Original Article

Serum uric acid levels are associated with high blood pressure in Chinese children and adolescents aged 10^15 years Shuo Pan a,b,, Chun-Hui He a,b,, Yi-Tong Ma a,b, Yi-Ning Yang a,b, Xiang Ma a,b, Zhen-Yan Fu a,b, Xiao-Mei Li a,b, Xiang Xie a,b, Zi-Xiang Yu a,b, You Chen a,b, Fen Liu b, Bang-Dang Chen b, and Tomohiro Nakayama c

Abbreviations: eGFR, estimated glomerular filtration rate; HDL, high-density lipoprotein; LDL, low-density lipoprotein; TC, total cholesterol; XCHDS, Xinjiang Congenital Heart Disease Survey

Objective: The present study examined the association between uric acid levels and high blood pressure in a multiethnic study of Chinese children and adolescents. Methods: The participants were divided into four different groups according to the uric acid quartiles. Three logistic regression models were conducted to investigate the relationship between the high blood pressure and uric acid levels. Model 1 adjusted age, sex and ethnicity. Model 2 adjusted age, sex, ethnicity, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, estimated glomerular filtration rate, fasting glucose and waist circumference. Model 3 adjusted all the confounding factors in model 2 except the waist circumference and BMI. The concentrations of uric acid in high blood pressure participants and normotensive participants were compared with or without adjustment for confounding factors. Results: A total of 3778 participants aged 10–15 years from the Xinjiang Congenital Heart Disease Survey were included in the present study. The percentages of the high blood pressure in the four different uric acid quartiles were 7.4, 8.6, 9.6 and 11.8%, respectively. In model 1, 2 and 3 of the logistic regression, the participants in the third and fourth uric acid quartiles had significantly higher chance of suffering the high blood pressure when compared with the participants in the first uric acid quartile [odds ratio 1.608, 1.587, 1.597, P ¼ 0.005, 0.015, 0.015, respectively, between participants in the first quartile and the third quartile; odds ratio 1.981, 1.945, 1.810, P ¼ 0.001, 0.002, 0.007, respectively, between participants in the first quartile and the fourth quartile). The concentrations of serum uric acid were 220.7 mmol/l in high blood pressure participants and 204.1 mmol/l in normotensive participants (P ¼ 0.024). After adjustment for confounding factors, the concentrations of serum uric acid were 219.7 vs. 204.5 mmol/l in one model (P < 0.001) and 219.3 vs. 204.5 mmol/l in the other model (P < 0.001). Conclusions: Among Chinese children and adolescents, increasing levels of serum uric acid are associated with high blood pressure. Keywords: adolescents, blood pressure, children, Chinese, cross-sectional studies, uric acid

INTRODUCTION

T

he prevalence of hypertension in children and adolescents is increasing worldwide [1–3], and elevated blood pressure in children predicts the development of hypertension in adulthood [4]. Therefore, it is important to understand the factors that can lead to hypertension at this young age for early detection and prevention purposes. Uric acid is the final oxidation product of purine metabolism in humans. In adults, there is evidence that elevated serum uric acid levels have been associated with hypertension in multiple large epidemiological studies [5–8]. In children and adolescents, a few studies focused on the association between the uric acid and metabolic syndrome [9]; they have reported the association in children with overweight and obesity [10] in different race and sex [11]. However, controversy remains as to whether serum uric acid is independently associated with the development of high blood pressure after adjustment of the confounding effects in children and adolescents. Especially among the Chinese children and adolescents, the prevalence of overweight and obesity were significantly lower than those in the US [12–15]. The uric acid statistics on the Chinese

Journal of Hypertension 2014, 32:998–1004 a

Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Cardiovascular Disease Research, Urumqi, People’s Republic of China and cDivision of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan b

Correspondence to Yi-Tong Ma, MD, PhD, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, People’s Republic of China. Tel: +86 991 4366169; e-mail: [email protected] 

Shuo Pan and Chun-Hui He contribute equally to the writing of the article.

