New developments in the epidemiology and genetics of gout

The prevalence of gout appears to be rapidly increasing worldwide and is no longer a disorder suffered primarily by over-fed alcohol consumers. Emerging risk factors include longevity, metabolic syndrome, and new classes of pharmacologic agents. In some ethnic populations, no obvious risk factors can explain the high incidence of hyperuricemia and gout, suggesting a genetic liability. Studies to identify genes associated with gout have included families with defects in purine metabolism, as well as families in whom the occurrence of gout is secondary to renal disorders such as juvenile hyperuricemic nephropathy and medullary cystic kidney disease. Case-control studies of isolated aboriginal cohorts suffering from primary gout have revealed several chromosomal loci that may harbor genes that are important to the development and/or progression of gout.     

Vascular mortality in patients with gout and in their families.

A mortality study was performed to determine death rates from coronary and cerebrovascular pathology in 180 patients with gout and their families. Lipid profiles were also analysed. Neither male nor female gout patients after presentation to hospital nor their male or female first-degree relatives were found to have an increased risk of dying from coronary artery or cerebrovascular disease. Families of hyperlipidaemic gout patients had a slightly increased incidence among males of death from coronary artery disease, a finding which may reflect the hypercholesterolaemia found among these relatives. It could have influenced the vascular mortality rate in families of hyperlipidaemic gout patients without any relationship to the diagnosis of gout itself.     

Gout: epidemiology and lifestyle choices

PURPOSE OF REVIEW: Recent scientific data serve to illuminate the links between dietary and other factors and the incidence of gout. This review summarizes recent literature about the prevalence and incidence of gout as well as risk factors for gout. RECENT FINDINGS: Epidemiologic studies suggest that the overall disease burden of gout is substantial and growing. Gout seems to be relatively common not only in men but also in older women. A recent large prospective study investigated several purported dietary factors for gout and confirmed some of the long-standing suspicions (red meats, seafood, beer, and liquor), exonerated others (total protein, wine, and purine-rich vegetables), and also identified potentially new protective factors (dairy products). A study based on the Third National Health and Nutrition Examination Survey suggested that these factors affect serum uric acid levels parallel to the direction of risk of gout. In addition, adiposity, weight gain, hypertension, and diuretics were all found to be independent risk factors for incident gout, whereas weight loss was found to be protective. SUMMARY: The disease burden of gout remains substantial and may be increasing. Some of the recently confirmed lifestyle factors may explain the increasing incidence of gout. The public health implications of dietary and lifestyle recommendations should take into account other associated health benefits and risks, because many of these factors have health effects beyond their influence on gout.     

Gout and hyperuricemia

The prevalence of gout in the United States has been rising steadily for the past two decades. Hyperuricemia is considered a necessary but not sufficient precondition for gout. Known risk factors for gout include male sex, hypertension, renal insufficiency, obesity/weight gain, diuretic use, lead exposure, and family history. The association of gout and hyperuricemia with coronary artery disease is controversial. Current evidence from the Framingham Study suggests that gout is in fact an independent risk factor for CHD. These data suggest that patients with gout should be screened for modifiable risk factors for CHD, and that early intervention in such patients may be worthwhile. Finally, the effect of AHU as risk factor for CHD remains unclear but is probably a weak one.     

Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the health professionals follow-up study

BACKGROUND: Limited prospective information exists on the relation between obesity and weight change and the risk of gout. Similarly, both hypertension and diuretic use have been considered risk factors for gout; however, their independent contributions have not been established prospectively. METHODS: We prospectively examined over a 12-year period (1986-1998) the relation between adiposity, weight change, hypertension, and diuretic use and incident gout in 47,150 male participants with no history of gout at baseline. We used a supplementary questionnaire to ascertain the American College of Rheumatology criteria for gout. RESULTS: During 12 years we documented 730 confirmed incident cases of gout. Compared with men with a body mass index (BMI) of 21 to 22.9, the multivariate relative risks (RRs) of gout were 1.95 (95% confidence interval [CI], 1.44-2.65) for men with a BMI of 25 to 29.9, 2.33 (95% CI, 1.62-3.36) for men with a BMI of 30 to 34.9, and 2.97 (95% CI, 1.73-5.10) for men with a BMI of 35 or greater (P for trend <.001). Compared with men who had maintained their weight (+/-4 lb) since age 21 years, the multivariate RR of gout for men who had gained 30 lb or more since age 21 years was 1.99 (95% CI, 1.49-2.66). In contrast, the multivariate RR for men who had lost 10 lb or more since the study baseline was 0.61 (95% CI, 0.40-0.92). The multivariate RRs of gout were 2.31 (95% CI, 1.96-2.72) for the presence of hypertension and 1.77 (95% CI, 1.42-2.20) for diuretic use. CONCLUSIONS: Higher adiposity and weight gain are strong risk factors for gout in men, while weight loss is protective. Hypertension and diuretic use are also important independent risk factors for gout.     

