Effect of Serum Spermidine on the Prognosis in Patients with Acute Myocardial Infarction: A Cohort Study

Spermidine, a natural polyamine, was found critically involved in cardioprotection and lifespan extension from both animal experiments and human studies. This study aimed to evaluate the effect of serum spermidine levels on the prognosis in patients with acute myocardial infarction (AMI) and investigate the potential mediation effect of oxidative stress in the above relationship. We included 377 patients with AMI in a prospective cohort study and measured serum spermidine and oxidative stress indexes (superoxide dismutase enzymes, glutathione peroxidase, and Malondialdehyde) using high-performance liquid chromatography with fluorescence detector and enzyme-linked immunosorbent assay, respectively. The associations of spermidine with AMI outcomes were evaluated using Cox proportional hazards models. 84 (22.3%) major adverse cardiac events (MACE) were documented during a mean follow-up of 12.3 ± 4.2 months. After multivariable adjustment, participants with serum spermidine levels of ≥15.38 ng/mL (T3) and 7.59-5.38 ng/mL (T2) had hazard ratio (HR) for recurrent AMI of 0.450 [95% confidence interval (CI): 0.213-0.984] and 0.441 (95% CI: 0.215-0.907) compared with the ≤7.59 ng/mL (T1), respectively. Participants in T3 and T2 had HR for MACE of 0.566 (95% CI: 0.329-0.947) and 0.516 (95% CI: 0.298-0.893) compared with T1. A faint J-shaped association was observed between serum spermidine levels and the risk of MACE (p-nonlinearity = 0.036). Comparisons of areas under receiver operator characteristics curves confirmed that a model including serum spermidine levels had greater predictive power than the one without it (0.733 versus 0.701, p = 0.041). A marginal statistically significant mediation effect of superoxide dismutase was shown on the association between spermidine and MACE (p = 0.091). Serum spermidine was associated with an improved prognosis in individuals with AMI, whereas the underlying mechanism mediated by oxidative stress was not found.