Association of serum 25-hydroxyvitamin D concentrations with all-cause and cause-specific mortality among individuals with gout and hyperuricemia.

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.

Allopurinol Initiation and All-Cause Mortality Among Patients With Gout and Concurrent Chronic Kidney Disease : A Population-Based Cohort Study.

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.

Crystal deposition measured with dual-energy computed tomography: association with mortality and cardiovascular risks in gout.

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.

Hyperuricemia and gout are associated with cancer incidence and mortality: A meta-analysis based on cohort studies.

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.

Assessment of Cardiovascular Risk in Older Patients With Gout Initiating Febuxostat Versus Allopurinol: Population-Based Cohort Study.

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.

Educational inequalities in all-cause and cause-specific mortality among people with gout: a register-based matched cohort study in southern Sweden.

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.

The net clinical benefits of febuxostat versus allopurinol in patients with gout or asymptomatic hyperuricemia - A systematic review and meta-analysis.

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).

Xanthine oxidase inhibitors for prevention of cardiovascular events: a systematic review and meta-analysis of randomized controlled trials.

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 (ORP = 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, I2 = 55%) and serious TCE (0.56, 0.36 to 0.86, I2 = 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.

Allopurinol initiation and all-cause mortality in the general population.

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.

Effect of allopurinol on all-cause mortality in adults with incident gout: propensity score-matched landmark analysis.

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.

[GOUT AND HYPERTENSION].

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.

The global burden of gout: estimates from the Global Burden of Disease 2010 study.

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.

Tophaceous gout and high level of hyperuricaemia are both associated with increased risk of mortality in patients with gout.

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.

Hyperuricemia and gout enhanced the risk of long-term mortality in hypertension: insights from the National Health and Nutrition Examination Survey 2007-2018.

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.

Association of C-reactive protein with all-cause and cause-specific mortality in people with gout.

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.

Hospital admissions associated with gout and their comorbidities in New Zealand and England 1999-2009.

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 Maori 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.

Gout Flares and Mortality After Sodium-Glucose Cotransporter-2 Inhibitor Treatment for Gout and Type 2 Diabetes.

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.

Mortality due to coronary heart disease and kidney disease among middle-aged and elderly men and women with gout in the Singapore Chinese Health Study.

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.