Is ritonavir boosting associated with gout?

Asymptomatic hyperuricaemia is associated with ritonavir therapy, but gout has rarely been reported. We present a retrospective cohort study of 1825 HIV-positive patients seen at one inner London HIV clinic over a two-year period. In all, 18 patients had gout, of whom 15 were receiving antiretroviral therapy. Seven had predisposing risk factors for gout (e.g. pyrazinamide therapy, haematological malignancy). Of the remaining 11 patients, two were on no medication and eight (73%) were receiving ritonavir as a boosted protease inhibitor (PI). By comparison, 11% of HIV-positive patients without gout were receiving ritonavir (odds ratio = 22; confidence interval = 5-104). Seven of the 18 patients had documented features of lipodystrophy and dyslipidaemia. Gout was seen in patients with known risk factors for gout or who were receiving ritonavir as a boosted PI and who also had lipodystrophy.     

Prevalence and risk factors for urolithiasis in primary gout: is a reappraisal needed?

OBJECTIVE: To assess the prevalence and risk factors for urolithiasis in primary gout. METHODS: One hundred forty patients with primary gout were studied. Urolithiasis was defined as a history of urolithiasis, or nephrolithiasis detected via ultrasonography in patients with no previous record of urolithiasis. Patient age, duration of gout, presence of tophi, obesity, alcoholism, high blood pressure, diabetes, hyperlipidemia, family history of urolithiasis, daily urine output, uricemia, urine pH, FeNa, FeUrate, urine pH/FeUrate index, and daily urine excretion of urate, sodium, calcium and potassium were compared between lithiasic and non-lithiasic subjects. RESULTS: Fifty-five (39%; 95% CI 31-47) patients had urolithiasis, of which 37 (26%) were diagnosed by clinical history and 18 (13%) by ultrasonography. Patients with a silent kidney stone diagnosed by ultrasound tended to have shorter evolution of gout. Aside from urinary H+ ion concentration (lithiasic subjects 5.17 +/- 3.9 microM/l; non-lithiasic subjects 3.80 +/- 3.01 microM/l; p = 0.02), no difference was found between lithiasic and non-lithiasic subjects for the other variables studied. CONCLUSION: Ultrasonography increased the probability of diagnosing urolithiasis by 50%, meaning the prevalence of urolithiasis in gout is likely higher than previously reported. A higher urinary H+ ion concentration was the only variable associated with urolithiasis. Due to advances in diagnosis of gout and urolithiasis, as well as biochemical assays, the prevalence and risk factors for urolithiasis in gout require reassessment.     

Determinants of vascular function in patients with chronic gout

Epidemiologic studies have proposed a relationship between hyperuricemia and cardiovascular (CV) risk. However, it is unclear whether uric acid (UA) is an independent risk factor for CV disease (CVD) after controlling for other predisposing conditions. Gout patients might have persistent systemic inflammation, which, in addition to hyperuricemia, may potentiate CVD. This study examined vascular function and markers of CV damage in gout patients when compared with healthy controls. Brachial artery flow-mediated dilatation, arterial compliance, and microvascular function were measured. Circulating apoptotic endothelial cells and endothelial progenitor cells were quantified by FACS and circulating biomarkers of CVD by enzyme-linked immunosorbent assay. Gout patients displayed significant increases in body mass index, C-reactive protein, UA, and triglycerides and decreases in high-density lipoprotein. There were no significant differences in other CV traditional risk factors, adhesion molecules, or chemokines. Gout patients did not differ from controls in vascular function. In univariate and multivariate analysis, UA was not associated with the quantified CV risk parameters. Despite an increase in several CV risk factors, inflammation, and UA, gout patients display normal endothelial function and no increases in biomarkers of CVD. These results do not support the notion that gout is an independent risk factor for premature CVD.     

