific mortality between patients whose allopurinol dose was escalated (dose escalators) and those whose allopurinol dose was not escalated or was reduced (non-escalators) over a 2-year period., Results: Among the 6,428 dose escalators and 6,428 matched non-escalators, there were 2,867 deaths during the observation period (40.4 deaths per 1,000 person-years). Dose escalators experienced an increase in all-cause mortality (hazard ratio [HR] 1.08, 95% confidence interval [95% CI] 1.01-1.17), with the effect sizes being similar for incidence of cardiovascular-related deaths (HR 1.08, 95% CI 0.97-1.21) and cancer-related deaths (HR 1.06, 95% CI 0.88-1.27), although neither reached statistical significance. Dose escalation to achieve the goal of lowering the serum urate (SU) level to <6.0 mg/dl was infrequent. At 2 years, 10% of dose escalators were receiving a final daily dose of >300 mg and 31% had achieved the SU goal. In a sensitivity analysis limited to dose escalators achieving the SU goal, there was a nonsignificant reduction of 7% in the hazard of cardiovascular-related mortality (HR 0.93, 95% CI 0.76-1.14)., Conclusion: This is the largest study to date to investigate the effects of allopurinol use on mortality and is the first to use a rigorous active-comparator design. Dose escalation was associated with a small (<10%) increase in all-cause mortality, thus showing that a strategy of allopurinol dose escalation, which in current real-life practice is characterized by limited dose increases, is unlikely to improve the survival of patients with gout., (© 2018, American College of Rheumatology.)

Astroviruses are recognized as a leading cause of gastroenteritis in humans and animals. They are also associated with extra-intestinal diseases, such as hepatitis in ducklings, nephritis in chickens, and encephalitis in cattle. In February 2017, a fatal infection of goslings characterized by visceral urate deposition was reported in the Shandong province, China. Our systematic investigation led to the isolation of an astrovirus, designated AAstV/Goose/CHN/2017/SD01, and similar disease was reproduced by experimental infection of healthy goslings, fulfilling Koch's postulates. The isolated astrovirus replicated well and resulted in 100% mortality of goose embryos. Complete genome sequence analysis revealed that the isolate was genetically distinct from known astroviruses and closely related to members of the avastrovirus genogroup II. Experimental infection showed that the isolate was highly pathogenic in goslings, causing clinical signs, growth repression and in many cases mortality. Histopathological examination indicated that lesions occurred mainly in the kidneys of infected birds. However, virus-specific genomic RNA was detected in all representative tissues, and virus shedding was detected up to 12 days after inoculation, suggesting that the isolate was able to spread systemically and replicate efficiently in vivo. Collectively, our study demonstrates, for the first time, the etiological role of a genetically distinct astrovirus in the fatal infection of goslings.

Background: Xanthine oxidase inhibitors (XOI), classified as purine-like (allopurinol and oxypurinol) and non-purine (febuxostat and topiroxostat) XOI, present antioxidant properties by reducing the production of reactive oxygen species derived from purine metabolism. Oxidative stress is an important factor related to endothelial dysfunction and ischemia-reperfusion injury, and may be implicated in the pathogenesis of heart failure, hypertension, and ischemic heart disease. However, there is contradictory evidence regarding the possible cardiovascular (CV) protective effect exerted by XOI. Our objective is to compare the incidence of major adverse cardiovascular events (MACE), mortality, total (TCE) and specific CV events in randomized controlled trials (RCTs) testing XOI against placebo or no treatment., Methods: PubMed, EMBASE, Web of Science, Cochrane Central, Lilacs databases were searched from inception to Dec 30 2016, along with hand searching. RCTs including exclusively adult individuals, lasting ≥ 4 weeks, with no language restriction, were eligible. Independent paired researchers selected studies and extracted data. Considering the expected rarity of events, Peto and DerSimonian/Laird odds ratios (OR), the latter in case of heterogeneity, were used for analysis. Random-effects meta-regression was used to explore heterogeneity., Results: The analysis of MACE included 81 articles (10,684 patients, 6434 patient-years). XOI did not significantly reduce risk of MACE (OR P  = 0.71, 95% CI 0.46-1.09) and death (0.89, 0.59-1.33), but reduced risk of TCE (0.60, 0.44-0.82; serious TCE: 0.64, 0.46 to 0.89), and hypertension (0.54, 0.37 to 0.80). There was protection for MACE in patients with previous ischemic events (0.42, 0.23-0.76). Allopurinol protected for myocardial infarction (0.38, 0.17-0.83), hypertension (0.32, 0.18-0.58), TCE (0.48, 0.31 to 0.75, I 2  = 55%) and serious TCE (0.56, 0.36 to 0.86, I 2  = 44%). Meta-regression associated increasing dose of allopurinol with higher risk of TCE and serious TCE (P < 0.05). Accordingly, lower doses (≤ 300 mg/day) of allopurinol reduced the risk of TCE, unlike higher doses. Non-purine-like XOI did not significantly reduce or increase the risk of adverse CV events, but confidence intervals were wide. Quality of evidence was generally low to moderate., Conclusions: Purine-like XOI may reduce the incidence of adverse CV outcomes. However, higher doses of allopurinol (> 300 mg/day) may be associated with loss of CV protection.

