Gout Highlights

Allan Gelber, M.D.

Abstract #2036: Weight Loss and the Risk of Hyperuricemia Among Men with A High Cardiovascular Risk Profile

Authors:

Y Zhu, Y Zhang, E Krishnan, HK Choi. Stanford University School of Medicine, Palo Alto CA, and Boston University School of Medicine, Boston MA.

Background:  

Recognizing that hyperuricemia is key precursor of gout, and that excess body weight, or adiposity, is a key determinant of serum uric acid levels, the authors sought to determine the relation of weight loss to the risk of hyperuricemia.

Methods:  

To examine this relationship, the investigators analyzed data from the Multiple Risk Factor Intervention (MRFIT) Trial.  This study includes information on body weight and serum uric acid, collected both at baseline and annually during follow-up, among 12,465 men, who possessed a high cardiovascular risk profile.

Results:  

Among the men in the cohort, the mean age and mean body mass index (BMI) at study entry were 46 years and 28 kg/m2, respectively.  Furthermore at baseline, the mean serum uric acid was 6.79 mg/dl; 73% of the men were found to be hyperuricemia. Importantly, weight loss was observed in 38% of visits (Table).  Furthermore, a clear dose response relationship was observed between change in body weight and risk of subsequent hyperuricemia. In particular, successively greater levels of weight loss were related to a successive lowering in risk of hyperuricemia As such, those men who had lost >= 10 kg during the period of follow-up had half (odds ratio 0.49; 95% confidence interval 0.43 – 0.55) the risk of incident hyperuricemia compared to those men whose weights were unchanged. In contrast, weight gain was associated to a successive increase in risk of developing hyperuricemia. As such, those men who gained 5 kg or more weight had an approximately 50% (odds ratio 1.55; 95%CI 1.29 – 1.86) greater risk of developing hyperuricemia than those men whose weights remain unchanged. These findings were observed in statistical modeling which adjusted for age, education, weight, as well as time-varying alcohol intake, hypertension, serum creatinine level, diuretic use and fructose use.

Conclusions:  

The authors conclude that weight reduction could result, in the general population, to a meaningful reduction in the rate of hyperuricemia. Moreover, these finding demonstrate that a weight loss of 10 kg or greater could cut the risk of subsequent hyperuricemia in half.

Editorial Comment:

The authors were able to undertake this examination in a well-known study, MRFIT. The present study furnishes rather compelling data that changes in body weight, in either the positive or negative direction, are directly related to the development of hyperuricemia. Furthermore, the observed dose-response relationship among such a large cohort of patients (>12,000 men) speaks to the causality of the relationship and is a strength of the study. One limitation is the definition of hyperuricemia that was studied. A cutoff value of 6 mg/dl is a relatively low cut-off value for hyperuricemia, and would tend to overestimate the burden of hyperuricemia. For example, at the Johns Hopkins Hospital, the upper limit of normal l serum uric acid, in normal is 7.2 mg/dl. It would be of interest to know the replication of their findings if the cutoff value for hyperuricemia were higher, at 7 mg/dl, rather than the employed cutoff value of 6 mg/dl. It is not expected that the direction of the observed relationships (of weight change and risk of hyperuricemia) would be altered, but that the frequency or incidence rate of hyperuricemia would be reduced.

Abstract #2037: Risk Factors for Incident Gout among Women: A Prospective Study

Authors:

V Bhole, M De Vera, MM Rahman, E Krishnan and HK Choi, Arthritis Research Centre of Canada, Vancouver, BC, Stanford University School of Medicine, Palo Alto, CA,  and Boston University School of Medicine, Boston, MA

Background:  

It is increasingly recognized that the incidence of gout is increasing in the adult population. It is also recognized that gout is becoming increasingly prevalent among the elderly and aging female component of the population. Yet, relatively little data are available regarding risk factors for (incident and/or prevalent) gout among women.  To further address this matter, the authors examined the relation between serum uric acid level and other purported risk factors for incident gout among women in the Framingham Heart Study.

