Relationship Between Serum Uric Acid Levels and QTc Interval Prolongation in Hypertensive Patients: A Cross-Sectional Analysis

Saifullah Khan¹, Amna Nasir Yousif Alawasia Alzaabi², Christiana Yeboah³, Emmanuel Asamoah⁴, Emmanuel Mensa Bonsu⁵, Alwaleed Alfadhli⁶, Asma maryam⁷, Joshua Odidison⁶, Muhammad Ahmed Ashfaque⁶, Muhammad Ali Niaz⁶

¹MedSTAR Washington Hospital

²MOI

³Hopewell Community Clinic, Accra, Ghana

⁴University of Cape Coast School of Medical Sciences

⁵Kwame Nkrumah University of Science and Technology, School of Medicine and Dentistry

⁶Royal College of Surgeons, Ireland

⁷Watim medical and dental college Rawalpindi

* Corresponding Author: Saifullah Khan, MedSTAR Washington Hospital.

Received: 25 February 2026; Accepted: 25 February 2026; Published: 03 July 2026

1. Introduction

Hypertension is one of the most prevalent chronic diseases worldwide and a major contributor to cardiovascular morbidity and mortality. It affects more than one billion people globally and is strongly associated with an increased risk of coronary artery disease, stroke, heart failure, and sudden cardiac death [1, 2]. Despite advances in pharmacological treatment, patients with hypertension remain vulnerable to adverse cardiovascular outcomes, highlighting the need to identify additional risk factors and early markers of cardiac dysfunction [3]. Serum uric acid, the final product of purine metabolism, has attracted increasing attention as a potential contributor to cardiovascular disease. Elevated serum uric acid levels, commonly referred to as hyperuricemia, have been associated with endothelial dysfunction, oxidative stress, systemic inflammation, and activation of the renin-angiotensin-aldosterone system [4]. These pathophysiological mechanisms may not only contribute to the development and progression of hypertension but may also affect cardiac electrophysiology. Growing evidence suggests that hyperuricemia may also be associated with an increased risk of arrhythmias and adverse cardiovascular events [5].

The QT interval on electrocardiography reflects the time required for ventricular depolarization and repolarization, while the corrected QT (QTc) interval adjusts for heart rate [6]. Prolonged QTc is a clinically important marker of delayed ventricular repolarization and is associated with a higher risk of life-threatening arrhythmias, including torsades de pointes and sudden cardiac death [7]. Although electrolyte disturbances, medications, and underlying cardiovascular conditions are well-recognized determinants of QTc duration, recent studies suggest that metabolic abnormalities may also play an important role [4, 8]. Although the association between serum uric acid and cardiovascular outcomes has been explored previously, the relationship between serum uric acid levels and QTc interval prolongation, particularly in hypertensive patients, has not been adequately investigated [9]. Because hypertension and hyperuricemia frequently coexist and may exert a synergistic effect on cardiac function, understanding this relationship is of considerable clinical importance. In addition, limited regional data, particularly from developing countries, highlight the need for further research in diverse populations [10].

Therefore, the present study was conducted to evaluate the relationship between serum uric acid levels and QTc interval prolongation in patients with hypertension using a cross-sectional design. By examining the potential link between a metabolic marker and an electrophysiological abnormality, this study aims to contribute to improved cardiovascular risk stratification and the early identification of hypertensive patients who may be at increased risk of cardiac complications.

2. Rationale and Objectives

Hypertension is commonly associated with a range of metabolic disturbances, among which elevated serum uric acid is considered a potential contributor to cardiovascular dysfunction. Hyperuricemia has been linked to endothelial injury, increased oxidative stress, and impaired regulation of vascular tone, all of which may influence cardiac electrophysiology. At the same time, prolongation of the corrected QT (QTc) interval is a recognized marker of myocardial electrical instability and is associated with a higher risk of potentially life-threatening arrhythmias and sudden cardiac death. The coexistence of these factors in hypertensive patients raises an important clinical question regarding their possible interrelationship.

Although the role of serum uric acid in cardiovascular disease has received increasing attention, its association with QTc interval prolongation has not been adequately investigated, particularly among patients with hypertension. This gap is especially relevant in developing countries such as Pakistan, where the burden of hypertension is high and access to advanced risk stratification tools may be limited. Exploring this relationship may provide valuable insight into the early identification of high-risk patients and support improved clinical management. Therefore, the present study was conducted to assess the relationship between serum uric acid levels and QTc interval prolongation in hypertensive patients using a cross-sectional design. It also aimed to compare QTc interval values between normouricemic and hyperuricemic patients, determine the frequency of QTc prolongation across uric acid groups, and evaluate this association after accounting for potential confounding factors, including age, gender, and body mass index.

