Trends in the manifestations of gout in Taiwan

S.-Y. Chen, C.-L. Chen, M.-L. Shen1 and N. Kamatani2

Clinic of Gout, Department of Internal Medicine, Taipei Municipal Ho-Ping Hospital, Taiwan, 1Division of Biometry, Department of Agronomy, National Taiwan University, Taiwan and 2Institute of Rheumatology, Tokyo Women’s Medical College, Japan.

Correspondence to: S.-Y. Chen, Clinic of Gout, Department of Internal Medicine, Taipei Municipal Ho-Ping Hospital, 33, Sect. 2, Chung-Hua Rd, Taipei city, Taiwan. E-mail: shihyangchen1{at}mac.com


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Objective. To elucidate the recent changes in the clinical manifestations, risk factors and disorders associated with gout.

Methods. All gouty cases in Ho-Ping Gout Database were divided into two groups according to the date of first visit to our clinic: 1983–1991 (earlier group) and 1992–1999 (later group). Study variables were compared between these two groups.

Results. In the later group, the age at onset of gout was lower by 2.7 yr (P < 0.0001) and the percentages of female gout and familial gout were higher (P = 0.0046 and P < 0.0001, respectively). Joint counts and the percentage of frequency of attacks >=6 times/yr were lower in the later group (P < 0.0001), while the percentage of tophaceous gout was higher by 0.8% in the later group (P = 0.0004). The percentage of first attack at ankle was higher (P < 0.0001), while those at Achilles tendon, knee and upper extremity were lower in the later group (P < 0.0001). The percentages of diuretic use and alcohol consumption were lower in the later group (P < 0.0001). The percentages of obesity, hypertriglyceridaemia and nephrolithiasis were higher (P < 0.0001), while the percentages of hypertension and hypercholesterolaemia were lower in the later group (P < 0.0001 and P = 0.0003, respectively). The percentages of type 2 diabetes mellitus and renal insufficiency were not significantly different in multivariate analyses.

Conclusion. The age of onset, clinical manifestations, risk factors and disorders associated with gout have recently changed in Taiwan.

KEY WORDS: Gout, Risk factors, Obesity, Hypertension, Diabetes mellitus, Hyperlipidaemia, Nephropathy.


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Gout is a common rheumatic disease in Taiwan with a frequency between 0.3 and 0.6% [1]. Although the aetiology of gout has not been fully elucidated, many risk factors including alcohol consumption, diuretic use, obesity and hereditary background have been indicated [2]. In addition to the articular involvements, gout is also associated with many disorders including hypertension, type 2 diabetes mellitus (DM), hyperlipidaemia, renal insufficiency and renal calculi [2, 3]. The associations of these disorders in gouty patients are also caused by the interplay of both genetic and environmental factors with different relative contributions [4].

Several studies have shown that hyperuricaemia and gout are on the increase in many countries [59] and a recent national survey in Taiwan has also shown this trend [10]. However, the aetiology of increased prevalence of gout in Taiwan is unclear. Also, the clinical manifestations of gout might have changed. To elucidate the recent changes in the clinical manifestations, risk factors and associated disorders with gout, we performed a retrospective study involving 27 190 gouty cases.


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Ho-Ping Gout Database
The Ho-Ping Gout Database is a database that contains the clinical and laboratory data of all gouty patients who have visited the out-patient department of the Gout Clinic at Taipei Municipal Ho-Ping Hospital. The patients came to our clinic independently, not by referral from primary care doctors; the patients were from various parts of Taiwan, mostly in the northern urban area. Although aborigines in Taiwan were reported to have a much higher prevalence of gout than other Taiwanese people [11], aborigines were very rare in this database. This database was set up in January 1983 by Dr Ching-Lang Chen for the purpose of studying clinical aspects of gout. All new patients diagnosed as having gout according to the Wallace criteria [12] at our clinic were routinely interviewed and physically examined by our rheumatologists to complete a questionnaire including their birth date, age at onset, other associated disorders, medications, family history of gout and amount of alcohol consumption.

