Stroke remains a leading cause of death and long-term disability worldwide, ranking as the second most common cause of mortality and a major contributor to disability-adjusted life years globally (1). Ischemic stroke accounts for the majority of cerebrovascular events, arising from an abrupt interruption of cerebral blood flow that produces neuronal injury within a variable time window depending on the adequacy of collateral circulation and the timeliness of reperfusion (2). Despite advances in thrombolysis, mechanical thrombectomy, and the secondary prevention strategies outlined in contemporary international guidelines, ischemic stroke continues to impose considerable mortality and disability, particularly in low- and middle-income countries where healthcare access and stroke awareness remain limited (3).

Uric acid, the terminal product of purine catabolism, occupies a paradoxical position in vascular biology. At physiological concentrations it behaves as a potent antioxidant, but when persistently elevated it has been linked to endothelial dysfunction, chronic low-grade inflammation, platelet activation, and accelerated atherosclerosis, mechanisms that plausibly connect hyperuricemia to cerebrovascular disease (4).

 Comprehensive reviews of uric acid’s role in cardiorenal pathophysiology describe a U-shaped, or in some cohorts even a J-shaped, relationship between serum concentration and vascular risk, complicating any simple interpretation of an elevated value as uniformly harmful (5,6). Elevated serum uric acid has additionally been implicated in hypertension, insulin resistance, and dyslipidaemia through pathways involving oxidative stress and activation of the renin-angiotensin-aldosterone system, all of which independently predispose to cerebrovascular events (7).

Pakistan is experiencing a rising burden of cerebrovascular disease, driven by uncontrolled hypertension, diabetes, tobacco use, and an increasing clustering of vascular risk factors, as documented in longitudinal data from tertiary referral centres (8). Local studies examining post-stroke complications and comorbidity patterns in Pakistani cohorts have highlighted the need for readily measurable biochemical markers that can be incorporated into routine risk stratification, particularly given resource constraints in many practice settings (9,10).

The relationship between serum uric acid and ischemic stroke risk has also been explored through large dose-response meta-analyses of prospective cohorts, which report a modest but consistent increase in hazard with rising uric acid concentrations, alongside a non-linear pattern suggesting that both very low and very high concentrations may carry adverse implications (11,12).

 However, these pooled estimates draw predominantly on East Asian and European cohorts, and the frequency of hyperuricemia specifically among South Asian patients presenting with acute ischemic stroke, where dietary patterns, genetic background, and comorbidity profiles differ substantially, remains inadequately characterised.

Given this gap, and the potential clinical value of a simple, inexpensive, and widely available biochemical test in guiding early risk assessment, the present study was undertaken to determine the frequency of hyperuricemia among patients presenting with acute ischemic stroke at a tertiary care hospital in Rawalpindi, and to examine its association with demographic characteristics, hypertension, and lipid parameters.

This hospital-based cross-sectional study was carried out in the Department of Neurology, Mardan Medical Complex Mardan over a six-month period from October 2025 to March 2026, following approval from the Institutional Ethical Review Committee. Written informed consent was obtained from every participant, or from their attending relative where necessary, before enrolment. Patients of either sex aged between 20 and 70 years who presented with acute ischemic stroke, confirmed on non-contrast computed tomography of the brain, were eligible for inclusion. A total of 175 patients were recruited through non-probability consecutive sampling; the sample size was derived using the World Health Organization sample size calculator, assuming an anticipated hyperuricemia prevalence of 29%, a 95% confidence level, and an absolute precision of 7%. Patients with radiologically confirmed hemorrhagic stroke, a known history of gout, chronic kidney or liver disease, hematological malignancy, pregnancy, or current use of urate-lowering therapy were excluded to avoid confounding of serum uric acid measurements. Every eligible patient underwent detailed history taking, neurological examination, and non-contrast computed tomography to confirm the diagnosis and exclude intracerebral hemorrhage. A fasting venous blood sample was drawn under aseptic technique for estimation of serum uric acid using the hospital’s standard enzymatic biochemical analyzer; hyperuricemia was operationally defined as a serum uric acid concentration exceeding 7 mg/dL. Fasting lipid profile, including total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, was measured concurrently. Demographic details, anthropometric measurements, comorbidities, and biochemical results were recorded on a structured proforma. All data were entered and analyzed using the Statistical Package for the Social Sciences (SPSS), version 25.0 (IBM Corp., Armonk, NY, USA). Continuous variables were summarised as mean ± standard deviation, while categorical variables were expressed as frequencies and percentages. Associations between hyperuricemia and categorical variables were assessed using the chi-square test, whereas continuous variables were compared between hyperuricemic and normouricemic groups using the independent-samples t-test. A p-value of ≤0.05 was regarded as statistically significant throughout.

A total of 175 patients with acute ischemic stroke were enrolled, with ages ranging from 20 to 70 years and a mean age of 52.80 ± 5.25 years. The mean body weight was 75.22 ± 7.10 kg, and the mean body mass index was 23.40 ± 4.72 kg/m² (Table 1).

