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Gout, just a nasty event or a cardiovascular signal? A study from primary care.

OBJECTIVE: Our aim was to examine the relationship between gout on the one hand and cardiovascular diseases and cardiovascular risk indicators on the other. METHODS: A case-control study was carried out in an aggregate primary care population of approximately 12 000 patients from four Dutch general practices, with follow-up of the cases free of cardiovascular diseases at the time of the first registered episode of gout. The subjects comprised 261 patients with a first episode of gout, 170 of whom were without prevalent cardiovascular diseases, and two control patients for each case matched for age, sex and practice. In the case-control study, the main outcome measures were the prevalence of cardiovascular morbidity (angina pectoris, myocardial infarction, heart failure, cerebrovascular accident, transient ischaemic attack, peripheral vascular disease), hypertension, diabetes mellitus, obesity and hypercholesterolaemia; in the follow-up study, the main outcome measure was the incidence of cardiovascular morbidity. RESULTS: Thirty-five percent of 261 gout patients and 26% of 522 controls had one or more prevalent cardiovascular diseases. Compared with controls, patients had a higher prevalence of hypertension (43% versus 18%), hypercholesterolaemia (14% versus 6%) and obesity (56% versus 30%). A total of 170 gout patients without prevalent cardiovascular diseases (compared with 340 controls) had a higher prevalence of hypertension (39% versus 14%), hypercholesterolaemia (8% versus 4%), diabetes mellitus (5% versus 1%) and obesity (52% versus 27%). The first occurrence of a cardiovascular disease (real end-point) was seen in 26% of the patients free of cardiovascular morbidity and in 21% of the controls. This difference was not significant. In a Cox proportional hazard model, controlling for the cardiovascular risk indicators, gout did not prove to be an independent determinant for the development of cardiovascular disease. CONCLUSION: Gout was found to be associated with cardiovascular diseases and with cardiovascular risk indicators, without evidence of it being an independent risk indicator itself. A gout attack should be an incentive to assess the cardiovascular risk profile, when a patient seeks medical help.

Adolescent↗

The epidemiology of hyperuricaemia and gout in Taiwan aborigines.

To determine the prevalence of hyperuricaemia, gout and gout-related factors in Central Taiwan Atayal aborigines, 342 subjects over 18 yr old were interviewed and examined. A questionnaire was designed to screen for signs and symptoms of gout and gout-related risk factors. Serum uric acid, triglyceride and creatinine were measured in all subjects. The prevalence of hyperuricaemia was 41.4% and that of gout 11.7% in aborigines. The uric acid level was 7.9+/-1.7 mg/dl in males and 5.7+/-1.5 in females, and differed significantly under age 70 yr (P < 0.001). Significantly increased triglyceride, creatinine and alcoholism was found in gouty patients compared with non-gouty patients. In 40 cases with gout, 54% had tophi and 35% of their first-degree relatives had gout. The high prevalence of hyperuricaemia and gout in Taiwan Atayal aborigines, a significant family predisposition, increased creatinine level and alcoholism suggest multiple factors affecting the hyperuricaemia.

Adult↗

Gout in black South Africans: a clinical and genetic study.

OBJECTIVE: To define the clinical characteristics of gout and determine if there were any genetic associations with gout in black South Africans. METHODS: The records of 107 patients with gout seen over a five year period were retrospectively analysed. The HLA class I and class II antigens were studied in a prospective survey of 46 patients. RESULTS: The male to female ratio was 6.6:1. The diagnosis of gout was based on identification of monosodium urate crystals from the synovial fluid, synovial tissue or tophaceous material in 62 patients (58%) and on clinical criteria in the remaining 45 patients (42%). The mode of presentation was monoarthritis in 40 patients (37.4%), pauciarthritis in 30 (28%) and polyarthritis in 37 (34.6%). The joints which were most frequently involved were the knee in 91 patients (85%), the first metatarsophalangeal in 80 (74.8%) and the ankle in 66 (61.7%). A secondary cause was identified in 52 patients (48.6%) (diuretic therapy in 48 patients and chronic renal impairment in four); 55 patients (51.4%) had primary gout. The genetic study showed an increased frequency of HLA-B14 in patients with primary gout compared with controls. CONCLUSIONS: Gout is more common in black Africans than previously recognised and frequently presents with involvement of more than one joint. There was an increased frequency of HLA-B14 in patients with primary gout but the clinical significance of this is uncertain.

