Insulin-Like Growth Factor-1 and Atherosclerosis: Mechanistic Insights and Clinical Implications.

Abstract

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality worldwide, with persistent residual risk despite optimal management of conventional risk factors. Insulin-like growth factor-1 (IGF-1), the principal effector of the growth hormone-IGF-1 axis, exerts dose-dependent dual effects on atherogenesis, yet its clinical value remains controversial and incompletely clarified. This review provides a concise overview of the core mechanistic basis of IGF-1 in atherosclerotic pathogenesis, synthesizes key epidemiological and clinical cohort evidence on the association between circulating IGF-1 and atherosclerotic cardiovascular events, evaluates its utility as a predictive and prognostic biomarker, and systematically summarizes the translational potential of IGF-1 axis-targeted interventions. Physiological IGF-1 concentrations confer endothelial protection, anti-inflammatory effects and plaque stability, whereas deviation to either excess or deficiency accelerates atherosclerotic progression. Circulating IGF-1 exhibits a non-linear association with ASCVD risk and prognosis, with routine clinical application currently limited by assay heterogeneity and metabolic confounders. Normalization of the IGF-1 axis at physiological levels delivers measurable vascular benefits, and pathway-selective modulators represent a promising direction for future translational research.