Samozai, Devarapalli, and Babu: A study on association of serum uric acid and blood pressure in hypertensives at a tertiary care centre


Introduction

Hypertension(HTN) is the most common and significant cardiovascular disease because of its prevalence and severity of the damage to the mankind globally. In India also, the prevalence and occurrence of HTN is increasing regularly and also found to be associated with certain age, sex, occupation, life style etc., resulting in increase of morbidity and mortality. These effects of HTN are known to be relate with incidence of myocardial infarction, heart failure, stroke, and renal failure.1, 2, 3, 4

Hyperuricemia, a condition of increased levels of Serum Uric acid (UA) has been proposed to have an association with hypertension in various studies. In certain studies, serum uric acid levels has been found to be an independent predictor for developing hypertension.5, 6, 7 Irrespective of the different ethnic origins & regions, a certain association between serum UA and blood pressure (BP) has been seen in African-Americans and whites8, 9 as well as in the Asians7, 10 including Koreans.11, 12, 13 In the study of causal role of serum UA in the development of hypertension, Mazzali et al.14 observed an elevation in the levels of serum UA followed by an increase in BP via a crystal-independent mechanism in rat models. Further it has also been found that reduction of serum UA was associated with a decrease in BP through the regulation of renin-angiotensin and nitric oxide system.15

On the basis of the above observations, we have proposed to the present study to compare the relationship between serum UA and hypertension in a single cohort with adjustment of all possible confounding factors. This study is focused on the association between serum UA and hypertension.

Materials and Methods

A total of 245 subjects (123 hypertensives and 122 normotensives; age >18 years) were enrolled in this study during a regular routine health checkup. All subjects were informed about the study aims and written informed consent was obtained from them prior to enrollment in the study. Individuals having a known history of gout and cardiac or severe renal diseases and patients who are already under medication for anti-hyperuricemic were excluded from the study. Ethical Clearance was obtained from the Institutional Ethical Committee, Dr.Patnam Mahender Reddy Institute of Medical Sciences, Chevella, Telangana. The procedure and the methods used in the present study were in accordance with the institutional guidelines and regulations.

General information like Name, Age, Sex, Occupation, Address along with history of any drug intake and anthropometric indices - body weight (BW), body height (BH), hip circumference (HC), waist circumference (WC), and lifestyle information have been obtained. BW was measured to the nearest 0.1 kg using a calibrated digital weighing machine and BH was recorded to the nearest 0.1 cm using a height measuring tape. Body mass index (BMI) was calculated as the weight in kg divided by height in meter square. WC was measured by placing the tape horizontally midway between the iliac crest on the mid-axilliary line and the ribs lowest border. HC was measured at the largest circumference of the buttocks. Blood pressure (BP) was measured by trained professionals using a digital BP machine (Omron M10, Omron Corporation, Tokyo, Japan) on the left arm in a sitting position after atleast 10 minutes of rest. Three recordings of blood pressure as systolic and diastolic blood pressure (SBP and DBP) has been taken after a minimum of 5 minutes of rest to avoid any possible effects of anxiety and with an interval of 5 minutes. The venous blood samples were obtained after an overnight fasting (≥12hrs). The blood sample was centrifuged and serum was stored at −20 °C for further analysis. The concentration of SUA, and serum lipids: total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), were determined calorimetrically using commercially available diagnostic kits (Human Diagnostic, Germany). All the biochemical tests were measured using a auto-analyzer (Humalyzer 3000, USA). Hypertension was defined as SBP ≥ 140 mm Hg and/or DBP ≥ 90 mm Hg and prehypertension as when SBP 120–139 mm Hg; and/or DBP 80–89 mm Hg.16 Hyperuricemia was defined as SUA levels >416.4 μmol/L (7.0 mg/dL) in men and >356.9 μmol/L (6.0 mg/dL) in women.17, 18 The participants were divided into groups – Normotensives and hypertensives and the prevalence of Urecemia in correlation with hypertension was studied in each group.