Adult↗

The prevalence of metabolic syndrome in patients with gout: a multicenter study.

It has been suggested that hyperuricemia and possibly gout are associated with the metabolic syndrome, but there have been no direct studies. This study was undertaken to obtain the prevalence of the metabolic syndrome in patients with gout and to compare it with those from the general population studies. This was a 4-institutional case-historical control study composed of 168 patients with gout. We assessed the prevalence of metabolic syndrome according to the ATP III criteria and compared the prevalence with that of the historical controls. To elucidate the factors in gout that were associated with metabolic syndrome, a multivariate analysis was done. The age-adjusted prevalence of metabolic syndrome in gout patients was 43.6%, which was significantly higher than that of the Korean control population (5.2%) from the previous studies. Patients with gout had more components of metabolic syndrome than did the controls. Body mass index (BMI, OR = 1.357 (95%CI 1.111-1.657)) and high density lipoprotein (HDL, OR = 0.774 (95%CI 0.705-0.850)) were the variables most significantly associated with the occurrence of metabolic syndrome in gout, but alcohol consumption did not show such associations. Gout is associated with the metabolic syndrome, and furthermore, obesity and dyslipidemia were the factors most associated with the syndrome in these patients.

Adult↗

Epidemiology of gout: is the incidence rising?

OBJECTIVE: To determine whether the incidence of gout is higher in 1995-1996 compared to 1977-1978. METHODS: Using the Rochester Epidemiology Project computerized medical record system, all potential cases of acute gout in the city of Rochester, Minnesota during the time intervals of 1977-1978 and 1995-1996 were identified. The complete medical records of all potential cases were screened and all who fulfilled the 1977 American College of Rheumatology proposed criteria for gout were included as incidence cases. Demographic data, body mass index, clinical presentation, and associated comorbid conditions were abstracted. The overall and age-gender adjusted incidence rates from the 2 cohorts were calculated and compared. RESULTS: A total of 39 new cases of acute gout were identified during the 2 year interval 1977-1978 representing an age and sex-adjusted annual incidence rate of 45.0/100,000 (95% CI: 30.7, 59.3). For the interval 1995-1996, 81 cases were diagnosed, representing an annual incidence rate of 62.3/100,000 (95% CI: 48.4, 76.2). There was a greater than 2-fold increase in the rate of primary gout (i.e., no history of diuretic exposure) in the recent compared to the older time periods (p = 0.002). The incidence of secondary, diuretic related gout did not increase over time (p = 0.140). CONCLUSION: Our results indicate that the incidence of primary gout has increased significantly over the past 20 years. While this increase might be a result of improved ascertainment of atypical gout, it may also be related to other, as yet unidentified, risk factors.

Adrenal Cortex Hormones↗

The effect of control and self-medication of chronic gout in a developing country. Outcome after 10 years.

OBJECTIVE: We describe a 10 year observation of the effect of control of hyperuricemia compared with self-medication alone in patients with chronic gout. METHODS: We studied 299 consecutively self-referred Malayo-Polynesian men with chronic gout, mean age 35 +/- 14.3 SD years. Subjects comprised 228 cases with chronic gout without tophi or urolithiasis (Group 1) and 71 with those complications (Group 2). Attacks of acute gouty arthritis were treated with nonsteroidal antiinflammatory drugs (NSAID) and/or corticosteroids. After acute arthritis had settled, urate-lowering drugs were instituted in both groups combined with low dose colchicine and/or low dose NSAID for at least 0.5-2 years. Urate levels were maintained longterm at a mean of < 5 mg/dl. After 10 years, the dropouts were traced and evaluated for comparison with baseline and those who remained in the study. In Group 2 the urate-lowering drugs were continued. RESULTS: Control of gout and hyperuricemia was achieved in all patients who remained under control: 91.6% of the 299 patients for at least 2 years (short-term), up to 5 years in 87.5% (medium term), and up to 10 years in 79.6% (longterm). In Group 1 (chronic gout without complication) only 36.8% had no attacks during 8 years, after they had tapered urate-lowering drug after the first 2 years of the study. In the 61 dropouts the intermittent symptomatic treatment and/or self-medication without longterm control of hyperuricemia resulted after 1 decade in chronic gout with more complications and associated conditions leading to increased morbidity, disability, and comorbidity, and 3 early mortalities. CONCLUSION: By controlling hyperuricemia, improvement of the prognosis of chronic gout, comorbidity, and early death was achieved compared with self-medication alone. Self-medication in a developing country if continued unchecked may become a public health problem in a population with a high prevalence rate of gout.