Objective: To examine whether illness perceptions independently predict mortality in early-onset gout., Methods: Between December 2006 and January 2014, a total of 295 participants with early-onset gout (<10 years) were recruited in Auckland and Wellington, New Zealand. The participants were followed up until February 2015, and mortality information was collected. Participants with complete data were included in the current study (n = 242). Cox proportional hazards models were used to examine the association between illness perceptions and mortality risk, after adjustment for covariates associated with disease severity and mortality in gout., Results: In a Cox proportional hazards model adjusted for predictors of disease severity and mortality in gout (number of tophi, serum urate level, and frequency of flares), consequence beliefs, identity beliefs, concern beliefs, and emotional response to gout were associated with all-cause mortality (hazard ratios [HRs] 1.29, 1.15, 1.18, and 1.19, respectively; P < 0.05 for all). In the fully saturated model, the association between consequence beliefs and mortality remained robust after additional adjustment for ethnicity, disease duration, diuretic use, serum creatinine, and pain score (HR 1.18 [95% confidence interval 1.02-1.37]; P = 0.029)., Conclusion: Negative beliefs about the impact of gout and severity of symptoms, as well as concerns about gout and the emotional response to gout, were independently associated with all-cause mortality. Illness perceptions are important and potentially modifiable risk factors to target in future interventions., (© 2016, American College of Rheumatology.)

Gout is the most common form of inflammatory arthropathy and is caused by an excess of uric acid in the blood (hyperuricemia). It is a chronic, debilitating condition that gradually increases in severity and affects an increasing number of people. It has a wide spectrum of clinical manifestations and is related to serious kidney and cardiovascular conditions and to an increased risk of mortality. The negative perception of the disease, historically seen as related to a life of dissipation, has led to underestimating its impact and focusing the attention on the short-term treatment of acute attacks rather than on the long-term management of the condition without, consequently, preventing the most serious complications. The most recent scientific evidence and the increasing understanding of the physio-pathologic mechanisms responsible for hyperuricemia and gout reveal a very different reality, in which gout is a condition which is only minimally affected by lifestyle and mainly by increasingly better identified genetic factors. Appropriate doctor training and patient education, catalyzed by the renewed attention to this disease and to new treatment options which overcome the limits of therapies currently available, will help to break down current barriers to allow for its optimal management.

Objective: To determine mortality rates and predictors of death at baseline in people with a recent onset of gout., Methods: People with gout disease duration < 10 years were recruited from primary and secondary care settings. Comprehensive clinical assessment was completed at baseline. Participants were prospectively followed for at least 1 year. Information about death was systematically collected from primary and secondary health records. Standardized mortality ratios (SMR) were calculated and risk factors for mortality were analyzed using Cox proportional hazard regression models., Results: The mean (SD) followup duration was 5.1 (1.6) years (a total 1511 patient-yrs accrued). Of the 295 participants, 43 (14.6%) had died at the time of censorship (SMR 1.96, 95% CI 1.44-2.62). In the reduced Cox proportional hazards model, these factors were independently associated with an increased risk of death from all causes: older age (70-80 yrs: HR 9.96, 95% CI 3.30-30.03; 80-91 yrs: HR 9.39, 95% CI 2.68-32.89), Māori or Pacific ethnicity (HR 2.48, 95% CI 1.17-5.29), loop diuretic use (HR 3.99, 95% CI 2.15-7.40), serum creatinine (per 10 µ mol/l change; HR 1.04, 95% CI 1.00-1.07), and the presence of subcutaneous tophi (HR 2.85, 95% CI 1.49-5.44). The presence of subcutaneous tophi was the only baseline variable independently associated with both cardiovascular (CV) cause of death (HR 3.13, 95% CI 1.38-7.10) and non-CV cause of death (HR 3.48, 95% CI 1.25-9.63)., Conclusion: People with gout disease duration < 10 years have an increased risk of death. The presence of subcutaneous tophi at baseline is an independent predictor of mortality, from both CV and non-CV causes.