Gout in African Americans

Purpose

African Americans have a substantially higher prevalence of risk factors for gout than Caucasians. The aim of the present study was to compare the risk for incident gout among African Americans and Caucasians.

Methods

Incidence rates of physician-diagnosed gout among 11,559 Caucasian men and 931 African American men aged 35 to 57 years and at high cardiovascular risk, observed for 7 years as a part of the Multiple Risk Factor Intervention Trial, were analyzed. Cox regression models were used to account for potential confounding by age, body mass index, diuretic use, hypertension and diabetes status, aspirin and alcohol consumption, and kidney disease.

Results

At baseline, after accounting for risk factors, African Americans had a 14% lower prevalence of hyperuricemia than Caucasians. Incidence of gout increased with increasing prevalence of risk factors in both Caucasians and African Americans. Ethnic disparities in incidence rates were most apparent among those without other risk factors for gout. In separate Cox regression models, after accounting for risk factors, African American ethnicity was associated with a hazard ratio of 0.78 (95% confidence interval [CI], 0.66-0.93) for physician-diagnosed gout and 0.88 (95% CI, 0.85-0.90) for incident hyperuricemia. Significant interactions were observed; the association was the strongest (hazard ratio 0.47; 0.37-0.60). These associations were unaffected by addition of serum urate as a covariate or by using alternate case definitions for gout.

Conclusions

After accounting for the higher prevalence of risk factors, African American ethnicity is associated with a significantly lower risk for gout and hyperuricemia compared with Caucasian ethnicity.     

Risk factors for gout developed from hyperuricemia in China: a five-year prospective cohort study

The aim of the study was to investigate the factors that promote the development of gout in Chinese patients with hyperuricemia. Chinese cohort with 659 patients with hyperuricemia who had no history of gout at base line had been followed up for 5 years. The baseline data of the general states (gender, age, occupation and education level), lifestyle and behavior (smoking, drinking, and diet), the major chronic diseases (diabetes and hypertension), family history and gout attacks, physical examination (height, weight and blood pressure), and blood parameters (creatinine, urea nitrogen, triglycerides, total cholesterol and high-density lipoprotein cholesterol) were recorded before the follow-up. Over the five-year period, 75 hyperuricemia patients developed gout. In the logistic regression model, shrimp intake and shell intake were the risk factors (P = 0.038 and P < 0.001, respectively) and, combined with diabetes, also served as risk factor for gout developed from hyperuricemia, with relative risk (RR) of 2.571 (95 % confidence interval (95 % CI), 1.110–5.953), and females served as protective factors of gout, with RR of 0.113 (95 % CI, 0.041–0.312, referred to male). We identified that shrimp intake and shell intake, combined with diabetes, were the independent risk factors, and females served as protective factors of gout in those suffering from hyperuricemia in coast regions of Shandong province, China.     

Recent advances in the epidemiology of gout

Gout remains among the most common of all inflammatory arthridities with an incidence that appears to have risen. Evidence is accumulating to support lifestyle and dietary factors, such as heavy consumption of beer and liquor as well as diets rich in meats and seafood as important gout risk factors. There is also a renewed interest in important associations between gout and other comorbidities like hypertension and cardiovascular disease. The importance of hyperuricemia on health considerations beyond the musculoskeletal system is an area worthy of even more study.     

Recent advances in the epidemiology of gout

Gout remains among the most common of all inflammatory arthridities with an incidence that appears to have risen. Evidence is accumulating to support lifestyle and dietary factors, such as heavy consumption of beer and liquor as well as diets rich in meats and seafood as important gout risk factors. There is also a renewed interest in important associations between gout and other comorbidities like hypertension and cardiovascular disease. The importance of hyperuricemia on health considerations beyond the musculoskeletal system is an area worthy of even more study.     