Adult↗

Interleukin-1 receptor antagonist gene polymorphism in Taiwanese patients with gout.

OBJECTIVE: The purpose of this study was to examine whether interleukin-1 receptor antagonist (IL-1Ra) gene polymorphism is a marker of susceptibility to or of the clinical characteristics of gout in Taiwanese patients. METHODS: 196 Taiwanese patients with gout and 103 unrelated normal healthy control subjects living in central Taiwan were studied. Polymorphism of the gene for IL-1Ra was typed from genomic DNA. Allelic frequencies and carriage rates were compared between gout patients and control subjects. The relationship between IL-1Ra genotypes and the clinical characteristics of gout was also evaluated. RESULTS: No significant differences were observed in genetic and allelic frequencies of the IL-1Ra gene polymorphism between patients with gout and healthy control subjects. Furthermore, we did not detect any association of IL-1Ra genotype with the clinical and laboratory profiles in patients with gout. CONCLUSION: The results from the present study suggest that the interleukin-1 receptor antagonist gene polymorphism is not a genetic marker of susceptibility to gout for Taiwanese. Furthermore, our study also suggests that the IL-1Ra gene polymorphism is unrelated to the clinical characteristics of gout.

Female↗

Factors associated with musculoskeletal disability and chronic renal failure in clinically diagnosed primary gout.

OBJECTIVE: . To assess the association between a set of sociodemographic, clinical, and biochemical variables and the presence of musculoskeletal (MSK) disability and chronic renal failure in patients with primary gout defined using Wallace criteria. METHODS: Subjects were 90 patients with primary gout (98% male, age 54 +/- 12 years, 11.3 +/- 9.8 years with gout). A cohort nested case-control design was used. Analysis was done of the association between MSK disability or renal failure and a series of variables: age; duration of gout; body mass index; education level; income; serum glucose, cholesterol, triglycerides, and uric acid; Health Assessment Questionnaire score; obesity; family history of gout; high blood pressure; alcoholism; smoking habit; presence of tophi; ischemic cardiopathy; and use of colchicine, glucocorticoids, nonsteroidal antiinflammatory drug, or allopurinol. RESULTS: Forty-two patients (47%) had MSK disability, and 25/80 (31%) had renal failure. On logistic regression, presence of tophi (relative risk 4.3, 95% confidence interval 1.2-15.1), hypertriglyceridemia (RR 3.4, 95% CI 1.1-10), and history of ischemic heart disease (RR 8.3, 95% CI 1.6-41) were associated with MSK disability. Patient age was the only variable associated with renal failure. CONCLUSION: Optimal medical control of gout and its comorbidities may improve prognosis of gout, as suggested by our findings, in which a marker for poorly controlled gout such as presence of tophi in addition to high blood triglyceride levels and ischemic heart disease were associated with MSK disability. Older age was the only factor associated with renal failure, although this may only reflect declining renal function in the elderly.

Adult↗

Gout and risk for subsequent coronary heart disease. The Meharry-Hopkins Study.

BACKGROUND: Patients with gout are encountered frequently in clinical practice. Previous studies have suggested that hyperuricemia and gout may represent risk factors for coronary heart disease (CHD), the most common cause of death in American men. METHODS: Prospectively collected data from 2 longitudinal cohort studies of former medical students--371 black men in the Meharry Cohort Study and 1181 white men in the Johns Hopkins Precursors Study--were analyzed. The development of gout and of CHD was determined by physician self-report, and validated by using published criteria. The risk for CHD associated with gout was evaluated using Cox proportional hazards analysis. RESULTS: During a median follow-up of 30 years, there were 38 gout cases and 44 CHD events among the Meharry men, and 68 gout cases and 138 CHD events among the Hopkins men. Prior gout was not associated with an increased risk for incident CHD (relative risk = 1.20; 95% confidence interval, 0.37-3.92) among the Meharry men or among the Hopkins men (relative risk = 0.66; 95% confidence interval, 0.24-1.79). Multivariate analysis adjusted for known CHD risk factors did not alter these findings. CONCLUSION: These results, in black and white male physicians, do not suggest a role in men for targeting gout identification in the primary prevention of CHD.