After the interview, patients’ body weights and heights were measured by a nurse. Patients’ serum samples were collected the next morning for biochemical tests after overnight fasting. If the patients were taking anti-hyperuricaemic, diuretic or lipid-lowering medications, they undertook the biochemical tests after 1 month of discontinuation of these medications. Only patients taking diuretics for hypertension, but not for congestive heart failure or renal insufficiency, were asked to discontinue this medication before the blood test and this process had been approved by our institutional ethical committee on conducting experiments on humans (The Committee of Medical Ethics of Ho-Ping Hospital). All the above results were keyed into a computer database for future analysis. After the second visit, every patient was followed up at our clinic every 3 months.

Protocol
A total of 27 190 patients in the Ho-Ping Gout Database from January 1983 to December 1999 were included in this study. Subjects were divided into two groups according to whether their first visit to our clinic was before or after January 1992, the midpoint of this study. Study variables were compared between the two groups.

Study variables
Age at onset, duration of disease, site of first attack, joint count, frequency of attacks, tophaceous gout, female gout, drinking history, diuretic use, positive family history, obesity, hypertension, type 2 DM, hypertriglyceridaemia, hypercholesterolaemia, renal insufficiency and renal calculi were selected as independent variables.

Study variables were defined as follows. The time elapsed since onset of gout was calculated as the result of age at first visit minus age of onset, and the value was recorded as 0 if the first attack occurred less than 1 yr before the first visit. Frequency of attacks was divided into <6 or >=6 times per year before the first visit, because in our previous report [3] about half the patients had >=6 attacks per year. Joint count was defined as the total number of joints involved since the first gouty attack. Positive drinking history was defined as drinking more than 1 bottle of alcoholic beverage every week by history. Positive history of diuretic use was defined as taking diuretics before the onset of gout. A patient could only be said to have a positive family history of gout if one or more of the gouty patient’s third-degree or closer relatives was also affected by gout and the diagnosis had been confirmed by a rheumatologist by history. Obesity was defined as a body mass index (BMI) of over 30 kg/m2. Hypertension and type 2 DM were defined as the diagnostic standards [13, 14] indicated. Hypertriglyceridaemia was defined as a serum triglyceride level of over 2.26 mmol/l, while hypercholesterolaemia was defined as a serum total cholesterol level of over 6.22 mmol/l. Renal insufficiency was defined as a serum creatinine level of over 132.6 µmol/l.

Laboratory tests
Sera extracted from blood samples were stored at -70°C and analysed within 24 h. Serum urate, glucose, total cholesterol and triglyceride concentrations were measured by an autoanalyser (Biotechnica model ARCO PC, Rome, Italy) at Taipei Municipal Ho-Ping Hospital.

Statistical analysis
Data of study variables were analysed by Student’s t or {chi}2 tests in univariate analyses. Although there was a great disparity in the number of patients between the two groups that could cause a greater variance of their differences on univariate analysis, the case numbers in each group were great enough to compensate for this defect. All variables were also examined together by logistic regression on multivariate analysis. Controlling for the covariates of age, gender and time elapsed since onset of gout that could bias the results, these three covariates were added into the model of multivariate analysis singly or together to see their effects. Also, because this is a retrospective study and some data were missing for various reasons, the valid and missing numbers for each variable were also given in the results.


    Results
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Background data (Table 1)
When the background data before and after 1992 were compared, the age at onset of gout decreased significantly by 2.7 yr, while the percentage of female gout increased significantly by 0.8%. The time elapsed since onset of gout was not significantly different between the two groups.


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TABLE 1. The background data of subjects before and after 1992

 
Clinical manifestations
Although both joint counts and the percentage of patients with attacks >=6 times a year decreased, the percentage of tophaceous gout increased significantly by 0.8% after 1992 (Table 2). These results did not change even after controlling for age, gender and time elapsed since onset of gout (P < 0.0005 for all the above variables). For the site of first attack, the percentage of podagra did not change significantly after 1992 (Table 3). However, the percentage of first attack at the ankle joint increased significantly by 5.2% and that at the Achilles tendon, knee and upper extremity decreased significantly after 1992 (Table 3).


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TABLE 2. The clinical manifestations, risk factors and associated disorders with gout before and after 1992

 

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TABLE 3. The comparison of sites of first gouty attack before and after 1992

 
Risk factors (Table 2)
After 1992, the percentages of alcohol consumption and diuretic use both decreased significantly by 3.9%. The percentage of diuretic use after 1992 was below 1%. However, the percentage of positive family history increased significantly and the percentage after 1992 was 1.7 times that before 1992. The above results did not change even after controlling for age, gender and time elapsed since onset of gout (P < 0.0001 for all the above variables).

