Acute myocardial infarction (AMI), commonly known as a heart attack, continues to be a leading global cause of morbidity and mortality^1,2. While traditional cardiac biomarkers such as cardiac troponins (cTnI and cTnT) and creatine kinase-MB (CK-MB) are essential for the diagnosis of AMI, there is increasing interest in adjunctive biomarkers that may aid in risk stratification and prognostication. One such marker is serum uric acid, a final product of purine metabolism, which has emerged as a potential indicator of cardiovascular risk and systemic stress in AMI^3,4. Under physiological conditions, uric acid functions as an antioxidant, capable of scavenging reactive oxygen species (ROS) and providing protection against oxidative damage⁵. However, in pathological states such as AMI, elevated serum uric acid levels (hyperuricemia) have been linked to a paradoxical pro-oxidant effect. This pro-oxidant shift contributes to endothelial dysfunction, promotes inflammation, and reduces nitric oxide bioavailability, thereby exacerbating myocardial ischemia and atherosclerotic progression^6-7. Clinical studies have demonstrated that hyperuricemia in AMI patients is associated with more severe clinical presentations, including higher Killip classification scores, indicating worse heart failure status⁸. Moreover, elevated uric acid levels are correlated with adverse short- and long-term outcomes, including increased in-hospital mortality and major adverse cardiac events⁹. These associations suggest that serum uric acid is not merely a bystander but may actively contribute to the pathophysiological mechanisms of myocardial injury, particularly through oxidative stress and inflammation. In summary, serum uric acid serves as a promising biomarker in the context of AMI, offering insights into disease severity and prognosis.¹⁰ Its dual role—as both an antioxidant and pro-oxidant—highlights the complex interplay between metabolic byproducts and cardiovascular health, warranting further investigation into its potential utility in clinical risk assessment. Serum uric acid is an emerging biomarker in AMI, reflecting oxidative stress and endothelial dysfunction. Hyperuricemia is associated with worse outcomes, including higher Killip class and increased mortality. It complements traditional markers by capturing the inflammatory and pro-oxidant milieu of AMI¹¹.Uric acid-lowering therapies, such as allopurinol or febuxostat, may improve vascular function. Non-cardiac factors and lack of standardized thresholds remain challenges in clinical application. Incorporating uric acid into risk models may enhance prognostic precision and guide targeted therapy¹².

AIM

Study of relationship of Serum Uric acid in Acute Myocardial Infarction.

This hospital-based observational case-control study focused on evaluating the role of serum uric acid in acute myocardial infarction (AMI). Conducted over 18 months from April 2023 to September 2024 at the Department of Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, the study included a total of 320 participants—160 patients diagnosed with AMI and 160 age- and sex-matched healthy controls. Participants were between 18 and 65 years of age and were either admitted to or presented at the outpatient or emergency departments during the study period. Diagnosis of AMI was based on European Society of Cardiology/ American College of Cardiology- fourth universal definition of myocardial infarction- 2018 guidelines, which included clinical symptoms such as chest pain and shortness of breath, electrocardiographic changes (ST- elevation/ depression) suggestive of infarction, elevated cardiac biomarkers (troponin – T/I, CK-MB), development of pathological Q wave or new-onset bundle branch block. For the purpose of isolating the impact of serum uric acid in AMI, individuals with conditions known to affect uric acid levels—such as gout, renal stones, chronic kidney disease, or haematological malignancies—were excluded from the study. Patients having past history of acute myocardial infarction or having recent history of blood transfusion were also excluded. This careful selection ensured a clearer evaluation of serum uric acid’s role as a potential biomarker in myocardial infarction.

Each participant, both cases and controls, was enrolled after obtaining informed written consent following a thorough explanation of the study protocol in their preferred language. A structured data collection proforma was used to ensure uniformity and completeness. Demographic details (age, gender), lifestyle habits (smoking, alcohol intake, physical activity), comorbidities (diabetes mellitus, hypertension, dyslipidaemia), and family history of cardiovascular disease were recorded meticulously.