Recent evidence would indicate that high serum uric acid (SUA) levels can be a significant and independent risk factor for hypertension and cardiovascular diseases, such as ischemic heart disease and heart failure. In the last few years an independent risk relationship between hyperuricemia, cardiovascular disease and mortality has also been reported. Hyperuricemia has been shown as an independent risk factor for acute myocardial infarction and an independent and conjoint association of either gout and SUA with total and cardiovascular mortality has been reported, with mortality impact in gout patients increasing with rising SUA concentrations, even for SUA levels in the normal to high range. These findings prompted a growing research interest on the possible benefits of uric acid lowering drugs in cardiovascular diseases. Indeed, clinical studies have reported on the beneficial effects of uric acid lowering drugs, in particular of xanthine oxidase inhibitors, in hypertension, ischemic heart disease and heart failure. Two main mechanisms have been claimed to explain the dangerous effects of hyperuricemia and, as a consequence, the benefits of uric acid lowering therapy: endothelial dysfunction and systemic inflammation. This brief review aims to summarize current evidence from human studies on the role of acid uric lowering therapy in cardiovascular diseases for practical and clinical purposes. The possible mechanisms underlying the benefits of acid uric lowering therapy are also addressed., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Osteoarthritis (OA) and gout have each been associated with increased cardiovascular disease (CVD), but their relative impact is unknown. We compared CVD rates among patients with gout versus patients with OA and no gout (OA-only)., Methods: We identified male patients at the VA New York Harbor Healthcare System with gout (with or without concur - rent OA) and with OA-only between August 2007 and August 2008. For each group, we collected baseline demographic data and CVD risk factors. The primary outcome was a composite index (CV4) of any diagnosis of coronary artery disease (CAD), angina, myocardial infarction (MI), or coro- nary bypass surgery (CABG). Secondary outcomes included individual diagnoses within the CV4, CHF, and death. We subsequently divided the gout patients into those who did versus did not have concurrent diagnoses of OA (gout-only; gout+OA). Logistic regression was used to compare the associations of OA-only, gout-only, and gout+OA with CV outcomes., Results: 1,280 gout subjects met inclusion criteria (983 gout- only and 297 gout+OA), along with 1,231 OA-only subjects. Gout subjects overall had more CVD risk factors at baseline, including hypertension, hyperlipidemia, and chronic kidney disease, versus OA-only. Compared with OA-only, gout subjects overall had increased rates of all outcomes except MI. Both the gout-only and gout+OA subgroups also had increased risk for all outcomes except MI, and CABG in the case of gout+OA subjects. After adjusting for traditional CVD risk factors, both gout-only and gout+OA subjects continued to have increased risk for multiple CVD outcomes. Gout+OA did not impart ad- ditional risk over gout-only for any outcome studied., Conclusion: Our data suggest that gout is associated with higher risk of CVD compared with OA, and that OA does not impart any additive CVD risk to patients who also have gout. Significance and Innovations: • In our dataset, gout subjects both with and without con- comitant OA had more cardiovascular disease (CVD) risk factors at baseline, and higher prevalence of CVD outcomes, than patients with OA only. • After adjusting for traditional CVD risk factors, gout-only and gout+OA subjects continued to have increased rates of multiple CVD outcomes, suggesting an intrinsic CVD risk to the diagnosis of gout, compared with OA. • These observations underline that gout patients represent a group at increased CVD risk, for whom both rheumatic disease management and CVD prevention need to be addressed.

Objective: To examine the association between allopurinol use and all-cause mortality for patients with incident gout., Methods: We compared all-cause mortality in incident gout patients who received allopurinol for at least 6 months within the exposure window (1 year or 3 years) with those who did not, using the UK Clinical Practice Research Data-link. Landmark analysis was used to account for immortal time bias and propensity score matching was used to control for potential effects of known confounders., Results: Of 23 332 incident gout patients identified, the propensity score-matched cohorts contained 1016 patients exposed to allopurinol on the date 1 year from diagnosis (landmark date) and 1016 allopurinol non-users. Over a median follow-up period of 10 years after the landmark date, there were 437 allopurinol users and 443 allopurinol non-users who died during follow-up. Allopurinol users and non-users had similar risk for all-cause mortality (hazard ratio 0.99; 95% CI 0.87, 1.12). In the 3-year landmark analysis, 3519 allopurinol users (1280 died) were compared with 3519 non-users (1265 died). The hazard ratio for all-cause mortality was 1.01 (95% CI 0.92, 1.09)., Conclusion: This propensity score-matched landmark analysis in a population of incident gout patients in the UK primary care setting found a neutral effect on the risk of all-cause mortality. Our study provides reassurance about the prescription of allopurinol for gout patients early in their disease course to prevent untoward consequences of chronic uncontrolled hyperuricaemia. However, whether higher than the commonly used dose of allopurinol could influence mortality remains to be determined., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To examine (1) the risk of death from cardiovascular disease (CVD) and from all causes in patients with gout who do not undergo urate-lowering therapy (ULT), and (2) the effect of ULT on mortality risk in patients with gout., Methods: In this prospective case-matched cohort study, 40,623 Taiwanese individuals aged ≥ 17 years were followed for 6.5 years. Mortality rate was compared between 1189 patients with gout who did not receive ULT and reference subjects (no gout, no ULT) matched for age, sex, and the index date of gout diagnosis (1:3 patients with gout/reference subjects), and between 764 patients with gout who received ULT and 764 patients with gout who did not receive ULT matched 1-to-1 based on their propensity score and the index date of ULT prescription. Cox proportional hazard modeling was used to estimate the respective risk of CVD (International Classification of Diseases, 9th ed. code 390-459) and all-cause mortality., Results: After adjustment, patients with gout not treated with ULT had an increased risk of CVD mortality (HR 2.43, 95% CI 1.33-4.45) and all-cause mortality (1.45, 1.05-2.00) relative to the matched reference subjects (no gout, no ULT). Patients with gout treated with ULT had a lower risk of CVD (0.29, 0.11-0.80) and all-cause mortality (0.47, 0.29-0.79) relative to patients with gout not treated with ULT. This survival benefit persisted for users of either allopurinol or benzbromarone., Conclusion: Patients with gout who received ULT had significantly better survival rates than those who did not. Thus, undertreatment of gout has serious negative consequences.

