Sex differences in the association of the uric acid to high-density lipoprotein cholesterol ratio with coronary artery disease risk among Chinese nondialysis patients with CKD stages 3-5.

BACKGROUND AND AIMS: Evidence has indicated that serum uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) are positively and negatively associated with coronary artery disease (CAD). The UA to HDL-C ratio (UHR) has recently drawn attention as a new predictor for metabolic syndrome, inflammation and atherosclerosis. However, the association between the UHR and CAD in nondialysis chronic kidney disease (CKD) patients is still unclear. METHODS AND RESULTS: We retrospectively analysed 733 733 nondialysis patients with CKD stage 3-5 who received their first coronary artery angiography (CAG), including 510 participants with CAD. All laboratory indicators were collected within one week before CAG. The median UHR of CAD and non-CAD patients was 15.52% and 12.29%, respectively. In multivariate analysis, female patients with a high UHR were 4.7 times more at risk of CAD than those with a lower UHR. Meanwhile, the positive association of the UHR with the severity of coronary artery stenosis (CAS) persisted significantly in female CAD subjects but not in males. In addition, receiver operating characteristic (ROC) curves were constructed for CAD and severe CAS. The area under the curve (AUC) for the UHR was higher than that for UA and HDL-C alone in female patients [UHR (AUC): 0.715 for CAD and 0.716 for severe CAS]. CONCLUSIONS: An elevated UHR was independently related to an increased CAD risk and the severity of CAS in nondialysis female patients with CKD stage 3-5, and was more predictive of the onset of CAD and the severity of CAS than UA or HDL-C alone.

Assessment of the relationship between serum uric acid levels and liver enzymes activity in Bangladeshi adults.

Serum uric acid (SUA) level has been suggested to be associated with cardiovascular disease, diabetes and metabolic syndrome. However, little is known about the relationship between SUA and liver enzymes activity in the general population. The present study aimed to assess the relationship between SUA and serum liver enzymes in an adult population in Bangladesh. In this cross-sectional study, a total of 410 blood samples were collected from apparently healthy adults aged > 18 years. SUA, liver enzymes, lipid profile and other biochemical markers were measured in the collected samples by using standard methods. Multinomial logistic regression model was used to assess the relationship between SUA and elevated levels of liver enzymes among the participants. Overall, the prevalence of hyperuricemia was 30.1% with 32.2% in male and 18.6% in female participants. About 33% of the participants had at least one or more elevated levels of liver enzymes. The mean level of SUA was significantly higher in males (389.3 ± 96.9 µmol/L) than in the female (290.4 ± 89.8 µmol/L) subjects (p < 0.001). There was a significant difference in the mean levels of serum ALT and GGT between the male (34.5 ± 16.0 U/L and 26.7 ± 19.5 U/L, respectively) and female (25.0 ± 13.0 U/L and 19.5 ± 13.2 U/L, respectively) participants (p < 0.001 and p < 0.01, respectively). An increasing trend was observed in the mean levels of serum ALT and GGT across the SUA quartile groups (p < 0.001 and p < 0.01, respectively). SUA showed a positive and significant correlation with serum ALT (p < 0.001) and GGT (p < 0.01). In further statistical analysis after adjustment for potential confounders, SUA showed an independent and significant association with serum ALT and GGT in all regression models. In conclusion, SUA was strongly associated with serum levels of ALT and GGT after adjustment for potential confounders. More prospective studies are needed to clarify the complex relationship between SUA and liver enzymes in the general population.

The application value of serum 25(OH)D3, uric acid, triglyceride, and homeostasis model assessment of insulin resistance in male patients with hyperuricemia combined with hypogonadism.

