Metabolic Syndrome Abstracts 3 – Uric Acid

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Effect of the metabolic syndrome and hyperuricemia on outcome in patients with coronary artery disease (from the Bezafibrate Infarction Prevention Study)
            (Brodov et al., 2010) Download
Hyperuricemia appears to be related to metabolic syndrome (MS), but its impact on cardiovascular risk in patients with MS is unclear. We evaluated the impact of hyperuricemia on cardiovascular risk in patients with MS. Of 2,963 patients with coronary artery disease enrolled in the Bezafibrate Infarction Prevention study, 1,410 had MS, as established by the presence of >/=3 of the following 5 criteria: serum fasting glucose >110 mg/dl, triglycerides >150 mg/dl, high-density lipoprotein cholesterol <40 mg/dl in men and <50 mg/dl in women, systolic and diastolic blood pressures >130 and 80 mm Hg, respectively, and body mass index >28 kg/m(2). The remaining 1,553 patients had no MS. Primary end points were defined as occurrence of acute myocardial infarction or sudden cardiac death. Hyperuricemia was defined as serum uric acid levels >7.0 mg/dl in men and >6.0 mg/dl in women, respectively. Higher rate of primary end point was noted in hyperuricemic patients (n = 284) versus normouricemic patients (n = 1,126) with MS (20.1% and 15.3%, respectively, p = 0.05). After adjustment for age, gender, smoking, diabetes, previous myocardial infarction, hypertension, New York Heart Association classes II to IV, estimated glomerular filtration rate, body mass index, total cholesterol, triglycerides, diuretics, antiplatelets, angiotensin-converting enzyme inhibitors, beta blockers, and bezafibrate treatment, hyperuricemic patients with MS demonstrated significantly higher risk for the primary end point compared to normouricemic patients with MS (hazard ratio 1.45, 95% confidence interval 1.00 to 2.17, p = 0.05). In conclusion, hyperuricemia is associated with increased risk of myocardial infarction and sudden cardiac death in patients with MS.

Uric acid: a surrogate of insulin resistance in older women
            (Chen et al., 2008) Download
OBJECTIVES: The relationship between serum uric acid (UA) and cardiovascular disease has been debated extensively and no conclusion has been reached yet. The main purpose of this study was to explore the sex-different relationship among insulin resistance, metabolic syndrome (MS) and hyperuricemia. METHODS: A community-based prospective study was conducted among people aged over 40 years in I-Lan County, Taiwan. A complete history taking, physical examination and laboratory tests were performed for each subject by the well-trained research staff. Insulin resistance was determined by the homeostasis model assessment (HOMA-IR). Serial comparisons were performed to evaluate the associations between MS, insulin resistance and hyperuricemia in both sexes. RESULTS: A total of 852 subjects (mean age=64.6+/-11.3 years, 56.7% female) were enrolled. The prevalence of obesity, hyperuricemia, chronic kidney disease (CKD), insulin resistance and MS was 42.2, 31.2, 30.9, 36.0 and 47.5%, respectively. Subjects with MS were significantly older (63.4+/-10.0 years versus 60.4+/-12.4 years, P=0.019), higher in body mass index (BMI) (26.3+/-3.5 kg/m(2) versus 23.6+/-3.0 kg/m(2), P<0.001), serum UA (6.1+/-2.1mg/dl versus 5.5+/-1.7 mg/dl, P=0.003), HOMA-IR (2.7+/-3.4 versus 1.0+/-0.8, P<0.001) and lower in glomerular filtration rate (GFR) (66.3+/-17.7 ml/min/1.73 m(2) versus 72.0+/-15.2 ml/min/1.73 m(2), P=0.001). Male gender, CKD, BMI>23 kg/m(2) and insulin resistance were all independent risk factor for hyperuricemia with the covariate of age. When age and BMI were controlled, females had significantly higher prevalence of CKD and insulin resistance, but less hyperuricemia than males (P all<0.05). Adjusted for age, BMI and GFR, hyperuricemia and MS were both independent risk factors for insulin resistance in females (P=0.006, <0.001, respectively). In males, MS remained significantly associated with insulin resistance (P=0.002) but not hyperuricemia (P=0.813). When age, BMI and GFR were controlled, serum UA was positively related to HOMA-IR in females (gamma=0.117, P=0.012), but not in males (P=0.93). CONCLUSION: A positive association was identified between serum UA and insulin resistance in older women but not in men. Studies related to insulin resistance may be needed when hyperuricemia was identified in older women.

