J Nephrol DOI 10.1007/s40620-014-0082-z
ORIGINAL ARTICLE
Prevalence of hyperuricemia among Chinese adults: a national cross-sectional survey using multistage, stratified sampling Hong Liu • Xiao-Min Zhang • Yan-Li Wang Bi-Cheng Liu
•
Received: 13 November 2013 / Accepted: 14 March 2014 Ó Italian Society of Nephrology 2014
Abstract Background Hyperuricemia is a non-communicable disease that threatens human health, and its prevalence has been increasing in recent decades. However, there have been no national surveys about hyperuricemia performed in China. We aimed to investigate the prevalence of hyperuricemia and its risk factors in Chinese adults. Methods Using data from 36,348 participants aged 18 years and older from the China National Survey of Chronic Kidney Disease (a nationwide cross-sectional survey with a randomized, multistage, stratified sampling strategy), we investigated the prevalence of hyperuricemia. Male subjects with serum uric acid C416.0 lmol/l (7.0 mg/dl) and female subjects with C357.0 lmol/l (6.0 mg/dl) were diagnosed with hyperuricemia. The prevalence of hyperuricemia was calculated, and the factors associated with hyperuricemia were analyzed using logistic regression. Results The adjusted prevalence of hyperuricemia among Chinese adults in 2009–2010 was 8.4 % [95 % confidence interval (CI) 8.0–8.8 %], and it was 9.9 % (9.2–10.6 %) in men and 7.0 % (6.5–7.5 %) in women. The prevalence was much higher among urban than rural residents (14.9 vs. 6.6 %, p \ 0.01). Areas with high per capita gross domestic product (GDP) levels had higher prevalence of hyperuricemia. In the multivariate regression model, the
estimated glomerular filtration rate was inversely associated with hyperuricemia. Alcohol consumption, body mass index and serum triglyceride levels were positively correlated with hyperuricemia. Other factors independently correlated with hyperuricemia were age, sex, education level, area of residence, and economic development. In order to demonstrate the discriminatory power for hyperuricemia of the risk factors all together, we calculated the probabilities by logistic regression analysis, which represented the combined effects of these risk factors. Then, receiver operating characteristic analysis was used to demonstrate the value of the probabilities for hyperuricemia diagnosis. Finally, ROC curve analysis revealed the area under the curve was 0.746 (95 % CI 0.739–0.754), statistically significant for the association with hyperuricemia of these risk factors considered all together (p \ 0.001). Conclusions Hyperuricemia is prevalent in the economically developed areas of China. Our report indicates the feasibility of studying the influence that economic changes have on the prevalence of hyperuricemia. Keywords China
Hyperuricemia Epidemiology Prevalence
Introduction H. Liu and X.-M. Zhang contributed equally to this work. On behalf of China National Survey Collaborative Group of Chronic Kidney Disease. H. Liu X.-M. Zhang Y.-L. Wang B.-C. Liu (&) Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing 210009, Jiangsu, China e-mail: [email protected]
In recent decades, hyperuricemia has received increasing attention as a major public health problem because of its high prevalence and the associated increases in the risk of hypertension, cardiovascular disease, diabetes and chronic kidney disease (CKD) [1–5]. Hyperuricemia has also emerged as one of the metabolic diseases that threaten human health. Epidemiologic studies have observed an
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increasing trend in the prevalence of hyperuricemia in recent years [6, 7]. The prevalence of hyperuricemia varies across different populations and different areas. The results reported by the Okinawa General Health Maintenance Association in Japan revealed that the overall prevalence of hyperuricemia was 25.8 % (34.5 % in men and 11.6 % in women) [8]. Among the population of Bangkok, 59 % of men and 11 % of women had hyperuricemia, and the overall prevalence was 24.4 % [9]. China is the world’s largest developing country, and is characterized by distinct regional and economic diversity. However, to date, no national cross-sectional surveys have been performed to determine the prevalence of hyperuricemia in China. Using the data from the China National Survey of Chronic Kidney Disease, we aimed to investigate the prevalence of hyperuricemia and associated factors in Chinese adults.
Subjects and methods Participants and assessment criteria The current study used data from 36,348 participants aged 18 years and older from the China National Survey of Chronic Kidney Disease, which was a national cross-sectional survey using a randomized, multistage, stratified sampling strategy [10]. The ethics committee of Peking University First Hospital approved the study. All participants gave written informed consent before data collection. Male subjects with serum uric acid C416.0 lmol/l (7.0 mg/dl) and female subjects with C357.0 lmol/l (6.0 mg/dl) were diagnosed with hyperuricemia [11]. Hypertension was defined as a systolic blood pressure of 140 mmHg or more, diastolic blood pressure of 90 mmHg or more, any use of antihypertensive medication in the past 2 weeks, or any self-reported history of hypertension. Diabetes was defined as a fasting plasma glucose level of 7.0 mmol/l (126 mg/dl) or more, by the presence of hypoglycemic agents despite normal fasting plasma glucose, or any self-reported history of diabetes. Body mass index (BMI) was calculated by dividing weight in kilograms by height in square meters: subjects with BMI 24–28 kg/m2 were defined as overweight, and C28 kg/m2 as obese [12]. The urinary albumin to creatinine ratio (ACR, mg/g creatinine) was calculated. Albuminuria was defined as an ACR greater than 30 mg/g. The estimated glomerular filtration rate (eGFR) was calculated using an equation from the Modification of Diet in Renal Disease (MDRD) equation, based on data from Chinese patients with chronic kidney disease [10]. The MDRD equation was as follows: eGFR (ml/min per 1.73 m2) = 175 9 Scr-1.234 9 age-0.179 [for females 9 0.79], where Scr is the serum creatinine
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concentration (in mg/dl) and age is included in years. CKD was defined as eGFR \60 ml/min per 1.73 m2 or albuminuria. Statistical analysis We determined the prevalence of hyperuricemia according to sex, age, urban or rural residency, gross domestic product (GDP) and eGFR levels. In addition to crude prevalence, we also weighted prevalence estimates and comparisons to represent the total adult population in China. Synthesized weights were calculated from a sampling weight, a non-response weight, and a population weight. These weights were used to adjust for different selection probabilities, different response proportions, and deviations in the sample compared to the standard population, particularly for sex and age. Data from the 2009 China Population Sampling Census were used as the standard population. Continuous data are presented as mean and standard deviation (SD), except for ACR, which is presented as a median (interquartile range, IQR) because data were highly skewed. Categorical variables are presented as proportions. Relevant characteristics are described and stratified according to the presence of hyperuricemia. The association between hyperuricemia and relevant covariates was determined using multivariate logistic regression analysis. Odds ratios (OR) were used to evaluate the risk of hyperuricemia associated with sex, age, alcohol intake, rural versus urban residency, GDP per capita, hypertension, diabetes, waist circumference, BMI, plasma triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol, albuminuria, and eGFR. Receiver operating characteristic (ROC) analysis was used to demonstrate the discriminatory power for hyperuricemia of the risk factors all together. We used Epidata software (version 3.1) for data entry and management. All p values were two-tailed, and a p value of less than 0.05 was considered significant. The analyses were conducted using SUDAAN (version 10) and SAS (version 9.1).
