Uric Acid

Serum Concentration of Uric Acid Associated With Prehypertension Among Chinese Population

Angiology 2014, Vol. 65(9) 800-805 ª The Author(s) 2013 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319713507628 ang.sagepub.com

Xundi Bao, MD1, Qing Wang1, Genwang Chen1, Qunan Wang, MS2, Ren Liang3, and Shunli Zhang, PhD4

Abstract We evaluated the association between serum uric acid (SUA) levels and prehypertension in a Chinese population. A cross-sectional study was performed during 2008 to 2010, and a total of 11199 participants without hypertension or other cardiovascular diseases (CADs), aged 35 years, were available for analysis. After adjusting for age, alcohol consumption, smoking status, body mass index, diabetes, total cholesterol, triglycerides, serum creatinine, the odds ratios (ORs) and 95% confidence intervals (CIs) of the prehypertension from the lowest (referent) to the highest levels of SUA were 1.00 (95% CI, 0.91-1.10), 1.12 (95% CI, 1.03-1.21), 1.17 (95% CI, 1.09-1.27), and 1.25 (95% CI, 1.13-1.39; linear trend P ¼ .002). This association persisted in subgroup analysis by gender and was also consistent with separate analysis by classification of age, smoking status, alcohol usage, overweight, and diabetes mellitus. Independent of other cardiovascular risk factors, higher SUA levels are positively associated with prehypertension in a Chinese population without hypertension and CADs. Prospective trials should evaluate interventions that lower the SUA levels. Keywords uric acid, prehypertension, hypertension

Introduction There is evidence that hypertension is an independent risk factor for cardiovascular disease (CVD).1 In China, hypertension is likely to be the most common disease, approximately 0.16 billion Chinese or 18.8% have hypertension according to the data from the 2002 National Nutrient Survey.2 However, the mechanisms underlying the development of hypertension are still not completely understood. With the exception of the results, which noted that some inflammatory markers (eg, C-reactive protein (CRP), fibrinogen, orosomucoid, and ceruloplasmin)3,4 are associated with the high rate of hypertension, the association of hyperuricemia with hypertension has long been recognized.5 Elevated serum uric acid (SUA) levels are present in the vast majority of adolescents with new-onset, untreated primary hypertension.6 The positive association has also been verified by several longitudinal epidemiologic studies7-11 but much controversy remains.12 In 2003, the National High Blood Pressure Education Program Coordinating Committee of the National Heart, Lung, and Blood Institute published the Seventh Report of the Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (the JNC 7 report). According to this report, a new term ‘‘prehypertension’’ was introduced, which defined as systolic blood pressure (SBP) ranging from 120 to139 mm Hg and/or diastolic blood pressure

(DBP) ranging from 80 to 89 mm Hg. The decision to establish this new blood pressure (BP) category was to focus attention on a segment of the population who were at higher than normal CVD risk and to delay or prevent the rate of progression to hypertension.13 Considering the continuous dose–response relationship in this association between SUA and clinical hypertension, Syamala et al8 reported an odds ratio (OR) of 1.96 (95% confidence interval [CI], 1.38-2.79) for the top versus bottom quartile of SUA with prehypertension, from a cross-section study with 4817 normative participants aged 18 years in the National Health and Nutrition Examination Survey 1999 to 2000. The association persisted in subgroup analyses by categories of race ethnicity, education, age, sex, smoking, and body mass index (BMI). However, little information is available

1

Anhui Chest Hospital, Hefei, China School of Public Health in Anhui Medical University, Hefei, China 3 DAAN Clinical Laboratory Center, Hefei, China 4 National Center for Clinical Laboratory, Beijing, China 2

Corresponding Author: Xundi Bao, Laboratory of An Hui Chest Hospital, 397, Jixi Rd, Hefei 230022, China. Email: [email protected]

Downloaded from ang.sagepub.com at Hestaleit ehf on March 25, 2015

Bao et al

801 smoking status, n ¼ 296; alcohol usage, n ¼ 71), self-identified history of coronary heart disease, myocardial infarction, angina, or stroke (n ¼ 1598). The remaining 11 199 individuals were included in our analysis.

Study Measures

Figure 1. Association between serum uric acid quartiles and prehypertension. Logistic regression analysis is adjusted by age, smoking, drinking, body mass index, diabetes, serum cholesterol, serum triglyceride, and serum creatinine for overall population and by sex. Error bars indicate 95% confidence intervals; Q1, less than 210; Q2, from 210 through 260; Q3, from 260 through 319; and Q4, higher than 319 mmol/L.

concerning the relationship between SUA and prehypertension in Chinese populations. Our objective was to evaluate the association between SUA and prehypertension in patients without a history of CVD in a cross-sectional, population-based survey.