BACKGROUND: The purpose of this study was to investigate the application value of serum 25(OH)D3, uric acid, triglyceride (TG), and homeostasis model assessment of insulin resistance (HOMA-IR) in male patients with hyperuricemia combined with hypogonadism. METHODS: From August 2018 to August 2020, a total of 198 male patients with primary hyperuricemia were prospectively enrolled in our hospital for inpatient treatment in the department of Metabolism and Endocrinology. They are divided into normal gonadal function group (normal group, n = 117) and hypogonadal function group (hypogonadism group, n = 81), according to free testosterone (FT) level, International Index of Erectile Function (IIEF-5), and androgen deficiency in the aging male (ADAM) questionnaires. Laboratory indexes were compared between two groups. Multivariate logistic regression was applied to analyze the influencing factors of hypogonadism. RESULTS: Among the 198 hyperuricemia patients, 40.91 % were hypogonadism. Compared with the normal group, the BMI, waist circumference (WC), and the prevalence of non-alcoholic fatty liver disease (NAFLD), hyperlipidemia (HLP), and obesity (OB) in the hypogonadism group were higher, and the difference was statistically significant (P < 0.05, respectively). The levels of fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), triacylglycerol (TG), serum uric acid (SUA), alanine transaminase (ALT) of hypogonadism group were higher than those of normal group, while the levels of TT, FT, E2, 25(OH)D3 of hypogonadism group were lower than those of normal group (P < 0.05, respectively). Pearson's linear correlation was used to analyze the correlation between the indicators with significant differences in general data and laboratory indicators and hypogonadism. BMI, WC, HOMA-IR, TG, SUA, TT, FT, 25(OH)D3, E2 were positively correlated with hypogonadism (r = 0.556, 0.139, 0.473, 0.143, 0.134, 0.462, 0.419, 0.572, 0.601, P = 0.012, 0.027, 0.018, 0.019, 0.028, 0.029, 0.030, 0.009, 0.003, respectively). Taking the above indicators as independent variables and hypogonadism as the dependent variable, logistic regression analysis found that the risk factors for hypogonadism were SUA, WC, BMI, HOMA-IR, TG, TT, FT, E2, and 25(OH) D3. CONCLUSIONS: Serum 25(OH)D3, SUA, HOMA-IR, TG levels were positively correlated with male hyperuricemia patients with hypogonadism. They have important application value in the diagnosis of male hyperuricemia patients with hypogonadism.

Combining Model-Based Clinical Trial Simulation, Pharmacoeconomics, and Value of Information to Optimize Trial Design.

The Bayesian decision-analytic approach to trial design uses prior distributions for treatment effects, updated with likelihoods for proposed trial data. Prior distributions for treatment effects based on previous trial results risks sample selection bias and difficulties when a proposed trial differs in terms of patient characteristics, medication adherence, or treatment doses and regimens. The aim of this study was to demonstrate the utility of using pharmacometric-based clinical trial simulation (CTS) to generate prior distributions for use in Bayesian decision-theoretic trial design. The methods consisted of four principal stages: a CTS to predict the distribution of treatment response for a range of trial designs; Bayesian updating for a proposed sample size; a pharmacoeconomic model to represent the perspective of a reimbursement authority in which price is contingent on trial outcome; and a model of the pharmaceutical company return on investment linking drug prices to sales revenue. We used a case study of febuxostat versus allopurinol for the treatment of hyperuricemia in patients with gout. Trial design scenarios studied included alternative treatment doses, inclusion criteria, input uncertainty, and sample size. Optimal trial sample sizes varied depending on the uncertainty of model inputs, trial inclusion criteria, and treatment doses. This interdisciplinary framework for trial design and sample size calculation may have value in supporting decisions during later phases of drug development and in identifying costly sources of uncertainty, and thus inform future research and development strategies.

Economic Status Moderates the Association Between Early-Life Famine Exposure and Hyperuricemia in Adulthood.

CONTEXT: The double burden of malnutrition (DBM), undernutrition in early life and an obesogenic environment later on, influences later risk of chronic disorders. The Great Famine in China from 1959 to1962 and remarkable economic development from the 1980s provided such a burden for a large number of people in their 60s. OBJECTIVE: We aimed to analyze the effect of economic status on the association between famine exposure in early life and hyperuricemia in adulthood. DESIGN AND SETTING: Participants numbering 12 666 were enrolled in China based on the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) Study from 2014 to 2016. PARTICIPANTS: Participants with fetal or childhood famine exposure (birth year 1949-1962) formed the exposure group. MAIN OUTCOME MEASURE: Hyperuricemia was defined as uric acid (UA) > 420 µmol/L for men and > 360 µmol/L for women. The association of famine with hyperuricemia was assessed via regression analyses. RESULTS: Early-life famine exposure was negatively associated with UA levels (P = .045) but was not associated with hyperuricemia (P = .226) in the whole study population. Economic status could moderate the association of famine exposure with UA and hyperuricemia (P ≤ .001). In participants with high economic status, early-life famine exposure was positively associated with UA levels (unstandardized coefficients 7.61, 95% CI 3.63-11.59, P < .001), and with hyperuricemia (odds ratio 1.47, 95% CI 1.19-1.81, P < .001). CONCLUSIONS: Economic status could moderate the association between exposure to famine in early life and hyperuricemia in adulthood, indicating that the DBM might affect hyperuricemia in an opposite direction of the effects of undernutrition in early life alone.

Influence of post-disaster evacuation on incidence of hyperuricemia in residents of Fukushima Prefecture: the Fukushima Health Management Survey.

