A study to assess relationship between Uric Acid and Blood pressure among patients attending tertiary care hospital in Central Gujarat

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1 ORIGINAL ARTICLE A study to assess relationship between Uric Acid and Blood pressure among patients attending tertiary care hospital in Central Gujarat Meenakshi Shah 1, Varsha Godbole 2, Upesh Parmar 3, Falgun Gosai 4, Tapan Pathak 5 1,2,3,4,5 Department of Internal Medicine,GMERS Medical College,Vadodara, Gujarat ABSTRACT BACKGROUND: The objective of this study was to investigate the relationship between the uric acid levels and blood pressure in patients attending a tertiary care hospital in central Gujarat. MATERIALS AND METHODS: Uric acid levels were measured in 100 hypertensive patients and an equal number of ages and sex matched normotensive patients. Hyperuricemia was defined as serum urate levels 6mg/dl. Quantitative variables between the two groups were tested using unpaired t test and of less than 0.05 was considered statistically significant. RESULTS: The mean uric acid level in hypertensive group was 6.1 ± 2.1 mg/dl as compared to 4.5 ± 1.1 mg/dl in normotensive group. This difference in the mean uric acid levels in two groups was statistically significant (P<.0001). CONCLUSIONS: In this cross sectional study a positive correlation between hyperuricemia and hypertension was observed. Keywords: Uric acid, Hypertension, Blood pressure INTRODUCTION Uric acid is a product of purine degradation with generation of oxidants. It is degraded in most mammals by enzyme urate oxidase to allantonin which is excreted freely in urine. In humans, it is the final byproduct due to mutated non functioning urate oxidase gene. Hyperuricemia is usually defined as > 7.0 mg/dl in male and > 6.0 mg/dl in female, based on the limits of solubility of monosodium urate in serum at temperature of 37 degree Celsius. 1 Uric acid level in the body depends on balance between urate generation and excretion. Factors that increase generation of uric acid levels account for 10% of hyperuricemia. These include high purine diet, alcohol consumption, high cell turnover or enzymatic defect in purine metabolism. Inefficient urate excretion accounts for 90% of cases of hyperuricemia. It occurs in renal insufficiency or use of thiazide diuretics which stimulate sodium and urate reabsorption in proximal tubule. In persons *Corresponding Author: Dr. Meenakshi Shah Department of Medicine, GMERS Medical College, Gotri, Vadodara, Gujarat. Phone: drmeenakshi30@yahoo.com with metabolic syndrome, hyperuricemia occurs because of sodium and urate reabsorption stimulated by insulin. 1 Uric acid is higher in men and also in post menopausal women because of uricosuric nature of estrogens. 2 Hypertension has shown an increasing prevalence in Indian adults and the numbers are estimated to be 213 million by Animal and human studies have long shown association of serum uric acid levels with development of hypertension. 4,5 The mechanism by which uric acid causes hypertension is postulated to be oxidative stress, endothelial dysfunction and activation of renin angiotensin system. 6 Decrease in renal blood flow and decreased tubular secretion of uric acid along with hyperinsulinemia secondary to insulin resistance contributes to hyperuricemia in hypertension but a causal role of uric acid in development of hypertension has been proposed in a number of studies. 1,8,9,10 Lowering the levels of uric acid with allopurinol and probenecid has been shown to reduced blood pressure in adolescents with hypertension. 17 With both hypertension and hyperuricemia showing an increasing prevalence globally this study was undertaken with a goal to investigate the relationship between the uric acid levels and hypertension in a tertiary care hospital. 24 Int J Res Med. 2015; 4(3);24-28 e ISSN: p ISSN:

2 MATERIALS AND METHODS find association between systolic blood This cross sectional study was conducted pressure, diastolic blood pressure and over a period of one year in the indoor and other parameters among hypertensive outdoor patient population in a tertiary patients as well as among normotensive care hospital. A total of 100 adult patients patients by correlation coefficient (r) and p with hypertension and an equal number of value of r less than 0.05 was considered as age and sex matched normotensive statistically significant association. subjects were included in the study. Descriptive statistics were used to mention Patients with secondary causes of about hyperuricemia among hypertensive hypertension, pregnancy, renal failure, any patients. acute illness and drugs likely to influence Informed written consent was obtained serum uric acid levels were excluded from from all study subjects. The study was the study conducted after obtaining the necessary A detailed history was taken which permission from the Institutional ethics included details of smoking and alcohol committee. consumption, dietary patterns and BMI RESULTS was calculate for every patient. A detailed A total of 200 subjects were studied. Out clinical examination was also done. Blood of the 100 hypertensive patients, 44% were pressure was measured using standard males and 56% were females. In the mercury sphygmomanometer in the right hypertensive group mean age was 56.3 ± arm. Hypertensive patients were defined as years. Mean BMI was 24.6 ± 5.01 those having systolic blood pressure 140 kg/m 2. Mean systolic blood pressure was and diastolic blood pressure 90 or ± 22.8 mm of Hg and diastolic was patients already on antihypertensive 91.1 ± 102 mm of Hg. Other baseline medications. Biochemical markers like characteristics of hypertensive group and uric acid, cholesterol, glucose, blood urea normotensive group are given in Table 1 and creatinine were measured in the and Table 2. fasting state. Uric acid was measured by Table 1: Basic details of normotensive enzymatic uricase method. Hyperuricemia and hypertensive patients was defined as serum uric acid levels Variables Normotensive Hypertensive 6mg/dl. patients patients (N=100) (N=100) Data was analysed using Med Calc Male software version Descriptive Female statistics have been mentioned in the form Smokers of percentages, mean and standard Alcohol deviation. Quantitative variables between users normotensive and hypertensive patients Veg diet were tested using unpaired t test and p Non Veg value of less than 0.05 was considered diet statistically significant. We also tried to Table 2: Descriptive statistics of variables among the two study groups (mean + SD) Variables Normotensive Patients (N=100) Hypertensive patients (N=100) Age (yrs) Height (meter) Weight (kg) BMI (kg/m 2 ) SBP (mm/hg) DBP (mm/hg) FBS (mg/dl) Unpaired t test Not applicable S. cholesterol (mg/dl) <0.0001* Blood urea(mg/dl) * S. creatinine(mg/dl) * S. Uric acid (mg/dl) <0.0001* 25 Int J Res Med. 2015; 4(3);24-28 e ISSN: p ISSN:

3 Table 3: Hyperuricemia (N = 46) among hypertensive patients Variables Hyperuricemic patients (N=46) Age group yrs yrs yrs yrs 14 More than 70 yrs 5 Male 19 Female 27 Smokers 13 Alcohol users 6 Veg diet 32 Mixed diet 14 BMI ( 25) 17 Cholesterol ( 180) 22 The mean uric acid level in hypertensive group was 6.1 ± 2.1 mg/dl as compared to 4.5 ± 1.1 mg/dl in normotensive group (statistically significant). Serum cholesterol levels in hypertensive group were 171± 48.9 mg/dl and in normotensive group were 140.2± 29.4 mg/dl (statistically significant).none of the patients in normotensive group had raised uric acid levels. Thus there was a significant association of elevated uric acid levels with hypertension (p<0.0001). Serum cholesterol levels were also significantly raised in hypertensive subjects. (p<0.0001). Table 3 shows that, in the hypertensive subjects 46% were hyperuricemic, with maximum numbers (34.78%) falling into years age group. Of the hyperuricemic hypertensive patients males accounted for 41.30% and females were 58.69%. Thirty seven percent patients had BMI 25 and 48% had raised cholesterol levels. Out of 46 hyperuricemic hypertensive subjects 13% had history of alcohol consumption and 28.24% were smokers. Non vegetarian diet was being consumed by of hypertensives with raised levels of Serum uric acid. Table 4: Correlation between systolic blood pressure, diastolic blood pressure and other parameters among hypertensive patients Factor Systolic blood pressure Diastolic blood pressure r (correlation r (correlation S. Cholesterol Blood urea S. Creat * * S. Uric acid 0.97 <0.0001* 0.94 <0.0001* Age BMI * * Table 5: Correlation between systolic blood pressure, diastolic blood pressure and other parameters among normotensive patients Factor Systolic blood pressure Diastolic blood pressure r (correlation r (correlation S. Cholesterol * Blood urea S. Creat S. Uric acid Age * * BMI Table 4 and Table 5 show the correlation between systolic blood pressure, diastolic blood pressure and other parameters in hypertensive as well as normotensive subjects. A strong correlation was established between serum uric acid levels and systolic and diastolic blood pressure ( P<. 0001) while no such correlation was found between uric acid levels and blood pressure in the normotensives. Also positive correlation was found between BMI, S.creatinine levels and systolic and diastolic blood pressure in the hypertensive patients which was not so in the normotensives. DISCUSSION 26 Int J Res Med. 2015; 4(3);24-28 e ISSN: p ISSN:

4 Hypertension is one of the important cholesterol and a single one time contributors to the global disease burden determination of uric acid levels. Uric acid and is responsible for increased can show variation with repeated cardiovascular morbidity and mortality. monitoring leading to misclassification. Various studies have shown that for the CONCLUSION development of hypertension, Our cross-sectional study showed a hyperuricemia is an important risk factor positive correlation between independent of the other traditional ones hyperuricemia and hypertension. A direct such as obesity, excess salt intake, renal and specific association was also observed disease etc. 18 Masuo et al have shown that between the BMI and cholesterol levels systolic blood pressure rises by 28 mm of with hypertension and hyperuricemia. Hg and diastolic by 15 mm of Hg per unit Nevertheless a descriptive clinical study in rise in serum uric acid. 12 larger population with adjustment for BMI In our study we found a statistically in hyperuricemic subjects is recommended significant correlation between to assess the relationship with hypertension and raised serum uric acid hypertension and to study the potential levels in hypertensive subjects with normal benefit of lowering uric acid in preventing serum creatinine levels whereas the hypertension. nonmotensive group showed no such REFERENCES correlation. In the hypertensive group, the 1. Johnson R J, Duk-Hee Kang, Feig D correlation was found to be strong between et al. Is there a pathogenetic role for both the systolic and diastolic blood Uric acid in hypertension and pressure measurements and the level of Cardiovascular and Renal Disease? serum uric acid. Hypertension. 2003; 41: In one study Peter Grayson et al 18, have 2. Galvan A Q, Natali A, Baldi S et al. demonstrated a more pronounced Effect of insulin on Uric acid excretion association between the increased uric acid in humans. Am J Physiol.1995; levels and hypertension in younger 268:E1-E5. population and in females. However in our 3. Mohan S, Campbell N, study no such association was found. Chockalingam A et al. Time to The possible mechanism for development effectively address hypertension in of hypertension due to uric acid is the India. Indian J Med Res.2013; endothelial dysfunction and vascular 137: smooth muscle proliferation by nitric acid 4. Johnson R J, Feig D I, Herrerasynthetase. Uric acid also directly Acosta J et al. Resurrection of uric stimulates the Renin Angiotension system. acid as a causal risk factor in essential These causal factors are more significant hypertension. Hypertension 2005; 45- in the early stages of hypertension. 19 However in our study all 5. Mazzali M Kanellis J, Han I et al. subjects were over 30 years of age hence Hyperuricemia induces a primary renal no such correlation could be found. arteriopathy in rats by a blood pressure Our study is also in accordance with the independent mechanism. Am J Physiol fact that increased BMI and Renal Physiol.2002; 22-F991-F997. hypercholesterolemia are associated with 6. Johnson R J, Sancez L G, Mazzali M hyperuricemia. About half of our et al. What are the key arguments hyperuricemic patients had high against uric acid as a true risk factor cholesterol levels. Treating hyperuricemia for hypertension? Hypertension 2013; and reducing the levels with drugs such as 61: Allopurinol may prevent hypertension and 7. Perlstein T S, Gumieniak O, decrease the complication of renal Williams G H et al. Uric acid and the 17, 18 parenchymal disease. development of hypertension the There are some limitations in this study. normative aging study. Hypertension They include a limited sample size, non 2006; 48: exclusion of subjects with high BMI and 27 Int J Res Med. 2015; 4(3);24-28 e ISSN: p ISSN:

5 8. Jossa F, Farinaro E, Panico s et al. Pradesh, India. J Obes Metab Res Serum uric acid and hypertension: the 2014; 1: Olivetti heart study. J Hum 13. Krishnan E, Kent Kwoh, Hypertens.1994; Schumacher H et al. Hyperuricemia 9. Imazu M, Yamamoto H, Toyofuku and Incidence of Hypertension among M et al. Hyperinsulinemia for the men without Metabolic Syndrome. development of hypertension: data Hypertensio.2007; 49: from Hawaii Los Angeles-Hiroshima 14. Sundstorm J, Sullivan L, D Agosino Study. Hyperten. Res. 2001;24:531- RB et al. Relation of serum uric acid 536. to longitudinal blood pressure tracking 10. Loeffler L F, Ana Navas-Acien, and hypertension incidence. Brady T M et al. Uric acid levels and Hypertension.2005; 45: elevated blood pressure in US 15. Feig D I, Nakagawa T, Karumanchi Adolescents. National Health and SA, et al. Hypothesis: Uric acid, Nutrition Examination Survey,1999- nephron number and the pathogenesis 206. Hypertension 2012; 59: of essential hypertension. Kidney Int 11. Nguedia Assob JC, Ngowe N, 2004; 66: Nsagha D S et al. The relationship 16. Feig Di, Soletsky B, Johnson R J et between Uric acid and Hypertension in al. Effect of allopurinol on blood Adults in Fako Division, SW Region pressure of adolescents with newly Cameroon. J Nutr Food Sci 2014 diagnosed hypertension: A randomised 4:257. trial. JAMA 2008; 300: Masuo k, Kawaguchi H, Mikami H 17. Grayson PC, Kim SY, LaValley M, et al. Serum uric acid and plasma Choi HK. Hyperuricemia and incident norephinephrine concentration predict hypertension: A systematic review and subsequent weight gain and blood meta-analysis. Arthritis Care Res pressure elevation. Hypertension (Hoboken) 2011;63: ;42: Watanabe S, Kang DH, Feng L et Raina S, Thakur S, Thakur PC et al. al. Uric acid, hominoid evolution, and Serum uric acid levels in hypertensive the pathogenesis of salt-sensitivity. patients with and without metabolic. Hypertension. 2002; 40(3): syndrome in the hills of Himachal 28 Int J Res Med. 2015; 4(3);24-28 e ISSN: p ISSN:

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