The data has been arranged in tables with mean ± SD for further analysis. The data is analyzed using IBM SPSS version 23. The difference between the groups for baseline variables was done by independent sample t-test (two-tailed). Pearson’s correlation coefficient test was performed to assess the interrelationships between baseline variables and SUA concentrations. The differences for the variables among the groups was determined by using One-way ANOVA analysis. The relationship between SUA and hypertension was evaluated by logistic regression modeling. A p-value < 0.05 was considered to be statistically significant.

Results

In our present study, increased Serum Uric Acid levels is significantly related to incidence of hypertension.

Table 1

Baseline characteristics of each group by age

Variables

Total

Normotensives

Hypertensives

Mean±SD

Mean±SD

Mean±SD

Age (years)

42.4±8.4

32.4±4.5

58.1±4.6

Height (cms)

164.4±5.1

166.4±5.4

160±1.2

Weight (kgs)

65.4±11.5

66.1±19.4

60.5±15.6

Waist circumference (cms)

69.4±34.4

62.4±35.4

78.4±27.8

Hip circumference (cms)

94.5±4.6

94.4±5.4

98.5±4.5

BMI (Kg/m2)

22.6±4.6

23.4±2.4

22.4±1.5

SBP (mmHg)

138.5±15.6

120.4±15.4

154.5±17.5

DBP (mmHg)

82.4±5.6

86.1±5.2

90.4±4.6

Serum UA (mg/dl)

7.3±1.2

6.1±1.4

8.1±1.1

Total Cholesterol (mg/dl)

185.4±26.4

188.5±34.5

194.5±25.4

HDL (mg/dl)

51.3±15.2

50.6±21.6

58.1±19.5

Tg (mg/dl)

106±64.4

126.4±45.6

146.1±41.6

LDL (mg/dl)

104±45.5

155.4±56.4

156±40.4

The baseline characteristics of all the subjects are presented in Table 1. Of the 245 subjects, mean age of the participants was 42.4 ± 8.4 years (range 18–70 years). There was no significant difference in the mean levels of Height, Weight and BMI between the two groups. Mean levels of WC, HC were significantly different between two group (p < 0.05) subjects. The mean levels of SBP and DBP were also significantly more in the hypertensive subjects (p < 0.001). In Pearson’s correlation coefficient test, SUA levels were significantly related with SBP and DBP (p < 0.001). Hypertensives have been found to have increased mean levels of SUA than in the normotensive subjects (p < 0.001). The average level of TG and HDL-C were also significantly different between the groups (p < 0.001). Overall, hyperuricemia prevalence was 9.7% with 0.9% in normotensive and 9.3% in hypertensive subjects.

Discussion

The present study reveals a positive association between elevated SUA levels and hypertension in a general adult cohort. This association was persisted after adjustment for age, sex, BMI, and lipid profile. An increasing trend for the incidence of prehypertension and hypertension was found with elevated levels of SUA in the quartiles. Some studies have demonstrated the relationship between hyperuricemia and hypertension in adult population.19, 20, 21, 22, 23, 24 A study of Japanese adults has showed that hypertension OR was 1.20 for each 1 mg/dL increase in SUA concentration.19 Another cross-sectional study in US observed elevated SUA levels were positively associated with prehypertension, and the multivariate OR comparing highest quartile of SUA (>356.9 μmol/L) with the lowest quartile (<237.9 μmol/L) was 1.96 (1.38–2.79).23 Another study conducted of non-hypertensives in US reported multivariate relative risk was 1.65 when compared to the highest quartile with the lowest quartile.22 Framingham Heart Study, after examining the participants for 4 years, have reported increased SUA levels by each standard deviation was related with an OR of 1.17 for developing hypertension.25 Similar to our findings, in some recent studies, a positive association between SUA and hypertension was found in adult cohorts of China and Korea.26, 27, 28, 29

In this study, we have observed comparatively a stronger relationship for SUA concentration with hypertension and prehypertension in the participants. It is known that hypertensives with uricemia are more vulnerable to hypertension.30 The extended mechanism for the effect of SUA on hypertension is yet to be elucidated. There are some hypotheses partly explain the association between SUA and high blood pressure. One of the possible mechanism might be uric acid deposition on the blood vessels walls activates the renin-angiotensin system, suppress the liberate of carbon monoxide, enhance inflammation, and leads to vasoconstriction on later stage, which consequently leads to hyperplasia and incidence of hypertension.31, 32, 33, 34 Another possibility involving oxidative stress and endothelial dysfunction associated with high SUA levels may contribute to high blood pressure.35

