Gout patients were included on the index date of a SUA measurement 6.8 mg/dl. patients we utilized for these analyses. Interested individuals may see https://www.optum.com/solutions/prod-nav/product-data.html for more information on accessing Optum data. The programming code for conducting data analysis in an analytic cohort is usually available through Harvard Dataverse (doi:10.7910/DVN/CPB8DP). Abstract Objective Gout patients have a high burden of co-morbid conditions including diabetes mellitus (DM), chronic kidney disease (CKD), and cardiovascular disease (CVD). We sought to evaluate the association between changes in serum uric acid (SUA) levels over time and the risk of incident DM, CVD, and renal function decline in gout patients. Methods An observational cohort study was conducted among enrollees of private health insurance programs in the US between 2004 and 2015. Gout patients were included on the index date of a SUA measurement 6.8 mg/dl. The exposure of interest was cumulative change in SUA levels from baseline. Hazard ratios (HR) and 95% confidence intervals (CI) for incident DM, incident CVD, and renal function decline (30% reduction in glomerular filtration rate) were derived using marginal structural models with stabilized inverse probability weights accounting for baseline confounders (age, gender, co-morbidities, co-medications) and time-varying confounders (serum creatinine, blood urea nitrogen, glycated hemoglobin). Results Among 26,341 patients with gout, the average age was 62, 75% were men, and the median baseline SUA was 8.6 mg/dl (interquartile range 7.7 to 9.5). The incidence rates/100 person-years (95% CI) were 1.63 (1.51C1.75) for DM, 0.77 (0.70C0.84) for CVD, and 4.32 (4.14C4.49) for renal function decline. The adjusted HR (95% CI) per 3 mg/dl reduction in SUA, corresponding on average to achieving the target level of 6 mg/dl in this populace, was 1.04 (0.92C1.17) for DM, 1.07 (0.89C1.29) for CVD, and 0.85 (0.78C0.92) for renal function decline. Conclusions Reduction in SUA in patients with gout may be associated with a reduced risk of renal function decline, but not with DM or CVD. Introduction Gout is the most common inflammatory arthritis affecting approximately 8.3 million Americans, and the incidence is increasing over time.[1C4] Acute gout is usually triggered by uric acid crystallization within the joints and lowering serum uric acid to subsaturating levels (6.8 mg/dl) to prevent crystal PSI-6206 deposition is the main approach of managing gout.[5] Many epidemiologic studies report that gout and hyperuricemia are associated with an increased risk of diabetes mellitus (DM), chronic kidney disease (CKD), cardiovascular disease (CVD) including myocardial infarction (MI) and stroke, and mortality.[6C14] Insight into managing the increased risk for these events is usually urgently needed to improve outcomes in patients with gout. Based on the consistently reported associations between high levels of serum uric acid and cardio-metabolic and renal events, it has been hypothesized that lowering the levels of serum uric acid in gout patients may reduce the excess risk of these events.[15, 16] However, the evidence directly testing this hypothesis is limited and conflicting. A majority of the evidence screening this hypothesis comes indirectly from studies suggesting a potential association between allopurinol, which is a urate lowering agent acting through inhibition of xanthine oxidase, and lowered risk of cardiovascular and renal events.[17C21] However, results from some other studies have observed no benefit of xanthine oxidase inhibitors on cardio-metabolic risks in gout.[22, 23] More recently, a large Mendelian randomization study observed no association between 28 single nucleotide polymorphisms known to regulate serum uric acid levels and DM, CVD, and heart failure, raising questions about the causal role of serum uric acid PSI-6206 in development of these events.[24] To add critical data to the ongoing debate of whether aggressively lowering serum uric acid in patient with gout can lower the risk PSI-6206 of future cardio-metabolic and renal events, we designed a large observational cohort study using a comprehensive database containing information on patients laboratory test results combined with their health insurance claims. The primary objective of our study was to evaluate the association between cumulative changes in serum uric acid levels over time and the risk of DM, CVD, and worsening of renal function in patients with gout. Material and methods Study design and data source An observational cohort study was conducted using de-identified data from.All the analyses were conducted using SAS 9.3 (SAS Institute, Cary, NC). Results Cohort selection We first identified 26,341 unique gout patients meeting all our inclusion