Characteristics of chronic gout in Northern Sulawesi, Indonesia

OBJECTIVE: To identify associations and possible risk factors for gout that may contribute to chronic tophaceous gout in rural and urban districts of North Sulawesi, Indonesia. METHODS: A total of 190 patients with chronic gout and 190 age and sex matched controls were selected from 28 community health centers. Potential risk factors including alcohol consumption, food habits, family history, body weight, related medical conditions, drug use, and laboratory investigations were sought. RESULTS: Alcohol consumption and certain food habits were associated with gout. A positive family history of gout and overweight were also significant risk factors. Renal impairment was found in 86.3% of patients and hyperuricemia in 92.1%. In controls, renal impairment and hyperuricemia were 7.4% and 32.6%, respectively. Patients with hypertension and nephrolithiasis were more at risk of having associated gout. There was a significant association between gout, hyperuricemia, hypercholesterolemia, hypertriglyceridemia, and higher levels of creatinine and urea. There was also a significantly lower level of urine uric acid in gout cases compared with controls. Gouty tophi were found in 91% of these cases with chronic gout. The use of diuretics for treating hypertension, continuing excessive alcohol consumption and purine-rich food habits in untreated gout, and hyperuricemia were associated with chronic and tophaceous gout. Urate-lowering drugs were not available in the community health centers. CONCLUSION: Severe tophaceous gout with deformities and disability is found in North Sulawesi. Prominent risk factors include alcohol, obesity, renal impairment, diet, hypertension, and family history. Improved education about gout seems needed. Urate-lowering drugs are not available in community health centers but are needed, especially in rural areas, as studied here.     

Association Between Gout and All-Cause as well as Cardiovascular Mortality: A Systematic Review

Gout affects 1% to 2% of the population, and the prevalence is increasing due to changes in diet and the ageing of the population. Its development and risk factors have been explored frequently, and recommendations for the diagnosis and management of gout implemented. Nevertheless, there is a lack of knowledge regarding the long-term impact on gouty patients. This systematic review therefore evaluates the association between gout and all-cause as well as cardiovascular mortality. A systematic literature search was performed, and seven long-term studies were ultimately analyzed. Six of them used multivariate regressions to assess the adjusted mortality ratio in gouty patients with reference to patients without the disorder. Despite differences in study designs, study populations, and definitions of gout, the results were consistent: There was an independent association between gout and all-cause as well as cardiovascular mortality. Knowing that patients with gout are at risk emphasizes the need for adequate care.     

原发性高尿酸血症及痛风易感基因研究进展

原发性高尿酸血症及痛风为多基因遗传性疾病.近期对该病进行的全基因组关联分析(GWAS)发现了多个与尿酸排泄及痛风发病相关的基因,为该病的病因学研究、疾病风险预测及防治提供了新思路.本文就此作一综述.

Abstract：

Primary hyperuricemia and gout are multifactorial conditions with strong genetic components. recently genome-wide association studies (GWAS) have revealed that several genes are related to primary hyperuricemia and gout which offers a thought for the research into the etiology, disease risk prediction, and prevention and treatment of this disease.     

An association of smoking with serum urate and gout: A health paradox

BackgroundThe potential effect of cigarette smoking on levels of serum urate and risk of gout has been considered by a large number of studies, either as the primary variable of interest or as a covariate.MethodsHere we systematically review the published evidence relating to the relationship of smoking with serum urate, hyperuricaemia, and gout.ResultsMany studies have reported that smoking reduces serum urate, however, the evidence has not been conclusive with other studies pointing to the opposite or no effect. It has also been suggested that smoking reduces the risk of gout, although there is some evidence to contradict this finding.ConclusionA consensus has yet to be reached as to the effect of smoking on serum urate levels and the risk of gout.     

