Objective: To provide guidance for the management of gout, including indications for and optimal use of urate‐lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations.Methods: Fifty‐seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta‐analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional.Results: Forty‐two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first‐line ULT, including for those with moderate‐to‐severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat‐to‐target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3–6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended.Conclusion: Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.

Objective: A novel rodent model and a recent randomized trial of hyperuricemic adolescents with hypertension suggest a pathogenetic role of uric acid in hypertension, but it remains unknown whether these findings would be applicable to adult populations where the larger disease burden exists. We conducted a systematic review and meta‐analysis to determine if hyperuricemia was associated with incident hypertension, particularly in various demographic subgroups.Methods: We searched major electronic databases using medical subject headings and keywords without language restrictions (through April 2010). We included prospective cohort studies with data on incident hypertension related to serum uric acid levels. Data abstraction was conducted in duplicate. We analyzed age, sex, and race subgroups.Results: A total of 18 prospective cohort studies representing data from 55,607 participants were included. Hyperuricemia was associated with an increased risk for incident hypertension (adjusted risk ratio [RR] 1.41, 95% confidence interval [95% CI] 1.23–1.58). For a 1 mg/dl increase in uric acid level, the pooled RR for incident hypertension after adjusting for potential confounding was 1.13 (95% CI 1.06–1.20). These effects were significantly larger in younger study populations (P = 0.02) and tended to be larger in women (P = 0.059). Two studies suggested that the effect may also be larger among African American individuals. Furthermore, later publication year and US‐based studies were significantly associated with a lower effect estimate (P values <0.02).Conclusion: Hyperuricemia is associated with an increased risk for incident hypertension, independent of traditional hypertension risk factors. This risk appears more pronounced in younger individuals and women.

Objective: The role of serum uric acid as an independent risk factor for cardiovascular disease remains unclear, although hyperuricemia is associated with cardiovascular disease such as coronary heart disease (CHD), stroke, and hypertension.Methods: A systematic review and meta‐analysis using a random‐effects model was conducted to determine the risk of CHD associated with hyperuricemia in adults. Studies of hyperuricemia and CHD were identified by searching major electronic databases using the medical subject headings and keywords without language restriction (through February 2009). Only prospective cohort studies were included if they had data on CHD incidences or mortalities related to serum uric acid levels in adults.Results: Twenty‐six eligible studies of 402,997 adults were identified. Hyperuricemia was associated with an increased risk of CHD incidence (unadjusted risk ratio [RR] 1.34, 95% confidence interval [95% CI] 1.19–1.49) and mortality (unadjusted RR 1.46, 95% CI 1.20–1.73). When adjusted for potential confounding, the pooled RR was 1.09 (95% CI 1.03–1.16) for CHD incidence and 1.16 (95% CI 1.01–1.30) for CHD mortality. For each increase of 1 mg/dl in uric acid level, the pooled multivariate RR for CHD mortality was 1.12 (95% CI 1.05–1.19). Subgroup analyses showed no significant association between hyperuricemia and CHD incidence/mortality in men, but an increased risk for CHD mortality in women (RR 1.67, 95% CI 1.30–2.04).Conclusion: Hyperuricemia may marginally increase the risk of CHD events, independently of traditional CHD risk factors. A more pronounced increased risk for CHD mortality in women should be investigated in future research.

Objective: To provide guidance for the management of gout, including indications for and optimal use of urate‐lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations.Methods: Fifty‐seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta‐analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional.Results: Forty‐two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first‐line ULT, including for those with moderate‐to‐severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat‐to‐target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3–6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended.Conclusion: Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.

Objective: To assess the association between hyperuricemia and risk of stroke incidence and mortality because hyperuricemia is hypothesized to be a risk factor for stroke and other cardiovascular disease, but, to date, results from observational studies are conflicting.Methods: A systematic review and meta‐analysis were conducted. Studies were identified by searching major electronic databases using the Medical Subject Headings and keywords without restriction in languages. Prospective cohort studies were included only if they contained data on stroke incidences or mortalities related to serum uric acid levels in adults. Pooled risk ratios (RRs) for the association of stroke incidence and mortality with serum uric acid levels were calculated.Results: A total of 16 studies including 238,449 adults were eligible and abstracted. Hyperuricemia was associated with a significantly higher risk of both stroke incidence (6 studies; RR 1.41, 95% confidence interval [95% CI] 1.05, 1.76) and mortality (6 studies; RR 1.36, 95% CI 1.03, 1.69) in our meta‐analyses of unadjusted study estimates. Subgroup analyses of studies adjusting for known risk factors such as age, hypertension, diabetes mellitus, and cholesterol still showed that hyperuricemia was significantly associated with both stroke incidence (4 studies; RR 1.47, 95% CI 1.19, 1.76) and mortality (6 studies; RR 1.26, 95% CI 1.12, 1.39). The pooled estimate of multivariate RRs did not differ significantly by sex.Conclusion: Hyperuricemia may modestly increase the risks of both stroke incidence and mortality. Future research is needed to determine whether lowering uric acid level has any beneficial effects on stroke.