Results The adjusted prevalence of hyperuricemia among Chinese adults in 2009–2010 was 8.4 % [95 % confidence interval (CI) 8.0–8.8 %]. The prevalences among men and women were 9.9 % (9.2–10.6 %) and 7.0 % (6.5–7.5 %), respectively. The mean serum urate levels were 332.4 lmol/l (5.6 mg/dl) among men and 268.9 lmol/l (4.5 mg/dl) among women. Urban residents had a much higher adjusted prevalence of hyperuricemia (14.9, 14.0–15.8 %)
J Nephrol Table 1 Prevalence of hyperuricemia by age, economic development and eGFR Number
Table 2 Characteristics of the study population according to hyperuricemia status
Hyperuricemia
With hyperuricemia (n = 5,381)
Without hyperuricemia (n = 30,967)
p
52.69 (15.95)
48.82 (15.52)
\0.01
n
Prevalence % (95 % CI)
16,019
2,775
9.9 (9.2–10.6)
Men
2,775 (51.6 %)
13,244 (42.8 %)
\0.01
Female 20,329 Area of residence
2,606
7.0 (6.5–7.5)
Urban residents
3,414 (63.45 %)
15,616 (50.43 %)
\0.01
High school education or above
2,370 (44.20 %)
11,479 (37.20 %)
\0.01
Current smoker
1,345 (25.00 %)
6,894 (22.26 %)
\0.01
Sex Male
Age (years)
Rural
17,318
1,967
6.6 (6.1–7.1)
Urban
19,030
3,414
14.9 (14.0–15.8) a
GDP per capita Tertile 1
14,528
1,507
10.4 (9.9–10.9)
Tertile 2
9,390
1,210
12.9 (12.2–13.6)a
2,664
a
Tertile 3
12,430
21.4 (20.7–22.2)
eGFR (ml/min per 1.73 m2)
Non-habitual drinker
875 (16.26 %)
4,549 (14.69 %)
\0.01
Habitual drinker
500 (9.29 %)
2,045 (6.60 %)
\0.01
Chronic cough
277 (5.3 %)
1,667 (5.63 %)
161 (2.99 %)
672 (2.17 %)
\0.01
2,323 (43.58 %)
10,328 (33.62 %)
\0.01
C90
23,308
2,734
11.7 (11.3–12.1)a
History of CVD
60–89
12,098
2,209
18.3 (17.6–18.9)a
Hypertension
a
\60
942
438
Total
36,348
5,381
46.8 (45.2–48.5) 8.4 (8.0–8.9)
GDP gross domestic product, eGFR estimated glomerular filtration rate, CI confidence interval a
The crude prevalences. The other prevalences are adjusted for synthesized weights
compared to rural residents (6.6, 6.1–7.1 %). Areas with high GDP levels had higher prevalence of hyperuricemia in both urban and rural areas (Table 1). As eGFR declined, the prevalence of hyperuricemia increased significantly. As many as 46.5 % of the participants with an eGFR less than 60 ml/min per 1.73 m2 had hyperuricemia (Table 1). The participants with hyperuricemia were older, more educated, and more likely to be men, to smoke, to consume alcohol, and to live in urban areas than those without hyperuricemia. The participants with hyperuricemia also had higher prevalences of cardiovascular disease, hypertension, and diabetes, compared to those without hyperuricemia (Table 2). Moreover, larger waist circumference, higher BMI, higher levels of serum triglycerides, and lower eGFR levels were observed in subjects with hyperuricemia. Table 3 shows the results of multiple logistic regression analysis: among all the variables listed in the table eGFR was most strongly associated with the serum urate level. An eGFR value between 60 and 90 ml/min was associated with an odds ratio (OR) of 2.76 (95 % CI 2.41–3.16) for hyperuricemia, and an eGFR less than 60 ml/min exhibited an OR of 12.61 (95 % CI 9.44–16.85) (Table 3). In addition, Table 3 shows that older age, being male, having a higher education level, alcohol intake, urban residency, economic development, obesity, and dyslipidemia were all independently associated with a higher risk of hyperuricemia. Compared with men, the odds ratio of having hyperuricemia was 0.65 for women. In order to demonstrate the discriminatory power for
0.35
Diabetes
523 (9.73 %)
1,966 (6.35 %)
\0.01
Waist circumference (cm)
82.52 (10.25)
79.45 (10.15)
\0.01
BMI (kg/m2)
24.40 (3.69)
23.39 (3.58)
\0.01
Total cholesterol (mmol/l)
5.36 (1.31)
4.79 (1.09)
\0.01
Triglycerides (mmol/l)
2.05 (1.72)
1.38 (1.18)
\0.01
LDL cholesterol (mmol/l) HDL cholesterol (mmol/l)
3.28 (1.09)
2.81 (0.90)
\0.01
1.41 (0.45)
1.44 (0.42)
\0.01
Scr (lmol/l)
82.99 (34.45)
72.32 (19.51)
\0.01
eGFR
92.86 (27.85)
106.72 (50.04)
\0.01
6.18 (10.99)
5.76 (13.17)
\0.01
(ml/min per 1.73 m2) Albuminuria [mg/g; median (IQR)] Data are presented as number (%) or mean (SD), unless stated otherwise. ACR is presented as a median because the data were highly skewed CVD cardiovascular disease, BMI body mass index, LDL low-density lipoprotein, HDL high-density lipoprotein, SCr serum creatinine, eGFR estimated glomerular filtration rate, ACR urinary albumin to creatinine ratio, IQR interquartile range
hyperuricemia of the risk factors all together in Table 3, we calculated the probabilities by logistic regression analysis, which represented the combined effects of these risk factors. Then, ROC analysis was used to demonstrate the value of the probabilities for hyperuricemia diagnosis. Finally, ROC curve analysis revealed an area under the curve of 0.746 (95 % CI 0.739–0.754), statistically significant for the association with hyperuricemia of these risk factors considered all together (p \ 0.001) (Fig. 1). Hypertension and diabetes were not significantly associated with an increased risk of hyperuricemia (p = 0.11, and p = 0.75, respectively).