AIM: After the Great East Japan Earthquake, over 160,000 residents in Fukushima Prefecture were forced to evacuate the area around the Fukushima Daiichi power plant following nuclear accident there. Health problems in these evacuees have since become a major issue. We have examined the association between evacuation and incidence of hyperuricemia among residents in Fukushima. METHODS: We conducted a cohort study of residents aged 40-90 years without hyperuricemia at the time of the Fukushima disaster. Among 8173 residents who met the inclusion criteria before the disaster, 4789 residents (men: 1971, women: 2818; follow-up duration: 1.38 years; and follow-up rate: 58.6%) remained available for follow-up examinations at the end of March 2013. The main endpoint was incidence of hyperuricemia, defined by the Japanese committee guidelines, using local health data from before and after the disaster. We divided participants by evacuation status and compared outcomes between groups. Using a logistic regression model, we estimated the odds ratio for incidence of hyperuricemia, adjusting for potential confounders, age, gender, waist circumference, physical activity, and alcohol consumption. RESULTS: Incidence of hyperuricemia was higher in evacuees (men 10.1%; women 1.1%) than in non-evacuees (men 7.4%, women 1.0%). Evacuees had higher body mass index, waist circumference, triglycerides, LDL-cholesterol, fasting plasma glucose, HbA1c, and lower HDL-cholesterol after the disaster than non-evacuees. We found that evacuation was associated with incidence of hyperuricemia (adjusted odds ratio: 1.38; 95% confidence interval: 1.03-1.86). CONCLUSION: This is the first study to demonstrate an association between evacuation after a disaster and increased incidence of hyperuricemia.

Association between long-term prescription of febuxostat and the progression of heart failure with preserved ejection fraction in patients with hypertension and asymptomatic hyperuricemia.

Both hypertension and hyperuricemia are closely associated with the morbidity and mortality of heart failure. This study was designed to evaluate the influences of long-term xanthine oxidase inhibitor (febuxostat) prescription on left ventricular hypertrophy (LVH), left ventricular (LV) diastolic function, and new-onset heart failure with preserved ejection fraction (HFpEF) in these patients. Using a propensity score matching of 1:2 ratio, this retrospective claims database study compared febuxosatat prescription (n = 96) and non-urate-lowering therapy (n = 192) in patients with hypertensive left ventricular hypertrophy (LVH) and asymptomatic hyperuricemia. With a follow-up of 36 months, febuxostat significantly decreased the level of serum uric acid as well as generated more prominent improvement in LVH and LV diastolic function. Besides, the new-onset symptomatic HFpEF occurred in 2 of 96 patients in febuxostat group and 13 of 192 patients in non-urate-lowering group (P = 0.091). No increased risk for major adverse cardiovascular events in patients prescribed with febuxostat was noted. In conclusion, long-term febuxostat exposure was associated with protective effects in terms of LVH or LV diastolic dysfunction in patients with hypertensive LVH and asymptomatic hyperuricemia. Febuxostat also displayed a trend for reduced risk of new-onset HFpEF in this population.

Hyperuricemia is a Risk Factor for One-Year Overall Survival in Elderly Female Patients with Acute Coronary Syndrome.

BACKGROUND: Hyperuricemia is a risk factor for cardiovascular diseases, but the impact of hyperuricemia and sex-related disparities is not fully clear in elderly patients with acute coronary syndrome (ACS). OBJECTIVE: To investigate the association between hyperuricemia and 1-year all-cause mortality in elderly patients with ACS. METHODS: This retrospective cohort study included 711 consecutive ACS patients aged ≥75 years, hospitalized in our center between January 2013 and December 2017. Serum uric acid (sUA), in-hospital events, and 1-year follow-up were analyzed. Multivariable logistic regression models were used to explore the risk factors for in-hospital events and 1-year all-cause mortality. RESULTS: sUA levels were higher in males than in females (381.4 ± 110.1 vs. 349.3 ± 119.1 µmol/l, P < 0.001). Prevalence of hypertension (80.5% vs. 72.6%, P < 0.001). Prevalence of hypertension (80.5% vs. 72.6%, P < 0.001). Prevalence of hypertension (80.5% vs. 72.6%, P < 0.001). Prevalence of hypertension (80.5% vs. 72.6%, P < 0.001). Prevalence of hypertension (80.5% vs. 72.6%, P < 0.001). Prevalence of hypertension (80.5% vs. 72.6%, P < 0.001). Prevalence of hypertension (80.5% vs. 72.6%, P < 0.001). Prevalence of hypertension (80.5% vs. 72.6%, P < 0.001). Prevalence of hypertension (80.5% vs. 72.6%. CONCLUSIONS: Hyperuricemia is an independent risk factor for 1-year all-cause mortality in elderly female patients with ACS.

Cardiovascular events in hyperuricemia population and a cardiovascular benefit-risk assessment of urate-lowering therapies: a systematic review and meta-analysis.

