Charting individualized pathways: IGF-1 and vitamin D in guiding personalized medicine for residual risk after AMI

Background: Insulin-like growth factor-1 (IGF-1) and vitamin D are crucial for overall health. Imbalances in these markers are increasingly recognized as pivotal contributors to cardiovascular and residual risks following acute myocardial infarction (AMI). This study evaluated the prognostic value of IGF-1 and vitamin D levels for CAD severity and long-term outcomes in AMI survivors. Methods: We included 681 AMI patients admitted to the University Hospital of Trieste between 2014 and 2023. Results: Mean age was 66.3 years; 73.2% were male, and 71.9% had STEMI. The median IGF-1 level was 539 pg/ ml and it was found to decline with ageing and with worsening kidney function. 56.1% of patients had hypo- vitaminosis D (HypoD), which was associated with higher levels of inflammation (CRP, IL-1β) and lower IGF-1 concentrations. Both low and high IGF-1 levels independently predicted severe CAD, indicating a U-shaped association. Over a median 51-month follow-up, 265 patients reached the composite endpoint and IGF-1 levels were lower in pa- tients with events. Furthermore, continuous hazard ratio analysis revealed that IGF-1 levels below the median were linearly associated with adverse outcomes. Patients with the dual burden of low IGF-1 and HypoD exhibited higher probability of the composite endpoint. This combination independently predicted adverse outcomes (HR 1.43), alongside traditional risk factors such as age, LVEF, elevated HbA1C, CAD severity and impaired renal function. Conclusion: Low IGF-1 levels were associated with severe CAD and worse prognosis. This risk was further increased in patients with co-existing HypoD, thus additional studies are needed to determine how these bio- markers can be integrated into the clinical management of the patients.