Adult↗

Renal function in gout patients.

Patients with gouty arthritis were examined at Veterans General Hospital to evaluate whether their renal function is impaired and to define the factor(s), if any, of renal function deterioration. A total of 152 cases were included in the study, and the patients were divided into two groups. One group (n = 80) exhibited pure gout without any associated medical problems or preexisting renal disorders. The second group (n = 72) included patients with gout and hypertension. The group with pure gout was further stratified into patients with tophi (n = 21) and those without (n = 59). Seventy-two sex- and age-matched normal adults served as the control group. We found (1) that the renal function was impaired in the pure-gout group when compared with sex- and age-matched normal individuals (serum creatinine 1.56 +/- 0.64 vs. 0.90 +/- 0.16 mg/dl, p = 0.0001; creatinine clearance 59.91 +/- 30.90 vs. 97.10 +/- 27.19 ml/min, p = 0.0001); (2) that the renal function was significantly more aggravated in patients with clinically visible tophi than in those without (gout with tophi vs. gout without tophi: serum creatinine 1.89 +/- 0.90 vs. 1.44 +/- 0.48 mg/dl, p = 0.040; creatinine clearance 47.27 +/- 31.90 vs. 64.40 +/- 29.53 ml/min, p = 0.030), and (3) that a further significant decline of the renal function was noted in gouty patients with an associated medical illness, i.e., hypertension (gout with hypertension vs. pure gout: serum creatinine 2.10 +/- 0.97 vs. 1.56 +/- 0.64 mg/dl, p = 0.0001; creatinine clearance 45.06 +/- 24.69 vs. 59.91 +/- 30.90 ml/min, p = 0.0029).(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Gouty↗

Tophaceous gout of the lumbar spine mimicking pyogenic discitis.

BACKGROUND CONTEXT: Gout of the spine is very rare. Forty-one cases of gout affecting the spine have been reported. PURPOSE: To present a patient with tophaceous gout of the lumbar spine mimicking pyogenic discitis. STUDY DESIGN: Case report. METHODS: The medical record, including operative notes, progress notes, discharge summary, clinical notes, radiological study, and pathological studies was reviewed. RESULTS: The patient had acute low back pain and radiculopathy with high spiking fever. Therefore, pyogenic discitis was suspected. However, histological diagnosis revealed tophaceous gout. CONCLUSIONS: Tophaceous gout of the spine is very rare. However, when a patient presents with acute back pain and fever, spinal gout should be considered, particularly in a patient with a previous history of hyperuricemia or gout.

Allopurinol↗

Sex differences in gout epidemiology: evaluation and treatment.

BACKGROUND: Little is known about the characteristics, evaluation and treatment of women with gout. OBJECTIVE: To examine the epidemiological differences and differences in treatment between men and women in a large patient population. METHODS: The data from approximately 1.4 million people who were members of seven managed care plans in the USA for at least 1 year between 1 January 1999 and 31 December 2003 were examined. Adult members who had pharmacy benefits and at least two ambulatory claims specifying a diagnosis of gout were identified. In addition, men and women who were new users of urate-lowering drugs (ULDs) were identified to assess adherence with recommended surveillance of serum urate levels within 6 months of initiating urate-lowering treatment. RESULTS: A total of 6133 people (4975 men and 1158 women) with two or more International Classification of Disease-9 codes for gout were identified. As compared with men with gout, women were older (mean age 70 (SD 13) v 58 (SD 14), p<0.001) and had comorbidities and received diuretics more often (77% v 40%; p<0.001). Only 37% of new users of urate-lowering treatment had appropriate surveillance of serum urate levels post-initiation of urate-lowering treatment. After controlling for age, comorbidities, gout treatments, number of ULD dispensings and health plan, women were more likely (odds ratio 1.36, 95% confidence interval 1.11 to 1.67) to receive the recommended serum urate level testing. CONCLUSIONS: Women with gout were older, had greater comorbidities and more often used diuretics and received appropriate surveillance of serum urate levels, suggesting that the factors leading to gout as well as monitoring of treatment are very different in women and men.