Background: Allopurinol is the most commonly used urate-lowering therapy, with rare but potentially fatal adverse effects. However, its impact on overall mortality remains largely unknown. In this study, we evaluated the impact of allopurinol initiation on the risk of mortality among individuals with hyperuricaemia and among those with gout in the general population., Methods: We conducted an incident user cohort study with propensity score matching using a UK general population database. The study population included individuals aged ≥40 years who had a record of hyperuricaemia (serum urate level >357 μmol/L for women and >416 μmol/L for men) between January 2000 and May 2010. To closely account for potential confounders of allopurinol use and risk of death, we constructed propensity score matched cohorts of allopurinol initiators and comparators (non-initiators) within 6-month cohort accrual blocks., Results: Of 5927 allopurinol initiators and 5927 matched comparators, 654 and 718, respectively, died during the follow-up (mean=2.9 years). The baseline characteristics were well balanced in the two groups, including the prevalence of gout in each group (84%). Allopurinol initiation was associated with a lower risk of all-cause mortality (matched HR 0.89 (95% CI 0.80 to 0.99)). When we limited the analysis to those with gout, the corresponding HR was 0.81 (95% CI 0.70 to 0.92)., Conclusions: In this general population study, allopurinol initiation was associated with a modestly reduced risk of death in patients with hyperuricaemia and patients with gout. The overall benefit of allopurinol on survival may outweigh the impact of rare serious adverse effects., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Hyperuricaemia, the biochemical precursor to gout, has been shown to be an independent risk factor for mortality from cardiovascular disease (CVD), although studies examining the clinical phenomenon of gout and risk of CVD mortality report conflicting results. This study aimed to produce a pooled estimate of risk of mortality from cardiovascular disease in patients with gout., Design: Systematic review and meta-analysis., Methods: Electronic bibliographic databases were searched from inception to November 2012, with results reviewed by two independent reviewers. Studies were included if they reported data on CVD mortality in adults with gout who were free of CVD at time of entry into the study. Pooled hazard ratios (HRs) for this association were calculated both unadjusted and adjusted for traditional vascular risk factors., Results: Six papers, including 223,448 patients, were eligible for inclusion (all (CVD) mortality n = 4, coronary heart disease (CHD) mortality n = 3, and myocardial infarction mortality n = 3). Gout was associated with an excess risk of CVD mortality (unadjusted HR 1.51 (95% confidence interval, CI, 1.17-1.84)) and CHD mortality (unadjusted HR 1.59, 95% CI 1.25-1.94)). After adjusting for traditional vascular risk factors, the pooled HR for both CVD mortality (HR 1.29, 95% CI 1.14-1.44) and CHD mortality (HR 1.42, 95% CI 1.22-1.63) remained statistically significant, but none of the studies reported a significant association with myocardial infarction., Conclusions: Gout increases the risk of mortality from CVD and CHD, but not myocardial infarction, independently of vascular risk factors., (© The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Gout is the most common rheumatic disease in the adult population. Hypertension is one of the most common comorbidities of gout. The combination of hypertension with metabolic abnormalities is the great importance. In patients with hypertension the high uric acid is an independent predictor of increased risk of cardiovascular events (including fatal cardiac events), and overall mortality. The review considers the pathogenic mechanisms by which uric acid participate in the development and progression of cardiovascular diseases, including hypertension, and the analysis of antihypertensive therapy in patients with gout.