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J Nephrol Table 3 Results of multiple logistic regression analysis of all the variables listed in the table which were associated with hyperuricemia Hyperuricemia (OR, 95 % CI)
p
Age (change of 10 years)
1.12 (1.06–1.18)
\0.01
Sex (women vs. men)
0.65 (0.55–0.77)
\0.01
Education Below high school (reference)
1.00
High school
1.29 (1.08–1.53)
\0.01
Above high school
2.14 (1.75–2.6)
\0.01
Current smoker
0.85 (0.72–1.01)
0.07
Alcohol intake Non-drinker (reference)
1.00
Non-habitual drinker
1.82 (1.56–2.13)
\0.01
Habitual drinker
2.31 (1.85–2.87)
\0.01
Hypertension
1.15 (0.97–1.36)
0.11
Diabetes
0.96 (0.76–1.22)
0.75
Urban residence
1.47 (1.24–1.75)
\0.01
(vs. rural residence) GDP per capita Tertile 1 (reference)
1.00
Tertile 2 Tertile 3
0.61 (0.50–0.75) 1.84 (1.52–2.23)
\0.01 \0.01
1.32 (1.12–1.55)
\0.01
Waist circumference
Fig. 1 ROC curve demonstrating the discriminatory power of the risk factors considered all together for hyperuricemia. Receiver operating characteristic (ROC) curve analysis demonstrated statistically significant value of these risk factors considered all together for hyperuricemia [area under the curve was 0.746 with 95 % confidence interval (CI) of 0.739–0.754, p \ 0.001]
BMI (kg/m2) \24 (reference)
1.00
24–28
1.15 (0.99–1.33)
[28 Total cholesterol
0.07
1.51 (1.20–1.91)
\0.01
1.24 (1.07–1.45)
\0.01
(C5.2 vs. \5.2 mmol/l) Triglycerides (mmol/l) \1.7 (reference)
1.00
1.7–2.26
2.10 (1.76–2.50)
\0.01
C2.26
3.23 (2.78–3.75)
\0.01
1.33 (1.12–1.58)
\ 0.01
C90 (reference) 60–89
1.00 2.76 (2.41–3.16)
\0.01
\60
12.61 (9.44–16.85)
\0.01
LDL-cholesterol (C2.59 vs. \2.59 mmol/l) eGFR (ml/min per 1.73 m2)
OR odds ratio, CI confidence interval, GDP gross domestic product, BMI body mass index, LDL low-density lipoprotein, eGFR estimated glomerular filtration rate
Discussion In this representative sample of Chinese adults, the prevalence of hyperuricemia was 8.4 %, which means that there were approximately 92.9 million adults with hyperuricemia in China in 2009 and 2010. A major strength of our study is that it is the first national cross-sectional survey using a
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multistage, stratified sampling design in a developing country with high regional and economic heterogeneity. Therefore, our study used a unique dataset to explore the effects of multiple variables on the burden of hyperuricemia and associated trends. Previous studies have estimated the prevalence of hyperuricemia in both developed and developing countries. The prevalence we found was similar to that found in some developing countries, such as Thailand (10.6 %) [13] and Saudi Arabia (8.4 %) [14], but it was much lower than in Taiwan (26.1 % among men and 17.0 % among women) [15] and in developed countries, such as the United States (21.4 %) and Japan (25.8 %) [6, 8]. However, areas in the top tertile of GDP per capita levels had a prevalence of hyperuricemia (21.4 %) that was similar to the prevalences in Taiwan and developed countries, and urban residents showed a higher prevalence than rural residents. Therefore, hyperuricemia is quite prevalent in areas with high GDP levels in China. The differences in prevalence of hyperuricemia may be attributed to the rapidly developing economy, the aging population [16], and discrepancies in lifestyle and dietary habits in Taiwan and developed countries. Moreover, developed countries have a heavier burden of related medical conditions, such as diabetes and stage 3–5 CKD, compared to developing countries. For example, a previous study reported that the prevalence of stage 3 CKD was 7.7 % in the USA, compared to 1.6 % in
J Nephrol
China [10]. Our study found that economic development is independently associated with hyperuricemia, which suggests the feasibility of studying the influence that economic changes have on the prevalence of hyperuricemia. Hyperuricemia is one of the important metabolic diseases related to lifestyle and dietary habits. In accordance with previous studies, we found that alcohol intake, BMI, and serum triglycerides levels were independently associated with hyperuricemia [17, 18]. And ROC analysis demonstrated a statistically significant value of these risk factors considered all together for hyperuricemia diagnosis. Economic level is an important factor that affects the intake of dietary nutrients and the content of the diets of Chinese residents, which may explain the relationship between economic development and hyperuricemia. Qiu et al. [19] also found that, compared with agricultural and pastoral areas, the odds ratio of having hyperuricemia was higher for people living in the big cities of northern China. Along with the rapid economic development of China, lifestyle and dietary habit have changed significantly and different geographic regions have unbalanced economic development and health education. Increased risk of hyperuricemia is the result of increased consumption of purine-rich animal products, high-fat foods, and alcohol, increasing obesity, and an aging population [20]. Meanwhile, studies have demonstrated that hyperuricemia is closely associated with an increased risk of hypertension, cardiovascular disease, diabetes and CKD, through pathophysiological mechanisms such as endothelial dysfunction, increased oxidative stress, vascular smooth muscle cell proliferation, insulin resistance, proinflammatory response and immune response [2, 5]. Therefore, hyperuricemia has emerged as an important chronic disease that threatens human health, and special attention should be paid to the prevention and treatment of hyperuricemia in the process of rapid economic development in developing countries. China is presently going through a period of economic transition and shifting dietary patterns, which constitutes an optimal time to prevent and reduce the increasing burden of hyperuricemia by improving lifestyle and dietary habits, promoting balanced diet, physical activity, weight control, and abstinence from alcohol. As was expected, eGFR was inversely associated with hyperuricemia, and nearly half of the subjects with stage 3–5 CKD had hyperuricemia in our study. Uric acid is clearly a marker for CKD as it is predominantly cleared by the kidneys and its level rises as GFR declines. In the past decades, some epidemiologic studies have demonstrated that hyperuricemia may also have a role in the pathophysiology of CKD progression [21, 22], which may work through some pathophysiological mechanisms mentioned above. However, the cross-sectional design limited our ability to make a causal inference. Larger interventional