BACKGROUND: Hyperuricemia and gout have become public health concerns; many important guidelines have recommended xanthine oxidase inhibitors (XOIs) as the first-line urate-lowering therapies (ULTs) to treat chronic gout with hyperuricemia. However, whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains controversial. The aim of this study was to assess the incident risk of cardiovascular (CV) events (CVE) in hyperuricemia population, assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk sub-groups, and specify the safety of different ULTs. METHODS: We searched PubMed, Embase, the Cochrane Library, Wanfang, Chongqing VIP (CQVIP, en.cqvip.com), and China National Knowledge Infrastructure Database for prospective cohort studies and randomized controlled trials (RCTs) in English and Chinese. Potential medications included XOIs, and uricosurics. RCTs were divided into sub-groups analysis based on blinding status and patients' history of CV diseases. Risk ratios (RRs) were calculated and were reported with corresponding 95% confidence intervals (CIs) by fixed-effects or random-effects model. RESULTS: Seven prospective cohort studies and 17 RCT studies were included. The risks of both major adverse cardiovascular events (MACE) (RR = 1.72, 95% CI 1.28-2.33) and CVE (RR = 1.35, 95% CI 1.12-1.62) were higher in the hyperuricemia population than non-hyperuricemia one. In seven RCT studies where XOIs were compared with no-treatment or placebo, the results of five low CV risk studies showed that XOIs lowered the risks of both MACE (RR = 0.35, 95% CI 0.20-0.62) and CVE (RR = 0.61, 95% CI 0.44-0.85); whereas two high CV risk studies showed that XOIs lowered the risk of CVE (RR = 0.69, 95% CI 0.54-0.88) rather than MACE (RR = 0.62, 95% CI 0.29-1.35). In nine RCT studies where the cardiovascular safety between febuxostat and allopurinol were compared, no statistical difference was found in the risk of MACE or CVE. CONCLUSIONS: The hyperuricemia population does have a higher incidence of CVE, and the results suggested that XOIs might reduce the incidence of MACE and total CVE. In addition, from the perspective of cardiovascular safety, febuxostat equaled allopurinol in our meta-analysis.

Salivary uric acid: Associations with resting and reactive blood pressure response to social evaluative stress in healthy African Americans.

High levels of uric acid are associated with greater risk of stress-related cardiovascular illnesses that occur disproportionately among African Americans. Whether hyperuricemia affects biological response to acute stress remains largely unknown, suggesting a need to clarify this potential connection. The current study examined how salivary uric acid (sUA) is associated with resting and reactive blood pressure - two robust predictors of hypertension and related cardiovascular disease and disparity. Healthy African Americans (N = 107; 32% male; M age = 31.74 years), completed the Trier Social Stress Test to induce social-evaluative stress. Systolic and diastolic blood pressure readings were recorded before, during, and after the task to assess resting and reactive change in blood pressure. Participants also provided a saliva sample at baseline that was assayed for sUA. At rest, and controlling for age, sUA was modestly associated with higher systolic (r = .201, p = .044), but not diastolic (r = .100, p = .319) blood pressure. In response to the stressor task, and once again controlling for age, sUA was also associated with higher total activation of both systolic (r = .219, p = .025) and diastolic blood pressure (r = .198, p < .044). A subsequent moderation analysis showed that associations between sUA and BP measures were significant for females, but not for males. Findings suggest that uric acid may be implicated in hypertension and cardiovascular health disparities through associations with elevated blood pressure responses to acute social stress, and that low levels of uric acid might be protective, particularly for females.

Ultrasonographic assessment of joint pathology in type 2 diabetes and hyperuricemia: The Fremantle Diabetes Study Phase II.

AIMS: The prevalence and consequences (articular and extra-articular) of hyperuricemia in type 2 diabetes, especially when asymptomatic (ASH), are incompletely understood. The aim of this study was to use ultrasonography to assess pathology associated with monosodium urate deposition in the joints of well-characterized hyperuricemic patients with type 2 diabetes. METHODS: A subset of 101 participants (mean age 70.4 years, 59.8% males, median diabetes duration 14.6 years) with hyperuricemia (fasting serum uric acid ≥0.42 mmol/L) from the community-based observational Fremantle Diabetes Study Phase II were assessed by ultrasound for signs of intra-articular urate deposition and inflammation in 14 joints at increased risk of involvement in patients with gout. RESULTS: Most participants had evidence of crystal deposition comprising aggregates (59.4%), tophi (19.8%) or a double contour sign (27.7%), and 37% had a power Doppler signal indicative of inflammation in at least one joint. There was no difference between the prevalence of these abnormalities in those with ASH (n = 60) versus participants with a history of gout (n = 41; P ≥ 0.15). There was no association between a history of ischemic heart disease (reported by 17.8% of participants) and either any abnormality on joint ultrasound or inflammatory changes assessed by power Doppler (P ≥ 0.41). CONCLUSIONS: Joint inflammation and/or urate deposition were present in the majority of community-based patients with type 2 diabetes and hyperuricemia regardless of whether there was a history of gout. Given the potential consequences of chronic inflammation for joint damage and extra-articular complications such as cardiovascular disease, these data have potential clinical implications.