3. Materials and Methods

The present cross-sectional study was conducted to determine the relationship between serum uric acid levels and QTc interval prolongation in patients with hypertension. The study was carried out at multiple healthcare facilities, including tertiary care hospitals and private cardiology clinics in Pakistan, in order to obtain a diverse and representative sample. A total of 200 participants (N = 200) with a confirmed diagnosis of hypertension were included in the study. The sample comprised 100 male and 100 female patients aged between 30 and 75 years. A non-probability consecutive sampling technique was used to recruit participants according to predefined inclusion and exclusion criteria. Eligible participants were required to have a documented history of hypertension for at least six months, along with a recent electrocardiographic (ECG) record and serum uric acid measurement. Patients with a history of cardiac arrhythmias, congenital long QT syndrome, electrolyte imbalance, chronic kidney disease, or use of medications known to affect the QT interval, including antiarrhythmic drugs, were excluded from the study.

Data were collected through both clinical and laboratory assessment. Venous blood samples were obtained from all participants for measurement of serum uric acid levels using standard biochemical analysis. The electrocardiographic analysis was performed using a standard 12-lead ECG, and the QT interval was corrected for heart rate using Bazett’s formula: QTc = QT / √RR. Demographic and clinical information, including age, sex, body mass index (BMI), duration of hypertension, and smoking status, was collected using a structured data collection form. Participants were categorized into normouricemic and hyperuricemic groups according to standard reference values. Hyperuricemia was defined as a serum uric acid level >7 mg/dL in males and >6 mg/dL in females. QTc interval prolongation was defined as a QTc value >440 ms in males and >460 ms in females. These classifications were used for group comparisons and risk assessment [6]. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 26. Descriptive statistics were used to summarize the data. Continuous variables were presented as mean ± standard deviation, whereas categorical variables were expressed as frequencies and percentages. Pearson correlation analysis was used to assess the relationship between serum uric acid levels and QTc interval duration. Independent-samples t tests were used to compare mean QTc values between normouricemic and hyperuricemic groups, while chi-square tests were applied to compare the frequency of QTc prolongation between the two groups [9]. In addition, multivariable logistic regression analysis was performed to determine the independent association between serum uric acid levels and QTc prolongation after adjustment for potential confounding variables, including age, sex, body mass index, smoking status, duration of hypertension, and blood pressure.

4. Results

A total of 200 hypertensive patients were included in the study, comprising 100 males (50.0%) and 100 females (50.0%). The mean age was 52.3 ± 10.6 years, and most participants were aged 41–60 years (n = 84, 42.0%). Regarding body mass index, 72 participants (36.0%) were overweight and 56 (28.0%) were obese. The mean duration of hypertension was 6.8 ± 3.5 years. Table 1 summarizes the demographic and clinical profile of the study participants. The sample showed a balanced sex distribution, with most participants falling in the middle-age category and a substantial proportion being overweight or obese.

Table 1: Demographic and Clinical Characteristics of Participants (N = 200)

BMI: body mass index; QTc: corrected QT interval.

Values are presented as frequency (n), percentage (%), and mean ± standard deviation (SD). QTc was calculated using Bazett’s formula. Hyperuricemia was defined as serum uric acid levels >7 mg/dL in males and >6 mg/dL in females. QTc prolongation was defined as QTc >440 ms in males and >460 ms in females. Table 2 presents the correlations among the study variables. Serum uric acid showed a positive relationship with QTc interval as well as with age, body mass index, and duration of hypertension.

Table 2: Correlation Matrix of Study Variables (N = 200)

QTc: corrected QT interval; BMI: body mass index.

Values are expressed as Pearson correlation coefficients (r). A positive value indicates a direct relationship between variables. The symbol (*) denotes statistical significance at p < 0.05. QTc was calculated using Bazett’s formula. Table 3 compares the demographic and clinical variables between normouricemic and hyperuricemic participants. The hyperuricemic group showed higher QTc interval values and a greater frequency of QTc prolongation.

Table 3: Comparison of Clinical Variables Between Normouricemic and Hyperuricemic Groups (N = 200)

QTc, corrected QT interval; BMI, body mass index; BP, blood pressure.