clinical trials are needed to evaluate the effect of uric acid reduction on the genesis and progression of CKD in the future. Diabetes was not significantly correlated with hyperuricemia in our study. One explanation might be that in the early stages of diabetic nephropathy (DN), glomerular hyperfiltration increases urate excretion [23], and urate levels tend to increase with the progression of DN and impaired renal function. In our study, 58.5 % of the diabetic patients were in the early stages of DN, and the mean eGFR was 103.4 ml/min. In addition, the definition of diabetes did not include a 2-h postprandial blood glucose level. Thus, diabetes may have been underestimated, which may have affected the results. Our study has several limitations. First, the definition of hyperuricemia was based solely on serum urate levels. There may have been some patients with hyperuricemia who were taking uric-acid-lowering drugs and had normal urate levels during the survey. Therefore, the reported prevalence of hyperuricemia may have been underestimated. Second, although we adjusted for a variety of important confounding variables, residual confounding by other factors, such as dietary habits, cannot be entirely excluded. Third, since uric acid levels were not measured in some areas, we were unable to study the variance in hyperuricemia prevalence across different geographic regions. Finally, the cross-sectional design of the study makes it impossible to infer a causal relationship between hyperuricemia and associated factors. In conclusion, hyperuricemia is quite prevalent in the economically developed areas of China. Economic development is independently associated with hyperuricemia through its correlation with lifestyle and dietary habits. Considering the increasing prevalence and the adverse consequences of hyperuricemia, special attention should be paid to the prevention and treatment of hyperuricemia as economic development progresses in developing countries. And the most important steps are improving lifestyle and dietary habits, and intervening to prevent related diseases. Our report provides evidence for the feasibility of studying the influence that economic changes have on the prevalence of hyperuricemia. Acknowledgments This study was supported by the National Key Technology R&D Program from the Ministry of Science and Technology (China; 2007BAI04B10); the Department of Health in Jiangsu Province (H200936); the Science and Technology Commission of Shanghai (08dz1900502 and 07JC14037); the Natural Science Funds of Ning Xia (NZ08102); the Science and Technology Department of National Natural Science Funds (30660069); the National Natural Science Foundation of China; the Key Scientific and Technology Project from the Sichuan Science and Technology Department (05SG1635); the Program for New Century Excellent Talents in Universities from the Ministry of Education (China; BMU2009131); the International Society of Nephrology Research Committee; and the China Health and Medical Development Foundation. We thank
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J Nephrol Haiyan Wang of the Peking University Institute of Nephrology for her contribution to the statistical analyses and her constructive comments on the report. Conflict of interest conflicts of interest.
The authors of the manuscript declare no
References 1. Kawano Y (2011) Uric acid and blood pressure. Circ J 75:2755–2756 2. Puddu P, Puddu GM, Cravero E, Vizioli L, Muscari A (2012) The relationships among hyperuricemia, endothelial dysfunction, and cardiovascular diseases: molecular mechanisms and clinical implications. J Cardiol 59:235–242 3. de Oliveira EP, Burini RC (2012) High plasma uric acid concentration: causes and consequences. Diabetol Metab Syndr. 4:12 4. Sluijs I, Beulens JW, van der A DL, Spijkerman AM, Schulze MB, van der Schouw YT (2013) Plasma uric acid is associated with increased risk of type 2 diabetes independent of diet and metabolic risk factors. J Nutr 143:80–85 5. Filiopoulos V, Hadjiyannakos D, Vlassopoulos D (2012) New insights into uric Acid effects on the progression and prognosis of chronic kidney disease. Ren Fail 34:510–520 6. Zhu Y, Pandya BJ, Choi HK (2011) Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum 63:3136–3141 7. Trifiro` G, Morabito P, Cavagna L et al (2013) Epidemiology of gout and hyperuricaemia in Italy during the years 2005–2009: a nationwide population-based study. Ann Rheum Dis 75:694–700 8. Naqahama K, Iseki K, Inoue T, Touma T, Ikemiya Y, Takishita S (2004) Hyperuricemia and cardiovascular risk factor clustering in a screened cohort in Okinawa, Japan. Hypertens Res. 27:227–233 9. Uaratanawong S, Suraamornkul S, Angkeaw S, Uaratanawong R (2011) Prevalence of hyperuricemia in Bangkok population. Clin Rheumatol 30:887–893 10. Zhang L, Wang F, Wang L et al (2012) Prevalence of chronic kidney disease in China: a cross-sectional survey. Lancet 379:815–822 11. Fang J, Alderman MH (2000) Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study,
123
12.
13.
14. 15.
16. 17.
18.
19.
20.
21.
22.
23.
1971–1992. National Health and Nutrition Examination Survey. JAMA 283:2404–2410 Zhou BF, Cooperative Meta-Analysis Group of the Working Group on Obesity in China (2002) Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults: study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Asia Pac J Clin Nutr. 11:S685–S693 Lohsoonthorn V, Dhanamun B, Williams MA (2006) Prevalence of hyperuricemia and its relationship with metabolic syndrome in Thai adults receiving annual health exams. Arch Med Res 37:883–889 Al-Arfaj AS (2001) Hyperuricemia in Saudi Arabia. Rheumatol Int 20:61–64 Chang HY, Pan WH, Yeh WT, Tsai KS (2001) Hyperuricemia and gout in Taiwan: results from the Nutritional and Health Survey in Taiwan (1993–96). J Rheumatol 28:1640–1646 Christensen K, Doblhammer G, Rau R, Vaupel JW (2009) Ageing populations: the challenges ahead. Lancet 374:1196–1208 Miao Z, Li C, Chen Y et al (2008) Dietary and lifestyle changes associated with high prevalence of hyperuricemia and gout in the Shandong coastal cities of Eastern China. J Rheumatol 35:1859–1864 Villegas R, Xiang YB, Cai Q et al (2010) Prevalence and determinants of hyperuricemia in middle-aged, urban Chinese men. Metab Syndr Relat Disord. 8:263–270 Qiu L, Cheng XQ, Wu J et al (2013) Prevalence of hyperuricemia and its related risk factors in healthy adults from Northern and Northeastern Chinese provinces. BMC Public Health. 13:664 No authors listed (2003) Diet, nutrition and the prevention of chronic diseases. World Health Organ Tech Rep Ser 916: i–viii, 1–149 Hsu CY, Iribarren C, McCulloch CE, Darbinian J, Go AS (2009) Risk factors for end-stage renal disease: 25-year follow-up. Arch Intern Med 169:342–350 Jolly SE, Mete M, Wang H et al (2012) Uric acid, hypertension, and chronic kidney disease among Alaska Eskimos: the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. J Clin Hypertens (Greenwich). 14:71–77 Bandaru P, Shankar A (2011) Association between serum uric acid levels and diabetes mellitus. Int J Endocrinol 2011:604715
ORIGINAL ARTICLE
Prevalence of hyperuricemia among Chinese adults: a national cross-sectional survey using multistage, stratified sampling Hong Liu • Xiao-Min Zhang • Yan-Li Wang Bi-Cheng Liu
•
Received: 13 November 2013 / Accepted: 14 March 2014 Ó Italian Society of Nephrology 2014
