Changes in uric acid and electrolyte level in hypertensive patients attending a rural tertiary hospital in Okada Edo State

¹Department of Medical Laboratory Science, Igbinedion University, Okada, Nigeria, ²Department of Obstetrics and Gynecology, Igbinedion University, Okada, Nigeria, ³Lone Star Circle of Help Clinics, Houston Campus, Texas, USA

^&Corresponding author
Mitsan Olley, Department of Medical Laboratory Science, Igbinedion University, Okada, Nigeria

Introduction    

High blood pressure represents a significant public health problem worldwide; approximately one-fourth of the adult population has hypertension. Hyperuricemia is a pathophysiological condition observed in association with chronic inflammatory diseases such as rheumatoid arthritis and cardiovascular and kidney diseases [1,2]. Similarly, the association of hyperuricemia with hypertension has long been recognized [3]. Elevated serum Uric acid is found to be associated with an increased risk of developing hypertension, diabetes, heart failure, diabetic kidney disease, and cerebrocardiovascular diseases [4-8]. Uric acid is the final product of the metabolism of purines, mainly generated from the breakdown of amino acids-rich diet, fructose, and alcohol consumption [9].

Hyperuricemia affects 25-40% of patients with untreated hypertension. However, there is a much lower prevalence in normotensives or the general population [10]. In addition to serving as an independent risk factor for incident hypertension in the general population, hyperuricemia may have significant differential effects in age, gender, and racial subgroups [11], though lower in premenopausal women compared to men in the same age bracket. Other factors that predispose to hyperuricemia include heat stress and dehydration, (which tend to promote the production of endogenous precursors), diuretics, acetylsalicylic acid, testosterone, and anti-cancer drugs [12,13]. The prevalence of hyperuricemia has been increasing in recent years, not only in advanced countries but also in developing countries [14].

Electrolytes and water are the most critical components of normal physiological function. Electrolytes are compounds that influence many aspects of body function, balance the amount of fluid inside and outside the cells throughout the body, and play a vital role in muscle contraction and heart function [15]. Without a correct balance of fluid and electrolytes, the body cells lack the electrical conductivity necessary for cellular energy production. This study is designed to evaluate Serum Electrolyte levels and uric acid and determine the correlation between uric acid and arterial blood pressure in hypertensive and normotensive patients.

Statement of the problem

Hyperuricemia is common in people who present with primary hypertension and tends to be especially common in those with accelerated (or malignant) hypertension [4]. Some of the Hyperuricemia might represent coexistent Chronic Kidney Disease (CKD) or the use of thiazide diuretics that increase serum uric acid levels. Hyperuricemia in hypertension may be due to decreased renal blood flow, microvascular diseases, and local tissue ischemia. Electrolyte imbalance affects the body and can lead to life-threatening cardiovascular conditions, including hypertension [16], which continues to be a major contributor to cardiovascular disease.

Methods     

Study area

This research study was implemented in the chemical pathology laboratory of Igbinedion University Teaching Hospital, Okada, Edo State.

Study design and population

The study was a cross-sectional study involving male and female participants and categorized into:

Control group: normotensive individuals (blood pressure systolic <120 mmHg, Diastolic: < 80 mmHg), confirmed by manually checking BP using a digital set.

Study group: patients receiving antihypertensive therapy for >6 months. Fifty-five (55) hypertensive patients were recruited for this research study, Of which twenty eight (28) were males and twenty seven females). Fifty (50) normal healthy adults were recruited as control subjects (including males and females).

Blood pressure (BP) was measured in the right upper arm using a sphygmomanometer with the patient in the supine position after 10 minutes of rest. The average of two measurements was used as baseline BP for analysis, a subject was considered normotensive if Systolic Blood Pressure (SBP) was < 120 mmHg and Diastolic blood pressure (DBP) was < 80 mmHg and hypertensive if SBP ≥130 mmHg and DBP ≥ 80 mmHg. These parameters were measured irrespective of any antihypertensive group received by subjects.

Total number of patients studied were 105 (males and females). Aside from the other tests such as blood sugar and lipid profile performed, additional tests, including uric acid level and serum electrolytes, were performed in all hypertensive patients.

Selection criteria

Inclusion criteria: the inclusion criteria comprise hypertensive patients who were recently diagnosed, those on antihypertensive drugs for >6 months, and normal healthy adults who were willing and gave their informed consent to participate in the research study.