Clinical features and CKD-related quality of life in patients with CKD G3a and CKD G3b in China: results from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE).

BACKGROUND: This study aimed to compare clinical features and health-related quality of life (HRQoL) in the Chinese chronic kidney disease (CKD) 3 population and determined the necessity of the subdivision of CKD3 in Chinese patients with CKD. METHODS: Participants with stage 3 CKD (18-74 years of age) were recruited at 39 clinical centers located at 28 cities in 22 provinces of China. The sociodemographic status, medical history, anthropometric measurements, and lifestyle behaviors were documented at entry, and blood and urine samples were collected. The estimated glomerular filtration rate was calculated using the CKD-EPI creatinine equation. The HRQoL was evaluated using the kidney disease quality-of-life instrument. A linear regression model was used to estimate the association between HRQoL and CKD stages (G3b vs G3a). RESULTS: The levels of intact parathyroid hormone, systolic blood pressure, uric acid, and high-density lipoprotein cholesterol were statistically significantly higher, whereas the levels of serum bicarbonate and hemoglobin were statistically significantly lower in the G3b group compared with the G3a group. Compared with CKD G3a group, the proportions of subjects with hyperuricemia and anemia were significantly higher in CKD G3b group (61.4% vs. 52.0% and 26.4% vs. 17.9%, respectively, P< 0.01). The HRQoL scores in "physical functioning (PCS)", "symptoms and problems", "effects of the kidney disease" and "burden of the kidney disease" were statistically significantly lower in the CKD G3b group compared with the CKD G3a group (90.88 ± 11.05 vs. 89.30 ± 11.52, 88.29 ± 11.94 vs. 86.49 ± 13.45, 55.86 ± 26.40 vs. 52.10 ± 27.64, 46.56 ± 8.16 vs. 44.51 ± 9.22, respectively, P< 0.01). Further, CKD G3b was associated with a lower score of physical functioning compared with G3a (regression coefficient =-1.12 [95%CI: -2.23, -0.16]). CONCLUSIONS: The preliminary results of this study suggested that modest differences existed in many important clinical features and KDQoL between patients with G3a and G3b CKD in a Chinese population. Also, a significant association between CKD3 subdivision of the disease and PCS was detected. Although further work is needed, we can speculate based on these results the CKD3 subdivision may be clinically meaningful for Chinese patients with CKD.

Assessment of subclinical left ventricular changes in essential hypertensive patients with hyperuricemia: A three-dimensional speckle-tracking echocardiography study.

OBJECTIVE: To evaluate the effect of hyperuricemia (HU) on subclinical changes of left ventricle (LV) function and structure in patients with hypertension (HT) using three-dimensional speckle-tracking echocardiography (3DSTE) and to explore the relationships between serum uric acid (SUA) levels and three-dimensional speckle tracking echocardiography (3DSTE) parameters in hypertensive and nonhypertensive patients with HU. METHODS: Four age- and sex-matched groups were studied: I: healthy controls, HT- HU- (n = 40); II: HT- HU+ (n = 40); III: HT+ HU- (n = 40); IV: HT+ HU+ (n = 44). Conventional echocardiography and 3DSTE were recorded. Relative wall thickness (RWT) and left ventricular mass index assessed by M-mode echocardiography (LVMi-M) were calculated. 3DSTE parameters including LV volumes and ejection fraction (EF), LVMi-3D, global longitudinal strain (GLS), and global circumferential strain (GCS) were compared. The relationships between SUA levels and 3DSTE parameters were investigated. RESULTS: Despite LV diameters, LV volumes and EF were similar among groups (all p > 0.05), GLS decreased and LVMi-3D increased from controls (group I) to patients with HU or HT alone (group II or III), and patients with both HU and HT (group IV) (all p < 0.05). SUA levels were significantly correlated with the absolute value of GLS (r = -0.461, p < 0.05) and LVMi-3D (r = 0.504, p < 0.05) in hypertensive and nonhypertensive patients with HU. CONCLUSIONS: HU may exacerbate LV systolic dysfunction and remodeling in hypertensive patients, which can be detected by 3DSTE. Early uric acid lowing treatment may be beneficial for hypertensive patients with HU.