Values are presented as mean ± standard deviation (SD) for continuous variables and frequency (percentage) for categorical variables. Independent sample t-test was used for continuous variables, while chi-square (χ²) test was applied for categorical variables. A p-value of <0.05 was considered statistically significant. QTc was calculated using Bazett’s formula. Effect size is expressed as Cohen’s d for continuous variables and Cramér’s V for categorical variables. Table 4 presents the association between serum uric acid levels and QTc interval prolongation. A higher proportion of prolonged QTc was observed in the hyperuricemic group than in the normouricemic group.

Table 4: Association Between Serum Uric Acid Levels and QTc Interval Prolongation (N = 200)

QTc, corrected QT interval.

Values are presented as frequency (n) and percentage (%). Chi-square (χ²) test was used to compare categorical variables between normouricemic and hyperuricemic groups. A p-value of <0.05 was considered statistically significant. QTc was calculated using Bazett’s formula. QTc prolongation was defined as QTc >440 ms in males and >460 ms in females. Cramér’s V was used as a measure of effect size for categorical comparisons. Table 5 presents the results of multivariable logistic regression analysis for predictors of QTc interval prolongation. Hyperuricemia remained significantly associated with QTc prolongation after adjustment for relevant confounding variables.

Table 5: Multivariable Logistic Regression Analysis for Predictors of QTc Interval Prolongation (N = 200)

OR, odds ratio; CI, confidence interval; QTc, corrected QT interval; BMI, body mass index; BP, blood pressure; Ref, reference category.

Crude OR represents unadjusted analysis, while adjusted OR accounts for potential confounding variables, including age, gender, body mass index, smoking status, duration of hypertension, and blood pressure. Logistic regression analysis was used to identify independent predictors of QTc interval prolongation. A p-value of <0.05 was considered statistically significant. QTc was calculated using Bazett’s formula.

5. Discussion

The present cross-sectional study evaluated the relationship between serum uric acid levels and QTc interval prolongation in patients with hypertension. The findings demonstrated a significant positive association between hyperuricemia and abnormalities of ventricular repolarization. Serum uric acid levels were positively correlated with QTc interval duration, and patients with hyperuricemia had higher mean QTc values as well as a greater frequency of QTc prolongation than normouricemic participants. In addition, multivariable logistic regression analysis showed that elevated serum uric acid remained independently associated with QTc prolongation after adjustment for age, gender, body mass index, smoking status, duration of hypertension, and blood pressure. Taken together, these findings suggest that hyperuricemia may have important clinical relevance in hypertensive patients with regard to myocardial electrical instability [11, 12].

A notable observation in this study was the clear difference in QTc interval characteristics between normouricemic and hyperuricemic patients. The hyperuricemic group demonstrated higher QTc values and a greater burden of QTc prolongation, supporting the view that serum uric acid may have prognostic value beyond its conventional metabolic role. Since prolonged QTc is associated with malignant arrhythmias and sudden cardiac death, hypertensive patients with elevated serum uric acid may represent a subgroup at increased cardiovascular risk [13, 14]. Several biological mechanisms may explain the observed association between serum uric acid and QTc interval prolongation. Uric acid is no longer regarded merely as a metabolic byproduct; it is increasingly recognized as a mediator of vascular and myocardial dysfunction [9, 15]. Elevated serum uric acid has been associated with oxidative stress, systemic inflammation, endothelial dysfunction, and activation of the renin-angiotensin-aldosterone system. These processes may impair myocardial perfusion and alter ion channel activity, thereby affecting ventricular repolarization. Because the QTc interval reflects ventricular depolarization and repolarization timing, any disturbance in myocardial electrical recovery may contribute to QTc prolongation [16]. Therefore, the association observed in this study is biologically plausible and consistent with the broader cardiovascular effects of hyperuricemia.

Another possible explanation relates to the interaction between hyperuricemia and hypertension itself. Hypertension is known to produce structural and functional cardiac changes, including left ventricular hypertrophy, arterial stiffness, and autonomic imbalance. When elevated serum uric acid coexists with hypertension, these pathological processes may be amplified, increasing the likelihood of electrophysiological abnormalities. In this context, serum uric acid may serve not only as a laboratory parameter but also as an indicator of cumulative metabolic, hemodynamic, and inflammatory burden. This may justify closer cardiovascular monitoring in hypertensive patients with hyperuricemia [17]. The sex-stratified findings also support the overall interpretation of the results. A higher frequency of prolonged QTc was observed in hyperuricemic participants of both sexes, suggesting that the association was not limited to one subgroup. This is clinically relevant because ventricular repolarization differs between males and females, and sex-specific QTc thresholds are already recognized in clinical practice [7, 18]. Although gender was not an independent predictor in the adjusted regression model, the distribution of QTc prolongation across both sexes strengthens the consistency of the observed relationship.