Adult↗

High-resolution ultrasonography of the first metatarsal phalangeal joint in gout: a controlled study.

OBJECTIVE: To compare high-resolution ultrasound (HRUS) with conventional radiography in the detection of erosions in the first metatarsophalangeal joints (1st MTPJs) of patients with gout and to identify the characteristic sonographic features of gout. METHODS: HRUS examination of the 1st MTPJs of both feet was performed by two independent sonographers. The presence of joint and soft-tissue pathology was recorded. x Ray examination of the feet was performed on the same day and reported by the same radiologist. RESULTS: 39 male patients with gout and 22 age-matched control subjects (14 with an inflammatory arthropathy and 8 disease free) were studied. The agreement on erosion between HRUS and x ray was poor, kappa = 0.229 (non-weighted), with McNemar's test being significant (p<0.001) indicating a large number of false negative x rays. 22 MTPJs in patients with gout had never been subjected to a clinical attack of acute gout. In these MTPJs, there were 10 erosions detected by HRUS and 3 erosions on x ray. HRUS features significantly more prevalent in the patients with gout were hard and soft tophus-like lesions (p<0.01) and the double contour sign (p<0.01). CONCLUSIONS: These data show that HRUS may assist in the management of gout in two ways: first, by aiding in the diagnosis by identifying the sonographic features that may be representative of the disease, and, second, by allowing the early detection of erosive joint damage and/or tophaceous deposits even in clinically silent joints.

Anti-Inflammatory Agents, Non-Steroidal↗

Prevention and management of gout.

Gout is a common disease with a worldwide distribution. The major risk factor for the development of gout is sustained asymptomatic hyperuricaemia. Although pharmacological therapy of asymptomatic hyperuricaemia is not recommended, primary prevention of gout can be achieved through lifestyle changes including weight loss, restricting protein and calorie intake, limiting alcohol consumption, avoiding the use of diuretics in the treatment of hypertension, and avoiding occupational exposure to lead. The arthritis of gout can be readily managed with the use of nonsteroidal anti-inflammatory drugs (NSAIDs); systemic steroids or corticotrophin (adrenocorticotrophic hormone; ACTH) should be used in patients with contraindications to NSAIDs, or who are intolerant of them. Because of potential toxicity, colchicine should not be used to treat acute gout, but should be used in low dosage (0.6 to 1.2 mg/day) for prophylaxis of recurrent attacks of gout. The other cornerstone of prevention of recurrent gouty attacks is control of hyperuricaemia, which can be effectively accomplished with antihyperuricaemic therapy. The choice of agents, either uricosuric drugs or xanthine oxidase inhibitors, is based on the level of urinary uric acid excretion, renal function, age of patient, history of renal calculi and presence of tophi. Treatment and prevention of gout are exceedingly effective and patients can usually be managed by their primary care physician.

Acute Disease↗

Gout medication treatment patterns and adherence to standards of care from a managed care perspective.

OBJECTIVE: To determine allopurinol treatment patterns and adherence to published standards of care for patients with gout. PATIENTS AND METHODS: This retrospective claims analysis in a managed care database included patients 18 years or older, with continuous eligibility for 1 year before and after the start date and 2 or more visits during which the gout disease code (274.xx) was assigned or 1 or more pharmacy prescriptions for a gout-specific medication between January 1, 2000, and December 31, 2002 (intake period). Factors associated with compliance with allopurinol therapy were measured based on the medication possession ratio, and adherence to 2 quality-of-care indicators for gout management was assessed using multivariable logistic regression analysis. RESULTS: A total of 64.9% of allopurinol users had a modal daily dose or the most commonly observed daily dose of 300 mg/d, median length of therapy was 3 months, and a high proportion of patients had a medication possession ratio of 10% or less. Suggested quality-of-care Indicators for gout had low performance: 53% of patients with renal impairment received a modal daily dose of 300 mg or greater, and 83% of patients who started taking allopurinol did not have their serum urate levels measured within 180 days. Patients with gout flares were less likely to be compliant with allopurinol (odds ratio, 0.50; 95% confidence interval, 0.40-0.63). Patients with renal impairment at baseline were 3.2 times more likely to undergo serum urate testing than patients without renal impairment (odds ratio, 3.20; 95% confidence Interval, 1.25-8.23). CONCLUSION: There was low compliance with allopurinol therapy for treatment of gout. Patients potentially received suboptimal quality of care as measured by serum urate testing and appropriateness of allopurinol dosing in patients with renal impairment.