Exclusion criteria: subjects with impaired renal conditions such as Chronic Kidney Disease (CKD), those with hypertension associated with diabetic complications, rheumatoid anthritis and any viral infections were excluded.

Sample size determination

The sample size was statistically determined using the formula:

Where: n = the minimum sample size; z = the confidence interval, usually set at 1.96 and also a constant; P = the prevalence rate of hypertension 60% [17]. Q = 1- P; d = degree of accuracy desired usually set at 0.05.

The required sample size was calculated as follows:

n=[(1.96)² (0.6) (1-0.6)]/(0.05)², n =368

Since the sample size is large, the intended population size can thus be adjusted using the formula below, as described by Cochran [18].

Where no is the sample size; N = the intended population size.

n=[368/(1+(368-1)/105], n=(368×105)/368, n= 105

The researchers used one hundred and five subjects (both control and hypertensive subjects) for this study.

Sampling analysis

About seven (7) ml of venous blood was collected from the subjects into a plain container. The sample was allowed to clot and retract for about an hour, then separated using a bucket centrifuge at 3500rpm for 5 minutes. The serum was separated from cells with a Pasteur pipette and stored frozen before analysis.

Electrolyte estimation

Serum electrolytes were estimated using the ion-selective electrode method, following the manufacturer's procedure.

Principle: an Ion-Selective Electrode (ISE) makes use of the unique properties of certain membrane materials to develop an electrical potential (electromotive force, EMF) for the measurements of ions in solution. The electrode has a selective membrane in contact with both the test solution and an internal filling solution.

Uric acid

Serum uric acid will be estimated using the enzyme method.

Principle: the LX20 uses a timed endpoint method to measure the concentration of uric acid in serum, plasma, or urine. Uric acid is oxidized by uricase to produce allantoin and hydrogen peroxide. The hydrogen peroxide reacts with 4-amino antipyrine (4-AAP) and 3.5-dichloro-2-hydroxybenzene sulfonate (DCHBS) in a reaction catalyzed by peroxidase to produce a colored product. The system monitors the change in absorbance at 520 nm at a fixed time interval. The change in absorbance is directly proportional to the concentration of uric acid in the sample.

Statistical analysis

Data was imputed into an Excel spreadsheet and then exported to Statistical Package for Social Sciences version 21 for analysis and was used to compare between variables where P-value <0.05 was deemed as statistically significant at a 95% confidence interval. An unpaired T-test was used for statistical analysis because it was grouped into a hypertensive patient and a control sample.

Ethical approval and consent to participate

Approval for the research project was obtained from the ethical committee, Igbinedion University Teaching Hospital, Okada (Ref: IUTH/R.24/VOL.1/50) and preserved by authors. All participants were informed of the intent of the study in simple, understandable language.

Results     

Uric acid

Table 1 shows that 34.6% of hypertensive subjects have normal levels of uric acid, 65.4% have hyperuricemia, while control subjects have 100% normal uric acid. The uric acid level was significantly increased (p<0.05) in hypertensive subjects when compared with control. The uric acid level in hypertensive subjects was higher than the normal range.

Sodium

Table 1 show that 50.9% of hypertensive subjects have normal levels of sodium ions compared with 96% of control. Hypernatremia is high (49.1%) in hypertensive subjects compared with control (0%). None of the hypertensive subjects had hyponatremia compared with 4% of control subjects. The sodium ion level was significantly increased (p<0.05) in hypertensive subjects when compared with control. The sodium ion in control subjects falls within the normal range.

Potassium

Table 1 shows that 10.1% of hypertensive subjects have normal levels of potassium ions compared with 92% observed in the control. Hypokalemia is high (88.9%) in hypertensive subjects compared with control (8%). The potassium ion level was significantly decreased (p<0.05) in hypertensive subjects compared to control. The potassium ion in control subjects falls within the normal range.

Bicarbonate

Table 1 show that the normal level of bicarbonate in hypertensive (100%) and control (94%) was similar. When compared with control, the bicarbonate ion level was significantly increased (p<0.05) in hypertensive subjects. The bicarbonate ion in hypertensive and control subjects falls within the normal range.

