Association of Chronic Kidney Disease With Allopurinol Use in Gout Treatment.

Importance: Clinicians are often cautious about use of allopurinol in patients with gout when renal function declines. Objective: To assess the association of allopurinol use in gout with the risk of developing chronic kidney disease stage 3 or higher. Design, Setting, and Participants: A time-stratified propensity score-matched, population-based, prospective cohort study of individuals with newly diagnosed gout who initiated allopurinol (≥300 mg/d) compared with those who did not initiate allopurinol, using the Health Improvement Network (THIN), a United Kingdom general practitioner electronic health records database, was carried out. The data were analyzed using Cox proportional hazards regression. Among adults aged 18 to 89 years with newly diagnosed gout, we propensity score matched 4760 initiators of allopurinol (≥300 mg/d) to the same number of noninitiators of allopurinol, excluding those with chronic kidney disease stage 3 or higher or urate-lowering therapy use before their gout diagnosis. Exposures: Allopurinol initiation at a dose of 300 mg or more per day. Main Outcomes and Measures: Development of chronic kidney disease stage 3 or higher. Results: Of the 4760 allopurinol initiators (3975 men, 785 women) and same number of noninitiators (3971 men, 789 women), 579 and 623, respectively, developed chronic kidney disease stage 3 or higher, with a mean follow-up time of 5 and 4 years, mean age of 57 years, and mean body mass index (calculated as weight in kilograms divided by height in meters squared) of 30 for both groups. Use of allopurinol of at least 300 mg/d was associated with lower risk of developing chronic kidney disease stage 3 or higher compared with nonusers, with a hazard ratio (HR) of 0.87 (95% CI, 0.77-0.97). Allopurinol initiation at less than 300 mg/d was not associated with renal function decline (HR, 1.00; 95% CI, 0.91-1.09). Conclusions and Relevance: In this large cohort, allopurinol initiation of at least 300 mg/d was associated with a lower risk of renal function deterioration. Because allopurinol does not appear to be associated with renal function decline, clinicians should consider evaluating other potential causes when patients with gout experience renal function decline.

Risk of myocardial infarction with use of selected non-steroidal anti-inflammatory drugs in patients with spondyloarthritis and osteoarthritis.

OBJECTIVES: Spondyloarthritis (SpA) is associated with an increased risk of myocardial infarction (MI) due to underlying inflammation and possibly due to medications such as certain non-steroidal anti-inflammatory drugs (NSAIDs). We sought to describe MI risk among patients with SpA who were prescribed NSAIDs, and to compare the pattern of risk in SpA with that in osteoarthritis (OA). METHODS: Nested case-control studies were performed using The Health Improvement Network (THIN). Underlying cohorts included adults with incident SpA or OA who had >1 NSAID prescription and no history of MI. Within each cohort, we matched each MI case to four controls without MI. NSAID use was categorised as: (a) current (prescription date 0-180 days prior to index date), (b) recent (181-365 days) or (c) remote (>365 days). We performed conditional logistic regression to compare the odds of current or recent NSAID use relative to remote use of any NSAID, considering diclofenac and naproxen specifically. RESULTS: Within the SpA cohort of 8140 and the OA cohort of 244 339, there were 115 and 6287 MI cases, respectively. After adjustment, current diclofenac use in SpA was associated with an OR of 3.32 (95% CI 1.57 to 7.03) for MI. Naproxen was not associated with any increase (adjusted OR 1.19, 95% CI 0.53 to 2.68). A ratio of ORs for SpA/diclofenac relative to OA/diclofenac was 2.64 (95% CI 1.24 to 5.58). CONCLUSIONS: MI risk in SpA is increased among current users of diclofenac, but not naproxen. The MI risk with diclofenac in SpA appears to differ from that in OA.

Independent impact of gout on the risk of diabetes mellitus among women and men: a population-based, BMI-matched cohort study.