Adolescent↗

Clinical manifestations of gout and their management.

Gout is an inflammatory response to deposition of monosodium urate crystals in and around joints. It is primarily a disease of adult men. In acute gout, treatment options include non-steroidal anti-inflammatory drugs (NSAIDs), colchicine and corticosteroids, administered either intra-articularly, orally or parenterally. Asymptomatic hyperuricaemia does not require specific treatment, but should prompt screening for atherosclerosis risk factors, and general lifestyle modification to reduce serum urate levels. Gout presents differently in the elderly. Both women and men are affected, attacks are frequently polyarticular and in the upper limbs, and the gout may be associated with diuretic use, hypertension and renal impairment. In patients with peptic ulcer disease, selective COX-2 inhibitors provide another treatment option. In the presence of renal impairment, allopurinol is the treatment of choice for urate lowering therapy, but doses of allopurinol and colchicine must be adjusted. Urate lowering therapy should only be used if recurrent episodes of gout occur despite aggressive attempts to reverse or control the underlying causes. It should not be introduced or discontinued during an acute episode of gout, and gout prophylaxis (NSAIDs or colchicine) should be prescribed during the introduction of urate lowering therapy.

Adult↗

Gout treatment: what is evidence-based and how do we determine and promote optimized clinical care?

Gout, a common form of inflammatory arthritis, has been markedly understudied relative to other rheumatologic conditions. As a result, evidence guiding clinical management in gout has traditionally been lacking. Burgeoning data suggests that quality of gout care in gout is frequently suboptimal. In this paper, we examine the evidence supporting gout management strategies in clinical practice. In addition, we examine consensus building efforts that have culminated in the recent publication of gout management quality indicators. We also discuss the need for future initiatives aimed at improving patient safety and quality of care in gout.

Anti-Inflammatory Agents↗

Spatial scaling of metagenomic diversity reveals ecological disruption in the gut microbiome of gout patients.

Gout, a painful inflammatory arthritis, is characterized by hyperuricemia and monosodium urate crystal deposition, with growing evidence linking its pathogenesis to gut microbiome dysbiosis. However, traditional diversity metrics fail to capture the complex spatial organization of microbial communities. This study addresses this gap by applying the novel metagenomic Diversity-Area Relationship (m-DAR) model to investigate scaling laws in the gout microbiome-quantifying how metagenomic diversity changes with the number of individuals sampled. Our analysis of gut microbiomes from gout patients and healthy controls revealed fundamental ecological disruptions. We found that gout microbiomes exhibited significantly altered scaling patterns: they showed greater inter-individual dissimilarity (higher z-values) at the level of rare genes (q&#x2009;=&#x2009;0), but weaker scaling of dominant genes (q&#x2009;=&#x2009;1-3) compared to healthy controls. Crucially, the maximal accrual diversity (MAD) was substantially lower in gout patients, indicating a severely constrained potential for total microbial gene diversity. Furthermore, profiling of metagenomic functional gene clusters (MFGCs) uncovered widespread functional perturbations, including increased diversity scaling for carbohydrate-active enzymes (CAZy) but decreased scaling in essential metabolic pathways (KEGG, KO). These results demonstrate that the gout gut microbiome is defined by a loss of ecological structure, featuring reduced homogeneity in dominant taxa, expanded rare biosphere variation, and an overall collapsed diversity capacity. This work introduces an ecological framework for characterizing dysbiosis in gout that complements traditional diversity metrics and may inform the development of microbiome-based therapeutic strategies. Further research is needed to translate these ecological patterns into clinical applications.

Humans↗