Mitochondrial DNA Copy Number and Mitochondrial Homeostasis Genes in Acute and Stable Coronary Artery Disease

Background Mitochondrial dysfunction is increasingly implicated in coronary artery disease (CAD), but the relationship between mitochondrial DNA copy number (mtDNA‐CN) and mitochondrial homeostasis across CAD presentations remains unclear. We investigated mtDNA‐CN together with the expression of key regulators of mitochondrial biogenesis (PGC‐1α and TFAM) and mitophagy (PINK1) in patients with stable angina (SA) and acute coronary syndrome (ACS). Methods This observational study included 334 patients: 170 ACS, 117 SA and 47 individuals with non‐obstructive coronary arteries (NCA). Peripheral blood mtDNA‐CN and the expression of PGC‐1α, TFAM and PINK1 were quantified by real‐time PCR. Associations with clinical characteristics, inflammatory markers and left ventricular ejection fraction (LVEF) were evaluated. Results ACS patients exhibited significantly lower mtDNA‐CN than SA and NCA groups ( p = 0.01 and p = 0.004, respectively). PINK1 expression was reduced in both ACS ( p = 0.005) and SA ( p = 0.01) compared with NCA. TFAM expression was increased in SA ( p = 0.009), while PGC‐1α expression was higher in ACS ( p = 0.02). MtDNA‐CN and mitochondrial biomarkers were inversely associated with inflammatory markers, whereas mtDNA‐CN and TFAM correlated positively with LVEF. Lower mtDNA‐CN was independently associated with ACS (OR = 0.98, p = 0.0004) and SA (OR = 0.99, p = 0.04), while higher PINK1 expression was associated with reduced odds of SA ( p = 0.03) and ACS ( p = 0.02). Conclusions Mitochondrial markers are altered across CAD phenotypes. ACS is characterized by lower mtDNA‐CN and altered expression of mitochondrial homeostasis‐related genes, whereas SA shows a pattern consistent with a possible compensatory response. Combined assessment of mtDNA‐CN and mitochondrial homeostasis–related gene expression may provide a novel biomarker strategy for CAD risk stratification and targeted therapies. Trial Registration VICTORIA study, ( ClinicalTrials.gov Identifier: NCT06313645)