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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 5  |  Issue : 3  |  Page : 191-196

Prevalence and Determinants of Hyperuricemia in South Indian Adult Patients with Stable Coronary Artery Disease


1 Department of Cardiology, Kerala Institute of Medical Sciences, Thiruvananthapuram, Kerala, India
2 Department of Society for Continuing Medical Education and Research (SOCOMER), Kerala Institute of Medical Sciences, Thiruvananthapuram, Kerala, India

Date of Submission02-Aug-2019
Date of Decision26-Sep-2019
Date of Acceptance20-Nov-2019
Date of Web Publication20-Dec-2019

Correspondence Address:
Govindan Vijayaraghavan
Department of Cardiology, Kerala Institute of Medical Sciences, Thiruvananthapuram - 695 029, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpcs.jpcs_48_19

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  Abstract 


Background: There is paucity of studies on the prevalence of hyperuricemia in Indian patients with coronary artery disease (CAD). Population differences have been observed in both the prevalence and relationship of hyperuricemia with CAD risk factors in previous studies. Objectives: Our study objectives were to analyze the prevalence and determinants of hyperuricemia in south Indian patients with stable and angiographic evidence of CAD. Methods: Study subjects were 520 patients with stable CAD. Severity of CAD was assessed by estimating the Gensini score. Patients in heart failure, those who had a recent myocardial infarction (< 7 days ), or liver disease or impaired renal function (GFR < 30ml/min), and those with hematological or oncological disorders were excluded from the study. Medical and dietitic history, clinical and laboratory data of patients were recorded. Hyperuricemia was diagnosed based on cut off values of ≥7mg/dl of serum uric acid in men and ≥ 6.5 mg/dl of serum uric acid in women. Results: Hyperuricemia was present in 242 patients (46.5%; 95% CI : 42.29-50.84%). A significant association (P < 0.001) was seen between hyperuricemia and consumption of a diet which could influence serum uric acid levels as well as history of regular alcohol consumption. There was no statistically significant association between hyperuricemia and intake of diuretics, presence of either diabetes or hypertension and serum cholesterol levels. Serum triglyceride levels were significantly more in those with hyperuricemia than in those with normal serum uric acid levels (P 0.03). There was no correlation between serum uric acid levels and presence or absence of urinary calculi. The mean Gensini score was 22.57 ± 9.99 in patients with hyperuricemia (n = 242) and the score was 9.42 ± 4.77 in those with normal serum uric acid levels (n = 278). This significant difference (P < 0.001) between the two groups indicate a more severe degree of severity of CAD in patients with hyperuricemia. Conclusion: Our study indicates a high prevalence of hyperuricemia in south Indian patients with stable CAD and that hyperuricemia is associated with severity of CAD, though it does not correlate with conventional risk factors such as diabetes, hypertension and elevated cholesterol levels.

Keywords: Cardiovascular disease, coronary artery disease, hyperuricemia


How to cite this article:
Patil S, Vijayaraghavan G, Kartha C C. Prevalence and Determinants of Hyperuricemia in South Indian Adult Patients with Stable Coronary Artery Disease. J Pract Cardiovasc Sci 2019;5:191-6

How to cite this URL:
Patil S, Vijayaraghavan G, Kartha C C. Prevalence and Determinants of Hyperuricemia in South Indian Adult Patients with Stable Coronary Artery Disease. J Pract Cardiovasc Sci [serial online] 2019 [cited 2020 Jul 16];5:191-6. Available from: http://www.j-pcs.org/text.asp?2019/5/3/191/273740




  Introduction Top


Uric acid is the metabolic end product of purine metabolism in humans and excess accumulation of uric acid in the body can lead to various vascular diseases.[1] Gertler et al., more than six decades ago, postulated that hyperuricemia could be a risk factor for coronary artery disease (CAD).[2] Later several studies found hyperuricemia to be an independent risk factor for CAD,[3],[4],[5],[6] while several others concluded that association of uric acid with conventional CAD risk factors such as diabetes mellitus, hypertension, dyslipidemia, and other coexisting conditions such as metabolic syndrome, impaired renal function, and diuretic therapy may confound the relation of serum uric acid with cardiovascular disease (CVD).[7],[8],[9],[10],[11],[12] Given the conflicting views, major professional societies do not recognize uric acid as a risk factor for CVD and they also do not advocate treatment of asymptomatic hyperuricemia to reduce cardiovascular (CV) disease risk.