Chloride

Table 1 show the normal bicarbonate level in hypertensive (76.6%) and control (98%). Almost 23.4% of hypertensive subjects are hyperchloremia compared with 0% observed in control subjects. Chloride ion level was significantly increased (p<0.05) in hypertensive subjects compared to control. The chloride ions in hypertensive and control subjects fall within the normal range.

Discussion     

Over sixty five of hypertensive patients were found to have elevated levels of serum uric acid (65.4%), while 49.1 percent of test subjects had hypernatremia. The prevalence of hypokalemia and hyperchloremia in hypertensive subjects were 88.9% and 23.4% respectively. All hypertensive patients had normal serum bicarbonate concentrations. A higher prevalence of uricemia was observed among hypertensive patients compared to control subjects (hypertensive vs control: 65.5% vs 0%) (Table 1 and Table 2). Our study's findings do not agree with the report from Israa, [19] whose study found an insignificant difference in uric acid level when compared with the control subjects.

The risk of developing hyperuricemia was found to be 189 times higher (OR=189.05) in hypertensive subjects compared to the control group with normal blood pressure. Being hypertensive was significantly associated with the development of hyperuricemia (P< 0.0001). Timerga et al. [20] found a significant association between hyperuricemia and hypertension. Male hypertensive patients were observed to have a higher prevalence of hyperuricemia than their female counterparts (male vs female: 75% vs 55.6%). Compared to female hypertensive patients, males are 2.4 times at a higher risk of developing hyperuricemia. However, Statistics did not show any significant difference in the prevalence of hyperuricemia concerning gender (P=0,162), this was similar to the findings of Lee et al. [21]. Age has no statistically significant influence on incidence of hyperuriceamia (P = 0.601). this association is also consistent with previous studies of [22-24]. Other identified risk factors for hyperuriceamia from other studies include smoking, abdominal obesity and increase in body mass index [23,24]. However, these risk factors were not evaluated in this study.. However, the use of specific antihypertensive drugs could affect the plasma uric acid. Drugs such as calcium channel blockers (e.g., Nifedipine) and Angiotensin 2 receptor blockers (e.g., losartan) can decrease the levels of plasma uric acid, while beta-blockers (e.g. metoprolol, atenolol), angiotensin-converting enzyme inhibitors (e.g., lisinopril, enalapril) can increase plasma uric acid concentration [22,24-26].

The highest prevalence of hyperuricemia was observed among hypertensive patients within the age group of 66-75 years, while the least was recorded among patients in the age bracket of 56-65 years. Overall, age was not found to significantly affect the prevalence of hyperuricemia in this study (P=0.601). Several studies have documented that the elevated Plasma Uric Acid (PUA) level is associated with developing essential hypertension or its complications, cardiovascular disease, and the risk factors of metabolic syndrome [21,22]. Uric acid has several reported effects by which it may play a pathogenic role in the development of hypertension [22,23]. Western/urban lifestyle, increase in age, and presence of metabolic syndromes are fingered to be responsible for elevation of PUA [24,25].

Hypernatremia was observed among 27 (49.1%) of hypertensive patients, while control subjects had a zero (0%) prevalence. Hypertensive patients were found to have a 120 times higher (OR=120.80) risk of developing hypernatremia than control subjects (Table 1), with statistics showing this risk significant (P < 0.0001). Our finding agrees with reports whose findings documented a substantial association between hypernatremia and hypertension [26,27]. Likewise, a higher prevalence of hyperchloremia was observed among male hypertensive patients than among females (male vs female: 25.0% vs. 22.2 %) (Table 1), statistics failed to show a significant difference in prevalence of hyperchloremia with respect to gender (P = 1.000). Chlorides are anions that are selectively reabsorbed with sodium in the renal tubules; the possible mechanism of hypochloremia may be similar to hyponatremia [28]. The prevalence of hyperchloremia was observed to be highest among hypertensive patients in the age group of 66-75 years, while the least was recorded among those aged 46-55 years. An insignificantly higher prevalence of hypernatremia was observed among hypertensive patients in comparison to control subjects (hypertensive vs control: 50% vs 40%; OR= 1.077; P =1.000). Hypertensive patients within the age group of 66-75 years recorded the lowest prevalence of hypernatremia. Although the highest prevalence of 68.7% was observed among those within the age group of 46-55 years, the prevalence of hypernatremia was not significantly affected by age (P=0.760). The finding has demonstrated that plasma concentrations of sodium are associated with hypertension irrespective of age and gender, as shown in Table 3 and Table 4. Prior studies have equally demonstrated that a slight increase of sodium above the reference range (140 ± 1mEq/l) may lead to hypertension [28,29].