Objective: Gout is the most common cause of inflammatory arthritis in men, but has not previously been included in Global Burden of Disease (GBD) studies. As part of the GBD 2010 Study, the Musculoskeletal Disorders and Risk Factors Expert Group estimated the global burden of gout., Methods: The American Rheumatism Association 1977 case definition of primary gout was used in the study. A series of systematic reviews were conducted to gather the age-specific and sex-specific epidemiological data for gout prevalence, incidence, mortality risk and duration. Two main disabling sequelae of gout were identified; acute episode gout and chronic polyarticular gout, and used in the surveys to collect data to derive disability weights. The epidemiological data together with disability weights were then used to calculate years of life lived with disability (YLDs) for gout, for 1990 and 2010. No evidence of cause-specific mortality associated with gout was found. Gout disability-adjusted life years (DALYs), therefore, have the same value as YLDs., Results: Global prevalence of gout was 0.08% (95% uncertainty interval (UI) 0.07 to 0.08). DALYs increased from 76 000 (95% UI 48 to 112) in 1990 to 114 000 (95% UI 72 to 167) in 2010. Out of all 291 conditions studied in the GBD 2010 Study, gout ranked 138th in terms of disability as measured by YLDs, and 173rd in terms of overall burden (DALYs)., Conclusions: The burden of gout is rising. With increasing ageing populations globally, this evidence is a significant prompt to optimise treatment and management of gout at individual, community and national levels., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Introduction: Previous studies have shown an association between gout and/or hyperuricemia and a subsequent increase in cardiovascular disease (CVD) outcomes. Allopurinol reduces vascular oxidative stress, ameliorates inflammatory state, improves endothelial function, and prevents atherosclerosis progression. Accordingly, we tested the hypothesis that a positive association between allopurinol therapy in gout patients and future cardiovascular outcomes is present using a population-based matched-cohort study design., Methods: Patients aged ≥40 years with newly diagnosed gout having no pre-existing severe form of CVD were separated into allopurinol (n = 2483) and non-allopurinol (n = 2483) groups after matching for age, gender, index date, diabetes mellitus, hypertension, hyperlipidemia, and atrial fibrillation. The two groups were also balanced in terms of uric acid nephrolithiasis, acute kidney injury, hepatitis, and Charlson comorbidity index., Results: With a median follow-up time of 5.25 years, the allopurinol group had a modest increase in cardiovascular risk [relative risk, 1.20; 95% confidence interval (CI), 1.08-1.34]. A Cox proportional hazard model adjusted for chronic kidney disease, uremia, and gastric ulcer gave a hazard ratio (HR) for cardiovascular outcomes of 1.25 (95% CI, 1.10-1.41) in gout patients receiving allopurinol compared with the non-allopurinol group. In further analysis of patients receiving urate-lowering therapy, the uricosuric agent group (n = 1713) had an adjusted HR of 0.83 (0.73-0.95) for cardiovascular events compared with the allopurinol group., Conclusions: The current population-based matched-cohort study did not support the association between allopurinol therapy in gout patients with normal risk for cardiovascular sequels and beneficial future cardiovascular outcomes. Several important risk factors for cardiovascular disease, such as smoking, alcohol consumption, body mass index, blood pressure were not obtainable in the current retrospective cohort study, thus could potentially bias the effect estimate.

Background: While several studies have reported a link between the presence of gout and adverse cardiovascular (CV) events in the general population, none has addressed the question of whether the mortality risk of patients with gout is influenced by disease severity., Methods: We applied survival analysis methodology to prospectively collected data on clinical and radiographic measures of disease severity and mortality in a specialty clinic based cohort of 706 patients with gout (1992-2008). Standardised mortality ratios (SMR) were calculated to assess the magnitude of excess mortality among patients with gout compared with the underlying general population., Results: Mean follow-up was 47 months. Tophaceous deposition was present in 30.5% of patients; >4 joints were involved in 34.6% of cases. Mean annual flare rate was 3.4. Arterial hypertension (41.2%), hyperlipidaemia (42.2%), diabetes mellitus (20.1%), renal function impairment (26.6%) and a previous CV event (25.3%) were recorded. 64 (9.1%) patients died, death being attributed to vascular causes in 38 (59%) patients. SMR for gout patients was 2.37 (95% CI 1.82 to 3.03), 1.57 (1.18 to 2.05) and 4.50 (2.06 to 8.54) overall, and in men and women, respectively. The presence of tophi and the highest baseline serum urate (SU) levels were independently associated with a higher risk of mortality, in addition to age, loop diuretic use and a history of a previous vascular event. In the multivariable survival regression models, with time varying covariates, the presence of tophi remained a significant mortality risk after adjustment for baseline SU levels (1.98; 1.24 to 3.20)., Conclusions: High baseline SU level and the presence of subcutaneous tophi were both associated with an increased risk of mortality in patients with gout, in most cases attributed to a CV cause. This suggests a plausible pathophysiological link between greater total body urate load and CV disease.

Objectives: To describe the national demographics, comorbidities and mortality of admissions associated with gout in New Zealand (NZ) from 1999 to 2009 and compare this with English gout admission data from the same period., Methods: The characteristics of all admissions due to or complicated by gout in NZ from 1999 to 2009 were analysed. These findings were then compared with the wider NZ population and the English National Health Service (NHS) gout admission rates from 1999 to 2009., Results: There were 10 241 admissions due to gout (group A) and 34 318 admissions complicated by gout (group B) in NZ from 1999 to 2009. There were 32 741 admissions due to gout in England over the same period. Gout admissions rose at 5.5% per year in NZ and at 7.2% per year in England over the study period. NZ gout patients admitted to hospital were more likely to be Māori or a Pacific Islander and had 3-7 comorbidities. Multiple admissions were common with 1479 NZ gout patients admitted more than once. Comorbidities varied between the NZ groups A and B: hypertension (19-39%), renal disease (16-27%) and diabetes mellitus (20-27%) were common. Heart failure (27.6%) and cardiovascular disease (39.1%) were common in those who had gout complicating their hospital admission. This group also had poorer survival compared with those admitted primarily for gout., Conclusion: This is the first study to describe the epidemiology of admissions associated with gout across an entire country. Admissions are rising in both countries studied and those admitted in NZ have a high rate of comorbidity and re-admission.

