Distinct circular RNA signatures distinguish STEMI from NSTEMI in acute myocardial infarction

Introduction: Heart attacks come in different forms, with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) being two important but distinct types. While doctors can tell them apart in the clinic, it's still unclear exactly how the molecules circulating in the blood differ between the two. Recently, scientists have been looking at circular RNAs (circRNAs), a type of stable non-coding RNA easily found in blood plasma, to see if they can offer new clues beyond traditional heart attack markers. This study set out to find out if the patterns of circRNAs in the blood could reliably tell STEMI and NSTEMI apart, and possibly uncover new, more specific biomarkers for each type. Methods: This exploratory observational study included 59 patients with STEMI, 78 with NSTEMI, and 109 hospital-based controls recruited from two hospitals in Eastern Saudi Arabia. Blood samples were collected in EDTA tubes within two hours after the diagnosis of acute myocardial infarction. Researchers then used advanced sequencing techniques to look for circRNAs in these blood samples. They compared the circRNA patterns between STEMI, NSTEMI, and control groups, making sure to account for differences in age and other factors. The team also checked how the circRNAs compared with the usual gene activity and tested how well these patterns could tell the two heart attack types apart using a standard accuracy metric. Results: A total of 297 circRNAs were differentially expressed between STEMI and NSTEMI at a false-discovery rate below 0.05. Several circRNAs, including hsa-PTPN12_000054, hsa-UBAC2_000001, hsa-STK39_000074, hsa-ERP44_000019, and hsa-LINC00299_000001, were enriched in STEMI cases. Meanwhile, circRNAs including hsa-CHD2_000062, hsa-PCCA_000138, hsa-RBM33_000015, and hsa-NPM1_000005 were more abundant in NSTEMI. An exploratory three-circRNA logistic model produced an apparent AUC of 0.866 and a five-fold cross-validated AUC of 0.813. Interestingly, these circRNA changes didn't always match up with changes in the genes they came from, suggesting that circRNAs might be regulated in their own unique way. Conclusion: Plasma circRNA profiles differed between STEMI and NSTEMI in this exploratory discovery cohort. The identified candidates provide a basis for technical confirmation and external validation, but they should not currently be considered clinically validated diagnostic biomarkers.