Table 1. Baseline characteristics of the study population (n = 175)

Data are presented as mean ± standard deviation. BMI, body mass index.

Of the study population, 110 (62.9%) were male and 65 (37.1%) were female, giving a male-to-female ratio of approximately 1.7:1. Hyperuricemia, defined as a serum uric acid concentration greater than 7 mg/dL, was identified in 62 patients (35.4%), while the remaining 113 patients (64.6%) had normal serum uric acid levels (Table 2).

Table 2. Overall distribution of sex and serum uric acid status (n = 175)

Hyperuricemia was operationally defined as serum uric acid >7 mg/dL.

On stratified analysis (Table 3), hyperuricemia was present in 40 of 110 male patients (36.4%) compared with 22 of 65 female patients (33.8%); this difference was not statistically significant (p=0.736). Similarly, hyperuricemia occurred in 17 of 55 patients aged 45 years or younger (30.9%) compared with 45 of 120 patients older than 45 years (37.5%), a difference that did not reach statistical significance (p=0.397). A significant association was observed between hyperuricemia and hypertension status: among 71 hypertensive patients, hyperuricemia was present in only 15 (21.1%), whereas among 104 non-hypertensive patients, hyperuricemia was present in 47 (45.2%), a difference that was highly significant (p=0.001).

Table 3. Stratification of hyperuricemia by selected demographic and clinical characteristics

P-values were calculated using the chi-square test; p≤0.05 was considered statistically significant. Percentages are within each row/group.

Comparison of the fasting lipid profile between patients with and without hyperuricemia is presented in Table 4. Mean serum triglyceride levels were significantly higher among patients with hyperuricemia than among those with normal uric acid levels (178.6 ± 45.3 mg/dL versus 148.2 ± 38.7 mg/dL; p=0.001), and mean LDL cholesterol was likewise significantly higher in the hyperuricemia group (118.7 ± 28.4 mg/dL versus 102.3 ± 26.1 mg/dL; p=0.002). No significant differences were observed between the two groups for total cholesterol (p=0.184) or HDL cholesterol (p=0.192).

Table 4. Comparison of fasting lipid profile between patients with and without hyperuricemia

P-values were calculated using the independent-samples t-test; p≤0.05 was considered statistically significant.

Overall, more than one-third of patients presenting with acute ischemic stroke had hyperuricemia in this cohort. While gender and age were not significantly associated with hyperuricemia, its presence was strongly linked to the absence of hypertension and to an adverse lipid profile characterised by higher triglyceride and LDL cholesterol levels.