Our study had a few limitations. First, the cross-sectional design of this study may preclude the cause-effect relationships between SUA concentrations and hypertension being assumed. Second, the sample size of this study was relatively small; therefore, the findings may not represent for the whole population. Third, we did not have individual information on family history of hypertension and physical activity which may affect the incidence of high blood pressure. Moreover, all participants of this study were apparently healthy adults; whether our finding is similar in other ethnic populations needs to be further studied. However, this study findings are worthy as a reference for future investigations. Further studies are required to establish the potential mechanism between SUA and hypertension in humans.

Conclusions

Increased levels of SUA were positively associated with hypertension among general adults. The SUA quartiles also showed significant correlation with SBP and DBP. Our study findings suggest an independent relationship of elevated SUA with hypertension and indicate the significance of maintaining normal SUA concentration to prevent hypertension. Early and proper management of SUA levels, as well as blood pressure, may be useful in preventing the development of future CVDs.

Source of Funding

None.

Conflict of Interest

The authors declare no conflict of interest.

References

1 

DI Feig RJ Johnson Hyperuricemia in childhood primary hypertensionHypertension20034224752

2 

J Coresh GL Wei G Mcquillan FL Brancati AS Levey C Jones Prevalence of high blood pressure and elevated serum creatinine level in the United States: findings from the third National Health and Nutrition Examination Survey (1988-1994)Arch Intern Med2001161120716

3 

JK Park Epidemiology of hypertensionJ Korean Soc Hypertens19951617

4 

JS Kim HC Lee WS Yoo UH Yoo Mean blood pressure, prevalence and epidemiologic characteristics of hypertension among representative Korean adult populationJ Korean Soc Hypertens199848998

5 

F Jossa E Farinaro S Panico V Krogh E Celentano R Galasso Serum uric acid and hypertension: the Olivetti heart studyJ Hum Hypertens1994867781

6 

FN Brand DL Mcgee WB Kannel J Stokes WP Castelli Hyperuricemia as a risk factor of coronary heart disease: the Framingham studyAm J Epidemiol1985121118

7 

Y Kansui T Ohtsubo K Goto S Sakata K Ichishima M Fukuhara Association of serum uric acid with blood pressure in Japanese men. Crosssectional study in work-site groupCirc J201175282732

8 

B Longo-Mbenza EL Luila P Mbete EK Vita Is hyperuricemia a risk factor of stroke and coronary heart disease among Africans?Int J Cardiol1999711722

9 

R Klein BE Klein JC Cornoni J Maready JC Cassel HA Tyroler Serum uric acid: its relationship to coronary heart disease risk factors and cardiovascular diseaseArch Intern Med197313240110

10 

M Kuwabara K Niwa Y Nishi A Mizuno T Asano K Masuda Relationship between serum uric acid levels and hypertension among Japanese individuals not treated for hyperuricemia and hypertensionHypertens Res2014377859

11 

YH Kim YD Suh SP Son YW Shim YW Shin YK Shin Observation of the serum uric acid in essential hypertensionKorean J Med1985285663

12 

HJ Chin KY Na Y Kim DW Chae S Kim The impact of uric acid and metabolic syndrome on the incidence of hypertension in a Korean populationKorean J Med2007735866

13 

TW Yoo KC Sung YC Kim ST Hwang SY Oh HS Shin The relationship of the hypertension, insulin resistance, and metabolic syndrome in the serum uric acid levelKorean Circ J20043487482

14 

M Mazzali J Hughes YG Kim JA Jefferson DH Kang KL Gordon Elevated uric acid increases blood pressure in the rat by a novel crystalindependent mechanismHypertension20013811016

15 

M Mazzali J Kanellis L Han L Feng YY Xia Q Chen Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure independent mechanismAm J Physiol Renal Physiol20022829917

