Abstract Body: Introduction: Acute myocardial infarction (MI) remains a leading cause of hospitalization and mortality worldwide. Beyond traditional cardiovascular risk factors, psychosocial conditions such as depression may influence clinical outcomes and healthcare utilization following acute MI. However, population-level data examining the association between depression and in-hospital outcomes in acute MI remain limited.

Hypothesis: We assessed the hypothesis that comorbid depression is associated with lower in-hospital mortality, complications, and healthcare utilization among patients hospitalized with acute MI.

Methods: Patients admitted with a primary diagnosis of acute MI were identified using the 2021 National Inpatient Sample. Patients were stratified based on the presence of comorbid depression. Logistic and linear regression models were used to evaluate in-hospital clinical and economic outcomes, adjusting for demographic characteristics and comorbidity burden using the Charlson Comorbidity Index. Univariate analyses were performed, followed by multivariable modeling. Statistical significance was defined as a two-tailed p-value less than 0.05.

Results: Among 428,464 hospitalizations for acute MI, 35,234 patients (8.2%) had concurrent depression. Compared with patients without depression, those hospitalized with acute MI and comorbid depression demonstrated lower odds of in-hospital mortality (aOR 0.66, 95% confidence interval [CI] 0.57–0.78), mechanical ventilation (aOR 0.72, 95% CI 0.63–0.84), renal replacement therapy (aOR 0.80, 95% CI 0.69–0.92), and intra-aortic balloon pump use (aOR 0.83, 95% CI 0.70–0.99). Patients with depression also experienced shorter length of stay (β −0.15 days, 95% CI −0.28 to −0.02) and lower total hospital charges (β −$10,773, 95% CI −$14,047 to −$7,500).

Conclusions: In conclusion, comorbid depression was independently and paradoxically associated with lower in-hospital mortality, fewer complications, shorter hospitalizations, and reduced costs among patients admitted with acute MI. These findings may reflect differences in clinical surveillance, medication adherence, or care coordination. Potential limitations include misclassification bias related to administrative coding and the inability to assess long-term outcomes such as readmission or post-discharge mortality.