Hyperuricemia as a Predictive Marker for Progression of Nephrosclerosis: Clinical Assessment of Prognostic Factors in Biopsy-Proven Arterial/Arteriolar Nephrosclerosis.

AIM: The influence of serum urate on kidney disease is attracting attention, but the effects of uric acid (UA) on nephrosclerosis have not been elucidated. METHODS: We reviewed data from 45 patients diagnosed with arterial/arteriolar nephrosclerosis. The renal outcomes of the arterial/arteriolar nephrosclerosis patients were assessed by performing logistic and Cox regression analyses. A Kaplan-Meier analysis was used to evaluate the impact of hyperuricemia (HU) on kidney survival. The renal outcomes of patients with and without HU were compared by using a propensity score-matched cohort. RESULTS: The logistic regression models showed no significant differences in renal outcomes, according to baseline parameters or follow-up parameters, except the serum UA value and body mass index (BMI). Baseline serum UA level had the highest odds ratio (OR) for estimated glomerular filtration rate (eGFR) decline (OR, 1.86; 95% confidence interval (CI), 1.12 to 3.45), among the parameters assessed. In the multivariate Cox regression analysis, HU (UA ≥8.0 mg/dL) (P=0.01) and BMI (P=0.03) were significantly associated with a ≥50% eGFR decline or ESRD. The Kaplan-Meier analysis in the propensity score-matched cohort indicated that the renal survival rate of the group of arterial/arteriolar nephrosclerosis patients with HU was significantly lower than that of the group without HU (log rank, P=0.03). CONCLUSION: The results of this study suggest that the baseline serum UA value can serve as a renal outcome predictor in arterial/arteriolar nephrosclerosis patients.

Prospective study of serum uric acid levels and incident metabolic syndrome in a Korean rural cohort.

OBJECTIVE: Recent studies have demonstrated an association between serum uric acid (SUA) levels and metabolic syndrome (MetS). However, paucity of available data regarding the cause and effect relationship between SUA and MetS in healthy adults is still a big challenge which remains to be studied. Therefore, we investigated whether SUA predicts new onset of MetS in a population-based cohort study. METHODS: The study included 1590 adults (661 men and 929 women) aged 40-70 years without MetS at baseline (2005-2008) and subjects were prospectively followed for 2.6 years. To evaluate the relationship between SUA and MetS, we divided the aforementioned subjects into quintiles (SUA-I to SUA-V) from the lowest to the highest values of SUA. SUA was measured by the enzymatic colorimetric method. We used category-free net reclassification improvement (NRI) and integrated discrimination improvement (IDI) to characterize the performance of predicted model. RESULTS: During a mean of 2.6 years of follow-up, 261(16.4%) adults developed MetS. MetS variables were significantly related to the baseline SUA level. Waist circumference (WC), blood pressure (BP), and serum triglyceride (TG) were significantly higher in the highest quintile of SUA compared to the lowest SUA quintile in men and women. After adjustment for age, total cholesterol and low-density lipoprotein cholesterol (LDL-C) in men and women, subjects in the fifth quintiles of SUA showed significantly higher ORs for incident MetS. The association between hyperuricemia and new onset of MetS were consistently stronger in women than men. Additionally, among women, we found an improvement in the area under the ROC curve in the models that added SUA to core components of MetS. CONCLUSION: Our study suggests that SUA is significantly correlated with future risk of WC, BP, TG and may predicted as a risk factor for developing MetS. SUA may have a clinical role in predicting new-onset metabolic syndrome among women. Large prospective study is needed to reveal the clinical significance of SUA in metabolic disease.

Patient and clinical characteristics associated with gout flares in an integrated healthcare system.