Received 23 May 2013 Revised 14 January 2014 Accepted 11 January 2014 J Hypertens 32:998–1004 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. DOI:10.1097/HJH.0000000000000126

998

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Serum uric acid levels and high blood pressure

children were rarely reported. In this circumstance, whether the serum uric acid is associated with the high blood pressure still needs to be further analyzed. In this study, we examined the association between uric acid level and high blood pressure in a multiethnic, prospective, observational cohort study of Chinese children and adolescents using data from Xinjiang Congenital Heart Disease Survey (XCHDS).

METHODS Ethics statement The study was approved by the Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University (Xinjiang, China). It was conducted according to the standards of the Declaration of Helsinki. As all participants were children and adolescents, the written informed consents were obtained from parents of our participants.

Participants We performed a cross-sectional analysis by using data from the XCHDS. The XCHDS is a prospective, observational cohort study designed to investigate the prevalence, incidence, and risk factors for congenital heart disease with cluster sampling method. This survey includes 5283 Han, Uygur, and Kazakh males and females aged 0–15 years in the Xinjiang Uygur Autonomous Region in northwest China. From October 2009 to June 2010, 2549 males and 2734 females were enrolled in the survey in total. All participants were recruited from three multiethnic inhabited cities in Xinjiang: Hetian, Kashi, and Fuhai. In XCHDS, the examining locations were the selected junior high schools, elementary schools, and kindergartens. All the young participants whose parents had signed the consents were included in the electrocardiogram, echocardiography, blood pressure, and routine physical examinations. All the basic information and past medical history of the young participants were documented and the fasting blood samples were collected. All the procedures were completed by professional doctors and nurses from the Department of Cardiology in the First Affiliated Hospital of Xinjiang Medical University. The quality control in the survey sites was strictly implemented and the collected data were input by two persons at the same time. In this study, the patients with various congenital heart diseases were excluded; we also excluded the patients with diseases which would affect the uric acid levels such as previously known kidney diseases. The definition of high blood pressure for the Chinese children and adolescents is available only for those aged at least 10 years [16]. Therefore, in this present study, we only enrolled 3778 young participants aged 10–15 years, among which 1787 young participants were male and 1991 young participants were female.

Definition of high blood pressure Because XCHDS obtained blood pressure measurements at a single study visit, thus, the formal diagnosis of hypertension was not possible, and participants were characterized Journal of Hypertension

as having ‘high blood pressure’. To define the high blood pressure among the young participants, we used the recent definition of the high blood pressure for Chinese children and adolescents who were at least 10 years old [16]. The participants had to meet the following criteria to be diagnosed as having high blood pressure: SBP at least P95 SBP in children within the same age and sex, or DBP at least P95 DBP in children within the same age and sex.

Physical and biochemical measurements The waist circumference was measured at the high point of the iliac crest at minimal respiration to the nearest 0.1 cm at the end of normal expiration with a steel measuring tape. The blood pressure was measured twice over 10 min for each participant; the mean value was used in the statistical analysis. The participants were seated with their right arm resting at the level of the heart. The blood samples of those young participants who had fasted for at least 8 h were collected. Then the samples were separated into plasma, serum and blood cells (including leukocytes), and stored at 808C for further routine blood biochemical tests. All the collected samples were transported on dry ice at prearranged intervals to our laboratory. The serum concentration of total cholesterol (TC), triglyceride, blood urea nitrogen (BUN), creatinine, low-density lipoprotein (LDL), highdensity lipoprotein (HDL), uric acid and fasting glucose were measured by the Clinical Laboratory Department of the First Affiliated Hospital of Xinjiang Medical University with the biochemical analyzer (Dimension AR/AVL Clinical Chemistry System, Newark, New Jersey, USA). Estimated glomerular filtration rate (eGFR; ml/min per 1.73 m2) was calculated via the creatinine-based formula of Schwartz: eGFR ¼ k (height in cm)/(serum creatinine in mg/dl), where k is 0.70 in boys and 0.55 in girls [17,18].

