The relationship of hyperuricemia and blood pressure in the Thai army populationS Ouppatham, S Bancha, P Choovichian
Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok 10400, Thailand
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0022-3859.43509
Source of Support: None, Conflict of Interest: None
Background: Previous studies have demonstrated a strong association of hypertension and renal disease with gout. Nevertheless, controversy remains concerning serum uric acid concentration as an independent factor of hypertension. Aim: To explore the relationship between systolic blood pressure (SBP) and diastolic blood pressure (DBP) with serum uric acid levels. Settings and Design: An observational study. Materials and Methods: A total of 5,564 subjects from the Armed Forces Research Institute of Medical Sciences were included in the study. Statistical Analysis: ANOVA tests, Chi-square test, correlation coefficients, and multiple regression analysis were performed. Results: Of the total subjects, 4,099 (73.7%) were male. Mean SBP and DBP were 128.73±17.06 and 81.62 ± 11.58 mm Hg, respectively. The mean serum uric acid level was 6.54 ± 1.71 mg/dL. A significant and positive correlation was found both between serum uric acid and SBP (r=0.186, P < 0.001) and between serum uric acid and DBP (r=0.255, P < 0.001). After multiple regression analysis of various clinical variables, serum uric acid levels were correlated with the severity of both SBP and DBP, increased age, increased body mass index, decreased glomerular filtration rate, increased serum cholesterol, and male gender. Conclusions: In this study, we suggest that serum uric acid be used to correlate with levels of blood pressure in the general population. Further investigation is required to establish the treatment for hyperuricemia in hypertensive patients.
Keywords: Blood pressure, glomerular filtration rate, hyperuricemia
Studies in the 1970s demonstrated a strong association of hypertension and renal disease with gout.  A major risk factor for renal progression and increased blood pressure is the presence of hyperuricemia or gout. Hyperuricemia is also predictive for the development of both hypertension and renal disease, and 40-60% of hypertensive individuals have hyperuricemia. 
Although, several studies have found that an elevated uric acid level is an independent risk factor for hypertension and renal disease after controlling for the contribution of established risk factors by multivariate analyses, ,,, not all epidemiological population studies support uric acid as an independent risk factor for hypertensive disease. , Nevertheless, controversy remains concerning serum uric acid concentration as an independent risk factor of hypertension or as an indirect marker of renal injury.
Due to lack of evidence, the precise role of serum uric acid in the development of hypertensive and renal progression is yet unknown in the Thai population. Thus, the aim of this study was to evaluate the role of uric acid as a risk factor for hypertension and to design human studies to address this controversy. The present cross-sectional study investigates the relationship between hyperuricemia and hypertension in the Thai population.
This was an observational study of Thai Army employees and their relatives who had routine yearly physical examinations from January to December 2007 at the Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. The institutional review board of Phramongkutklao Hospital and College of Medicine approved the study protocol.
Random samples of all participants aged 18-60 years from the register of the Thai Army in Bangkok were reviewed to retrieve medical and personal data, including baseline demographic characteristics, history of smoking, alcohol consumption, hypertension, and use of antihypertensive or lipid-lowering medications, and co-morbidity. A physical examination was administered on all subjects including blood pressure (BP) and anthropometry. The BP was measured in the right arm of seated participants after a five min rest using a random-zero sphygmomanometer; the first and second readings were averaged. Body weight, height, waist circumference and hip circumference were measured according to standard protocol. Body mass index (BMI) and waist-hip ratio (WHR) were then calculated. Blood samples were collected in the morning after an overnight fast of at least 12 h. Serum uric acid, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and fasting plasma glucose level were measured by standardized methods. Serum creatinine levels were measured by Jaffe's Method and urea levels were determined by kinetic test with the Urease Method. Laboratory services provided testing to the entire Thai Army in Bangkok using a single regional laboratory and standardized methods. An estimate of the glomerular filtration rate (GFR) was obtained by the Cockcroft-Gault Formula using variables for age, gender, body weight, and serum creatinine.
GFR = [(140-age) x weight (x 0.85 if female)]/ 72 x serum creatinine
Data are expressed as mean ± SD. Comparisons among serum uric acid quartiles were made by ANOVA test, as appropriate, for continuous variables and by Chi-square test for categorical variables. Correlation coefficients were calculated by simple regression analysis. Multiple regression analysis was performed to explore the relationship between systolic blood pressure (SBP) and diastolic blood pressure (DBP) with serum uric acid levels. All analyses were performed using statistical software for Windows (SPSS Version 12.0, Chicago, IL), and differences were considered statistically significant at P < 0.05.