For cases, detailed history was taken at admission, focusing on the onset, duration, nature, and radiation of chest pain, associated symptoms, and past cardiac events. A thorough clinical examination was performed including vital signs, cardiovascular system examination, and systemic assessment. A 12-lead electrocardiogram (ECG) was recorded for all patients on admission and repeated as necessary. Blood samples were drawn within the first 24 hours of admission for laboratory evaluation.

All study participants underwent the following laboratory investigations: Complete Blood Count (CBC), Liver Function Tests (LFTs), Renal Function Tests (RFTs), Fasting and Postprandial Blood Glucose, Lipid Profile (Total cholesterol, LDL, HDL, Triglycerides), Serum Uric Acid, Serum Creatine Kinase-MB (CK-MB), Troponin-T (Trop-T) assay.

Serum samples were analysed using standardized automated analysers following institutional quality control protocols. Hyperuricemia was defined as serum uric acid levels >6.5 mg/dL (386.6 µmol/L) in males and >5.8 mg/dL (345.0 µmol/L) in females, as per accepted clinical cut-offs. Data from both groups were tabulated and processed for statistical comparison of biochemical and clinical variables. All data collection was performed by trained physicians and lab personnel under the supervision of senior investigators, ensuring adherence to ethical and scientific standards. Statistical testing was conducted with the statistical package for the social science system version SPSS 20.0. Continuous variables were presented as Mean ± SD or median (IQR) for non-normally distributed data. Categorical variables were expressed as frequencies and percentages. The comparison of normally distributed continuous variables between the groups was performed using Student‘s t test else Mann Whitney U test was used for non-normal distribution data. Nominal categorical data between the groups were compared using Student t-test, Chi-squared test, Fisher‘s exact test or as appropriate. Multivariate analysis was done in the end. For all statistical tests, a p value less than 0.05 were taken to indicate a significant difference. Results were graphically represented where deemed necessary. Graphical representation was done in MS Excel 2010.

Table 1: Mean Age between MI and non-MI Groups

The mean age of the MI group (57.6 ± 11.2 years) was slightly higher than the non-MI group (54.8 ± 11.4 years), but this difference was not statistically insignificant (p = 0.0531).

Table 2: Gender Distribution in MI and non-MI Groups

The majority of patients in both groups were male, with 78.1% in the MI group and 75.6% in the non-MI group. Female representation was slightly higher in the non-MI group (24.4%) compared to the MI group (21.9%). The p-value (0.5966) indicates that there is no statistically significant difference in gender distribution between the MI and non-MI groups.

Table 3: Comparison of Abnormal Serum Uric Acid Levels between MI and non-MI Groups

This study found that serum uric acid levels were significantly higher in myocardial infarction (MI) patients compared to non-MI controls, with 64.4% of MI patients showing hyperuricemia versus only 17.5% in the non-MI group (p < 0.0001). Normal uric acid levels were significantly more prevalent in the non-MI group (82.5%), indicating a strong inverse association between normal uric acid levels and MI risk. These findings underscore hyperuricemia as a potential marker for cardiovascular risk.

Table 4: Comparison of Mean Serum Uric Acid Levels between MI and Non-MI Groups

The mean uric acid level in MI patients was (7.10 ± 0.90 mg/dL), notably higher than (5.62 ± 0.58 mg/dL) in non-MI group (p < 0.0001), reinforcing the role of increased uric acid levels in cardiovascular risk.

Table 5: Correlation of Serum Uric Acid with Established Markers of Acute Myocardial Infarction

Serum uric acid showed a moderate positive correlation with Troponin-I (r = 0.55) and CK-MB (r = 0.58), both statistically significant (p < 0.0001), indicating its association with myocardial injury. Its correlation with LDH (r = 0.49, p = 0.673) and hs-CRP (r = 0.32, p = 0.568) was weak and not statistically significant. These results suggest that elevated uric acid levels may reflect cardiac damage more than systemic inflammation. Thus, serum uric acid could serve as a supportive marker in assessing the severity of myocardial infarction.