Statistical analysis All continuous variables were expressed as mean  SD and compared using the analysis of variance (ANOVA). Differences in categorical variables were analyzed using the chi-squared test. Because of the absence of any universally accepted threshold to define hyperuricemia in children and adolescents, we calculated the prevalence of high blood pressure for each quartile of concentration of uric acid. To investigate the relationship between the high blood pressure (categorical) and concentrations of uric acid, we conducted three logistic regression models (stepwise forward): model 1 adjusted for age (continuous), sex (boys, girls), and ethnicity (Han, Uygur, Kazakh); model 2 adjusted for age, sex, ethnicity, TC, HDL, LDL, triglycerides, eGFR, fasting glucose, and waist circumference; model 3 adjusted all the confounding factors in model 2 except the waist circumference and BMI. The concentrations of uric acid between participants with the high blood pressure and normotensive participants were calculated and compared with the t test. The uric acid concentrations were adjusted with analysis of covariance in two different models, one was adjusted for age, TC, HDL, LDL, triglycerides, eGFR, fasting glucose, and www.jhypertension.com

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Pan et al.

RESULTS A total of 3778 participants aged 10–15 years were included in the present study. In this sample, there were 1787 male participants and 1991 female participants. One thousand one hundred and twenty-eight (542 male and 586 female) participants were from Fuhai, 1299 (595 male and 704 female) participants were from Hetian, and 1351 (650 male and 701 female) participants were from Kashi. The concentrations of uric acid ranged from 72.0 to 613.7 mmol/l with a mean  SD of 205.6  65.2 mmol/l. In male participants, the uric acid concentrations (mean  SD) were 254.3  71.0 mmol/l in Han, 198.5  65.0 mmol/l in Uygur, and 222.5  59.4 mmol/l in Kazak. In female participants, the uric acid concentrations (mean  SD) were 222.5  55.1 mmol/l in Han, 197.1  64.5 mmol/l in Uygur, and 195.4  47.3 mmol/l in Kazak. The SBP and DBP values in different percentile and uric acid values in different quartiles of blood pressure were presented in Figs 1 and 2. Table 1 showed the clinical characteristics of the study participants by the serum uric acid quartiles. The three cutting concentrations of uric acid of the four quartiles were 160.8, 199.0, and 242.3 mmol/l, respectively. In this table, we can see that age, DBP, BMI, LDL, HDL, TC, fasting glucose, the incidence of high blood pressure, and hyperglycemia showed an increasing trend as the uric acid level increased. However, we did not notice the increasing trend in SBP, waist circumference, and triglyceride. The percentages of the high blood pressure in the four different uric acid groups were 7.4, 8.6, 9.6, and 11.8%, respectively. Table 2 showed the adjusted odds ratios (ORs) [95% confidence interval (CI)] for associations between the high blood pressure and serum concentrations of uric acid among participants after the logistic regression. In models

Diastolic blood pressure (DBP) Systolic blood pressure (SBP)

113

107

56

60

60

60

63

72

90 %

% 80

50

40 %

% 30

FIGURE 1 SBP and DBP levels at different percentiles among participants aged 10–15 years.

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DBP

220

213.7±2.4 208.3±2.2 200.5±1.7 199.9±2.4

200

216.7±2.4 209.8±1.6 199.8±3.0 190.9±1.9

100 0 SBP

DBP

FIGURE 2 Concentrations of serum uric acid (mean  SE) in each quartile of blood pressure (SBP and DBP) among participants aged 10–15 years.