Prevalence of the metabolic syndrome in individuals with hyperuricemia
            (Choi and Ford, 2007) Download
PURPOSE: The link between hyperuricemia and insulin resistance has been noted, but the prevalence of the metabolic syndrome by recent definitions among individuals with hyperuricemia remains unclear. Our objective was to determine the prevalence of the metabolic syndrome according to serum uric acid levels in a nationally representative sample of US adults. METHODS: By using data from 8669 participants aged 20 years and more in The Third National Health and Nutrition Examination Survey (1988-1994), we determined the prevalence of the metabolic syndrome at different serum uric acid levels. We used both the revised and original National Cholesterol Education Program Adult Treatment Panel (NCEP/ATP) III criteria to define the metabolic syndrome. RESULTS: The prevalences of the metabolic syndrome according to the revised NCEP/ATP III criteria were 18.9% (95% confidence interval [CI], 16.8-21.0) for uric acid levels less than 6 mg/dL, 36.0% (95% CI, 32.5-39.6) for uric acid levels from 6 to 6.9 mg/dL, 40.8% (95% CI, 35.3-46.4) for uric acid levels from 7 to 7.9 mg/dL, 59.7% (95% CI, 53.0-66.4) for uric acid levels from 8 to 8.9 mg/dL, 62.0% (95% CI, 53.0-66.4) for uric acid levels from 9 to 9.9 mg/dL, and 70.7% for uric acid levels of 10 mg/dL or greater. The increasing trends persisted in subgroups stratified by sex, age group, alcohol intake, body mass index, hypertension, and diabetes. For example, among individuals with normal body mass index (<25 kg/m2), the prevalence increased from 5.9% (95% CI, 4.8-7.0), for a uric acid level of less than 6 mg/dL, to 59.0%, (95% CI, 20.1-97.9) for a uric acid level of 10 mg/dL or greater. With the original NCEP/ATP criteria, the corresponding prevalences were slightly lower. CONCLUSIONS: These findings from a nationally representative sample of US adults indicate that the prevalence of the metabolic syndrome increases substantially with increasing levels of serum uric acid. Physicians should recognize the metabolic syndrome as a frequent comorbidity of hyperuricemia and treat it to prevent serious complications.

Role of uric acid in hypertension, renal disease, and metabolic syndrome
            (Heinig and Johnson, 2006) Download
Hyperuricemia has long been known to be associated with cardiovascular disease, and it is particularly common in people with hypertension, metabolic syndrome, or kidney disease. Most authorities have viewed elevated uric acid as a secondary phenomenon that is either innocuous or perhaps even beneficial, since uric acid can be an antioxidant. However, recent experiments have challenged this viewpoint. In this paper we argue that uric acid is a true risk factor for cardiovascular disease. Furthermore, we suggest that the recent increased intake in the American diet of fructose, which is a known cause of hyperuricemia, may be contributing to the current epidemic of obesity and diabetes.

Hyperuricemia, cardiovascular disease, and the metabolic syndrome
         (Indraratna et al., 2009) Download

Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort
            (Iseki et al., 2004) Download
BACKGROUND: Uric acid may be a true mediator of renal disease and progression. However, epidemiological evidence for the significance of serum uric acid levels on the risk for developing end-stage renal disease (ESRD) is scarce in a setting of community-based screening. METHODS: Participants in a 1993 mass screening conducted by the Okinawa General Health Maintenance Association in Okinawa, Japan, were investigated: 48,177 screenees (22,949 men, 25,228 women) older than 20 years for whom serum uric acid data were available were studied. All dialysis patients treated in Okinawa were independently registered in the Okinawa Dialysis Study registry. Participants in the 1993 screening who later entered a dialysis program were identified by using 2 computer registries. The cumulative incidence of ESRD was calculated according to quartiles of baseline serum uric acid levels for each sex. The significance of hyperuricemia (serum uric acid level > or = 7.0 mg/dL [> or =416 micromol/L] in men and > or = 6.0 mg/dL [> or =357 micromol/L] in women) for the risk for developing ESRD was evaluated by means of the Cox model after adjusting for age, blood pressure, body mass index, proteinuria, hematocrit, and total cholesterol, triglyceride, fasting blood glucose, and serum creatinine levels. RESULTS: Mean serum uric acid level was 6.4 +/- 1.4 (SD) mg/dL (381 micromol/L) in men and 4.8 +/- 1.1 mg/dL (286 micromol/L) in women. Prevalences of hyperuricemia were 31.9% in men and 13.6% in women. By the end of 2000, a total of 103 screenees (53 men, 50 women) entered dialysis programs. Calculated incidences of ESRD per 1,000 screenees were 1.22 for men without hyperuricemia and 4.64 for men with hyperuricemia and 0.87 for women without hyperuricemia and 9.03 for women with hyperuricemia. Adjusted hazard ratios for hyperuricemia were 2.004 (95% confidence interval, 0.904 to 4.444; P = not significant) in men and 5.770 (95% confidence interval, 2.309 to 14.421; P = 0.0002) in women. CONCLUSION: Screenees with hyperuricemia were associated with a greater incidence of ESRD. Hyperuricemia (serum uric acid > or = 6.0 mg/dL [> or =357 micromol/L]) was an independent predictor of ESRD in women. Strategies to control serum uric acid levels in the normal range may reduce the population burden of ESRD.

Normal liver enzymes are correlated with severity of metabolic syndrome in a large population based cohort.
            (Kälsch et al., 2015) Download
Key features of the metabolic syndrome are insulin resistance and diabetes. The liver as central metabolic organ is not only affected by the metabolic syndrome as non-alcoholic fatty liver disease (NAFLD), but may contribute to insulin resistance and metabolic alterations. We aimed to identify potential associations between liver injury markers and diabetes in the population-based Heinz Nixdorf RECALL Study. Demographic and laboratory data were analyzed in participants (n = 4814, age 45 to 75 y). ALT and AST values were significantly higher in males than in females. Mean BMI was 27.9 kg/m(2) and type-2-diabetes (known and unkown) was present in 656 participants (13.7%). Adiponectin and vitamin D both correlated inversely with BMI. ALT, AST, and GGT correlated with BMI, CRP and HbA1c and inversely correlated with adiponectin levels. Logistic regression models using HbA1c and adiponectin or HbA1c and BMI were able to predict diabetes with high accuracy. Transaminase levels within normal ranges were closely associated with the BMI and diabetes risk. Transaminase levels and adiponectin were inversely associated. Re-assessment of current normal range limits should be considered, to provide a more exact indicator for chronic metabolic liver injury, in particular to reflect the situation in diabetic or obese individuals.

Hyperuricemia and risk of stroke: a systematic review and meta-analysis
            (Kim et al., 2009) Download
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.

Hyperuricemia and incidence of hypertension among men without metabolic syndrome
            (Krishnan et al., 2007) Download
The aim of this project was to study the risk of developing hypertension over a 6-year follow-up in normotensive men with baseline hyperuricemia (serum uric acid >7.0 mg/dL) but without diabetes/glucose intolerance or metabolic syndrome. We analyzed the data on men without metabolic syndrome or hypertension at baseline from the Multiple Risk Factor Intervention Trial. These men (n=3073; age: 35 to 57 years) were followed for an average of 6 years by annual examinations. Follow-up blood pressure among those with baseline was consistently higher than among those with normal serum uric acid concentration. We used Cox regression models for adjustment for the effects of serum creatinine, body mass index, age, blood pressure, proteinuria, serum cholesterol and triglycerides, alcohol and tobacco use, risk factor interventions, and use of diuretics. In these models, normotensive men with baseline hyperuricemia had an 80% excess risk for incident hypertension (hazard ratio: 1.81; 95% CI: 1.59 to 2.07) compared with those who did not. Each unit increase in serum uric acid was associated with a 9% increase in the risk for incident hypertension (hazard ratio: 1.09; 95% CI: 1.02 to 1.17). We conclude that the hyperuricemia-hypertension risk relationship is present among normotensive middle-aged men without diabetes/glucose intolerance or metabolic syndrome.