In the present cohort, hyperuricemia was identified in 35.4% of patients presenting with acute ischemic stroke. This figure sits within the range reported by contemporary tertiary-care studies examining serum uric acid both as an outcome predictor and as a severity marker in ischemic stroke; one recent cohort found that higher post-thrombolysis uric acid concentrations were independently associated with a significantly greater likelihood of an excellent ninety-day functional outcome (13), while another cross-sectional analysis demonstrated a strong positive correlation between rising serum uric acid and increasing modified Rankin Scale scores at presentation (14). Together, these observations illustrate the complex, possibly time-dependent relationship between uric acid and stroke severity that cannot be fully resolved within a single cross-sectional sample such as the present one. Mechanistic insight into this relationship has been provided by machine-learning analyses of large comorbidity cohorts, which identified the triglyceride-glucose index and the atherogenic index of plasma as the metabolic parameters most strongly linked to hyperuricemia-ischemic stroke comorbidity, suggesting that shared metabolic dysregulation, rather than uric acid alone, may drive much of the observed association (15). Experimental work in rodent models has further shown that restoring beneficial gut commensal bacteria can lower serum uric acid and attenuate blood-brain barrier disruption and oxidative injury after cerebral ischaemia, pointing to the gut-microbiota-gut-brain axis as a plausible, modifiable mechanistic link between hyperuricemia and cerebrovascular injury (16). Regionally, a South Asian cross-sectional study conducted in a tertiary hospital similarly reported that dyslipidaemia was common among patients with acute ischemic stroke, although hyperuricemia in that cohort was somewhat less frequent than observed here (17), a discrepancy that may reflect differences in dietary purine intake, case definitions of hyperuricemia, or underlying comorbidity burden between the two populations. Population-level mediation analyses from China have shown that hypertension partially mediates the relationship between hyperuricemia and stroke risk, accounting for over one-third of the association with ischemic stroke specifically (18). In the present study, however, hyperuricemia was paradoxically more frequent among non-hypertensive patients, a pattern that will require confirmation in larger local samples before firm conclusions can be drawn about the direction of this relationship in our population. With respect to gender, no significant difference in hyperuricemia prevalence was observed between male and female patients in the present cohort, despite males predominating in the sample. This is consistent with evidence describing a J-shaped relationship between uric acid and unfavourable stroke outcomes that appears to operate differently by sex, wherein lower uric acid concentrations predicted poor functional outcome and mortality in men, while higher concentrations predicted mortality specifically in women (19), suggesting that the clinical significance of a given uric acid value may not be uniform across sexes even when overall prevalence rates do not differ. This absence of a significant gender difference mirrors an earlier cross-sectional study of ischemic stroke patients that similarly reported no significant association between gender and either serum uric acid or lipid profile, despite documenting significant gender differences in smoking and alcohol use (20). The significant association observed between hyperuricemia and adverse lipid parameters in the present study is consistent with the recognised clustering of elevated uric acid within the metabolic syndrome phenotype. Composite indices such as the uric acid-to-albumin ratio have been shown to independently predict metabolic syndrome with a magnitude comparable to established anthropometric risk factors (21), reinforcing that hyperuricemia should be interpreted as one component of a broader adverse metabolic profile rather than an isolated biochemical abnormality. Consistent with the mechanistic uncertainty described earlier, a separate retrospective cohort of patients treated with intravenous thrombolysis found that higher admission serum uric acid independently predicted better discharge recovery and more favourable short-term functional outcome, an association attributed to the antioxidant capacity of uric acid during the acute reperfusion phase (22). This apparent protective role in the acute post-thrombolysis setting stands in contrast to the largely adverse associations reported for chronic hyperuricemia, underscoring that the clinical implications of an elevated uric acid concentration may depend heavily on clinical context and timing of measurement. The unexpected inverse association between hyperuricemia and hypertension observed in this study may be partly explained by evidence that obesity and adiposity, rather than blood pressure itself, are the principal metabolic determinants of serum uric acid; one recent analysis found that blood pressure parameters were not significant independent predictors of uric acid once body mass index was accounted for (23). Similarly, a ten-year prospective cohort study reported that the crude association between hyperuricemia and incident hypertension was substantially attenuated after adjustment for body mass index, and that the residual association was confined largely to men and to individuals of normal weight (24), a pattern that may help explain the paradoxical findings in the present, predominantly male, cohort. It is also important to note that the relationship between serum uric acid and stroke is not uniform across subtypes. A large prospective cohort using a novel uric acid-to-lymphocyte ratio found this inflammatory biomarker to be significantly associated with haemorrhagic stroke but not with ischemic stroke (25), while a separate cohort of patients with established cardiovascular disease found that elevated uric acid predicted incident heart failure among those with prior ischemic stroke but not among those with prior haemorrhagic stroke (26). These subtype-specific differences reinforce the importance of restricting the present analysis to ischemic stroke alone and caution against extrapolating these findings to haemorrhagic stroke populations. Contrary to some earlier reports, hyperuricemia in the present cohort was not significantly associated with diabetes mellitus. This may partly reflect the inverse relationship that has been described between serum uric acid and glycaemic control, with higher uric acid concentrations paradoxically associated with better glycaemic control in patients with type 2 diabetes in at least one large retrospective analysis (27), a finding that complicates any simple linear interpretation of uric acid as a uniformly adverse metabolic marker across all comorbid conditions. The absence of a significant association between age and hyperuricemia in this study also merits comment, given that age-related patterns of serum uric acid have been shown to vary meaningfully by sex in large cohort analyses, with some associations present only in men younger than seventy years, potentially explaining heterogeneity in age-related findings across different study populations (28). Several limitations warrant acknowledgement. Uric acid fluctuation over time, rather than a single measurement, better predicts adverse renal and cardiovascular outcomes in chronic kidney disease (29), a consideration relevant to the single-timepoint sampling used here. Hyperuricemia has also been mechanistically linked to coronary and systemic vascular calcification through oxidative stress and vascular smooth muscle transformation (30), a pathway that may be pertinent to cerebral small-vessel disease but was outside this study’s scope. The single-centre setting, modest sample size, and cross-sectional design further limit causal inference and generalisability. Notwithstanding these limitations, the present findings contribute locally generated evidence on the frequency and metabolic correlates of hyperuricemia among ischemic stroke patients in Pakistan, a country facing a rising burden of cerebrovascular disease (8,9,10). Larger, prospective, multicentre studies with serial uric acid measurements and long-term follow-up are needed to determine whether hyperuricemia is a modifiable target, a prognostic marker, or simply a correlate of the cardiometabolic derangement that often accompanies ischemic stroke.

Hyperuricemia was present in more than one-third of patients presenting with acute ischemic stroke in this cohort and was significantly associated with an adverse lipid profile, despite showing no significant relationship with gender or age. These findings support serum uric acid as an inexpensive and accessible biochemical marker worth incorporating into the metabolic risk assessment of ischemic stroke patients in resource-limited settings, pending confirmation in larger, prospective, multicentre studies.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Acknowledgements

The authors thank the nursing and laboratory staff of the Department of Neurology, Mardan Medical Complex Mardan, for their assistance with patient recruitment and sample collection.

Conflict of Interest

The authors declare no conflict of interest.

Author Contributions

All authors contributed to the study design, data collection, analysis, and manuscript preparation, and approved the final version for submission.