Abstract Background Hyperuricemia is a non-communicable disease that threatens human health, and its prevalence has been increasing in recent decades. However, there have been no national surveys about hyperuricemia performed in China. We aimed to investigate the prevalence of hyperuricemia and its risk factors in Chinese adults. Methods Using data from 36,348 participants aged 18 years and older from the China National Survey of Chronic Kidney Disease (a nationwide cross-sectional survey with a randomized, multistage, stratified sampling strategy), we investigated the prevalence of hyperuricemia. Male subjects with serum uric acid C416.0 lmol/l (7.0 mg/dl) and female subjects with C357.0 lmol/l (6.0 mg/dl) were diagnosed with hyperuricemia. The prevalence of hyperuricemia was calculated, and the factors associated with hyperuricemia were analyzed using logistic regression. Results The adjusted prevalence of hyperuricemia among Chinese adults in 2009–2010 was 8.4 % [95 % confidence interval (CI) 8.0–8.8 %], and it was 9.9 % (9.2–10.6 %) in men and 7.0 % (6.5–7.5 %) in women. The prevalence was much higher among urban than rural residents (14.9 vs. 6.6 %, p \ 0.01). Areas with high per capita gross domestic product (GDP) levels had higher prevalence of hyperuricemia. In the multivariate regression model, the
estimated glomerular filtration rate was inversely associated with hyperuricemia. Alcohol consumption, body mass index and serum triglyceride levels were positively correlated with hyperuricemia. Other factors independently correlated with hyperuricemia were age, sex, education level, area of residence, and economic development. In order to demonstrate the discriminatory power for hyperuricemia of the risk factors all together, we calculated the probabilities by logistic regression analysis, which represented the combined effects of these risk factors. Then, receiver operating characteristic analysis was used to demonstrate the value of the probabilities for hyperuricemia diagnosis. Finally, ROC curve analysis revealed the area under the curve was 0.746 (95 % CI 0.739–0.754), statistically significant for the association with hyperuricemia of these risk factors considered all together (p \ 0.001). Conclusions Hyperuricemia is prevalent in the economically developed areas of China. Our report indicates the feasibility of studying the influence that economic changes have on the prevalence of hyperuricemia. Keywords China
Hyperuricemia Epidemiology Prevalence
Introduction H. Liu and X.-M. Zhang contributed equally to this work. On behalf of China National Survey Collaborative Group of Chronic Kidney Disease. H. Liu X.-M. Zhang Y.-L. Wang B.-C. Liu (&) Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing 210009, Jiangsu, China e-mail: [email protected]
In recent decades, hyperuricemia has received increasing attention as a major public health problem because of its high prevalence and the associated increases in the risk of hypertension, cardiovascular disease, diabetes and chronic kidney disease (CKD) [1–5]. Hyperuricemia has also emerged as one of the metabolic diseases that threaten human health. Epidemiologic studies have observed an
123
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increasing trend in the prevalence of hyperuricemia in recent years [6, 7]. The prevalence of hyperuricemia varies across different populations and different areas. The results reported by the Okinawa General Health Maintenance Association in Japan revealed that the overall prevalence of hyperuricemia was 25.8 % (34.5 % in men and 11.6 % in women) [8]. Among the population of Bangkok, 59 % of men and 11 % of women had hyperuricemia, and the overall prevalence was 24.4 % [9]. China is the world’s largest developing country, and is characterized by distinct regional and economic diversity. However, to date, no national cross-sectional surveys have been performed to determine the prevalence of hyperuricemia in China. Using the data from the China National Survey of Chronic Kidney Disease, we aimed to investigate the prevalence of hyperuricemia and associated factors in Chinese adults.
Subjects and methods Participants and assessment criteria The current study used data from 36,348 participants aged 18 years and older from the China National Survey of Chronic Kidney Disease, which was a national cross-sectional survey using a randomized, multistage, stratified sampling strategy [10]. The ethics committee of Peking University First Hospital approved the study. All participants gave written informed consent before data collection. Male subjects with serum uric acid C416.0 lmol/l (7.0 mg/dl) and female subjects with C357.0 lmol/l (6.0 mg/dl) were diagnosed with hyperuricemia [11]. Hypertension was defined as a systolic blood pressure of 140 mmHg or more, diastolic blood pressure of 90 mmHg or more, any use of antihypertensive medication in the past 2 weeks, or any self-reported history of hypertension. Diabetes was defined as a fasting plasma glucose level of 7.0 mmol/l (126 mg/dl) or more, by the presence of hypoglycemic agents despite normal fasting plasma glucose, or any self-reported history of diabetes. Body mass index (BMI) was calculated by dividing weight in kilograms by height in square meters: subjects with BMI 24–28 kg/m2 were defined as overweight, and C28 kg/m2 as obese [12]. The urinary albumin to creatinine ratio (ACR, mg/g creatinine) was calculated. Albuminuria was defined as an ACR greater than 30 mg/g. The estimated glomerular filtration rate (eGFR) was calculated using an equation from the Modification of Diet in Renal Disease (MDRD) equation, based on data from Chinese patients with chronic kidney disease [10]. The MDRD equation was as follows: eGFR (ml/min per 1.73 m2) = 175 9 Scr-1.234 9 age-0.179 [for females 9 0.79], where Scr is the serum creatinine
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concentration (in mg/dl) and age is included in years. CKD was defined as eGFR \60 ml/min per 1.73 m2 or albuminuria. Statistical analysis We determined the prevalence of hyperuricemia according to sex, age, urban or rural residency, gross domestic product (GDP) and eGFR levels. In addition to crude prevalence, we also weighted prevalence estimates and comparisons to represent the total adult population in China. Synthesized weights were calculated from a sampling weight, a non-response weight, and a population weight. These weights were used to adjust for different selection probabilities, different response proportions, and deviations in the sample compared to the standard population, particularly for sex and age. Data from the 2009 China Population Sampling Census were used as the standard population. Continuous data are presented as mean and standard deviation (SD), except for ACR, which is presented as a median (interquartile range, IQR) because data were highly skewed. Categorical variables are presented as proportions. Relevant characteristics are described and stratified according to the presence of hyperuricemia. The association between hyperuricemia and relevant covariates was determined using multivariate logistic regression analysis. Odds ratios (OR) were used to evaluate the risk of hyperuricemia associated with sex, age, alcohol intake, rural versus urban residency, GDP per capita, hypertension, diabetes, waist circumference, BMI, plasma triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol, albuminuria, and eGFR. Receiver operating characteristic (ROC) analysis was used to demonstrate the discriminatory power for hyperuricemia of the risk factors all together. We used Epidata software (version 3.1) for data entry and management. All p values were two-tailed, and a p value of less than 0.05 was considered significant. The analyses were conducted using SUDAAN (version 10) and SAS (version 9.1).