Age also emerged as an important predictor of QTc prolongation in the adjusted model, which is consistent with previous cardiovascular literature. Advancing age is associated with changes in autonomic tone, myocardial compliance, vascular stiffness, and comorbidity burden, all of which may influence ventricular repolarization [11]. However, the persistence of serum uric acid as a significant factor after adjustment suggests that the association between serum uric acid and QTc prolongation cannot be explained by age alone. This finding supports the possibility that hyperuricemia may contribute independently to repolarization abnormalities. In contrast, body mass index was not independently associated with QTc prolongation in the adjusted analysis, although a mild relationship was observed in unadjusted analysis. A similar pattern was seen for smoking status, duration of hypertension, and blood pressure measurements, which lost significance after adjustment. These findings suggest that the relationship between hyperuricemia and QTc prolongation is not merely a reflection of conventional cardiovascular risk factors. Rather, serum uric acid appears to retain potential predictive value even when other clinically relevant variables are considered simultaneously [18, 19].

The findings of this study may have practical clinical implications. Serum uric acid testing is inexpensive, widely available, and routinely performed in many healthcare settings. Electrocardiography is also a simple and accessible diagnostic tool. Together, these measures may help identify hypertensive patients who are at increased risk of arrhythmogenic complications [20]. This may be particularly valuable in low-resource settings, where access to more advanced cardiovascular risk stratification tools may be limited. In such contexts, patients with both hypertension and hyperuricemia may benefit from closer ECG surveillance, medication review, and more comprehensive cardiovascular assessment. This study also contributes to the growing literature on the cardiovascular significance of hyperuricemia. Although serum uric acid has traditionally been discussed in relation to gout and renal disease, increasing evidence suggests its association with hypertension, endothelial dysfunction, vascular injury, heart failure, and arrhythmic risk [21]. By specifically examining QTc interval prolongation in hypertensive patients, the present study adds an important electrophysiological dimension to this body of literature. Since QTc prolongation is a clinically established marker of adverse cardiac outcomes, the identification of serum uric acid as a possible independent correlate may have relevance for both preventive cardiology and routine hypertension care.

The study has several strengths. The relatively balanced representation of male and female participants improved the interpretability of sex-based comparisons. In addition, the use of both correlation analysis and multivariable regression strengthened the analytical framework. Adjustment for clinically relevant covariates, including age, body mass index, smoking status, duration of hypertension, and blood pressure, also added rigor to the analysis. However, certain limitations should be acknowledged. First, the cross-sectional design does not allow causal inference. Although an association between serum uric acid and QTc prolongation was observed, it cannot be concluded that hyperuricemia directly causes repolarization abnormalities [15, 22]. Second, the study was conducted in selected healthcare settings in Pakistan, which may limit the generalizability of the findings to other populations. Third, some potentially important confounders, including renal function, antihypertensive medication subtype, serum electrolytes, diabetes status, and left ventricular hypertrophy, were not assessed in detail. Finally, QTc was calculated using Bazett’s formula, which is widely used in clinical research but may overcorrect or undercorrect under certain heart rate conditions.

Despite these limitations, the consistency of the findings across correlation analysis, group comparisons, categorical distribution, and multivariable regression supports the overall robustness of the observed association. The repeated pattern of higher QTc values and greater QTc prolongation among hyperuricemic patients suggests that this relationship is unlikely to be incidental [23]. Overall, the present study indicates that elevated serum uric acid may be associated with QTc interval prolongation in hypertensive patients and may have potential value in cardiovascular risk stratification. Further longitudinal and multicenter studies are needed to clarify causality, explore underlying mechanisms, and determine whether reducing serum uric acid levels can lower QTc-related cardiovascular risk.

Conclusion

Elevated serum uric acid may be associated with QTc interval prolongation in hypertensive patients and may help identify individuals at increased risk of ventricular repolarization abnormalities. These findings highlight the potential clinical relevance of serum uric acid as an accessible marker in cardiovascular risk stratification. However, prospective longitudinal studies are needed to clarify the causal relationship and determine whether lowering serum uric acid can reduce QTc-related cardiovascular risk.