Gout and the risk of acute myocardial infarction

OBJECTIVE: To determine if hyperuricemia and gouty arthritis are independent risk factors for acute myocardial infarction (MI) and, if so, whether they are independent of renal function, diuretic use, metabolic syndrome, and other established risk factors. METHODS: We performed multivariable logistic and instrumental variable probit regressions on data from the Multiple Risk Factor Intervention Trial (MRFIT). RESULTS: Overall, there were 12,866 men in the MRFIT who were followed up for a mean of 6.5 years. There were 118 events of acute MI in the group with gout (10.5%) and 990 events in the group without gout (8.43%; P = 0.018). Hyperuricemia was an independent risk factor for acute MI in the multivariable regression models, with an odds ratio (OR) of 1.11 (95% confidence interval [95% CI] 1.08-1.15, P < 0.001). In multivariable regressions in which the above risk factors were used as covariates, gout was found to be associated with a higher risk of acute MI (OR 1.26 [95% CI 1.14-1.40], P < 0.001). Subgroup analyses showed that a relationship between gout and the risk of acute MI was present among nonusers of alcohol, diuretics, or aspirin and among those who did not have metabolic syndrome, diabetes mellitus, or obesity. In separate analyses, a relationship between gout and the risk of acute MI was evident among those with and without those hyperuricemia. CONCLUSION: The independent risk relationship between hyperuricemia and acute MI is confirmed. Gouty arthritis is associated with an excess risk of acute MI, and this is not explained by its well-known links with renal function, metabolic syndrome, diuretic use, and traditional cardiovascular risk factors.     

Diet, alcohol, and gout: How do we advise patients given recent developments?

The disease burden of gout remains substantial and may be increasing as a result of trends in demographics and lifestyles. Recent scientific data serve to illuminate the links between dietary and other factors and risk for gout. These lifestyle factors affect not only the risk for gout, but also are risk factors for other chronic diseases of public health importance. Accordingly, dietary and lifestyle recommendations related to gout should consider their effect on many diseases beyond gout. These recommendations should reinforce established recommendations where the influence on gout parallels the influence on other diseases, and consider modifying the recommendations where they are divergent.     

Racial differences in the incidence of gout

Objective. To estimate the incidence of and examine risk factors for the development of gout in black and white male physicians. Methods. Data from 2 cohorts of former medical students, 352 black men in the Meharry Cohort Study and 571 white men in the Johns Hopkins Precursors Study, were analyzed. Cases of gout were identified by self-report. Baseline variables and incident hypertension were examined as risk factors for the development of gout in both cohorts. Results. The incidence of gout was 3.11 and 1.82 per 1,000 person-years in the black men and the white men, respectively (P < 0.05); the cumulative incidence was 10.9% and 5.8%, respectively (P = 0.04). The relative risk (RR) for gout among the black men was 1.69 (95% confidence interval [95% CI] 1.02–2.80). This excess risk persisted after adjustment for baseline systolic blood pressure (adjusted RR = 1.96 [95% CI 1.14–3.38]). Incident hypertension was independently associated with the development of gout in univariate analysis (RR = 3.78 [95% CI 2.18–6.58]); when this variable was included as a time-dependent covariate in a Cox model, the excess risk for gout in black men was reduced and no longer significant (adjusted RR = 1.30 [95% CI 0.77–2.19]). Conclusion. The approximately 2-fold excess risk for gout among black men is explained, in part, by a greater risk of incident hypertension.     

Clinical and family studies in Hungarian patients with gout

Summary In this study we examined 22 Hungarian male probands with gout and 105 of their first degree relatives. This was the first family study in Hungary in which the characteristics of distribution of gout and hyperuricaemia among patients with gout and their first degree relatives, as well as the possible correlation between the prevalence of the disease and MHC class I antigens was investigated. Our gout patients showed the following characteristics: (1) There was a typical onset after age 40, benign oligoarticular form of arthritis, underexcretion of uric acid, moderate hypertension without evidence of reduced renal function, and a relatively high frequency of hyperostosis. (2) The prevalence of hyperuricaemia and gout exceeded the general population level in the first degree relatives of our gout patients. (3) The distribution of MHC class I antigens among the first degree relatives of our patients with gout showed no characteristic patterns. (4) There was no correlation between HLA B27 antigens and prevalence of gout or hypeostosis in family sibling studies. (5) The high frequency of gout and hyperuricaemia, as well as the lack of characteristic HLA patterns among the first degree relatives of gout patients in our family studies, point to the possible cumulative effect of several genes and environmental factors in the etiopathogenesis of this disease.