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Aim: To determine if the association between hyperuricaemia and poor outcomes in heart failure (HF) varies by chronic kidney disease (CKD)., Methods and Results: Of the 2645 systolic HF patients in the Beta-Blocker Evaluation of Survival Trial with data on baseline serum uric acid, 1422 had hyperuricaemia (uric acid ≥6 mg/dL for women and ≥8 mg/dL for men). Propensity scores for hyperuricaemia, estimated for each patient, were used to assemble a matched cohort of 630 pairs of patients with and without hyperuricaemia who were balanced on 75 baseline characteristics. Associations of hyperuricaemia with outcomes during 25 months of median follow-up were examined in all patients and in those with and without CKD (estimated glomerular filtration rate of <60 mL/min/1.73 m(2)). Hyperuricaemia-associated hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality and HF hospitalization were 1.44 (1.12-1.85, P = 0.005) and 1.27 (1.02-1.58, P = 0.031), respectively. Hazard ratios (95% CIs) for all-cause mortality among those with and without CKD were 0.96 (0.70-1.31, P = 0.792) and 1.40 (1.08-1.82, P = 0.011), respectively (P for interaction, 0.071), and those for HF hospitalization among those with and without CKD were 0.99 (0.74-1.33, P = 0.942) and 1.49 (1.19-1.86, P = 0.001), respectively (P for interaction, 0.033)., Conclusion: Hyperuricaemia has a significant association with poor outcomes in HF patients without CKD but not in those with CKD, suggesting that hyperuricaemia may predict poor outcomes when it is primarily a marker of increased xanthine oxidase activity, but not when it is primarily due to impaired renal excretion of uric acid.

Background: Serum uric acid may serve as a marker for the activation of oxidative stress and may therefore be a marker for subsequent cardiovascular events. Our goal was to assess the association of serum uric acid levels and the outcomes of patients who have undergone percutaneous coronary intervention (PCI)., Methods: We performed a retrospective cohort study of patients who underwent PCI between 1/1/2000 and 12/31/2007. Data were retrieved from the Cardiac Lab Interventional Clinical Database as well as the medical records. Outcomes of mortality as well as major adverse cardiac events (MACE) that include death, myocardial infarction (MI), and target vessel revascularization were obtained. There were 10,632 unique patients who had a PCI at the Mayo Clinic in Rochester and allowed use of their records for research. During this time, 1,916 had a uric acid measure within 2 years prior to the day of PCI., Results: Of the 1,916 patients in our cohort, 1,353 had normal uric acid levels and 563 had elevated uric acid. After multivariable analysis, there was a strong trend in association with follow-up mortality in patients with elevated uric acid (HR = 1.25, 95% CI 0.98-1.59, P = 0.07). The association with mortality or MI (HR = 1.15, 95% CI 0.93-1.43, P = 0.20) and the association with MACE (HR = 1.04, CI 0.86- 1.25, P = 0.71) were not significant., Conclusions: In a large single-center database with complete follow-up, elevated serum uric acid was associated with increased mortality in PCI patients. These data show a trend for uric acid in the pathophysiology of atherosclerotic coronary artery disease and highlight the need for further research.

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.

Aim: This study evaluated the impact of hyperuricemia (HUR) on outcome in patients with different types of impaired renal function (IRF) and acute myocardial infarction (AMI) treated invasively., Methods: Out of 3,593 consecutive AMI patients treated invasively, 1,015 IRF patients were selected. The IRF group consisted of patients with baseline kidney dysfunction (BKD group) and/or patients with contrast-induced nephropathy (CIN group). HUR was defined as a serum uric acid concentration (SUAC) >420 μmol/l (>7 mg/dl). Independent predictors of death and major adverse cardiovascular events (MACE) were selected by the multivariate Cox-regression model., Results: Remote mortality rates were higher in HUR patients: IRF (32.7 vs. 18.6%), BKD (41.3 vs. 25.9%), CIN (35.4 vs. 16.7%); all p < 0.001. HUR was an independent predictor of death in BKD (hazard ratio (HR) 1.38, p < 0.05). Each 100-μmol/l increase in SUAC was associated with a significant increase of HR for mortality: 1.087 in IRF patients, 1.108 in BKD patients, 1.128 in CIN patients; all p < 0.05. Remote major adverse cardiovascular event rates were higher in HUR patients: IRF (55.4 vs. 48.9%), CIN (56.8 vs. 48%); both p < 0.05., Conclusions: In AMI patients treated invasively, an increase in SUAC is an independent predictor of death within all types of renal dysfunction; HUR defined as SUAC >420 μmol/l (>7 mg/dl) is a predictor only in BKD patients., (Copyright © 2010 S. Karger AG, Basel.)