Subject characteristics are shown in [Table 1]. A total of 5,564 subjects were included in the study, 4099 (73.7%) of whom were male. The mean age of the population was 45.76 ± 6.49 years, and 6.76% had hypertension as a co-morbid disease. Mean SBP and DBP were 128.73 ± 17.06 and 81.62 ± 11.58 mmHg, respectively.
For further analysis, serum uric acid levels were categorized into four groups: 1) first quartile (below 5.2 mg/dL), 2) second quartile (5.3-6.4 mg/dL), 3) third quartile (6.5-7.6 mg/dL), and 4) fourth quartile (over 7.7 mg/dl). [Table 2] displays the subject data according to serum uric acid level quartiles. The serum uric acid fourth quartile group had significantly higher BMI, higher waist circumference, higher BUN, higher serum creatinine, higher serum cholesterol, and a higher prevalence of males as compared with the other quartile groups, but GFR was not different from that in other quartile groups. The SBP and DBP also increased in tandem with serum uric acid quartiles. However, only the serum uric acid fourth quartile group had significantly higher age as compared with the serum uric acid second quartile group.
The mean serum uric acid levels in the population were 6.54±1.71 mg/dL. A significant and positive correlation was found both between serum uric acid levels and SBP ( r =0.186, P < 0.001, [Figure 1]) and between serum uric acid levels and DBP ( r =0.255, P < 0.001, [Figure 2]).
[Table 3] represents the results of multiple regression analysis of various clinical variables to evaluate their independent associations with serum uric acid levels in the general population. In Model 1, the mean DBP, age, gender, BMI, GFR, and serum cholesterol were independent factors associated with serum uric acid levels. In Model 2, which included the mean SBP in place of the mean DBP, it emerged as a significant and independent factor associated with serum uric acid levels, in addition to other factors.
The present study describes the relationship of serum uric acid levels with BP levels in the Thai Army population. The results indicate that in the studied population, serum uric acid levels are correlated with the severity of both SBP and DBP. Serum uric acid levels are also associated with increased age, increased BMI, decreased GFR, increased serum cholesterol, and male gender.
Our outcome shows that hyperuricemia relates to hypertension according to the previous data. It was reported that up to 50-70% of the hyperuricemic population had hypertension.  Experimental studies have reported that hyperuricemia induces systemic hypertension and renal injury via activation of the renin angiotensin system, and direct entry of uric acid into both endothelial and vascular smooth muscle cells, resulting in local inhibition of endothelial nitric oxide levels, stimulation of vascular smooth muscle cell proliferation, and stimulation of vasoactive and inflammatory mediators. ,
Recent epidemiological studies have further demonstrated that uric acid is a major and independent risk factor for the development of hypertension and renal disease in the other populations including the Framingham Heart Study. ,, Thus, both experimental and epidemiologic studies including ours clearly show that hyperuricemia is a marked associated factor for hypertension. In the present study, although we showed that serum uric acid levels are correlated with the severity of both SBP and DBP, the correlation coefficients were 0.186 and 0.255, respectively, a significant correlation. The reason may stem from the multiple factors in the pathogenesis of hypertension. Increased serum uric acid levels are thought to be only one of many pathogenesis factors that lead to high blood pressure.
Our study, linking an elevated serum uric acid level with an increase of blood pressure, is possibly of great interest. The application of the key finding in this study, that is, a graded increase in the risk of developing essential hypertension based on the serum uric acid level, is likely to be more far-reaching than earlier reports because of the larger sample size and the comprehensive adjustment for confounding variables. However, further studies are necessary to rule out a pathogenic role for uric acid in the development of hypertension and renal disease.
Whereas our study confirmed initial impressions of a close association of uric acid with levels of blood pressure and renal function, our cross-sectional study design could not determine or draw inferences regarding causality among hyperuricemia with levels of hypertension in the general population. We are planning to confirm our results by conducting a prospective cohort trial to determine the long-term effects of uric acid on blood pressure and renal function.
The major observations in our study were that males had high serum uric acid levels, high fasting cholesterol levels, and high fasting glucose levels. The study had certain limitations concerning the generalizations made from the findings.
In this study, we report that serum uric acid seems to be promisingly correlated with levels of blood pressure and renal function in the Thai Army population. Further investigation is required to establish the treatment for hyperuricemia in hypertensive patients. Finally, the utility of serum uric levels, relative to other emerging markers for hypertension, needs to be determined.
This study was supported by a grant from the Department of Medicine, Phramongkutklao Hospital and College of Medicine. We thank the Armed Forces Research Institute of Medical Sciences for support with patient enrollment and data acquisition.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]