1, 2, and 3, the participants in the third and fourth uric acid quartiles had significantly higher chance of suffering the high blood pressure when compared with the participants in the first uric acid quartile (OR 1.608, 1.587, 1.597, P ¼ 0.005, 0.015, 0.015, respectively between participants in the first quartile and the third quartile; OR 1.981, 1.945, 1.810, P ¼ 0.001, 0.002, 0.007, respectively, between participants in the first quartile and the fourth quartile). The adjusted ORs of the high blood pressure in the fourth uric acid quartile were higher than those in the third uric acid quartile in each model. There was no significant difference in the high blood pressure status between participants in the first uric acid quartile and participants in the second uric acid quartile because the high blood pressure did not enter the final stepwise logistic regression in all three models. Figure 3 presents the unadjusted and adjusted concentrations of serum uric acid by the blood pressure status among participants. The unadjusted mean concentration of serum uric acid in participants with the high blood pressure was 220.7 mmol/l and the mean concentration of serum uric acid in normotensive participants was 204.1 mmol/l. After the t test, the mean concentrations of serum uric acid in the two groups were significantly different (P ¼ 0.024). When adjusted for age, TC, HDL, LDL, triglycerides, eGFR, fasting glucose, and waist circumference, the serum uric acid concentrations were 219.7 mmol/l in participants with the high blood pressure and 204.5 mmol/l in normotensive participants (P < 0.001). Meanwhile, when adjusted for age, TC, HDL, LDL, triglycerides, eGFR, fasting glucose, and BMI, the serum uric acid concentrations were 219.3 mmol/l in participants with the high blood pressure and 204.5 mmol/l in normotensive participants (P < 0.001).

DISCUSSION 70

0

1000

SBP

100

70 %

50

100

98

93

90

60 %

48

20 %

50

90

85

%

100

10 %

Blood pressure (mmHg)

150

240

Uric acid (µmoI/l)

waist circumference; and the other one was adjusted for age, TC, HDL, LDL, triglycerides, eGFR, fasting glucose, and BMI. Statistical significance was established at P less than 0.05. Statistical analyses were performed using SPSS software for Windows, version 17.0 (SPSS, Chicago, Illinois, USA).

In this study, we found that the mean serum uric acid value of Chinese participants in XCHDS was 205.6 mmol/l. However, the mean serum uric acid value was 301.9 mmol/l in US [9]. The serum uric acid levels among US children and adolescents were apparently higher than those among Chinese children and adolescents. One reason for the difference may be the age difference; the age in US participants ranged from 12 to 17 years, which was 2 years more than the participants in our study. Another reason may be that the prevalence of overweight and obesity among the Volume 32  Number 5  May 2014

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Serum uric acid levels and high blood pressure TABLE 1. Characteristics of study participants aged 10–15 years by serum uric acid quartiles 160.8 mmol/l

>160.8 to 199.0 mmol/l

>199.0 to 242.3 mmol/l

>242.3 mmol/l

P

973 11.60  1.24 97.12  12.21 50.81  11.07 16.67  2.14 61.42  7.23 0.73  0.37 1.33  0.49 0.98  0.48 2.56  0.67 4.13  0.78 33.37  8.68 3.76  1.09 248.43  59.43 428 (44.0%) 72 (7.4%)

965 11.70  1.27 96.60  11.90 59.18  11.33 16.91  2.43 61.16  7.56 0.74  0.37 1.44  0.46 1.01  0.33 2.78  0.62 4.31  0.70 38.46  8.40 3.97  1.01 205.29  47.02 427 (44.2%) 83 (8.6%)

933 11.72  1.31 97.44  11.44 60.49  10.87 17.13  2.42 60.95  7.72 0.71  0.33 1.57  0.51 1.04  0.31 2.95  0.66 4.43  0.70 41.86  9.37 3.97  1.07 193.93  44.55 461 (49.4%) 90 (9.6%)

907 11.79  1.38 99.40  12.02 62.55  10.75 17.93  3.06 61.96  8.19 0.79  0.46 1.68  0.53 1.03  0.41 3.21  0.71 4.50  0.73 48.14  10.56 4.20  1.09 173.62  35.60 471 (51.9%) 107 (11.8%)

0.011 < 0.001

Serum uric acid levels are associated with high blood pressure in Chinese children and adolescents aged 10-15 years.

The present study examined the association between uric acid levels and high blood pressure in a multiethnic study of Chinese children and adolescents...
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