Associated disorders (Table 2)
After 1992, the percentage of hypertension decreased significantly by 12.6%. The percentage of obesity and hypertriglyceridaemia increased significantly by 3.5% and 3.7%, respectively. However, the percentage of hypercholesterolaemia decreased significantly by 2.5%. The above differences also remained significant on multivariate analysis and after controlling for age, gender and time elapsed since onset of gout (P < 0.0005 for all the above variables). Although the percentage of type 2 DM and renal insufficiency decreased significantly on univariate analysis, the difference became insignificant on multivariate analysis that included all variables or after controlling for age, gender and time elapsed since onset of gout (P > 0.1 for both variables). The percentage of renal calculi increased significantly by 2.2%, and the difference remained significant on multivariate analysis that included all variables or after controlling for age, gender and time elapsed since onset of gout (P < 0.0001).


    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Our results demonstrate that the age at onset of gout in Taiwan has decreased, while the percentage of female gout has increased. Therefore, the growing population of patients with gout in Taiwan should partly be attributed to the increases in young and female cases. Also, we found that the clinical manifestations of gout have changed. Although the first metatarsophalangeal (MTP) joint is still the most frequent site of first attack, first attack now occurs more frequently at the ankle joint and less frequently at the Achilles tendon, knee and upper extremity. The aetiology of changes in the site of first attack is not clear and it might be caused by the changes in the composition and risk factors of the gouty population, which should be determined by further study. Although the time elapsed since onset of gout has not changed, this study shows that the joint counts and frequency of attacks have now decreased. However, the decrease in the extent and frequency of gouty attack was not associated with a reduction in the prevalence of tophaceous gout. On the contrary, the prevalence of tophaceous gout in Taiwan has increased. These results may suggest the presence of some unknown factors other than the extent or frequency of arthritic attacks that could contribute more to tophus formation, and further study on the aetiology of tophaceous gout could be helpful in elucidating this trend.

This study also shows that the risk factors for gout in Taiwan have changed recently. The contribution of alcohol consumption has decreased, and diuretic use is no longer an important environmental factor for gout. On the contrary, familial gout has increased dramatically and its percentage in our clinic has nearly doubled since 1992. There is no evidence for an increase in the proportion of consanguineous sexual intercourse in Taiwan. Increased interaction between genetic and environmental factors may be attributable. The rapid increase in environmental risk factors, such as excess intake of a high caloric and purine-rich diet, may have uncovered the hidden defective genes for gout in Taiwan, with subsequent increased prevalence of familial gout. However, further studies are needed to validate this idea.

Also, our results show that the metabolic disorders associated with gout have changed recently. Gout has become more closely associated with obesity and hypertriglyceridaemia, but hypertension and hypercholesterolaemia, both of which should be related to obesity and hypertriglyceridaemia [15], do not follow this trend. The decreased association of gout with hypertension and hypercholesterolaemia is contrary to the trend in the general population of Taiwan, where the prevalence of these disorders is increasing [16]. Although the prevalence of type 2 DM in the general population is also increasing [16], this study shows that the association of gout with type 2 DM has decreased and the decreased association is confounded by other variables such as hypertension or hypercholesterolaemia. The above results indicate that different mechanisms are responsible for individual metabolic disorders associated with gout. Further studies are needed to determine these mechanisms.

In addition, the proportion of the patients with renal calculi and renal insufficiency has changed. Male gender, hypertension and obesity are all risk factors of nephrolithiasis [17], but the increased prevalence of renal calculi in gout is independent of the changes in these factors in this study. Other factors such as acidity of urine or amount of uric acid excretion, which were not analysed in this study, might be more attributable. On the contrary, the decrease in the percentage of renal insufficiency in gouty patients is confounded by other covariates. The decrease in the prevalence of hypertension should be most attributable, while the other factors such as age, gender and tophaceous gout may be less attributable.

In conclusion, we have shown that the features of gout have changed recently in Taiwan. We found differences in the age of onset, clinical manifestations, risk factors and associated disorders of gout between the patients before 1992 and those thereafter. This work for the first time demonstrated the changes in the features of gout in a country using a large-scale clinical database.


    References
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Submitted 1 February 2002; Accepted 28 April 2003





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