Diagnostic Value of Long Non-Coding RNA NORAD in Acute Coronary Syndrome: A Diagnostic Biomarker Study

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Purpose: Acute coronary syndrome (ACS), a critical condition with high morbidity and mortality, lacks reliable non-invasive biomarkers for timely diagnosis. Traditional biomarkers like troponins lack sensitivity in unstable angina, and troponin levels often remain within the normal range in the early phase of myocardial infarction. Long non-coding RNAs (lncRNAs), implicated in vascular inflammation and atherosclerosis, may serve as novel biomarkers. This study evaluated four lncRNAs (NORAD, MIR181A1HG, HEAT4, MERRICAL) for ACS diagnosis and their correlation with inflammatory cytokines [Interleukin (IL)-1β, IL-6, Tumor Necrosis Factor-alpha (TNF-α)]. Patients and Methods: A total of 156 ACS patients and 100 non-coronary artery disease (CAD) chest pain patients were enrolled from April 2021 to April 2023, with an independent validation cohort (36 ACS and 24 non-CAD) recruited from May to August 2023. Serum levels of lncRNAs were measured via quantitative polymerase chain reaction (qPCR; normalized to GAPDH), and inflammatory cytokines via Enzyme-Linked Immunosorbent Assay (ELISA). Multivariable logistic regression, receiver operating characteristic (ROC) analysis, and Spearman correlation were used to assess diagnostic performance and associations. Results: NORAD (P<0.0001) and MIR181A1HG (P=0.0279) were significantly upregulated in ACS patients, whereas HEAT4 and MERRICAL did not differ significantly. Multivariate regression identified NORAD as an independent predictor of ACS [adjusted odds ratio (OR)=2.567, 95% confidence interval (CI) 1.724-3.823, P<0.001]. ROC analysis showed NORAD alone achieved an Area Under the Curve (AUC) of 0.726 (95% CI 0.661-0.790), with sensitivity 81.1% and specificity 56.0% at the optimal cutoff. Incorporating NORAD into a model with traditional risk factors improved diagnostic accuracy (AUC: 0.700 vs 0.763, P=0.024), validated in the independent cohort (AUC: 0.823 vs 0.690, P=0.015). NORAD levels correlated positively with IL-1β (R=0.40, P<0.001) and IL-6 (R=0.34, P<0.001), but not TNF-α. Conclusion: NORAD is a promising diagnostic biomarker for ACS. Its correlation with inflammatory cytokines underlying its involvement in ACS pathogenesis.

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