Methods:

Using data from the Framingham Study, conducted over greater than 50 years (1950-2002), the authors examined the association of serum uric acid in relation to incident gout among 2,476 women and 1,951 men. In particular, the incidence of gout was determined according to various categories of serum uric acid. The risk of incident gout associated with a given category of uric acid was further adjusted for age, education, obesity, hypertension, diuretic use, alcohol use, glucose and cholesterol level, and menopausal status. Finally, the investigators explored where an interaction existed by gender by adding an interaction term to the final multivariate models.

Results:

At entry into the Framingham Study, the average age of the cohort was 47 years. Furthermore, among the women in the study, 50% of the women were originally postmenopausal. In addition, the average baseline uric acid level was 4.0 mg/dL among the women in the cohort. Among the women, the proportions with obesity, hypertension, diuretic use, and heavy alcohol use were 14%, 15%, 6%, and 6%, respectively. Over a median follow-up of 28 years, 304 incident gout cases were recorded, including 104 in women. Notably, the incidence of gout for women for uric acid levels of <5.0, 5.0-5.9, 6.0-6.9, 7.0-7.9 and ≥8.0 mg/dL were 0.8, 2.5, 4.2, 13.1, and 27.3, respectively, per 1000 person years of follow-up (p for trend <0.0001). Interestingly, among women, the magnitude of the association between categories of serum uric acid and incident gout was significantly lower than that observed among the men in the Framingham Study (p for interaction, 0.0002). In addition, the strength of the association of age, body mass index, diuretic use, and alcohol consumption with incident gout was similar among both the women and the men in the study.

Conclusions:

The authors concluded that higher levels of serum uric acid increase the risk of gout in a dose-response fashion among women as in men, but note that the incident rates, at give levels of serum uric acid, are lower in women than among men. The latter finding furnishes further insight as to why the incidence of gout among women is lower than that among men, beyond the lower baseline serum uric acid levels observed among women. Furthermore, age, obesity, hypertension, alcohol consumption, and diuretic use were related to incident gout among women, as among men.

Editorial:

It is of substantial interest to better understand the incidence of gout among women, inasmuch as national data increasingly support the notion that gout may be the leading cause of inflammatory arthritis in adult women, as has been the case among adult men. This abstract reinforces the long established finding that uric acid is related to incident gout, with an observed dose-response relationship among woman. But, the incidence of gout for a given category of serum uric acid is actually lower among women than among men. The reason for this discrepancy by gender has not as yet been explained. At the same time, the present abstracts also emphasizes that the association of  age, obesity, hypertension, alcohol consumption, and diuretic use and risk of incident gout is observed in women, just as has previously been demonstrated in men.

Abstract #2038: Drinking Water Can Reduce the Risk of Recurrent Gout Attacks.

Authors:

T Neogi, C Chen, C Chaisson, DJ Hunter, Y Zhang. Boston University School of Medicine, NEBH, Boston MA.

Background:

Dehydration is considered to be a possible trigger for attacks of acute gout. To test this hypothesis, the authors examined whether water consumption may reduce the risk for recurrent gout attacks.

Methods:

The authors conducted an internet-based case-crossover study to examine a set of putative risk factors for recurrent gout attacks and to assess whether exposure to these putative factors distinguishes those study participants who did, versus those who did not, experience a recurrent attack of gout. Importantly, in this methodology, each participant functions as his/her own control. In this manner, the frequency of a particular risk factor is compared during a period of a gout attack with that observed during periods free of any such attack. In terms of overall study design, the participants with an attack of gout within the past year were recruited online. Furthermore, they were asked to provide access to medical records with regard to their gout diagnosis. To examine the hydration (vs. dehydration) hypothesis, data were obtained regarding the amount of water consumed over the 24-hour period preceding an attack of gout in comparison to the amount consumed  over the 24-hour period during an intercritical period.

