Association of mitochondrial DNA copy number with prior myocardial infarction in patients with coronary artery disease and type 2 diabetes

Background Mitochondrial dysfunction contributes to cardiac remodeling in coronary artery disease (CAD) and type 2 diabetes (T2D), while ACE I/D polymorphism may influence cardiovascular phenotype. However, the role of mitochondrial DNA(mtDNA) copy number and its interaction with ACE genotype remain unclear. Methods Sixty-seven patients with CAD and T2D were enrolled. Patients were stratified according to history of myocardial infarction (MI+ vs MI−). Telomere length and mtDNA copy number were measured in peripheral blood leukocytes using quantitative real-time PCR, with telomere length expressed as the T/S ratio according to Cawthon’s method. Additionally, ACE I/D polymorphism (II/ID/DD) was analyzed in an additive genetic model, where the D allele is associated with higher ACE activity and potentially increased cardiovascular risk. Between-group comparisons (MI+ vs MI−) were performed using the Mann–Whitney U test. Hardy–Weinberg equilibrium was assessed using the χ² goodness-of-fit test. Genotype distribution was compared using the χ² test. Multivariable linear regression analysis was performed to assess independent predictors of mtDNA copy number, adjusting for age, diabetes duration, HbA1c and estimated glomerular filtration rate (eGFR). A two-sided p value <0.05 was considered statistically significant. The trend toward difference was noted in case of 0.1>p>0.05”. Results Patients with prior myocardial infarction (MI+) were significantly older and had longer diabetes duration compared to those without MI (MI−). MI+ patients also demonstrated lower eGFR. No differences were observed in HbA1c levels or ACE genotype distribution. Telomere length did not differ significantly between groups. In patients with prior myocardial infarction it was the trend toward reduction of mtDNA copy number compared to MI- group, which didn’t reach statistical significance (1.030 [0.826–1.322] vs 1.312 [0.967–1.614]; p=0.053). The main characteristics of the groups are presented in Table 1. In multivariable analysis, prior MI was independently associated with reduced mtDNA (β=−0.323; 95% CI −0.606 to −0.040; p=0.025). HbA1c was also independently correlated with lower mtDNA (β=−0.078; p=0.010). ACE I/D polymorphism showed no independent association and no interaction with MI status (β=0.025; 95% CI −0.170 to 0.220; p=0.798). Conclusions Although the between-group comparison demonstrated only a trend toward reduced mtDNA copy number in MI+ patients, multivariable analysis revealed an independent association between prior myocardial infarction and lower mtDNA levels after adjustment for potential confounders. ACE I/D polymorphism was not associated with mtDNA copy number and did not modify this relationship. Overall, these findings suggest a potential link between prior ischemic injury and mitochondrial impairment in patients with CAD and T2D. Larger prospective studies are required to confirm these observations.