16 

AV Chobanian GL Bakris HR Black WC Cushman LA Green JL Izzo Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood PressureHypertension200342120652

17 

X Sui TS Church RA Meriwether F Lobelo SN Blair Uric acid and the development of metabolic syndrome in women and menMetabolism20085784552

18 

L You A Liu G Wuyun H Wu P Wang Prevalence of hyperuricemia and the relationship between serum uric acid and metabolic syndrome in the Asian Mongolian areaJ. Atheroscler Thromb20142135565

19 

M Kuwabara K Niwa Y Nishi A Mizuno T Asano Relationship between serum uric acid levels and hypertension among Japanese individuals not treated for hyperuricemia and hypertensionHypertens Res2014378785910.1038/hr.2014.75

20 

TS Perlstein O Gumieniak GH Williams D Sparrow, PS Vokonas Uric acid and the development of hypertension: the normative aging studyHypertension20064861031610.1161/01.HYP.0000248752.08807.4c

21 

J Sundström L Sullivan RB D'Agostino DLevy WB Kannel RS Vasan Relations of serum uric acid to longitudinal blood pressure tracking and hypertension incidenceHypertension1979451283310.1161/01.HYP.0000150784.92944.9a

22 

A Shankar R Klein BEK Klein FJ Nieto The association between serum uric acid level and long-term incidence of hypertension: Population-based cohort studyJ Hum Hypertens20062093745

23 

S Syamala J Li A Shankar Association between serum uric acid and prehypertension among US adultsJ Hypertens20072515839

24 

H Yokokawa Association Between Serum Uric Acid Levels/Hyperuricemia and Hypertension Among 85,286 Japanese WorkersJ. Clin. Hypertens2016185359

25 

BF Culleton MG Larson WB Kannel D Levy Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart StudyAnn Intern Med1999131713

26 

W Cheng S Wen Y Wang Z Qian Y Tan H Li The association between serum uric acid and blood pressure in different age groups in a healthy Chinese cohortMedicine (Baltimore)2017968953

27 

L Cui HJ Shi SL Wu R Shu N Liu GY Wang Association of serum uric acid and risk of hypertension in adults: a prospective study of Kailuan Corporation cohortClin Rheumatol201736110310

28 

X Lai L Yang S Légaré F Angileri X Chen Q Fang Dose-response relationship between serum uric acid levels and risk of incident coronary heart disease in the Dongfeng-Tongji CohortInt J Cardiol201622429930410.1016/j.ijcard.2016.09.035

29 

JJ Lee J Ahn J Hwang SW Han KN Lee JB Kim Relationship between uric acid and blood pressure in different age groupsClin Hypertens20152114 10.1186/s40885-015-0022-9

30 

PC Grayson SY Kim M Lavalley HK Choi Hyperuricemia and incident hypertension: A systematic review and metaanalysis: Risk of Incident Hypertension Associated With HyperuricemiaArthritis Care Res20116310210

31 

AM Sarki CU Nduka S Stranges NB Kandala OA Uthman Prevalence of Hypertension in Low- and Middle-Income Countries: A Systematic Review and Meta-AnalysisMedicine (Baltimore)2015941959

32 

P Bjornstad RP Wadwa JC Sirota JK Snell-Bergeon K McFann M Rewers Serum uric acid and hypertension in adults: a paradoxical relationship in type 1 diabetesJ Clin Hypertens2014162838

33 

PHF Gois ERM Souza Pharmacotherapy for hyperuricemia in hypertensive patientsCochrane Database Syst Rev20174CD008652 10.1002/14651858.CD008652

34 

YC Ma L Zuo JH Chen Q Luo XQ Yu Y Li Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney diseaseJ Am Soc Nephrol20061710293744

35 

UM Khosla S Zharikov JL Finch T Nakagawa C Roncal W Mu Hyperuricemia induces endothelial dysfunctionKidney Int200567517394210.1111/j.1523-1755.2005.00273.x



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Article History

Received : 19-10-2021

Accepted : 13-11-2021

Available online : 07-12-2021


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https://doi.org/10.18231/j.ijcap.2021.058


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