Gout flares have been challenging to identify in retrospective databases due to gout flares not being well documented by diagnosis codes, making it difficult to conduct accurate database studies. Previous studies have used different algorithms, and in this study, we used a computer-based method to identify gout flares. The objectives of this study were to identify gout flares in gout patients newly initiated on urate-lowering therapy and evaluate factors associated with a patient experiencing gout flares after starting drug treatment. This was a retrospective cohort study identifying gout patients newly initiated on a urate-lowering therapy (ULT) during the study time period of January 1, 2007-December 31, 2010. The index date was the first dispensed ULT prescription during the study time period. Patients had to be ≥18 years of age on index date, have no history of prior ULT prescription during 12 months before index date, and were required to have 12 months of continuous membership with drug benefit during pre-/post-index. Electronic chart notes were reviewed to identify gout flares; these reviews helped create a validated computer-based method to further identify patients with gout flares and were categorized into 0 gout flares, 1-2 gout flares, and ≥3 gout flares during the 12 months post-index period. Multivariable logistic regression was used to examine patient and clinical factors associated with gout flares during the 12-month follow-up period. There were 8905 patients identified as the final cohort and 68 % of these patients had one or more gout flares during the 12-month follow-up: 2797 patients (31 %) had 0 gout flares, 4836 (54 %) had 1-2 gout flares, and 1272 patients (14 %) had ≥3 gout flares. Using a multivariate regression analyses, factors independently associated with 1-2 gout flares and ≥3 gout flares versus no gout flares were similar, however, with slight differences, such as younger patients were more likely to have 1-2 gout flares and patients ≥65 years of age had ≥3 gout flares. Factors such as male gender, not attaining sUA goal, having ≥3 comorbidities, diuretics use, no changes in initial ULT dose, and not adhering to ULT all were associated with gout flares versus no gout flares. Using a new method to identify gout flares, we had the opportunity to compare our findings with the previous studies. Our study findings echo other previous studies where older patients, male, diuretics, having a greater number of comorbidities, and non-adherence are more likely to have more gout flares during the first year of newly initiating ULT. There is an unmet need for patients with gout to be educated and managed more closely, especially during the first year.

Impact of sex on uric acid levels and its relationship with the extent of coronary artery disease: A single-centre study.

BACKGROUND: Serum uric acid (SUA) elevation has been largely addressed in the past as a possible risk factor for cardiovascular disease. However, uric acid has not clearly emerged as independent risk factor for coronary artery disease. Several studies in literature have assessed sex-related differences in the association between elevated SUA levels and cardiovascular events with conflicting results. Therefore, aim of the current study was to evaluate the relationship between uric acid levels and the extent of coronary artery disease in male and female patients undergoing coronary angiography. METHODS: Our population is represented by 3520 consecutive patients undergoing coronary angiography from March 2007 to October 2012. Patients were divided according to Tertiles of SUA (Males, Group 1, ≤5.5 mg/dL-0.33 mmol/mol, n = 762, Group 2, 5.5-6.8 mg/dL-0.33-0.40 mmol/mol, n = 829 and Group 3 ≥6.8 mg/dL-0.40 mmol/mol, n = 851), (Females, Group 1, ≤4.8 mg/dL-0.28 mmol/mol, n = 349, Group 2, 4.8-6.3 mg/dL-0.28-0.37 mmol/mol, n = 359 and Group 3 ≥ 6.3 mg/dL-0.37 mmol/mol, n = 370). Fasting samples were collected for uric acid levels assessment. Coronary disease was defined for at least 1 vessel stenosis >50% as evaluated by QCA. Severe coronary disease was defined as three-vessel disease and/or left main disease. RESULTS: Among 3520 patients, we identified 2442 men (69.4%) and 1078 women (30.6%). Males had higher levels of uric acid than women (6.33 ± 1.7 vs 5.8 ± 1.9 - p < 0.001). The association between elevated uric acid (≥7 mg/dl or 0.42 mmol/l) and male gender was confirmed after correction for baseline confounding factors (Adjusted OR = 1.28 [1.01-1.62], p = 0.004). Males displayed a significantly higher prevalence and extent of CAD (p < 0.001) and more complex coronary lesions (p < 0.001). However, no significant relationship was observed between uric acid and CAD (Adjusted OR [95%CI] = 0.90 [0.76-1.06], p = 0.22) or severe CAD (Adjusted OR [95%CI] = 0.89 [0.79-1.01], p = 0.08). Among females, higher SUA levels were significantly associated with higher prevalence of severe CAD (p < 0.001) (Adjusted OR [95% CI] = 1.29 [1.03-1.62], p = 0.03). CONCLUSION: Our study showed that uric acid levels are significantly higher in men. However, high uric acid levels are associated with severe CAD only in women. Future large studies are certainly needed to confirm our findings and to evaluate the effects of SUA lowering therapies on cardiovascular prevention and outcome, especially in women.

Assessment of a possible link between hyperhomocysteinemia and hyperuricemia.

BACKGROUND/AIM: Hyperhomocysteinemia and hyperuricemia are both considered risk factors for coronary artery disease. However, the relationship between the 2 has not yet been thoroughly investigated. This study aimed to evaluate this relationship more closely. MATERIAL AND METHODS: This study is a retrospective cross-sectional analysis of data from a screening center in Israel assessing 16,477 subjects, within an age range of 20 to 80 years. RESULTS: The mean age of the study sample was 46 years, and 68% were males. Hyperuricemia was found in 24.9% and 14.6% of subjects with elevated and normal homocysteine serum levels, respectively (P < 0.001). A positive association was found between homocysteine serum levels and uric acid serum levels. Compared with subjects with normal homocysteine serum levels, those with hyperhomocysteinemia had an odds ratio (OR) for hyperuricemia of 1.7 (95% confidence interval [CI], 1.5-1.9) and 1.6 (95% CI, 1.1-2.5) for males and females, respectively. After multivariate adjustment for age, hypertension, body mass index, estimated glomerular filtration rate, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and thiazide use, the association remained significant in males (OR, 1.5; 95% CI, 1.3-1.7; P < 0.001) but not in females (OR, 0.9; 95% CI, 0.6-1.6; P = 0.82). CONCLUSIONS: This large cohort showed a significant association between hyperhomocysteinemia and hyperuricemia. Sex differences were observed. This study suggests that accelerated atherosclerosis may be a consequence of the combined effect of these 2 factors.

