Preliminary exploration of dynamic changes in circulating mitochondrial DNA (ΔmtDNA) as a prognostic biomarker for...

Mitochondrial DNA (mtDNA) likely contributes to myocardial ischemia-reperfusion injury, yet the prognostic value of its dynamic changes (ΔmtDNA) for major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) in acute ST-segment elevation myocardial infarction (STEMI) patients remains unclear.

This prospective study enrolled 236 STEMI patients undergoing emergency PCI. We measured serum mtDNA levels both before and after the procedure to calculate ΔmtDNA. Based on their ΔmtDNA values, patients were stratified into three groups: a Low ΔmtDNA group (T1, ΔmtDNA < 1.46), an Intermediate ΔmtDNA group (T2, 1.46 ≤ ΔmtDNA ≤ 3.62), and a High ΔmtDNA group (T3, ΔmtDNA > 3.62).

During a 1-year follow-up, 58 MACE cases occurred (incidence 24.5%). The Cox proportional hazards model indicated that each standard deviation increase in ΔmtDNA was associated with a 23.9% higher MACE risk (HR 1.239, 95% CI 1.161-1.321, P < 0.001). When ΔmtDNA was analyzed by tertiles, the risk displayed a dose-response relationship (P for trend < 0.001). Restricted cubic spline analysis supported a linear positive association (P for nonlinear = 0.263). Survival curves showed significantly different cumulative MACE risks among the ΔmtDNA groups (Log-rank P < 0.001). Subgroup analysis revealed a significantly stronger association between ΔmtDNA and MACE risk in patients treated with β-blockers or PCSK9 inhibitors (P for interaction < 0.05).

This study demonstrates that ΔmtDNA is significantly associated with post-PCI MACE risk in STEMI patients, an association primarily driven by recurrent angina rather than hard endpoints such as mortality or myocardial infarction. These findings suggest that ΔmtDNA could serve as an exploratory biomarker to identify patients at elevated risk for ischemia-driven symptomatic events, but its clinical utility requires further validation through formal discrimination analyses and comparisons with established risk scores.