Results The adjusted prevalence of hyperuricemia among Chinese adults in 2009–2010 was 8.4 % [95 % confidence interval (CI) 8.0–8.8 %]. The prevalences among men and women were 9.9 % (9.2–10.6 %) and 7.0 % (6.5–7.5 %), respectively. The mean serum urate levels were 332.4 lmol/l (5.6 mg/dl) among men and 268.9 lmol/l (4.5 mg/dl) among women. Urban residents had a much higher adjusted prevalence of hyperuricemia (14.9, 14.0–15.8 %)
J Nephrol Table 1 Prevalence of hyperuricemia by age, economic development and eGFR Number
Table 2 Characteristics of the study population according to hyperuricemia status
Hyperuricemia
With hyperuricemia (n = 5,381)
Without hyperuricemia (n = 30,967)
p
52.69 (15.95)
48.82 (15.52)
\0.01
n
Prevalence % (95 % CI)
16,019
2,775
9.9 (9.2–10.6)
Men
2,775 (51.6 %)
13,244 (42.8 %)
\0.01
Female 20,329 Area of residence
2,606
7.0 (6.5–7.5)
Urban residents
3,414 (63.45 %)
15,616 (50.43 %)
\0.01
High school education or above
2,370 (44.20 %)
11,479 (37.20 %)
\0.01
Current smoker
1,345 (25.00 %)
6,894 (22.26 %)
\0.01
Sex Male
Age (years)
Rural
17,318
1,967
6.6 (6.1–7.1)
Urban
19,030
3,414
14.9 (14.0–15.8) a
GDP per capita Tertile 1
14,528
1,507
10.4 (9.9–10.9)
Tertile 2
9,390
1,210
12.9 (12.2–13.6)a
2,664
a
Tertile 3
12,430
21.4 (20.7–22.2)
eGFR (ml/min per 1.73 m2)
Non-habitual drinker
875 (16.26 %)
4,549 (14.69 %)
\0.01
Habitual drinker
500 (9.29 %)
2,045 (6.60 %)
\0.01
Chronic cough
277 (5.3 %)
1,667 (5.63 %)
161 (2.99 %)
672 (2.17 %)
\0.01
2,323 (43.58 %)
10,328 (33.62 %)
\0.01
C90
23,308
2,734
11.7 (11.3–12.1)a
History of CVD
60–89
12,098
2,209
18.3 (17.6–18.9)a
Hypertension
a
\60
942
438
Total
36,348
5,381
46.8 (45.2–48.5) 8.4 (8.0–8.9)
GDP gross domestic product, eGFR estimated glomerular filtration rate, CI confidence interval a
The crude prevalences. The other prevalences are adjusted for synthesized weights
compared to rural residents (6.6, 6.1–7.1 %). Areas with high GDP levels had higher prevalence of hyperuricemia in both urban and rural areas (Table 1). As eGFR declined, the prevalence of hyperuricemia increased significantly. As many as 46.5 % of the participants with an eGFR less than 60 ml/min per 1.73 m2 had hyperuricemia (Table 1). The participants with hyperuricemia were older, more educated, and more likely to be men, to smoke, to consume alcohol, and to live in urban areas than those without hyperuricemia. The participants with hyperuricemia also had higher prevalences of cardiovascular disease, hypertension, and diabetes, compared to those without hyperuricemia (Table 2). Moreover, larger waist circumference, higher BMI, higher levels of serum triglycerides, and lower eGFR levels were observed in subjects with hyperuricemia. Table 3 shows the results of multiple logistic regression analysis: among all the variables listed in the table eGFR was most strongly associated with the serum urate level. An eGFR value between 60 and 90 ml/min was associated with an odds ratio (OR) of 2.76 (95 % CI 2.41–3.16) for hyperuricemia, and an eGFR less than 60 ml/min exhibited an OR of 12.61 (95 % CI 9.44–16.85) (Table 3). In addition, Table 3 shows that older age, being male, having a higher education level, alcohol intake, urban residency, economic development, obesity, and dyslipidemia were all independently associated with a higher risk of hyperuricemia. Compared with men, the odds ratio of having hyperuricemia was 0.65 for women. In order to demonstrate the discriminatory power for
0.35
Diabetes
523 (9.73 %)
1,966 (6.35 %)
\0.01
Waist circumference (cm)
82.52 (10.25)
79.45 (10.15)
\0.01
BMI (kg/m2)
24.40 (3.69)
23.39 (3.58)
\0.01
Total cholesterol (mmol/l)
5.36 (1.31)
4.79 (1.09)
\0.01
Triglycerides (mmol/l)
2.05 (1.72)
1.38 (1.18)
\0.01
LDL cholesterol (mmol/l) HDL cholesterol (mmol/l)
3.28 (1.09)
2.81 (0.90)
\0.01
1.41 (0.45)
1.44 (0.42)
\0.01
Scr (lmol/l)
82.99 (34.45)
72.32 (19.51)
\0.01
eGFR
92.86 (27.85)
106.72 (50.04)
\0.01
6.18 (10.99)
5.76 (13.17)
\0.01
(ml/min per 1.73 m2) Albuminuria [mg/g; median (IQR)] Data are presented as number (%) or mean (SD), unless stated otherwise. ACR is presented as a median because the data were highly skewed CVD cardiovascular disease, BMI body mass index, LDL low-density lipoprotein, HDL high-density lipoprotein, SCr serum creatinine, eGFR estimated glomerular filtration rate, ACR urinary albumin to creatinine ratio, IQR interquartile range
hyperuricemia of the risk factors all together in Table 3, we calculated the probabilities by logistic regression analysis, which represented the combined effects of these risk factors. Then, ROC analysis was used to demonstrate the value of the probabilities for hyperuricemia diagnosis. Finally, ROC curve analysis revealed an area under the curve of 0.746 (95 % CI 0.739–0.754), statistically significant for the association with hyperuricemia of these risk factors considered all together (p \ 0.001) (Fig. 1). Hypertension and diabetes were not significantly associated with an increased risk of hyperuricemia (p = 0.11, and p = 0.75, respectively).
