The prevalence of hyperuricemia in China: a meta-analysis

Background The prevalence of hyperuricemia varied in different populations and it appeared to be increasing in the past decades. Recent studies suggest that hyperuricemia is an independent risk factor for cardiovascular disease. However, there has not yet been a systematic analysis of the prevalence of hyperuricemia in China. Methods Epidemiological investigations on hyperuricemia in China published in journals were identified manually and on-line by using CBMDISC, Chongqing VIP database and CNKI database. Those Reported in English journals were identified using MEDLINE database. Selected studies had to describe an original study defined by strict screening and diagnostic criteria. The fixed effects model or random effects model was employed according to statistical test for homogeneity. Results Fifty-nine studies were selected, the statistical information of which was collected for systematic analysis. The results showed that the pooled prevalence of hyperuricemia in male was 21.6% (95%CI: 18.9%-24.6%), but it was only 8.6% (95%CI: 8.2%-10.2%) in female. It was found that thirty years was the risk point age in male and it was fifty years in female. Conclusions The prevalence of hyperuricemia is different as the period of age and it increases after 30 years in male and 50 in female. Interventions are necessary to change the risk factors before the key age which is 30 years in male and 50 in female.


Background
Hyperuricemia (HU) is a result of multifactor interactions including gender, age, genetic and environmental factors. Classically, the following conditions are associated with HU: alcoholism, obesity, hypertension, dyslipidemia, hyperglycemia, diabetes mellitus, lithiasis, renal failure, and medication use (diuretics, cyclosporine, low-dose aspirin) [1]. In the past several decades, the prevalence varied greatly and appeared to be increasing. There was lots information that demonstrated the importance of serum uric acid to the clinical prognosis, so the importance of HU is increasing. It reported that 18.8% of the patients with HU developed into gout in a 5 year follow-up [2]. Independent association between HU and cardiovascular disease has been found in many studies [3,4]. Hyperuricemia has been reported to be associated with several components of metabolic syndrome (MetS) and authors have postulated that increased concentrations of uric acid may be another important component of the syndrome [5].
With rapid economic development, possibility of improved nutrition and promotion of successful heath and medical care programs in China, life expectancy has been prolonged and the elderly population has increased; thus prevention and control of chronic diseases have become more important than before. Hyperuricemia may induce many complications, such as chronic gout, distortion of joint and renal failure, which may increase medical care costs. Therefore, it is important to study the hyperuricemia in China, in all developing countries, even in the whole world.

Search strategy
Studies were identified from the following electronic databases: CBMDISK, Chongqing VIP, CNKI and MEDLINE, using the terms 'hyperuricemia', 'HU' and 'prevalence'. No attempt was made to retrieve unpublished studies. The study did not include epidemiological studies in the areas of Hong Kong, Macao and Taiwan, because they are different from the Chinese mainland in the cultural activity and socioeconomic status and hence the prevalence of hyperuricemia and gout in those areas would be different from the Chinese mainland.

Inclusion and exclusion criteria
In order to meet the analysis requirements and reduce deviation, selected studies fulfilled the following criteria: (i) case collection based on field survey; (ii) the study based on population samples rather than volunteers; (iii) There should be validated diagnostic criteria and accurate study dates; (iv) If there were many articles based on the same sample, only the one that reported the most detailed data was included. It was confirmed that all articles had the same diagnostic criteria. Studies were excluded if we could not obtain information necessary for the computation of prevalence in different sex and age from the articles or the authors.

Quality of the studies
We accessed the quality of studies using the framework suggested by the Cochrane Collaboration. For the inclusion decision, quality assessment was carried out independently by three reviewers. If two of them or three agreed, the study can be included to the meta-analysis. The data from all included studies were clearly tabulated, and deviations were taken into account and identified during the quality assessment stage.

Data analysis
We used a published systematic analysis technique to calculate the pooled prevalence of hyperuricemia and gout from all eligible studies. Summary of prevalence estimates were obtained using fixed-effects or random-effects metaanalysis which determined by I 2 . Statistical heterogeneity was assessed through I 2 statistic and its values of 25%, 50% and 75% correspond to low, moderate and high heterogeneity. The date which was low heterogeneity was chose the fixed-effects meta-analysis and others were chose random-effects meta-analysis. Subgroup analysis including sexes, ages and areas was also performed. Figure 1 summarized the process of identifying eligible epidemiological studies. There were 59  studies left after the quality assessment. Table 1 showed the characteristics of the studies, which covered 23 provinces in the review. The prevalence of HU and 95%CI in male and female were calculated separately for each study, also the sample size and published years can be found ( Figure 2, Figure 3). The male population of 223,315 was investigated, and cases of 52,998 HU were selected. It was 165,620 in female, and cases of 19,586 HU were selected. The pooled prevalence of hyperuricemia in male was 21.6% (95%CI: 18.9%-24.6%) and it was only 8.6% (95%CI: 8.2%-10.2%) in female (Table 2), it was also found that the prevalence in female was lower than that in male in every age group. Table 2 also showed the prevalence of hyperuricemia in different gender and area. Heterogeneity of the analysis was moderate. The prevalence ranged from 8.4% to 8.6% in female, and it ranged from 19.6% to 26.8% in male. Table 3 demonstrated the prevalence of hyperuricemia in different age and area. It was found that thirty was the risk point age in male and it was fifty in female. The prevalence of female in northern and eastern China was 2.6% in~30 age group, and it was high to 31.2% in western China of male in 51-60 age group.