In this study, all control subjects had a plasma chloride concentration within the normal range. This was not the same for hypertensive patients who had 13 (23.6%) (Table 1) patients expressing elevated levels of serum chloride (hyperchloremia). Hypertensive patients were found to have an 18 times higher risk of developing hyperchloremia than control subjects. Hypertension was identified as a risk factor for the development of hyperchloremia in this study (P = 0.006). This finding agrees with reports of Israa et al., Diana et al. and Testani et al. [19,30,31]. However, chlorides are selectively reabsorbed with sodium in the renal tubules, and hypochloremia may increase the likelihood of mortality [27]. All hypertensive and control subjects had no significant difference in serum bicarbonate concentration (Table 1). A total of 49 (88.1%) patients with hypertension were observed to have reduced serum potassium concentration (hypokalemia) (Table 1) as against 4 (8.0%) recorded in the control group of subjects. Hypertensive patients were forty-six times (OR=46.00) more likely to develop hypokalemia than their non-hypertensive (control) counterparts). This report agrees with the findings of Wu et al. [32]. In general, there was a statistically significant association between hypertension and development of hyperkalemia in this study (P = 0.0001).

Compared to female patients, male hypertensive patients had a lower prevalence of hypokalemia (male vs female), with a prevalence of 85.7% and 92.6%, respectively (Table 3). In general, the prevalence of hypokalemia was not significantly affected by gender (P = 0.669). All (100%) hypertensive patients within the age group of 56-65 had reduced potassium (hypokalemia). Those in the age group of 66-75 years had the lowest prevalence of 71.4%. Age was not identified as a risk factor for hypokalemia in hypertensive patients in this study (P = 0.678) (Table 4). The prevalence obtained in this study was contrary to what was obtained by Wu et al. [32], with prevalence of 6.3% but in line with the results of Lago et al. [33], with 82.8% for mild hypokalemia. The reasons for this disparity among different study groups could be attributed to the use of complexity in types of diuretic and dietary salt intake [34]. Diuretics are associated with hypokalemia, and excretion of potassium also depends on sodium intake, which is normally recommended for hypertensive individuals; this may affect plasma potassium.

Generally, age was not identified as a risk factor for the development of hyperchloremia among hypertensive patients in this study (P = 0.267) (Table 4) and was in line with data obtained from Nnadi et al. [35]. This study, however, has some limitations, as it did not take cognizance of the type of antihypertensive medications patients are subjected to, thereby hindering inferences about the end effects of such on uric acid, thereby creating a bias of the association of uric acid and hypertension.

Recommendations

The findings in this study have implications for hypertension management and necessitate the need for routine uric acid assay for all hypertensive patients. Early detection of elevated uric acid is cost-effective, especially in primary health care settings, and will reduce complications associated with high blood pressure.

Conclusion     

This study found a significant increase in uric acid, sodium, and chloride and a reduced potassium level among the hypertensive subjects compared to the control subjects. Serum bicarbonate levels showed no significant differences between the hypertensive patients and the control subjects. Hyperuricemia was more prevalent in male subjects than female subjects and also was most prevalent in age group 66-75 among the hypertensive patients. There was a high prevalence of hypernatremia and hyperchloremia among the hypertensive subjects. Serum bicarbonate showed no significant difference between the hypertensive subjects and the control subjects.

Competing interests     

The authors declare that no competing interests.

Authors' contributions     

OM performed the write-up, analysis of samples using the chemistry autoanalyzer, and statistical analysis. ZS conceptualized the study and was a major contributor in writing the manuscript. GS recruited subjects and performed blood pressure checks on participants. EK did the final editing of the manuscript. All authors read and approved the final manuscript.

Acknowledgments     

Members of this research team sincerely appreciate staff and management of Igbinedion University Teaching Hospital, Okada, for the use of the facility.

Tables     

Table 1: uric acid and electrolyte level in study subjects

Table 2: effect of hypertension on plasma uric acid concentration

Table 3: effect of gender on prevalence of hyperuricemia and electrolytes concentrates in study subjects

Table 4: effect of age on prevalence of hyperuricemia and electrolyte levels

References