Fixed, low-dose rasburicase for the treatment or prevention of hyperuricemia in adult oncology patients.

PURPOSE: Rasburicase is a recombinant urate oxidase enzyme administered to high risk patients or to those with preexisting hyperuricemia from tumor lysis syndrome (TLS). The objective of this retrospective review is to evaluate and characterize the use of fixed, low-dose rasburicase for the treatment of hyperuricemia in adult patients. PATIENTS/METHODS: A retrospective chart review from 1 October 2005 to 31 December 2011 was conducted in adult oncology patients who received fixed, low-dose rasburicase. Patients who met the inclusion criteria were evaluated for the uric acid level change from baseline and the achievement of uric acid level less than 8 mg/dL. RESULTS: Forty-five patients were included in the analysis in which 26 (58%) patients received 3 mg rasburicase. For the 39 patients with baseline uric acid levels 8 mg/dL or higher, 80% achieved a uric acid level lower than 8 mg/dL with a single rasburicase dose. Six patients (13%) required renal replacement therapy despite rasburicase. The median uric acid level reduction 24 h post rasburicase dose 1.5 mg, 3 mg, 4.5 mg, and 6 mg were 5.5, 5.8, 3.8, and 10.05 mg/dL, respectively. There was no clinical difference between obese and non-obese patients in terms of their median uric acid reduction, 5.5 vs. 7 mg/dL, respectively. CONCLUSION: Fixed, low dose rasburicase produced a consistent lowering of uric acid levels and may be utilized in the management of hyperuricemia in TLS. Further study is necessary to determine if a larger fixed dose would be required in those patients with a higher baseline uric acid level.

Prevalence of hyperuricemia among Chinese adults: a national cross-sectional survey using multistage, stratified sampling.

BACKGROUND: Hyperuricemia is a non-communicable disease that threatens human health, and its prevalence has been increasing in recent decades. However, there have been no national surveys about hyperuricemia performed in China. We aimed to investigate the prevalence of hyperuricemia and its risk factors in Chinese adults. METHODS: Using data from 36,348 participants aged 18 years and older from the China National Survey of Chronic Kidney Disease (a nationwide cross-sectional survey with a randomized, multistage, stratified sampling strategy), we investigated the prevalence of hyperuricemia. Male subjects with serum uric acid ≥416.0 µmol/l (7.0 mg/dl) and female subjects with ≥357.0 µmol/l (6.0 mg/dl) were diagnosed with hyperuricemia. The prevalence of hyperuricemia was calculated, and the factors associated with hyperuricemia were analyzed using logistic regression. RESULTS: The adjusted prevalence of hyperuricemia among Chinese adults in 2009-2010 was 8.4 % [95 % confidence interval (CI) 8.0-8.8 %], and it was 9.9 % (9.2-10.6 %) in men and 7.0 % (6.5-7.5 %) in women. The prevalence was much higher among urban than rural residents (14.9 vs. 6.6 %, p < 0.01). Areas with high per capita gross domestic product (GDP) levels had higher prevalence of hyperuricemia. In the multivariate regression model, the estimated glomerular filtration rate was inversely associated with hyperuricemia. Alcohol consumption, body mass index and serum triglyceride levels were positively correlated with hyperuricemia. Other factors independently correlated with hyperuricemia were age, sex, education level, area of residence, and economic development. In order to demonstrate the discriminatory power for hyperuricemia of the risk factors all together, we calculated the probabilities by logistic regression analysis, which represented the combined effects of these risk factors. Then, receiver operating characteristic analysis was used to demonstrate the value of the probabilities for hyperuricemia diagnosis. Finally, ROC curve analysis revealed the area under the curve was 0.746 (95 % CI 0.739-0.754), statistically significant for the association with hyperuricemia of these risk factors considered all together (p < 0.001). CONCLUSIONS: Hyperuricemia is prevalent in the economically developed areas of China. Our report indicates the feasibility of studying the influence that economic changes have on the prevalence of hyperuricemia.