Serum uric acid and leptin levels in metabolic syndrome: a quandary over the role of uric acid
            (Lin et al., 2007) Download
This study investigates the impact of uric acid (UA) on the risk factors associated with metabolic syndrome. In addition, this study explores the relationship between UA and insulin resistance and serum leptin levels in metabolic syndrome. A total of 470 subjects (252 women and 218 men) were recruited from the Department of Health Management at Chang Gung Medical Center (Linkou, Taiwan). Metabolic syndrome was defined using a modified Adult Treatment Panel III (ATP III) definition. The formula for the homeostasis model assessment of insulin resistance (HOMA-IR) is as follows: fasting serum insulin (microU/mL) x fasting plasma glucose (mmol/L)/22.5. Diabetes mellitus was diagnosed in 45 subjects (9.6%); 82 subjects (17.4%) had hypertension. Hyperuricemia was diagnosed in 144 subjects (30.6%). Of these subjects, 115 (63 females and 52 males) (24.5%) were diagnosed as having metabolic syndrome. Patients with hyperuricemia had increased body mass index, waist-to-hip ratio, and triglyceride (Tg) level. The subjects also had lower high-density lipoprotein and greater hypertension. Hormone assays showed an elevation of leptin, immunoreactive insulin (IRI), and HOMA-IR in the hyperuricemia group. Uric acid appeared to be better correlated with Tg, blood pressure (both systolic and diastolic), obesity, immunoreactive insulin, and HOMA-IR. Uric acid did not correlate with leptin or blood glucose levels. Metabolic syndrome and Tg/high-density lipoprotein ratio showed a statistically significant difference in HOMA-IR using 3.8 as a cutoff value. Otherwise, there was no difference in leptin value. In conclusion, serum UA is significantly related to risk factors of metabolic syndrome except for blood glucose. Waist-to-hip ratio and HOMA-IR were statistically different in subjects with and without metabolic syndrome.

In addition to insulin resistance and obesity, hyperuricemia is strongly associated with metabolic syndrome using different definitions in Chinese populations: a population-based study (Taichung Community Health Study)
            (Lin et al., 2008) Download


The paradoxical relationship between serum uric acid and cardiovascular disease
            (Lippi et al., 2008) Download
Uric acid (urate), an organic compound comprised of carbon, nitrogen, oxygen and hydrogen, is the final oxidation product of purine catabolism in humans, higher primates and in a particular species of dog (Dalmatians). For decades it has been hypothesized that the antioxidant properties of uric acid might be protective against aging, oxidative stress, and oxidative cell injury. However, recent epidemiological and clinical evidences suggest that hyperuricaemia might be a risk factor for cardiovascular disease, where enhanced oxidative stress plays an important pathophysiological role. It has also been hypothesized that hyperuricaemia might be involved in chronic heart failure and metabolic syndrome. The apparent paradox between protective and toxic effects is supported by clinical evidences that antioxidant compounds may become pro-oxidant compounds in certain situations, particularly when they are present in blood at supranormal levels. The aim of this article is to review uric acid metabolism and physiology, highlighting its association with cardiovascular disease.

The conundrum of hyperuricemia, metabolic syndrome, and renal disease
            (Nakagawa et al., 2008) Download
The level of serum uric acid in human has been increasing over the last decades, and correlates with an increase prevalence of renal disease and metabolic syndrome. Understanding the role of uric acid in these conditions may provide clues for preventing the current epidemic of renal disease. Controversy still remains if hyperuricemia is simply a consequence or a cause of renal disease although epidemiological studies have attempted to resolve this issue. In this review, we discuss the clinical and experimental evidence for a causal role of hyperuricemia in renal diseases and potential relationships of hyperuricemia with metabolic syndrome.

Do thiazides worsen metabolic syndrome and renal disease? The pivotal roles for hyperuricemia and hypokalemia
            (Reungjui et al., 2008) Download
PURPOSE OF REVIEW: The aims of this article are to review the current controversies related to the use of thiazide diuretics as first-line treatment of hypertension and to discuss the causal roles for hyperuricemia and hypokalemia on the adverse consequences of thiazide usage. RECENT FINDINGS: Thiazides significantly reduce morbidity and mortality in hypertensive subjects. There remains, however, debate about thiazide usage as first-line treatment of hypertension. This negative impact of thiazides may be partially attributed to the ability of thiazides to exacerbate features of metabolic syndrome or increase the risk for developing diabetes. Several clinical trials suggest that thiazide-induced hyperuricemia and hypokalemia may account for some of these negative effects. Thiazide treatment is also associated with a decline of renal function in spite of a lowering blood pressure. In this review, we discuss the clinical and experimental evidence supporting a potential role of hyperuricemia and hypokalemia on the development of renal injury and worsening of the metabolic syndrome. SUMMARY: Hyperuricemia and hypokalemia may have pivotal roles in the exacerbation of the metabolic syndrome in response to thiazides. We propose that controlling serum uric acid and serum potassium could improve thiazide efficacy and also reduce its risk for inducing metabolic syndrome or diabetes.