References

1. He Y, et al. Association between serum uric acid and hypertension in a large cross-section study in a Chinese population. Journal of Cardiovascular Development and Disease 9 (2022): 346.
2. Wang R, et al. A nonlinear correlation between the serum uric acid to creatinine ratio and the prevalence of hypertension: a large cross-sectional population-based study. Renal Failure 46 (2024): 2296002.
3. Lee M-C, et al. QTc interval is associated with atrial fibrillation in individuals with metabolic syndrome phenotype. International Journal of General Medicine (2022): 6189-6198.
4. Abdelraheem N, et al. Hemodialysis Impact on QTc Interval: An Arrhythmia Precursor. Suez Canal University Medical Journal 27 (2024): 1-10.
5. Lee T-L, et al. Association between triglyceride glucose index and corrected QT prolongation in Chinese male steelworkers. International Journal of Environmental Research and Public Health 18 (2021): 4020.
6. Gigante A, et al. The Role of Serum Uric Acid and Serum Creatinine Ratio as Possible Markers of Autonomic Dysfunction and Left Ventricular Mass Index in Atherosclerotic Renal Artery Stenosis. Journal of Cardiovascular Development and Disease 12 (2025): 202.
7. Wu S, et al. Serum uric acid levels and health outcomes in CKD: a prospective cohort study. Nephrology Dialysis Transplantation 39 (2024): 510-519.
8. Wang Y, et al. Association of UHR and ECG parameters with type 2 diabetes mellitus in non-alcoholic fatty liver disease. Frontiers in Endocrinology 16 (2025): 1643842.
9. Korucuk N, et al. Tp-e Interval, Tp-e/QT, Tp-e/QTc ratios are associated with Resistant Hypertension Running Tittle: Tp-e Interval and Repolarization Markers in Resistant Hypertension (2026).
10. Fang X-X, et al. Correlation between lactate dehydrogenase and QTc interval prolongation in maintenance hemodialysis patients: a cross-sectional study. Annals of Palliative Medicine 11 (2022): 3444454-3443454.
11. Huddam B, et al. Increased QT Dispersion and High Risk of Ventricular Arrhythmias is Associated with Hyperuricemia in Individuals with Normal Renal Function (2021).
12. Deng C, et al. Association of QTc interval with risk of cardiovascular diseases and related vascular traits: a prospective and longitudinal analysis. Global heart 15 (2020): 13.
13. Khalil O A, et al. Evaluation of QT Intervals in Compensated and Decompensated Chronic Hepatitis C Cirrhotic Patients. The Egyptian Journal of Hospital Medicine 79 (2020): 435-441.
14. Agarwal K, et al. Electrocardiography indices in healthy metabolic syndrome patients: Markers for future cardiovascular risk. Journal of Clinical and Preventive Cardiology 10 (2021): 2-7.
15. Hansildaar R, et al. Cardiovascular risk in inflammatory arthritis: rheumatoid arthritis and gout. The Lancet Rheumatology 3 (2021): 58-70.
16. Eder M, et al. Markers of potassium homeostasis in salt losing tubulopathies-associations with hyperaldosteronism and hypomagnesemia. BMC nephrology 21 (2020): 256.
17. Mulia E P, et al. Electrocardiographic abnormalities among late-stage non-dialysis chronic kidney disease patients. Journal of Basic and Clinical Physiology and Pharmacology 32 (2021): 155-162.
18. Nagdev G M and V Gawande. A Study Protocol on Assessment of ECG and Echocardiography Changes in Stroke Patients. Journal of Pharmaceutical Research International 33 (2021): 2915-2921.
19. Yilmaz H, E Güner, and M Altuntas. Results of favipiravir combined treatment in intensive care patients with Covid-19 (2020).
20. Rosas G, et al. Cardiovascular safety risks associated with gout treatments. Expert Opinion on Drug Safety 19 (2020): 1143-1154.
21. Prolongation Q I. in Patients with Liver Cirrhosis (2020).
22. Amini M, et al. Electrocardiographic Manifestations of Endocrine and Metabolic Disorders (2023).
23. Hou Z, et al. Overview of the pharmacokinetics and pharmacodynamics of URAT1 inhibitors for the treatment of hyperuricemia and gout. Expert Opinion on Drug Metabolism & Toxicology 19 (2023): 895-909.