Methods Study Population We performed a representative cross-sectional survey of the noninstitutionalized civilian Chinese population through a cluster sampling design. A face-to-face interview approach was designed to collect information from a structured questionnaire from 2008 to 2010. Data including social demographic survey, physical activity, dietary characteristics, physical examination with anthropometric measurements, and laboratory testing were collected by trained physicians or medical students. The study received approval from local ethnical committee, and all patients obtained verbal and written information about the study’s aims and procedures and signed the informed consent (illiterate participants approved with a fingerprint). Of 28 438 participants aged 35 years old, BP and SUA were available for 21 994 (77.34%) patients . Further 10 795 participants were excluded from the current analysis for the following reasons: hypertension defined as a SBP 140 mm Hg or DBP 90 mm Hg or current use of antihypertensive medications based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) criteria (n ¼ 8772), missing values for important covariates (age, n ¼ 25; BMI, n ¼ 33;

Clinical Examinations. The participants were seated with their right arm (if usable) at the level of the heart. The BP was measured twice with 3 readings each by skilled, trained physicians after 5 minutes rest in the sitting position using an automatic digital BP monitor (Omron HEM-757, Omron Inc, Japan). The average of last 2 readings was recorded to estimate SBP and DBP. Study patients with SBP of 120 to 140 mm Hg or DBP of 80 to 90 mm Hg were defined as prehypertension according to the criteria of the JNC 7 and the International Society of Hypertension.13 Body mass index was defined as weight (kg) divided by squared height (m2). Current smoking and alcohol use were ascertained from a standardized questionnaire. In our study, cigarette smoking status was categorized as currently smokes, ever smoked, or never smoked; alcohol intake was recorded as currently drinks, ever drank, and never drank. Diabetes was defined as history of diabetes, current use of glucose-lowering medications, or fasting glucose 7.0 mmol/L.14 Hyperuricemia was defined using these thresholds: 357 mmol/L (6 mg/dL) for women and 416 mmol/L (7 mg/dL) for men.15 Individuals were classified according to approximately equal quartiles of SUA levels (319 mmol/L). Blood Sampling and Analytic Methods. Venous blood was collected after overnight fasting, and frozen serum was sent to DAAN clinical laboratory center for analysis. Total cholesterol was measured by means of oxidation and peroxidation reactions; lowdensity lipoprotein cholesterol (LDL-C) was calculated using the Friedewald formula; high-density lipoprotein cholesterol (HDLC) concentration was measured after the precipitation of other lipoproteins with a heparin–manganese chloride mixture; plasma glucose concentration was measured by the glucose hexokinase method; SUA was measured by a colorimetric method in which uric acid is oxidized by uricase to form allantoin and H2O2. Serum creatinine was measured using Jaffe method. All of the abovementioned biochemical parameters were measured using standard laboratory techniques and procedure on a Hitachi model 7180 analyzer (Hitachi Inc, Japan). Quality controls were assessed daily for all determinations.

Statistical Analysis Continuous variable data are expressed as mean + standard deviation (SD). One-way analysis of variance was used for comparison of mean values across the SUA quartile groups. For dichotomous variables, the chi-square test was used to evaluate the difference among groups. Multiple linear regression and Pearson correlation analyses were performed to determine the strength of the association between SUA and other continuous parameters. Multivariate logistic regression analysis was used to estimate ORs for each SUA level, with corresponding 95%

Downloaded from ang.sagepub.com at Hestaleit ehf on March 25, 2015

802

Angiology 65(9)

Table 1. Characteristics of the Study Population by Categories of Serum Uric Acid.a Quartiles of Serum Uric Acid, mmol/L Characteristic No. at risk Age, y Male, % Body mass index, kg/m2 Total cholesterol, mmol/L Triglyceride, mmol/L LDL-C, mmol/L HDL-C, mmol/L Creatinine, mmol/L Diabetes, % Smoking, % Current smoker Ever smoker Never smoker Drinking, % Current drinker Ever drinker Never drinker SBP, mm Hg DBP, mm Hg Prehypertension, %

I (324)

n ¼ 2815 45.57 (8.44) 517 (18.37) 23.03 (3.39) 4.26 (0.79) 1.10 (0.69) 2.46 (0.62) 1.30 (0.31) 78.01 (12.72) 123 (4.37)

n ¼ 2806 47.11 (8.76) 870 (31.00) 23.45 (3.39) 4.40 (0.85) 1.26 (0.72) 2.55 (0.65) 1.28 (0.30) 85.74 (11.12) 135 (4.81)

n ¼ 2788 47.97 (8.87) 1289 (46.23) 23.93 (3.27) 4.49 (0.86) 1.44 (0.90) 2.57 (0.68) 1.27 (0.29) 91.24 (11.57) 144 (5.16)

n ¼ 2790 48.73 (9.09) 1898 (68.03) 24.66 (3.44) 4.59 (0.95) 1.88 (1.25) 2.47 (0.75) 1.26 (0.29) 99.21 (14.08) 141 (5.05)

331 (11.76) 31 (1.10) 2453 (87.14)

536 (19.10) 56 (2.00) 2214 (78.90)

798 (28.62) 76 (2.73) 1914 (68.65)

1113 (38.89) 124 (4.44) 1553 (55.66)

266 (9.45) 24 (0.85) 2525 (89.70) 120.97 (10.75) 75.97 (7.43) 1745 (61.99)

429 (15.29) 48 (1.71) 12329 (83.00) 121.16 (10.74) 76.28 (7.13) 1753 (62.47)

614 40 2134 121.40 76.80 1803

(22.02) (1.43) (76.54) (10.94) (7.48) (64.67)

918 (32.90) 63 (2.26) 1809 (64.84) 121.93 (10.28) 78.00 (6.96) 1893 (67.85)

Abbreviations: LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; SBP, systolic blood pressure; DBP, diastolic blood pressure; SD, standard deviation. a Data are expressed as n (column percentages) for category variable or mean (SD) for continuous characteristics.

CIs calculated using the floating absolute risk method.16 Trends in the OR of prehypertension across increasing SUA category were determined, modeling uric acid categories as an ordinal variable. To examine the consistency of the observed association between SUA levels and prehypertension, we performed subgroup analyses by gender, age (