Admission serum mitochondrial DNA relative abundance is associated with angiographic no-reflow or slow-flow after primary percutaneous coronary intervention in STEMI

This study aimed to evaluate the independent association of admission serum mitochondrial DNA (mtDNA) relative abundance with no‑reflow or slow‑flow (NR/SF) after primary percutaneous coronary intervention (PPCI) in patients with acute ST‑segment elevation myocardial infarction (STEMI), and to quantify its incremental predictive value along the clinical timeline. We prospectively enrolled 892 consecutive STEMI patients undergoing PPCI and measured pre‑procedural serum mtDNA relative abundance using quantitative real‑time polymerase chain reaction (qPCR). After overlap weighting adjustment for 17 baseline covariates, high mtDNA abundance was independently associated with an increased risk of NR/SF (OR = 2.461, 95% CI 1.535–3.948, P < 0.001), with an absolute risk difference of 11.73%, and the exposure–response relationship exhibited a significant non‑linear threshold pattern (non‑linear P = 0.006). This association remained significant for both the NR component (OR = 2.689, 95% CI 1.377–5.250, P = 0.004) and the SF component (OR = 1.940, 95% CI 1.044–3.604, P = 0.036), and high mtDNA levels were also associated with higher in‑hospital risks of cardiogenic shock, acute heart failure, and severe arrhythmias. In predictive modeling, adding mtDNA to the early admission baseline model significantly improved the area under the curve (AUC) from 0.616 to 0.680 (ΔAUC = 0.064, DeLong P = 0.001), with a net reclassification improvement index of 0.453 and an integrated discrimination improvement index of 0.035. However, once angiographic or periprocedural characteristics were introduced, the incremental predictive value no longer reached statistical significance (ΔAUC = 0.023, P = 0.056–0.068). In conclusion, elevated admission serum mtDNA relative abundance is independently associated with post‑PPCI angiographic NR/SF in STEMI patients, showing a threshold‑like exposure–response relationship; its incremental predictive value is confined to the pre‑angiographic phase, suggesting that it may serve as an auxiliary biomarker for pre‑procedural risk stratification rather than an independent predictive tool. Graphical abstract Admission serum mitochondrial DNA relative abundance and angiographic no-reflow/slow-flow after primary PCI in STEMI. In this prospective cohort of 892 STEMI patients, higher admission serum mtDNA was independently associated with post-PPCI NR/SF, exhibiting a threshold-like effect. While mtDNA improved early pre-procedural risk prediction, its incremental value was not significant after incorporating angiographic data. These findings suggest admission serum mtDNA may serve as an auxiliary biomarker for early risk stratification, rather than an independent predictive tool. Abbreviations: mtDNA, mitochondrial DNA; NR/SF, no-reflow or slow-flow; PPCI, primary percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction; qPCR, quantitative real-time polymerase chain reaction; AUC, area under the curve; NRI, net reclassification improvement; IDI, integrated discrimination improvement.