Objectives: Whether the link between gout and mortality is causal or confounded by lifestyle factors or comorbidities remains unclear. Studies in Asia are warranted due to the rapid modernisation of the locale and ageing of the population., Methods: The association between gout and mortality was examined in a prospective cohort, the Singapore Chinese Health Study, comprising 63 257 Singapore Chinese individuals, aged 45-74 years during the enrolment period of 1993-8. All enrollees were interviewed in person on lifestyle factors, current diet and medical histories. All surviving cohort members were contacted by telephone during 1999-2004 to update selected exposure and medical histories (follow-up I interview), including the history of physician-diagnosed gout. Cause-specific mortality in the cohort was identified via record linkage with the nationwide death registry, up to 31 December 2009., Results: Out of 52 322 participants in the follow-up I interview, 2117 (4.1%) self-reported a history of physician-diagnosed gout, with a mean age at diagnosis of 54.7 years. After a mean follow-up period of 8.1 years, there were 6660 deaths. Relative to non-gout subjects, subjects with gout had a higher risk of death (HR 1.18; 95% CI 1.06 to 1.32), and specifically from death due to coronary heart disease (CHD) (HR 1.38, 95% CI 1.10 to 1.73) and kidney disease (HR 5.81, 95% CI 3.61 to 9.37). All gout-mortality risk associations were present in both genders but the risk estimates appeared higher for women., Conclusion: Gout is an independent risk factor for mortality, and specifically for death due to CHD and kidney disease.

Gout affects 1% to 2% of the population, and the prevalence is increasing due to changes in diet and the ageing of the population. Its development and risk factors have been explored frequently, and recommendations for the diagnosis and management of gout implemented. Nevertheless, there is a lack of knowledge regarding the long-term impact on gouty patients. This systematic review therefore evaluates the association between gout and all-cause as well as cardiovascular mortality. A systematic literature search was performed, and seven long-term studies were ultimately analyzed. Six of them used multivariate regressions to assess the adjusted mortality ratio in gouty patients with reference to patients without the disorder. Despite differences in study designs, study populations, and definitions of gout, the results were consistent: There was an independent association between gout and all-cause as well as cardiovascular mortality. Knowing that patients with gout are at risk emphasizes the need for adequate care.

Aim: To assess survival and lethal outcome risk fahctors in gout patients., Material and Methods: The study included 286 gout patients (246 males, 86% and 49 females, 14%) treated for gout in the Research Institute of Rheumatology from 2001 to 2006. From 2010 to May 2011 a telephone survey was made to obtain information about death of the above examinees. After the survey clinical condition of the dead patients was compared to that of survivors., Results: Of 286 participants of the trial, 38 did not response. By information from the relatives, there were 31 (12.5%) lethal outcomes of 248 patients. A cause of death in 20 patients, irrespective of age, were cardiovascular complications, 6 patients died of cancer; one patient--of chronic renal failure, one--of infection, one--of trauma and 2 - of unknown cause. Median of age at death was 62.1 years, median of gout duration--12.8 years. 65% of the deceased patients had risk factors of cardiovascular complications (type 2 diabetes mellitus, coronary heart disease, acute myocardial infarction, stroke, chronic cardiac failure). Median of time since examination in the clinic to death was 4.3 years., Conclusion: Gout patients' mortality is high. 7-year survival was 85% in high overall mortality. 2/3 patients died of cardiovascular diseases. Survival of gout patients with normuricemia is the same ofthose with hyperuricemia. A high level of highly sensitive CRP is a factor of poor prognosis (death) for gout patients.