OBJECTIVE: Evidence on the potential independent impact of gout on the risk of diabetes is limited to a single study of men with a high cardiovascular risk profile. Our objective was to examine this relation in the general population, particularly among women. METHODS: We conducted a sex-stratified matched cohort study using data from The Health Improvement Network (THIN), an electronic medical records database representative of the UK general population. Up to five non-gout individuals were matched to each case of incident gout by year of birth, year of enrolment and body mass index (BMI). Multivariate HRs for incident diabetes were calculated after additionally adjusting for smoking, alcohol consumption, physician visits, comorbidities and medication use. RESULTS: Among 35 339 gout patients (72.4% men, mean age of 62.7 years), the incidence rates of diabetes in women and men were 10.1 and 9.5 cases per 1000 person-years, respectively, whereas the corresponding rates were 5.6 and 7.2 cases per 1000 person-years among 137 056 non-gout subjects. The BMI-matched univariate and multivariate HRs of diabetes were higher among women compared with those among men (1.71; 95% CI 1.51 to 1.93 vs 1.22; 95% CI 1.13 to 1.31) and (1.48; 95% CI 1.29 to 1.68 vs 1.15; 95% CI 1.06 to 1.24), respectively (p values for interaction <0.001). This sex difference persisted across age-specific subgroups. CONCLUSIONS: This general population-based study suggests that gout may be independently associated with an increased risk of diabetes and that the magnitude of association is significantly larger in women than in men.

Sleep Apnea and the Risk of Incident Gout: A Population-Based, Body Mass Index-Matched Cohort Study.

OBJECTIVE: Sleep apnea is associated with hyperuricemia owing to hypoxia-induced nucleotide turnover. We undertook this study to assess the relationship between incident sleep apnea and the risk of incident gout. METHODS: Using data from The Health Improvement Network in the UK, we identified individuals with a first-ever physician diagnosis of sleep apnea. For each patient with sleep apnea, up to 5 individuals without sleep apnea were matched by sex, age, birth year, and body mass index (within ±0.5 kg/m(2) ). We estimated the incidence rates of gout and examined the relationship between sleep apnea and the risk of incident gout using a Cox proportional hazards model, adjusting for potential confounders. In addition, we assessed the rate difference in gout due to sleep apnea using an additive hazard model. RESULTS: Among 9,865 patients with newly diagnosed sleep apnea and 43,598 matched individuals without sleep apnea, we identified 270 incident cases of gout over 1 year of followup, resulting in incidence rates of 8.4 per 1,000 person-years and 4.8 per 1,000 person-years, respectively. The crude and multivariable rate ratios of incident gout in patients with sleep apnea were 1.7 (95% confidence interval [95% CI] 1.3, 2.2) and 1.5 (95% CI 1.1, 2.1), respectively. The corresponding rate differences between patients with sleep apnea and the comparison cohort were 3.6 (95% CI 1.6, 5.6) and 2.8 (95% CI 0.7, 4.9) per 1,000 person-years. The effect of sleep apnea persisted across subgroups. CONCLUSION: This general population-based study indicates that sleep apnea is independently associated with an increased risk of incident gout. Future research should examine the potential benefits of correcting sleep apnea-induced hypoxia on the risk of hyperuricemia and gout flares.

Trajectories of gait speed predict mortality in well-functioning older adults: the Health, Aging and Body Composition study.

BACKGROUND: Although gait speed slows with age, the rate of slowing varies greatly. To date, little is known about the trajectories of gait speed, their correlates, and their risk for mortality in older adults. METHODS: Gait speed during a 20-m walk was measured for a period of 8 years in initially well-functioning men and women aged 70-79 years participating in the Health, Aging and Body Composition study. We described the trajectories of gait speed and examined their correlates using a group-based mixture model. Also risk associated with different gait speed trajectories on all-cause mortality was estimated using a Cox-proportional hazard model. RESULTS: Of 2,364 participants (mean age, 73.5 ± 2.9 years; 52% women), we identified three gait speed trajectories: slow (n = 637), moderate (n = 1,209), and fast decline (n = 518). Those with fast decline slowed 0.030 m/s per year or 2.4% per year from baseline to the last follow-up visit. Women, blacks, and participants who were obese, had limited knee extensor strength, and had low physical activity were more likely to have fast decline than their counterparts. Participants with fast decline in gait speed had a 90% greater risk of mortality than those with slow decline. CONCLUSION: Despite being well-functioning at baseline, a quarter of older adults experienced fast decline in gait speed, which was associated with an increased risk of mortality.