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.

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.

Background: The association of elevated serum uric acid (UA) with cardiovascular events in patients with severe coronary artery stenosis was examined., Methods and Results: Patients with stenosis > or = 75% (n=8,832) were followed for "all events" (cardiovascular events and all-cause mortality) for 3 years. The group was divided into quartiles based on baseline UA level. The incidence rate of all events was significantly different among quartiles (58.3, 56.5, 61.2, 76.3/1,000 patients-year, P<0.001). Cox's proportional hazard regression analysis showed that the hazard ratio (HR) for all events was 1.25 [95% confidence interval (CI): 1.07-1.45, P<0.01] in the highest quartile (UA > or = 6.8 mg/dl). The group in which UA increased > or = 1.0 mg/dl after 6 months had significantly higher cardiovascular events rate than the group in which UA did not change (70.6 vs 58.8/1,000 patients-year, P=0.042). Propensity score matching was performed and 4,206 patients were divided into the highest quartile and the rest. High UA remained an independent predictor of all events (HR 1.25, 95%CI 1.06-1.43). However, no significant difference was observed between the group with increased UA > or = 1.0 mg/dl and the group with unchanged UA level., Conclusions: Elevated UA is an independent predictor of cardiovascular events and all-cause mortality combined in patients with coronary artery stenosis.

Background: Hyperuricemia is a prevalent condition in chronic heart failure (CHF), describing increased oxidative stress and inflammation. Although there is evidence that serum uric acid (UA) predicts mortality in CHF, its role as a prognostic biomarker in acute heart failure (AHF) has not yet been well assessed. The aim of this study was to determine if UA levels predict all-cause mortality. Additionally, as a secondary endpoint we sought the clinical predictors of UA serum level in this population., Methods: We analyzed 560 consecutive patients with AHF admitted in a single university center. UA (mg/dl) was measured during early hospitalization. Patient survival status was followed up after discharge (median follow-up: 330 days). The independent association of UA level with all-cause mortality was analyzed using Cox regression analysis., Results: During follow-up 165 (29.5%) deaths were identified. Patients with UA levels above the median value (>or=7.7 mg/dl) exhibited higher mortality rates (21.1 vs. 37.9%; p<0.001). In multivariable analysis, after adjusting for recognized prognostic factors and potential confounders, UA>or=7.7 mg/dl and per change in 1 mg/dl of UA was associated with an increased risk of mortality (HR 1.45, CI 95%=1.03-2.44; p=0.03 and HR 1.08, CI 95%=1.01-1.15; p=0.03, respectively)., Conclusion: UA serum levels is an independent predictor of all-cause mortality in an unselected patients admitted with AHF.

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.

Background: Hyperuricemia has been proposed as a risk marker in chronic heart failure, but its value as an independent prognostic is not well established., Aim: To determine the prognostic value of hyperuricemia, in patients with chronic stable heart failure., Patients and Methods: Forty six male patients with chronic heart failure, aged 62 +/- 13 years, were studied. Their election fraction was less than 40% and their serum creatinine was less than 2 mg/dl. Serum uric acid and catecholamines, maximal oxygen consumption (VO2 max) and left ventricular ejection fraction were measured. Mortality and the need for cardiac transplant were recorded as endpoints during a mean follow up of 39 +/- 18 months. The relationship between basal measures and the occurrence of events was analyzed using univariate and multivariate methods., Results: Basal VO2 max and left ventricular ejection fraction were 16 +/- 4.6 ml/kg/min and 22 +/- 7% respectively. Eighteen patients died and three required transplantation during the follow up. Patients reaching these endpoints had a lower VO2 max and left ventricular ejection fraction and higher uric acid levels. Multivariate analysis accepted left ventricular ejection fraction (relative risk 0.89, 95% CI 0.82-0.97) and serum uric acid (relative risk 1.335 95% CI 1.02-1.74) as significant predictors of events. The relative risk for cardiac transplantation was 7.07 times higher among those with a serum uric acid over 7 mg/dl., Conclusions: A high serum uric acid is an independent predictor of bad prognosis in patients with stable chronic heart failure.