Serum uric acid is independently associated with metabolic syndrome in subjects with and without a low estimated glomerular filtration rate
            (See et al., 2009) Download
OBJECTIVE: The relationship among serum uric acid (SUA), metabolic syndrome, and chronic kidney disease (CKD) is unclear. We examined whether SUA level is an independent risk factor for chronic kidney disease and whether the association between SUA and metabolic syndrome is affected by kidney function. METHODS: We analyzed 28,745 subjects (17,478 men, 11,267 women, age 20-49 yrs) who underwent health examinations at this hospital between 2000 and 2007. Hyperuricemia was defined as SUA level > 7.7 mg/dl in men or > 6.6 mg/dl in women. Kidney function was assessed by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease Study equation modified for Chinese subjects. Impaired renal function with low GFR was defined as eGFR < 90 ml/min/1.73 m(2). The UA-low GFR groups were defined according to the observed combination of hyperuricemia and low GFR: Group A (absence of both hyperuricemia and low GFR); Group B (presence of low GFR but no hyperuricemia); Group C (presence of hyperuricemia but not low GFR); and Group D (presence of both hyperuricemia and low GFR). RESULTS: The prevalence of hyperuricemia, metabolic syndrome, and impaired kidney function with low GFR was 20.3% (27.6% in men, 8.9% in women), 7.6% (10.6% in men, 3.0% in women), and 9.9% (11.6% in men, 7.1% in women), respectively. The Pearson correlation between SUA and eGFR was only -0.26 (-0.21 in men, -0.22 in women; p < 0.001). In men, the age-adjusted odds ratio (OR) of metabolic syndrome was 1.41 (Group B), 2.45 (Group C), and 2.58 (Group D) in comparison with Group A. In women, the age-adjusted OR of metabolic syndrome was 0.83 (Group B), 5.47 (Group C), and 3.31 (Group D) in comparison with Group A. CONCLUSION: Hyperuricemia is prevalent in the Taiwan population. Hyperuricemia is only weakly associated with renal function, but is strongly associated with metabolic syndrome with or without a low eGFR.

Is high serum uric acid a risk marker or a target for treatment? Examination of its independent effect in a large cohort with low cardiovascular risk
            (Wen et al., 2010) Download
BACKGROUND: Cohort studies evaluating increased uric acid level as a cardiovascular disease (CVD) risk factor have shown variable results; studies are particularly lacking in lower risk populations. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 484,568 adults participating in a medical screening program in Taiwan since 1994 were followed up for a median of 8.5 years. Two subgroups were constructed: the first (n = 246,697; 51%) excluded participants with either overt CVD or overt CVD risk factors (including hypertension, diabetes, obesity, and hypertriglyceridemia) and the second (n = 157,238; 32%) further excluded individuals with early-stage CVD risk factors (including prehypertension, prediabetes, overweight, and borderline hypertriglyceridemia). PREDICTOR: Serum uric acid. OUTCOMES & MEASUREMENTS: All-cause and CVD mortality risk assessed using Cox proportional hazards models for categorical and continuous serum uric acid levels. As applicable, models adjusted for 14 variables. Population-attributable fraction was applied to compare contributions to mortality between high uric acid level and other CVD risk factors. RESULTS: In the total cohort, mean age was 41.4 +/- 14.0 years and 26.2% had serum uric acid levels >or=7 mg/dL. Through 2007, there were 16,246 deaths (3.4% of all participants), with 35.2% of deaths occurring in individuals with hyperuricemia. Adjusted HRs associated with serum uric acid levels >or=7 mg/dL for all-cause and CVD mortality were 1.10 (95% CI, 1.04-1.17) and 1.38 (95% CI, 1.20-1.58), respectively. In individuals with hyperuricemia, 64.3% had overt CVD risk factors and 82.5% had either overt or early-stage CVD risk factors. Individuals with serum uric acid levels >or=8 mg/dL without overt CVD risk factors constituted 13.5% of the total study population with hyperuricemia; in analyses excluding those with overt CVD risk factors, serum uric acid level >or=8 mg/dL was significantly associated with all-cause and CVD mortality, with HRs of 1.37 (95% CI, 1.18-1.60) and 2.30 (95% CI, 1.51-3.49), respectively. In the subgroup of those with serum uric acid levels >or=8 mg/dL but who lacked both overt and early-stage CVD risk factors, the HRs for all-cause and CVD mortality were also significant and were 1.39 (95% CI, 1.08-1.78) and 2.38 (95% CI, 1.24-4.54), respectively. HRs for individuals with the same risk profiles but with serum uric acid of 7.0-7.9 mg/dL were not significant. In all groups, inclusion of proteinuria and glomerular filtration rate in models substantially attenuated the association between uric acid level and outcomes. High uric acid levels contributed a relatively insignificant portion to mortality (1.2%) and CVD deaths (4.5%) in this population. LIMITATIONS: A single measurement of uric acid was used. CONCLUSION: Increased serum uric acid level is a minor, but significant, risk factor for all-cause and CVD mortality. However, except for a small proportion (13.5%), increased serum uric acid level is more a risk marker than a target for treatment and is not an independent risk. Determining appropriate groups to target in clinical trials for uric acid-lowering therapy is critical.