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J Nephrol Table 3 Results of multiple logistic regression analysis of all the variables listed in the table which were associated with hyperuricemia Hyperuricemia (OR, 95 % CI)
p
Age (change of 10 years)
1.12 (1.06–1.18)
\0.01
Sex (women vs. men)
0.65 (0.55–0.77)
\0.01
Education Below high school (reference)
1.00
High school
1.29 (1.08–1.53)
\0.01
Above high school
2.14 (1.75–2.6)
\0.01
Current smoker
0.85 (0.72–1.01)
0.07
Alcohol intake Non-drinker (reference)
1.00
Non-habitual drinker
1.82 (1.56–2.13)
\0.01
Habitual drinker
2.31 (1.85–2.87)
\0.01
Hypertension
1.15 (0.97–1.36)
0.11
Diabetes
0.96 (0.76–1.22)
0.75
Urban residence
1.47 (1.24–1.75)
\0.01
(vs. rural residence) GDP per capita Tertile 1 (reference)
1.00
Tertile 2 Tertile 3
0.61 (0.50–0.75) 1.84 (1.52–2.23)
\0.01 \0.01
1.32 (1.12–1.55)
\0.01
Waist circumference
Fig. 1 ROC curve demonstrating the discriminatory power of the risk factors considered all together for hyperuricemia. Receiver operating characteristic (ROC) curve analysis demonstrated statistically significant value of these risk factors considered all together for hyperuricemia [area under the curve was 0.746 with 95 % confidence interval (CI) of 0.739–0.754, p \ 0.001]
BMI (kg/m2) \24 (reference)
1.00
24–28
1.15 (0.99–1.33)
[28 Total cholesterol
0.07
1.51 (1.20–1.91)
\0.01
1.24 (1.07–1.45)
\0.01
(C5.2 vs. \5.2 mmol/l) Triglycerides (mmol/l) \1.7 (reference)
1.00
1.7–2.26
2.10 (1.76–2.50)
\0.01
C2.26
3.23 (2.78–3.75)
\0.01
1.33 (1.12–1.58)
\ 0.01
C90 (reference) 60–89
1.00 2.76 (2.41–3.16)
\0.01
\60
12.61 (9.44–16.85)
\0.01
LDL-cholesterol (C2.59 vs. \2.59 mmol/l) eGFR (ml/min per 1.73 m2)
OR odds ratio, CI confidence interval, GDP gross domestic product, BMI body mass index, LDL low-density lipoprotein, eGFR estimated glomerular filtration rate
Discussion In this representative sample of Chinese adults, the prevalence of hyperuricemia was 8.4 %, which means that there were approximately 92.9 million adults with hyperuricemia in China in 2009 and 2010. A major strength of our study is that it is the first national cross-sectional survey using a
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multistage, stratified sampling design in a developing country with high regional and economic heterogeneity. Therefore, our study used a unique dataset to explore the effects of multiple variables on the burden of hyperuricemia and associated trends. Previous studies have estimated the prevalence of hyperuricemia in both developed and developing countries. The prevalence we found was similar to that found in some developing countries, such as Thailand (10.6 %) [13] and Saudi Arabia (8.4 %) [14], but it was much lower than in Taiwan (26.1 % among men and 17.0 % among women) [15] and in developed countries, such as the United States (21.4 %) and Japan (25.8 %) [6, 8]. However, areas in the top tertile of GDP per capita levels had a prevalence of hyperuricemia (21.4 %) that was similar to the prevalences in Taiwan and developed countries, and urban residents showed a higher prevalence than rural residents. Therefore, hyperuricemia is quite prevalent in areas with high GDP levels in China. The differences in prevalence of hyperuricemia may be attributed to the rapidly developing economy, the aging population [16], and discrepancies in lifestyle and dietary habits in Taiwan and developed countries. Moreover, developed countries have a heavier burden of related medical conditions, such as diabetes and stage 3–5 CKD, compared to developing countries. For example, a previous study reported that the prevalence of stage 3 CKD was 7.7 % in the USA, compared to 1.6 % in
J Nephrol
China [10]. Our study found that economic development is independently associated with hyperuricemia, which suggests the feasibility of studying the influence that economic changes have on the prevalence of hyperuricemia. Hyperuricemia is one of the important metabolic diseases related to lifestyle and dietary habits. In accordance with previous studies, we found that alcohol intake, BMI, and serum triglycerides levels were independently associated with hyperuricemia [17, 18]. And ROC analysis demonstrated a statistically significant value of these risk factors considered all together for hyperuricemia diagnosis. Economic level is an important factor that affects the intake of dietary nutrients and the content of the diets of Chinese residents, which may explain the relationship between economic development and hyperuricemia. Qiu et al. [19] also found that, compared with agricultural and pastoral areas, the odds ratio of having hyperuricemia was higher for people living in the big cities of northern China. Along with the rapid economic development of China, lifestyle and dietary habit have changed significantly and different geographic regions have unbalanced economic development and health education. Increased risk of hyperuricemia is the result of increased consumption of purine-rich animal products, high-fat foods, and alcohol, increasing obesity, and an aging population [20]. Meanwhile, studies have demonstrated that hyperuricemia is closely associated with an increased risk of hypertension, cardiovascular disease, diabetes and CKD, through pathophysiological mechanisms such as endothelial dysfunction, increased oxidative stress, vascular smooth muscle cell proliferation, insulin resistance, proinflammatory response and immune response [2, 5]. Therefore, hyperuricemia has emerged as an important chronic disease that threatens human health, and special attention should be paid to the prevention and treatment of hyperuricemia in the process of rapid economic development in developing countries. China is presently going through a period of economic transition and shifting dietary patterns, which constitutes an optimal time to prevent and reduce the increasing burden of hyperuricemia by improving lifestyle and dietary habits, promoting balanced diet, physical activity, weight control, and abstinence from alcohol. As was expected, eGFR was inversely associated with hyperuricemia, and nearly half of the subjects with stage 3–5 CKD had hyperuricemia in our study. Uric acid is clearly a marker for CKD as it is predominantly cleared by the kidneys and its level rises as GFR declines. In the past decades, some epidemiologic studies have demonstrated that hyperuricemia may also have a role in the pathophysiology of CKD progression [21, 22], which may work through some pathophysiological mechanisms mentioned above. However, the cross-sectional design limited our ability to make a causal inference. Larger interventional