A recent meta-analysis revealed that hyperuricemia may increase the risk of CAD events, independently of traditional CAD risk factors.[13] Thus, the nature of the relationship between uric acid and CV disease continues to remain a subject of debate. Patients with hyperuricemia when compared with those with normal serum uric acid levels are considered to have a 3–5-fold increased risk for CAD or cerebrovascular disease. A 1-mg/dl increase in serum uric acid levels has been found to be associated with a 26% increase in CVD-related mortality.

In this report, we present the prevalence of serum uric acid levels in adult patients with stable CAD admitted to a tertiary care hospital in South India and the association of hyperuricemia with diabetic history, alcohol consumption, drug intake, diabetes, hypertension, lipid profile, and severity of CAD in them. Our study is significant given the paucity of studies on the prevalence of hyperuricemia in Indian patients with CAD and also the population differences observed in previous studies elsewhere, in both the prevalence and relationship with CAD risk factors.


  Methods Top


Our study was conducted in the Department of Cardiology of Kerala Institute of Medical Sciences (KIMS), a large multispecialty tertiary care hospital at Trivandrum in southern India. Study participants were 520 patients with stable CAD confirmed by coronary angiography. A sample size of 516 was derived based on a previous recent Indian study.[14] The expected proportion of hyperuricemia was 42.68% with a relative precision of 10% and 95% confidence interval. Severity of CAD was assessed by estimating the Gensini score. The study was initiated after obtaining approval from the Human Ethics Committee of the institution. Patients in heart failure, those who had a recent myocardial infarction (<7 days), or liver disease or impaired renal function (glomerular filtration rate <30 ml/min), and those with hematological or oncological disorders were excluded from the study.

Medical and dietetic history, clinical and laboratory data including serum glucose levels and lipid profile, and information on drug intake of patients were recorded. Serum uric acid was analyzed using uricase method. Hyperuricemia was diagnosed based on cutoff values of ≥7 mg/dl of serum in men and ≥6.5 mg/dl of serum in women. Ultrasound examination of the abdomen was done in all patients for detection of renal and ureteric calculi. All patients who had hyperuricemia were prescribed with Zyloric 100 mg twice daily in addition to the dietetic advices as per the hospital protocol.

All data were entered in to MS Excel and analyzed using SPSS version 17.0 (Chicago, SPSS Inc, IL, USA). Results on categorical measurements were represented using frequency (percentage), and results on continuous measurements were represented using mean (standard deviation). Normalities were checked by plotting histograms. Box plot was used to compare the Gensini score and serum uric acid levels. Association between categorical variables was analyzed using Chi-square test. Student's t-test was used for the analysis of continuous variables. P < 0.05 was considered as statistically significant.


  Results Top


The distribution of demographic and continuous variables in our patients is given in [Table 1]. Association of hyperuricemia with the different variables is given in [Table 2], [Table 3]a and 3b.
Table 1: Distribution of Demographic Variables in South Indian adult Patients With Stable Coronary Artery Disease

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Table 2: Distribution of Continuous Variables in South Indian adult Patients with Stable Coronary Artery Disease

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There were 442 men (85%) and 78 women (15%) in our study. Mean age was 62.4 ± 10.6 years. Hyperuricemia was present in 242 patients (46.5%; 95% confidence interval: 42.29%–50.84%). The mean age group of patients with hyperuricemia was 63.6 ± 10.38 and the mean age of those with normal uric acid levels was 61.3 ± 10.8). Among men, 84.7% had elevated uric acid levels, and among women, 15.3% had elevated uric acid levels. In patients with hyperuricemia, the mean body mass index (BMI) was 24.84 ± 2.583. When compared to the BMI of those with normal serum uric acid levels (24.12 ± 2.618), there was a significant difference (P = 0.002).

Among the 520 patients studied, 300 patients gave a history of consuming a diet which could influence serum uric acid levels. Among them, 222 patients (91.7%) had elevated serum uric acid levels. Association of hyperuricemia with consumption of a diet which could influence serum uric acid levels was significant (P < 0.001). Two hundred and forty-two patients gave a history of regular alcohol consumption. Among them, 155 patients had hyperuricemia. Association of hyperuricemia with alcohol consumption was also significant (P < 0.001).