Results:

There were 535 participants who participated in this case-crossover, internet-based study. They were 78% male with a mean age of 53 years. Using logistic regression analysis, with adjustment for use of diuretic medication, alcohol consumption and purine intake, the main finding of the study was that increasing water intake was in fact related to a diminution in risk for recurrent attacks of gout. Notably, those study participants who consumed 2-4 glasses of water per day experienced a reduced rate of gout attacks [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.59-1.18]. Moreover, with even greater quantity of water consumed during the 24 hr period (i.e. >8 glasses per day), there was an even greater reduction in risk of gout attack [OR 0.54; 95%CI 0.32-0.90].

Conclusions:

The authors in fact demonstrated that water intake in the prior 24-hour was related to a significant reduction in risk for recurrent gout attacks. They further point out that drinking adequate water may be a simple, safe, and effective strategy to prevent recurrent gout attacks among patients with established gout.
Editorial: The overall hypothesis, namely that hydration status is directly related to the frequency of recurrent gout attacks, and that as an extension of this premise, that improved hydration might lead to a diminution in risk of recurrent gout attacks was most ably studied by the investigators. The authors further demonstrate a dose-response relationship between greater levels of water consumed over a 24 hour period with a successively greater reduction in rates of recurrent attacks of gout. The findings have tremendous broad implication and may potentially lead to a substantial reduction in attack rates in the general population, with excellent tolerability of the intervention. It would be of further interest to know, and is a limitation of the present undertaken, as to whether water specifically need be the hydration source, or if other beverages, more broadly, may achieve the same clinical end.

Abstract #2033: Hyperuricemia as an Early Marker for Type 2 Diabetes among Young Adults.

Authors:

M Bennett, BJ Pandya, E Krishnan, A Hariri, L Chung, HK Choi and O Dabbous, Stanford University School of Medicine, Palo Alto, CA, Takeda Pharmaceuticals International, Inc., Deerfield, IL, Boston University School of Medicine, Boston, MA

Background:

The authors sought to determine whether elevated levels of serum uric acid, or hyperuricemia, might predict the development of diabetes mellitus, a leading chronic health problem in western society. Moreover, the authors examined whether the association of uric acid with incident diabetes was independent of obesity, physical activity, and other known risk factors for diabetes.

Methods:

The investigators examined this question among a cohort of 5,012 adults, aged 18-30 years, who were free of diabetes at study entry. The study participants were composed of 46% men and 54% women and were followed prospectively for 15 years. The outcome of interest was the development of diabetes, which fulfilled the American Diabetes Association diagnostic criteria or which required use of hypoglycemic medication. The relationship between serum uric acid (sUA) and risk for subsequent diabetes was studied using logistic regression models, with adjustment for age, gender, ethnicity, body mass index (BMI), diastolic blood pressure, smoking, fasting glucose concentration, family history of diabetes, and a physical activity score.

Results:

Just over half (51%) of the study participants were African-American. The mean±SD age at study entry was 24.8 years. Average BMI (kg/m2) was in the normal range at 22.4 kg/m2. Mean diastolic blood pressure and physical activity score (1 to 5 scale of increasing activity level) were 68.6±9.6 mm Hg and 3.3±1.1, respectively, at baseline. In multivariable regression models, the highest category of sUA (≥7.0 mg/dL) was associated with a two-fold (RR 1.94; 95% CI 1.16- 3.25) increase in risk of incident diabetes, after adjustment  for age, gender, ethnicity, BMI, diastolic BP, smoking fasting glucose and family history of diabetes as well as physical activity score.

Conclusions:

In this study, increased levels of sUA were associated with an increase in risk for type 2 diabetes. These data expand on previously established, cross-sectional associations between hyperuricemia and diabetes.

Editorial:

A strength of the study is the nearly equal composition of African Americans and non-African Americans, lending claim to generalizability to more than one racial group. At the same time , it would be of interest to explicitly perform analyses which are stratified according to race, to confirm this association in more than one racial group. In addition, the main implication of the study is that gout, as the primary clinical manifestation of hyperuricemia, may in and of itself be a risk factor for type 2 diabetes mellitus. This potential association has, however, not as yet been demonstrated.  The actual pathogenic link between uric acid and diabetes has also not as yet been defined.

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