criteria upon a recorded serum uric acid measurement of 6.8 mg/dl or higher. see https://www.optum.com/solutions/prod-nav/product-data.html for PSI-6206 more information on accessing Optum data. The programming code for conducting data analysis in an analytic cohort is available through Harvard Dataverse (doi:10.7910/DVN/CPB8DP). Abstract Objective Gout patients have PSI-6206 a high burden of co-morbid conditions including diabetes mellitus (DM), chronic kidney disease (CKD), and cardiovascular disease (CVD). We sought to evaluate the association between changes in serum uric acid (SUA) levels over time and the risk of incident DM, CVD, and renal function decline in gout patients. Methods An observational cohort study was conducted among enrollees of private health insurance programs in the US between 2004 and 2015. Gout patients were included on the index date of a SUA measurement 6.8 mg/dl. The exposure of interest was cumulative change in SUA levels from baseline. Hazard ratios (HR) and 95% confidence intervals (CI) for incident DM, incident CVD, and renal function decline (30% reduction in glomerular filtration rate) were derived using marginal structural models with stabilized inverse probability weights accounting for baseline confounders (age, gender, co-morbidities, co-medications) and time-varying confounders (serum creatinine, blood urea nitrogen, glycated hemoglobin). Results Among 26,341 patients with gout, the average age was 62, 75% were men, and the median baseline SUA was 8.6 mg/dl (interquartile range 7.7 to 9.5). The incidence rates/100 person-years (95% CI) were 1.63 (1.51C1.75) for DM, 0.77 (0.70C0.84) for CVD, and 4.32 (4.14C4.49) for renal function decline. The adjusted HR (95% CI) per 3 mg/dl reduction in SUA, corresponding on average to achieving the target level of 6 mg/dl in this population, was 1.04 (0.92C1.17) for DM, 1.07 (0.89C1.29) for CVD, and 0.85 (0.78C0.92) for renal function decline. Conclusions Reduction in SUA in patients with gout may be associated with a reduced risk of renal function decline, but not with DM or CVD. Introduction Gout is the most common inflammatory arthritis affecting approximately 8.3 million Americans, and the incidence is increasing over time.[1C4] Acute gout is triggered by uric acid crystallization within the joints and lowering serum uric acid to subsaturating levels (6.8 mg/dl) to prevent crystal deposition is the primary approach of managing gout.[5] Many epidemiologic studies report that gout and hyperuricemia are associated with an increased risk of diabetes mellitus (DM), chronic kidney disease (CKD), cardiovascular disease (CVD) including myocardial infarction (MI) and stroke, and mortality.[6C14] Insight into managing the increased risk for these events is urgently needed to improve outcomes in patients with gout. Based on the consistently reported associations between high levels of serum uric acid and cardio-metabolic and renal events, it has been hypothesized that lowering the levels of serum uric acid in gout patients may reduce the excess risk of these events.[15, 16] However, the evidence directly testing this hypothesis is limited and conflicting. A majority of the evidence testing this hypothesis comes indirectly from studies suggesting a potential association between allopurinol, which is a urate lowering agent acting through inhibition of xanthine oxidase, and lowered risk of cardiovascular and renal events.[17C21] However, results from some other studies have observed no benefit of xanthine oxidase inhibitors on cardio-metabolic risks in gout.[22, 23] More recently, a large Mendelian randomization study observed no association between 28 single nucleotide polymorphisms known to regulate serum uric acid levels and DM, CVD, and heart failure, raising questions about the causal role of serum uric acid in development of these events.[24] To add critical data to the ongoing debate of whether aggressively lowering serum uric acid in patient with gout can lower the risk of future cardio-metabolic and renal events, we designed a large observational cohort study using a comprehensive database containing information on patients laboratory test results combined with their health insurance claims. The primary objective of our study was to evaluate the association between cumulative changes in serum uric acid levels over time and the risk of DM, CVD, and worsening of renal function in patients with gout. Material and methods Study design and data source An observational cohort study was conducted using de-identified data from Rabbit polyclonal to AGAP9 Clinformatics ? Datamart (OptumInsight, Eden Prairie, MN) database for the period of January, 2004 to September, 2015. We used the subset of this database where health insurance claims data are combined with laboratory test results for enrollees.