Abstract: Introduction: Calcitonin gene-related peptide (CGRP), particularly its alpha isoform, might play a role in restoring physiological cardiovascular functioning. While its involvement in acute myocardial infarction (AMI) pathophysiology has been suggested, human data remain scarce. This study analyzed circulating alpha-CGRP levels during AMI, comparing them to healthy controls (HC) and post-AMI resolution levels. Methods: A total of 26 AMI patients and 26 age- and sex-matched HC were recruited. Blood samples were collected from patients within four hours of AMI onset and, when possible, six months post-event. Alpha-CGRP serum concentrations were measured using a validated ELISA assay. Results: Alpha-CGRP levels were significantly higher in AMI patients at admission (mean±SD: 96.0±77.4 pg/ml) compared to HC (42.0±25.8 pg/ml, p<0.0001), with an average increase of 129%. Among nine patients available for follow-up, levels normalized to the HC range (45.1±26.7 pg/ml, p=0.011). Patients with poor outcomes had numerically lower alpha-CGRP levels (72.6±37.2 pg/ml) than those with a satisfactory resolution (100.3±82.5 70.6 pg/ml; p=0.241). Discussion: Alpha-CGRP is acutely elevated during AMI, likely as a compensatory vasodilator response to ischemia. Its post-AMI normalization suggests a transient protective mechanism. Further research is needed to explore its role in AMI-related pathophysiology and usefulness as a therapeutic agent.

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