Cystatin C in atherosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of global mortality. While traditional risk factors are central to prevention, there is a pressing need for novel biomarkers to improve risk stratification and identify individuals with a high burden of disease. Cystatin C (CysC), a cysteine protease inhibitor, has emerged as a promising candidate due to its dual role as a sensitive marker of renal function and its direct involvement in inflammatory and vascular pathophysiology. This review aims to synthesise the extensive clinical evidence on the utility of CysC as a diagnostic and prognostic biomarker across the full spectrum of ASCVD, discuss current limitations, and outline future perspectives for its clinical implementation. A comprehensive literature review was conducted to identify key studies, including cross-sectional analyses, prospective cohorts, and meta-analyses, that have evaluated the association between circulating CysC levels and various manifestations of ASCVD. The evidence consistently demonstrates that elevated CysC levels are strongly associated with the presence and severity of subclinical atherosclerosis, including increased carotid intima-media thickness and arterial stiffness. In patients with established ASCVD, higher CysC is a powerful and independent predictor of adverse outcomes, including major adverse cardiovascular events (MACE), all-cause mortality, and disease progression across diverse conditions such as CAD, AMI, HF, and stroke. This prognostic value often persists after adjustment for traditional risk factors and creatinine-based estimates of renal function, highlighting a role for CysC beyond being a simple marker of nephropathy. Cystatin C is a multifaceted and robust biomarker with significant diagnostic and prognostic utility across the landscape of ASCVD. © 2025 Elsevier B.V.