 


References

Brodov, Y., et al. (2010), ‘Effect of the metabolic syndrome and hyperuricemia on outcome in patients with coronary artery disease (from the Bezafibrate Infarction Prevention Study)’, Am J Cardiol, 106 (12), 1717-20. PubMedID: 21126615
Chen, L. K., et al. (2008), ‘Uric acid: a surrogate of insulin resistance in older women’, Maturitas, 59 (1), 55-61. PubMedID: 18082342
Choi, H. K. and E. S. Ford (2007), ‘Prevalence of the metabolic syndrome in individuals with hyperuricemia’, Am J Med, 120 (5), 442-47. PubMedID: 17466656
Heinig, M. and R. J. Johnson (2006), ‘Role of uric acid in hypertension, renal disease, and metabolic syndrome’, Cleve Clin J Med, 73 (12), 1059-64. PubMedID: 17190309
Indraratna, P. L., et al. (2009), ‘Hyperuricemia, cardiovascular disease, and the metabolic syndrome’, J Rheumatol, 36 (12), 2842-3; author reply 2844. PubMedID: 19966196
Iseki, K., et al. (2004), ‘Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort’, Am J Kidney Dis, 44 (4), 642-50. PubMedID: 15384015
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Krishnan, E., et al. (2007), ‘Hyperuricemia and incidence of hypertension among men without metabolic syndrome’, Hypertension, 49 (2), 298-303. PubMedID: 17190877
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Lin, W. Y., et al. (2008), ‘In addition to insulin resistance and obesity, hyperuricemia is strongly associated with metabolic syndrome using different definitions in Chinese populations: a population-based study (Taichung Community Health Study)’, Ann Rheum Dis, 67 (3), 432-33. PubMedID: 18292110
Lippi, G., et al. (2008), ‘The paradoxical relationship between serum uric acid and cardiovascular disease’, Clin Chim Acta, 392 (1-2), 1-7. PubMedID: 18348869
Nakagawa, T., et al. (2008), ‘The conundrum of hyperuricemia, metabolic syndrome, and renal disease’, Intern Emerg Med, 3 (4), 313-18. PubMedID: 18320146
Reungjui, S., et al. (2008), ‘Do thiazides worsen metabolic syndrome and renal disease? The pivotal roles for hyperuricemia and hypokalemia’, Curr Opin Nephrol Hypertens, 17 (5), 470-76. PubMedID: 18695387
See, L. C., et al. (2009), ‘Serum uric acid is independently associated with metabolic syndrome in subjects with and without a low estimated glomerular filtration rate’, J Rheumatol, 36 (8), 1691-98. PubMedID: 19531754
Wen, C. P., et al. (2010), ‘Is high serum uric acid a risk marker or a target for treatment? Examination of its independent effect in a large cohort with low cardiovascular risk’, Am J Kidney Dis, 56 (2), 273-88. PubMedID: 20605302