clinical trials are needed to evaluate the effect of uric acid reduction on the genesis and progression of CKD in the future. Diabetes was not significantly correlated with hyperuricemia in our study. One explanation might be that in the early stages of diabetic nephropathy (DN), glomerular hyperfiltration increases urate excretion [23], and urate levels tend to increase with the progression of DN and impaired renal function. In our study, 58.5 % of the diabetic patients were in the early stages of DN, and the mean eGFR was 103.4 ml/min. In addition, the definition of diabetes did not include a 2-h postprandial blood glucose level. Thus, diabetes may have been underestimated, which may have affected the results. Our study has several limitations. First, the definition of hyperuricemia was based solely on serum urate levels. There may have been some patients with hyperuricemia who were taking uric-acid-lowering drugs and had normal urate levels during the survey. Therefore, the reported prevalence of hyperuricemia may have been underestimated. Second, although we adjusted for a variety of important confounding variables, residual confounding by other factors, such as dietary habits, cannot be entirely excluded. Third, since uric acid levels were not measured in some areas, we were unable to study the variance in hyperuricemia prevalence across different geographic regions. Finally, the cross-sectional design of the study makes it impossible to infer a causal relationship between hyperuricemia and associated factors. In conclusion, hyperuricemia is quite prevalent in the economically developed areas of China. Economic development is independently associated with hyperuricemia through its correlation with lifestyle and dietary habits. Considering the increasing prevalence and the adverse consequences of hyperuricemia, special attention should be paid to the prevention and treatment of hyperuricemia as economic development progresses in developing countries. And the most important steps are improving lifestyle and dietary habits, and intervening to prevent related diseases. Our report provides evidence for the feasibility of studying the influence that economic changes have on the prevalence of hyperuricemia. Acknowledgments This study was supported by the National Key Technology R&D Program from the Ministry of Science and Technology (China; 2007BAI04B10); the Department of Health in Jiangsu Province (H200936); the Science and Technology Commission of Shanghai (08dz1900502 and 07JC14037); the Natural Science Funds of Ning Xia (NZ08102); the Science and Technology Department of National Natural Science Funds (30660069); the National Natural Science Foundation of China; the Key Scientific and Technology Project from the Sichuan Science and Technology Department (05SG1635); the Program for New Century Excellent Talents in Universities from the Ministry of Education (China; BMU2009131); the International Society of Nephrology Research Committee; and the China Health and Medical Development Foundation. We thank
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J Nephrol Haiyan Wang of the Peking University Institute of Nephrology for her contribution to the statistical analyses and her constructive comments on the report. Conflict of interest conflicts of interest.
The authors of the manuscript declare no
References 1. Kawano Y (2011) Uric acid and blood pressure. Circ J 75:2755–2756 2. Puddu P, Puddu GM, Cravero E, Vizioli L, Muscari A (2012) The relationships among hyperuricemia, endothelial dysfunction, and cardiovascular diseases: molecular mechanisms and clinical implications. J Cardiol 59:235–242 3. de Oliveira EP, Burini RC (2012) High plasma uric acid concentration: causes and consequences. Diabetol Metab Syndr. 4:12 4. Sluijs I, Beulens JW, van der A DL, Spijkerman AM, Schulze MB, van der Schouw YT (2013) Plasma uric acid is associated with increased risk of type 2 diabetes independent of diet and metabolic risk factors. J Nutr 143:80–85 5. Filiopoulos V, Hadjiyannakos D, Vlassopoulos D (2012) New insights into uric Acid effects on the progression and prognosis of chronic kidney disease. Ren Fail 34:510–520 6. Zhu Y, Pandya BJ, Choi HK (2011) Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum 63:3136–3141 7. Trifiro` G, Morabito P, Cavagna L et al (2013) Epidemiology of gout and hyperuricaemia in Italy during the years 2005–2009: a nationwide population-based study. Ann Rheum Dis 75:694–700 8. Naqahama K, Iseki K, Inoue T, Touma T, Ikemiya Y, Takishita S (2004) Hyperuricemia and cardiovascular risk factor clustering in a screened cohort in Okinawa, Japan. Hypertens Res. 27:227–233 9. Uaratanawong S, Suraamornkul S, Angkeaw S, Uaratanawong R (2011) Prevalence of hyperuricemia in Bangkok population. Clin Rheumatol 30:887–893 10. Zhang L, Wang F, Wang L et al (2012) Prevalence of chronic kidney disease in China: a cross-sectional survey. Lancet 379:815–822 11. Fang J, Alderman MH (2000) Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study,
123
12.
13.
14. 15.
16. 17.
18.
19.
20.
21.
22.
23.
1971–1992. National Health and Nutrition Examination Survey. JAMA 283:2404–2410 Zhou BF, Cooperative Meta-Analysis Group of the Working Group on Obesity in China (2002) Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults: study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Asia Pac J Clin Nutr. 11:S685–S693 Lohsoonthorn V, Dhanamun B, Williams MA (2006) Prevalence of hyperuricemia and its relationship with metabolic syndrome in Thai adults receiving annual health exams. Arch Med Res 37:883–889 Al-Arfaj AS (2001) Hyperuricemia in Saudi Arabia. Rheumatol Int 20:61–64 Chang HY, Pan WH, Yeh WT, Tsai KS (2001) Hyperuricemia and gout in Taiwan: results from the Nutritional and Health Survey in Taiwan (1993–96). J Rheumatol 28:1640–1646 Christensen K, Doblhammer G, Rau R, Vaupel JW (2009) Ageing populations: the challenges ahead. Lancet 374:1196–1208 Miao Z, Li C, Chen Y et al (2008) Dietary and lifestyle changes associated with high prevalence of hyperuricemia and gout in the Shandong coastal cities of Eastern China. J Rheumatol 35:1859–1864 Villegas R, Xiang YB, Cai Q et al (2010) Prevalence and determinants of hyperuricemia in middle-aged, urban Chinese men. Metab Syndr Relat Disord. 8:263–270 Qiu L, Cheng XQ, Wu J et al (2013) Prevalence of hyperuricemia and its related risk factors in healthy adults from Northern and Northeastern Chinese provinces. BMC Public Health. 13:664 No authors listed (2003) Diet, nutrition and the prevention of chronic diseases. World Health Organ Tech Rep Ser 916: i–viii, 1–149 Hsu CY, Iribarren C, McCulloch CE, Darbinian J, Go AS (2009) Risk factors for end-stage renal disease: 25-year follow-up. Arch Intern Med 169:342–350 Jolly SE, Mete M, Wang H et al (2012) Uric acid, hypertension, and chronic kidney disease among Alaska Eskimos: the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. J Clin Hypertens (Greenwich). 14:71–77 Bandaru P, Shankar A (2011) Association between serum uric acid levels and diabetes mellitus. Int J Endocrinol 2011:604715