Seventy seven (14.8%) of the patients were consuming diuretics. Among those with hyperuricemia, 48 (19.8%) were taking diuretics, whereas among those with normal serum uric acid levels 29 (10.4%) were taking diuretics. Twenty seventy-five (52.9%) had type 2 diabetes and 271 (52.1%) had hypertension. Among those with diabetes, 125 (51.7%) had elevated serum uric acid levels. Among the hypertensives, 133 (55%) had elevated serum uric acid levels. There was no statistically significant association between either diabetes or hypertension with hyperuricemia.

Ninety-three (17.9%) patients had the presence of urinary calculi as detected by abdominal ultrasound examination. There was no correlation between serum uric acid levels and the presence or absence of urinary calculi. There were 15 (2.9%) patients who were earlier diagnosed to have gout and were on treatment for hyperuricemia and gout.

Eighty percent among both statin naïve patients and those who were not on statins or lipid-lowering agents had fasting serum total cholesterol levels below 200 mg/dl. 68% had serum low-density lipoprotein levels <100 mg/dl and 55% had serum high-density lipoprotein levels <40 mg/dl. There was no significant difference in the serum lipid levels between those who had hyperuricemia and those who had normal serum uric acid levels. In patients with elevated serum uric acid levels, mean serum triglyceride level was 133 ± 65 mg/dl. This level was significantly more than the mean serum triglyceride level of 116.7 ± 63.5 mg/dl seen in those with normal serum uric acid levels (P = 0.03).

The mean Gensini score was 22.57 ± 9.99 in patients with hyperuricemia (n = 242) and the score was 9.42 ± 4.77 in those with normal serum uric acid levels (n = 278) [Figure 1]. This significant difference (P < 0.001) between the two groups indicates a more severe degree of CAD in patients with hyperuricemia.
Figure 1: Association of hyperuricemia with Gensini score in South Indian patients with stable coronary artery disease.

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Three hundred and thirty-seven patients (64.8%) underwent percutaneous transluminal angioplasty. One hundred and six (20.4%) had coronary artery bypass grafting and 77 (14.8%) of the patients had only optimal medical management.


  Discussion Top


Our study revealed a high prevalence of hyperuricemia in South Indian patients with stable CAD. Increased serum levels of uric acid were associated with intake of a diet influencing serum acid levels in the body and also regular alcohol consumption. Hyperuricemia was also associated with a more severe degree of CAD as assessed by the Gensini score.

Uric acid is an end product of purine metabolism. Xanthine oxidoreductase converts xanthine, the immediate precursor of uric acid to uric acid. An increase in serum uric acid level is associated with endothelial dysfunction, antiproliferative effects, generation of free radicals and high oxidative stress and thrombus formation, all of which promote atherosclerosis and its sequelae. Endothelial dysfunction is regarded as the main mechanism by which hyperuricemia promotes atherosclerosis. Patients with persistently elevated levels of uric acid in blood serum have significantly higher levels of endothelial dysfunction markers. Uric acid acts like an antioxidant in the early stages of the atherosclerotic process and also is the strongest determinant of plasma antioxidant capacity. When serum uric acid level rises above 6 mg/dl in women and 6.5–7 mg/dl in men, antioxidant state is paradoxically reverses into a pro oxidant state in the later stage of the atherosclerotic process. This paradoxical state appears to be dependent on several factors such as the stage of the disease process, acidity of the tissues, reduction in other local antioxidants and presence of oxidant substances and enzymes.

Elevated serum uric acid level has been found to be closely associated with male sex, old age, smoking, increased waist-hip ratio, diuretics treatment, dyslipidemia, hypertriglyceridemia, diabetes mellitus, hypertension, renal disease, obesity, and metabolic syndrome.[15],[16] Studies have indicated gender differences in the association of uric acid level with Cardiac events. Zheng et al. and Kawabe et al. in their study confirm our finding that the uric acid level is higher in men than women. Female sex hormone – estrogen lessens circulation of UA in women, and it facilitates renal urate clearance and reduction of tubular urate postsecretory reabsorption.[17],[18]

Serum uric acid level has also been found to be an independent risk factor for poor prognosis in patients with moderate and severe heart failure, stroke, and CV events in patients with hypertension. Whether serum uric acid is an independent risk factor for CVD or only a marker of coexisting conditions is a matter of controversy.