Discussion
The prevalence of hyperuricemia varies in different populations and areas. In Turkey [65], one study reported that 19% of the men and 5.8% of the women had hyperuricemia and the overall prevalence of hyperuricemia was 12.1% in the urban population. In Nepal [66], 3794 people which were from Chitwan districts were investigated, and the prevalence of hyperuricemia was 21.42%. In Seychelle [67], the cross-sectional health examination survey based on a population random sample which included 1011 subjects aged 25 to 64 years showed that the prevalence of hyperuricemia was 35.2% and 8.7% in men and women, respectively. In Thailand [68], an across-sectional study of  1381 patients who firstly participated in annual health examinations during the period of July 1999 through February 2000 reported that the prevalence of hyperuricemia was 10.6%, but it was 18.4% and 7.8% in men and women, respectively. In Java [69], the prevalence of hyperuricemia was investigated by a survey of a total population of 4683 rural adults and the result was 24.3%. In United States [70], the prevalence rate of asymptomatic hyperuricemia in the general population was estimated at 2-13%. The prevalence of gout and/or hyperuricemia increased about 2 cases per 1000 enrollees over 10 year (1990-1999) in the overall population. In Japan [71], a total of 9,914 individuals (6,163 men and 3,751 women aged from 18 to 89 years) who were screened at Okinawa General Health Maintenance Association was screened. The result showed that the prevalence of hyperuricemia was 25.8% and it was 34.5%, 11.6% in men and women respectively. In New Zealand [72], hyperuricemia was more common in Maori men (27.1%) than in European men (9.4%) and in Maori women (26.6%) than in European women (10.5%). In Saudi Arabia [73], the prevalence of hyperuricemia was only 8.84%. In Taiwan island of China [74], the prevalence of hyperuricemia was high to 49.4% in Ayatals, but it was only 27.4% in non-aborigines. From the analysis, it was found that age and sex affected the serum uric acid levels and the prevalence of hyperuricemia: The factor of age It was found that the prevalence of hyperuricemia increased with the age in male and female. The prevalence was higher in male who were after 30 years old than that younger. But the point age was 50 in female. The physiologic and economic reasons may explain this difference. After 30 years old, the male would have a stable family and career. In female, the influence of sexual hormones may explain the point age. Young children of both sexes have equally low urate levels, so the prevalence is low. The study of Katrine demonstrated that the 45-64 age group was higher prevalence compared with the 18-44 age group [75]. Vitool's study showed that the prevalence were 4.3% and 1.3% in men and women, who were younger than 18 years, but it increased to 17.4% and 15.4% in the men and women from 30 to 39 [68]. A study about elderly people in Taiwan reported that Men at age 65 to 69 had the highest proportion of hyperuricemia which was 69.8%, but  woman at age more than 80 had the higher prevalence which was 50% [76].

The factor of sex
From the previous studies, it was found that serum uric acid levels were higher in men than in women, but it tended to be consistent between man and woman after the age of 50 [77,78]. The study of Gordon explained it that serum uric acid level increased after the menopause in females which attributed to the influence of sexual hormones [79]. The results of the study showed that male subjects had a higher prevalence of hyperuricemia than women, which was in line with findings of many studies from different countries [65][66][67][68][69][70][71][72][73][74].

Health Education and life customs
From the result of meta-analysis, it was found that the prevalence in different age of southern China was higher than that in northern China and the prevalence in western was higher than that in eastern, especially in male. The reason for that may be different life customs. In southern China, the mainly food is rice and it is sweat in northern China.
In the eastern China, the health service is better than that in western China. More health educations were carried out and the people had more health knowledge in eastern China, which may affect the prevalence of hyperuricemia. The reasons for the difference in prevalence need further research.

Conclusions
In conclusion, aging trend is more and more serious in China, even all the word, and the prevalence of hyperuricemia is higher in elderly. It was found that urate levels correlate with many recognized cardiovascular risk factors, including hypertension, diabetes mellitus, hypertriglyceridemia, obesity and insulin resistance. Multiple Risk Factor Intervention Trial (MRFIT) database showed that hyperuricemia was an independent risk factor for acute myocardial infarction [75]. The Italian Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study showed that serum urate levels in the highest quartile were associated with increased risk of all cardiovascular events (relative risk [RR] = 1.73) and fatal cardiovascular events (RR = 1.96) compared with urate levels in the second quartile [76]. So it is important to control the prevalence in elderly. Interventions are necessary to change the risk factors before the key age which is 30 years in male and 50 in female. At the same time, intervention to high risk group is urgent. In China, most of the studies concerned the eastern, especially in the urban areas, but it is necessary to study the western of China and rural areas. The cohort study with larger sample is necessary. This article only provides the narrowing window of hyperuricemia in China.