Table 6: Relationship of Serum Uric Acid with Established Risk Factors of Acute Myocardial Infarction

Serum uric acid showed a strong and significant correlation with hypertension (r = 0.59, p < 0.0001) and diabetes mellitus (r = 0.61, p < 0.0001), indicating its potential link to major cardiovascular risk factors. Correlations with smoking (r = 0.53, p = 0.584), dyslipidaemia (r = 0.57, p = 0.751), and obesity (r = 0.60, p = 0.538) were moderate but not statistically significant. These findings highlight uric acid’s stronger association with metabolic and hypertensive risk over lifestyle or lipid-related factors.

Table 7: Reliability of Serum Uric Acid as Clinical Markers for Acute Myocardial Infarction

Similarly, the AMI group showed elevated serum uric acid levels (7.10 ± 0.90 mg/dL) compared to the control group (5.62 ± 0.58 mg/dL), with a p-value of <0.001, indicating statistical significance. The sensitivity for serum uric acid in diagnosing AMI was 74.5%, while the specificity was 79.2%, suggesting a reasonable accuracy in identifying AMI patients. The AUC for serum uric acid was 0.613 (95% CI: 0.53-0.70), indicating a slightly lower diagnostic capability compared to serum ferritin.

The analysis revealed that individuals aged ≥61 years were more prevalent in the MI group (28.2%) compared to the non-MI group (3.7%), indicating a significant age-related risk (p < 0.0001).

Current study shows that 64.4% of MI patients had serum uric acid levels ≥7.0 mg/dL, while only 17.5% of non-MI patients fell into this category, again reflecting a statistically significant difference (p < 0.0001). Uric acid, a final breakdown product of purine metabolism, is increasingly recognized as more than just a metabolic waste. It acts as a pro-oxidant under conditions of oxidative stress and contributes to endothelial dysfunction, inflammation, and vascular stiffness. During myocardial ischemia, hypoxia-induced xanthine oxidase activity leads to increased production of uric acid and ROS, thus creating a vicious cycle of oxidative injury. A meta-analysis by Xu et al.13 supports this finding, reporting that high serum uric acid significantly increases both short-term (RR: 3.09) and long-term mortality (RR: 2.32) in AMI patients [289]. Similarly, Gosar et al.¹⁴ found that uric acid levels were significantly higher in AMI patients (6.43 ± 2.60 mg/dL) compared to controls (4.05 ± 0.95 mg/dL), indicating its potential use as a prognostic biomarker [290]. Therefore, the findings of current study not only reinforce the utility of serum uric acid in AMI risk prediction but also suggest that it could potentially serve as a target for therapeutic intervention.

In the present study, serum uric acid levels demonstrated moderate but statistically significant positive correlations with established cardiac markers, including Troponin-I (r = 0.55, p < 0.0001) and CK-MB (r = 0.58, p < 0.0001), indicating a potential link between elevated uric acid and myocardial injury severity. Although a positive correlation was also observed with hs-CRP (r = 0.32), it did not reach statistical significance (p = 0.568), suggesting a weaker association with systemic inflammation compared to other markers. The correlation with lactate dehydrogenase (LDH) was similarly modest and statistically insignificant (r = 0.49, p = 0.673), reinforcing the notion that uric acid is more closely related to oxidative stress and myocardial necrosis than to generalized tissue injury. These findings align with prior studies by Fang and Alderman¹⁵ (2000) and Ndrepepa¹⁶ (2018), which have implicated serum uric acid not only as a marker but also as a mediator of cardiovascular risk, particularly in the setting of acute coronary syndromes. Overall, the study supports the role of uric acid as a meaningful adjunct biomarker in assessing the severity and systemic impact of acute myocardial infarction.

In conclusion, this study demonstrates that serum uric acid levels are significantly elevated in patients with acute myocardial infarction (AMI) compared to healthy controls. Uric acid showed moderate but statistically significant positive correlations with established cardiac markers such as Troponin-I and CK-MB, indicating its potential involvement in the oxidative stress and inflammatory pathways associated with myocardial injury. Although its correlation with hs-CRP was weaker and not statistically significant, the overall findings support the role of serum uric acid as an adjunctive biomarker in the evaluation of AMI. Given its accessibility and known associations with cardiovascular outcomes, uric acid may enhance early risk assessment and prognostication in AMI patients. However, further large-scale studies are needed to validate its clinical utility and establish standardized thresholds for effective integration into cardiovascular risk stratification protocols.

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