Objectives: Accumulating evidence suggests that gout is associated with increased overall and cardiovascular mortality. Using data from a large consecutive cohort of gout sufferers who were followed for 8 years, we investigated mortality among gout sufferers and compared the results with data from the general population of Taiwan., Methods: The study comprised 6631 people who had gout diagnosis at outpatient department of the Chang Gung Memorial Hospital in 2000. Survival status and cause of death were ascertained by examining the National Death Registry of Taiwan through 2008., Results: During 53,048 person-years of follow-up in 6631 gout patients, 1273 (male, 941; female, 332) deaths were identified, corresponding to the crude mortality rate was 21.3 (male, 20.0; female, 26.1) per 1000 patient-years, which was significantly higher than that of the national population. As compared with the national population of Taiwan in 2000, the all-cause standardized mortality ratio (95% confidence interval) was 1.29 (1.21-1.37) for men and 1.70 (1.53-1.89) for women. Both men and women in this cohort had higher standardized mortality ratios for death due to kidney diseases (men, 3.10; women, 3.54), endocrine and metabolic diseases (men, 2.24; women, 2.71), and cardiovascular diseases (men, 1.58; women, 1.81). Multivariate Cox regression showed no difference in mortality between genders., Discussion/conclusions: Individuals with gout have increased mortality risk in both sexes; however, the extent of risk increment is higher in women. Kidney diseases, endocrine and metabolic diseases, and cardiovascular diseases are primary causes of death., (Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Background: Gout is a common inflammatory arthritis that affects ∼4% of the US population. Most patients with gout are >50 years of age and have multiple comorbidities. Gout is caused by the deposition of monosodium urate crystals in joints secondary to hyperuricemia. Gout typically presents as an acute painful inflammation (flare) involving one or more joint. Left untreated it can progress into a more chronic polyarthritis. Acute gout flare treatment options include colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), and corticosteroids. The safety and efficacy of colchicine, especially in the presence of comorbidity and potential contraindications, has only recently been systematically investigated., Methods: Through the use of a systematic computer-based literature analysis, this pharmacoeconomic review evaluated costs, risks, and benefits of Colcrys (colchicine) compared with other treatments for gout in the US., Results: Both colchicine and NSAIDs are historically associated with gastrointestinal (GI) adverse events (AEs). Colchicine has very low risk for AEs, even in patients with GI disorders; whereas, NSAIDS are contraindicated in patients with GI disorders, renal insufficiency, and heart failure. The monthly cost of treating 100 patients with Colcrys was $33,100 compared with $3000 for NSAIDs. However, hospitalization for GI complications (1.8%) and heart failure (1.9%) is common with NSAIDs and can increase the monthly cost of treating 100 patients with NSAIDs to $161,000, considering $15,000-20,000 per day of hospitalization., Conclusions: Considering high costs associated with treating patients with gout, it seems prudent to choose the treatment with greatest benefit, lowest cost, and least risk. Despite higher cost per dose, colchicine appears to be more cost effective for management of gout flares than NSAIDs.

Aims: To characterize patients with urate measurements by urate-lowering therapy (ULT) use and to study the impact of allopurinol treatment on cardiovascular and mortality outcomes., Methods: A cohort study using a record-linkage database. The study included 7135 patients aged ≥60 years with urate measurements between 2000 and 2002 followed up until 2007. A Cox regression model was used. The association between urate levels, dispensed allopurinol and cardiovascular hospitalization and mortality was determined., Results: Six thousand and forty-two patients were not taking ULT and 45.9% of those (2774 of 6042) had urate concentrations ≤6 mg dl(-1) . Among 1035 allopurinol users, 44.7% (45.6% for men and 43.3% for women) reached target urate concentration. There was no significant increased risk of cardiovascular events for allopurinol users when compared with non-ULT users [adjusted hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.95-1.26] and the non-ULT group with urate >6 mg dl(-1) (adjusted HR 1.07, 95% CI 0.89-1.28). Within the allopurinol use cohort, cardiovascular event rates were 74.0 (95% CI 61.9-86.1) per 1000 person years for the 100 mg group, 69.7 (49.6-89.8) for the 200 mg group and 47.6 (38.4-56.9) for the ≥300 mg group. Compared with low-dose (100 mg) users, high-dose (≥300 mg) users had significant reductions in the risk of cardiovascular events (adjusted HR 0.69, 95% CI 0.50-0.94) and mortality (adjusted HR 0.75, 95% CI 0.59-0.94)., Conclusions: Less than 50% of patients taking allopurinol reached target urate concentration. Higher doses of allopurinol were associated with better control of urate and lower risks of both cardiovascular events and mortality., (© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.)

Objective: The relation of gout and hyperuricaemia to cardiovascular diseases has been well documented. This study investigates the survival impact of both gout and hyperuricaemia., Methods: The subjects of this study comprised participants of a health screening programme conducted by the Chang Gung Memorial Hospital in Taiwan from 2000 to 2006. The status and causes of death were ascertained by the Taiwan National Death Registry 2000-07. Cox proportional hazard model was performed to examine the association., Results: Among 61 527 subjects, 1383 deaths (198 cardiovascular deaths) were identified, corresponding to a crude mortality rate of 4.86 deaths per 1000 person-years. Crude mortality rates were 4.50, 5.61 and 10.46 deaths per 1000 person-years for subjects with normouricaemia, hyperuricaemia and gout, respectively. Compared with subjects with normouricaemia, the hazard ratios (HRs) of all-cause mortality were 1.46 (95% CI 1.12, 1.91) for individuals with gout and 1.07 (95% CI 0.94, 1.22) for those with hyperuricaemia, respectively, after adjustments were made for age, sex, component number of metabolic syndrome and proteinuria. The adjusted HRs of cardiovascular mortality were 1.97 (95% CI 1.08, 3.59) for individuals with gout and 1.08 (95% CI 0.78, 1.51) for those with hyperuricaemia. Moreover, the risk of all-cause or cardiovascular mortality for gout remained unchanged when limiting the data to those with an estimated glomerular filtration of >60 ml/min/1.73 m(2)., Conclusion: This study demonstrates a link of gout, not hyperuricaemia, with a higher risk of death from all causes and cardiovascular diseases.

