European Journal of Cardiovascular Medicine

Coronary artery bypass grafting (CABG) is the most commonly performed cardiac surgery globally, aimed at revascularizing ischemic myocardium. Despite advances in surgical techniques, postoperative complications such as acute kidney injury (AKI), atrial fibrillation (AF), and prolonged ICU stays contribute to increased morbidity and mortality. These adverse outcomes are largely attributed to ischemia-reperfusion injury and systemic inflammation, which promote oxidative stress. [1]Non-enzymatic antioxidants—uric acid, albumin, and bilirubin—play protective roles against oxidative damage. Their potential as predictive biomarkers in CABG outcomes has not been fully explored. This study investigates the prognostic utility of these biomarkers for predicting postoperative complications following elective CABG surgery

This prospective observational study included 120 adult patients undergoing elective on-pump CABG at a tertiary care hospital. Inclusion criteria were age >18 years, elective isolated CABG, and preoperative normal hepatic and renal function. Exclusion criteria included patients undergoing combined procedures or having chronic liver/kidney disease.

Preoperative blood samples were collected within 24 hours before surgery. Serum uric acid, albumin, and total bilirubin levels were measured using standardized biochemical methods. Patients were monitored for postoperative AKI (KDIGO criteria), new-onset AF, prolonged ICU stay (>72 hours), and 30-day mortality. Data were analyzed using SPSS v25.0. ROC curves evaluated predictive power of individual and combined antioxidant scores.

Among the 120 patients (mean age 61.2 ± 9.3 years; 84 males), 23 developed AKI (19.2%), 17 had AF (14.2%), and 29 had prolonged ICU stay (24.1%). Serum uric acid >6.5 mg/dL was associated with AKI (p = 0.02), while albumin <3.5 g/dL was linked with prolonged ICU stay (p = 0.01). Low bilirubin (<0.7 mg/dL) showed significant association with AF (p = 0.04). A combined antioxidant risk score (ARS), calculated by assigning points for high-risk levels of each marker, demonstrated AUC of 0.81 (95% CI: 0.74–0.88), with better sensitivity and specificity than individual markers.

TABLE 1 Baseline Characteristics

TABLE 2 Antioxidant Levels (Preoperative)

TABLE 3 Associations with Postoperative Outcomes

*p < 0.05

Antioxidant Risk Score (ARS) Analysis

Each abnormal biomarker (UA >6.5 mg/dL, ALB <3.5 g/dL, BIL <0.7 mg/dL) scored 1 point.

• ARS 0–1 (n=62): Low risk
• ARS 2–3 (n=58): High risk

Outcomes:

• AKI: 5% (low ARS) vs 24% (high ARS)
• ICU >72h: 13% vs 45%
• AUC for ARS = 0.81 (95% CI: 0.74–0.88)

This study highlights the prognostic potential of uric acid, albumin, and bilirubin in predicting postoperative outcomes in CABG.

Uric acid is an end-product of purine metabolism with paradoxical effects. While it has antioxidant properties, elevated levels often indicate increased oxidative stress, endothelial dysfunction, and a pro-inflammatory state. These mechanisms are particularly relevant in cardiac surgery where ischemia-reperfusion injury is common. In our study, hyperuricemia (>6.5 mg/dL) was significantly associated with AKI and AF after CABG.This finding is consistent with the results of Cakir et al., who demonstrated a strong association between elevated serum uric acid and postoperative AF in CABG patients [3].

Hypoalbuminemia reflects malnutrition and impaired antioxidant defense, predisposing patients to infections and prolonged recovery.Albumin, a key protein synthesized in the liver, is a well-established marker of nutritional status and also exhibits potent antioxidant and anti-inflammatory functions. Hypoalbuminemia, common in chronically ill patients and those undergoing major surgery, correlates strongly with adverse outcomes. In our cohort, albumin levels <3.5 g/dL were significantly associated with longer ICU stay and higher infection rates.The prognostic value of hypoalbuminemia in surgical outcomes is extensively documented. Vincent et al., through a meta-analysis of cohort studies, established hypoalbuminemia as a robust independent predictor of morbidity and mortality in critically ill and surgical patients [4].More recently, Shao et al. confirmed its association with postoperative complications in gastrointestinal cancer surgeries, adding to the cross-specialty relevance of albumin as a risk marker [5].

Bilirubin, an endogenous antioxidant, protects against lipid peroxidation and myocardial injury. [2]Though classically used as a hepatic function marker, bilirubin is now recognized for its antioxidant potential, capable of scavenging peroxyl radicals and protecting against lipid peroxidation. In our findings, mild elevations in total bilirubin (within reference range) were associated with fewer complications such as infection and AF.Wang et al. investigated this phenomenon in patients with end-stage renal disease and observed that higher bilirubin levels correlated with reduced cardiac remodeling and improved survival outcomes (2). Their study provides important context for interpreting bilirubin as a protective biomolecule in oxidative stress-mediated disease processes, such as those encountered in CABG.

These observations are also supported by Rodrigo et al., who highlighted oxidative stress markers (including bilirubin and uric acid) in myocardial ischemia-reperfusion damage, emphasizing their prognostic and pathophysiological roles [1].

Similar findings have been reported in recent studies associating oxidative stress markers with surgical outcomes. However, the novelty of this study lies in proposing a simple and cost-effective preoperative ARS for clinical use.

Preoperative levels of uric acid, albumin, and bilirubin serve as valuable, accessible biomarkers for predicting adverse outcomes after CABG. The combined antioxidant risk score may guide perioperative management and improve surgical outcomes.

Limitations and Future Scope

This study was limited by its single-center nature and modest sample size. Enzymatic antioxidant markers (e.g., glutathione peroxidase, catalase) were not measured, and post-surgical dynamics of these antioxidants were not explored. Furthermore, causality cannot be inferred from observational data.

Future studies should aim to:

• Incorporate both enzymatic and non-enzymatic oxidative stress markers,
• Evaluate serial changes in biomarkers perioperatively,
• Explore interventions (e.g., nutritional therapy, xanthine oxidase inhibitors) to correct abnormal levels and improve outcomes.

Acknowledgments

We acknowledge the cooperation of the Departments of CTVS and Anesthesia, and the medical laboratory staff at BKASMC Chandauli.

Conflicts of Interest

The authors declare no conflict of interest.

1. Rodrigo R, Libuy M, Feliú F, Hasson D. Oxidative stress-related biomarkers in essential hypertension and ischemia-reperfusion myocardial damage. Dis Markers. 2013;35(6):773–90.
2. Wang AY, Woo J, Lam CW, et al. Association of serum bilirubin with cardiac remodeling and mortality in end-stage renal disease patients. Kidney Int. 2005;68(1): 160–167.
3. Cakir H, Yildiz A, Demir M, et al. Predictive value of serum uric acid levels on early postoperative atrial fibrillation in patients undergoing isolated coronary artery bypass grafting. Kardiol Pol. 2014;72(4):339–45.
4. Vincent JL, Dubois MJ, Navickis RJ, Wilkes MM. Hypoalbuminemia in acute illness: is there a rationale for intervention? A meta-analysis of cohort studies and controlled trials. Ann Surg. 2003;237(3):319–334.
5. Shao M, Tang W, Shen Y, et al. Preoperative albumin and postoperative complications in patients with gastrointestinal cancer: a meta-analysis. Surg Oncol. 2019;28:70–77.