Several population studies.[3],[5],[9],[19],[20],[21],[22],[23],[24],[25] have demonstrated an independent association between serum uric acid levels and CV risk suggesting that uric acid may be an important factor for adverse CV outcomes. Many other epidemiologic investigations,[26],[27],[28],[29],[30],[31] including the Framingham Heart Study,[25] have however indicated that, after adjustment for well-established CV risk factors, uric acid per se does not have a causal association with development of CAD, death from CVD, or death from all causes. Investigators of these studies suggest that apparent association of serum uric acid levels with CAD is attributable to a correlation of serum uric acid levels with other risk factors for CVD.[32],[33] Uric acid levels in serum seem inextricably linked to hypertension, dyslipidemia, and disordered glucose metabolism, each of which may play a casual role in the pathogenesis of CAD. Differences in the compositions of the populations studied, length of follow-up, study endpoints, and accounting for confounding variables may all contribute to the conflicting conclusions in different studies. Lack of consistent evidence in several previous investigations may also be because of small sizes of the sample and less number of clinical events.

There are only a few studies which analyzed serum uric acid levels and its association with CAD in Indian patients. In a study by Pramanik et al., the prevalence of hyperuricemia in 82 patients with CAD in western India was 42.68%.[14] In our study of 520 patients, we found the prevalence of hyperuricemia to be significantly higher.

Association of hyperuricemia with hypertension has been recognized for a long time.[34] Uric acid has been suggested as a cause of hypertension or renal disease. Uric acid is considered to play a pathogenic role in hypertension through several mechanisms such as inflammation, vascular smooth muscle cell proliferation in renal microcirculation, endothelial dysfunction, and activation of the renin–aldosterone–angiotensin system.

Nguedia Assob et al. found in their study in 297 patients a significant independent association between uric acid with both systolic and diastolic blood pressure; an increase in both systolic and diastolic blood pressure was also marked by a corresponding increase in serum uric acid concentration.[35]

An assessment of the independent prognostic value of serum uric acid levels is thus clinically relevant in the specific setting of essential hypertension, in which hyperuricemia is frequent and CV risk stratification is of utmost importance. In a recent cohort study in individuals with hypertension, the association between serum uric acid levels and future CV events remained significant after adjustment for concomitant diuretic therapy, previous CV events, and other risk factors such as office blood pressure (BP). In contrast, the European Working Party on High Blood Pressure in the Elderly trial found that pretreatment serum uric acid level is not an independent predictor of CV events.[36] In contrast to previous studies studies, we found no association of hyperuricemia and systemic hypertension. We also did not find an association with serum cholesterol levels or presence of diabetes in our patients.

None of the previous studies have investigated the relationship between hyperuricemia and consumption of a diet which influence uric acid levels in the body. When a diet survey was done among 520 patients with CAD, we found that 300 patients had a history of consuming a uric acid influencing diet and among them 222 had hyperuricemia, which is a significant association (with P < 0.001). We did not do a quantitative diet survey and hence our inference has limitations.

We found an association of hyperuricemia with severity of CAD assessed using Gensini scores in angiograms. Sinan Deveci et al. had also earlier observed an association of serum uric acid level with the presence and severity of CAD.[37] Ehsan Qureshi et al. also reported association of hyperuricemia with higher Gensini score, more frequent total coronary occlusions, and presence of critical lesions in men presenting with acute coronary syndrome.[38] Duran et al. observed a higher Gensini score, high number of diseased vessels, as well as more number of critical lesions and total occlusions in patients with hyperuricemia. They also found that serum uric acid level is an independent predictor of multivessel disease[39] and that hyperuricemia is associated with CAD severity even in nondiabetic and nonhypertensive patients. Xiong et al. used clinical SYNTAX severity scores and found a significant association of hyperuricemia with the severity and complexity of CAD.[40]

In summary, our study reveals a high prevalence of hyperuricemia and association of high serum uric acid levels with severity of CAD in South Indian patients with stable CAD. Consumption of a diet which influence uric acid levels and alcohol consumption are associated with high serum uric acid levels. As we do not know the prevalence of hyperuricemia in normal general population in South India, whether hyperuricemia contributes to disease risk needs to be further explored.

Acknowledgment

We acknowledge the help from Mr. Jayakumar for statistical analysis of the data.

Ethical clearance

The study was approved by the Institutional Human Ethics Committee.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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