Objectives: While studies have suggested that gout and hyperuricaemia are associated with the risk of premature death, none has investigated the role of urate-lowering therapy on this critical outcome. We examined the impact of allopurinol, the most commonly used urate-lowering drug, on the risk of mortality in hyperuricaemic patients., Methods: From a population of hyperuricaemic veterans of [serum urate level >416 micromol/l (7.0 mg/dl)] at least 40 years of age, we compared the risk of death between incident allopurinol users (n = 2483) and non-users (n = 7441). We estimated the multivariate mortality hazard ratio (HR) of allopurinol use with Cox proportional hazards models., Results: Of the 9924 veterans (males, 98% and mean age 62.7 years), 1021 died during the follow-up. Patients who began treatment with allopurinol had worse prognostic factors for mortality, including higher BMI and comorbidities. After adjusting for baseline urate levels, allopurinol treatment was associated with a lower risk of all-cause mortality (HR 0.78; 95% CI 0.67, 0.91). Further adjustment with other prognostic factors did not appreciably alter this estimate (HR 0.77; 95% CI 0.65, 0.91). The mean change from baseline in serum urate within the allopurinol group was -111 micromol/l (-1.86 mg/dl). Adjusting for baseline urate level, allopurinol users had a 40 micromol/l (0.68 mg/dl) lower follow-up serum urate value than controls (95% CI -0.55, -0.81)., Conclusion: Our findings indicate that allopurinol treatment may provide a survival benefit among patients with hyperuricaemia.

Multiple epidemiologic studies confrm an association between hyperuricemia and cardiovascular disease (CVD), but it remains uncertain whether hyperuricemia is an independent or dependent risk factor for CVD. The question is particularly complex since patients with gout frequently have multiple comorbid conditions and adjusting for these conditions tends to reduce the strength of hyperuricemia as a risk factor. In this article, we review the data supporting a possible independent role for hyperuricemia in CVD. A close reading of the literature suggests that hyperuricemia may be both an independent and dependent risk factor, and is more likely to act as an independent risk factor in blacks, women, and patients with high risk for CVD. We also review the literature that suggests that hyperuricemia may directly contribute to the development of a number of comorbid conditions that in turn contribute to CVD risk (e.g., hypertension, glucose intolerance, renal insuffciency, and adiposity), suggesting that adjusting studies for these risk factors may be biologically inappropriate. Finally, we review the limited literature addressing the question of whether gout per se, above and beyond the presence of hyperuricemia, may convey an additional independent CVD risk. Given the ready ability of physicians to pharmacologically manage serum urate levels, a better understanding of the interaction between hyperuricemia, gout and vascular disease may be critical for the reduction of morbidity and mortality in high-risk CVD patients.

This review provides an update on the most recent data on mortality in people with gout. A large prospective study among men found that those with gout have a higher risk of death from all causes. Among men who did not have pre-existing coronary heart disease, the increased mortality risk is due primarily to an elevated risk of cardiovascular death, particularly from coronary heart disease. Also, an extension study of a large clinical trial among men with above-average risk for coronary heart disease found that a diagnosis of gout accompanied by an elevated uric acid level is associated with increased long-term (approximately 17 years) risk of all-cause mortality that arises largely from an increased risk of cardiovascular disease (CVD) mortality. Although limited, these emerging data suggest that men with gout have a higher risk of death from all causes and the increased mortality risk is primarily due to an elevated risk of CVD death. These findings would provide support for the aggressive management of cardiovascular risk factors in men with gout. More data that adjust comprehensively for various associated CVD markers are needed to reinforce this concept. Furthermore, given apparent potential sex differences in gout epidemiology and its risk factors, prospective studies specifically among women would be valuable.

Background: Although gout and hyperuricemia are related to several conditions that are associated with reduced survival, no prospective data are available on the independent impact of gout on mortality. Furthermore, although many studies have suggested that hyperuricemia is associated with cardiovascular disease (CVD), limited data are available on the impact of gout on CVD., Methods and Results: Over a 12-year period, we prospectively examined the relation between a history of gout and the risk of death and myocardial infarction in 51,297 male participants of the Health Professionals Follow-Up Study. During the 12 years of follow-up, we documented 5825 deaths from all causes, which included 2132 deaths from CVD and 1576 deaths from coronary heart disease (CHD). Compared with men without history of gout and CHD at baseline, the multivariate relative risks among men with history of gout were 1.28 (95% confidence interval [CI], 1.15 to 1.41) for total mortality, 1.38 (95% CI, 1.15 to 1.66) for CVD deaths, and 1.55 (95% CI, 1.24 to 1.93) for fatal CHD. The corresponding relative risks among men with preexisting CHD were 1.25 (95% CI, 1.09 to 1.45), 1.26 (95% CI, 1.07 to 1.50), and 1.24 (95% CI, 1.04 to 1.49), respectively. In addition, men with gout had a higher risk of nonfatal myocardial infarction than men without gout (multivariate relative risk, 1.59; 95% CI, 1.04 to 2.41)., Conclusions: These prospective data indicate that men with gout have a higher risk of death from all causes. Among men without preexisting CHD, the increased mortality risk is primarily a result of an elevated risk of CVD death, particularly from CHD.