Clonal hematopoiesis of indeterminate potential: a unifying mechanism linking metainflammation and cardiometabolic diseases

Clonal hematopoiesis of indeterminate potential (CHIP) refers to the age-related expansion of hematopoietic stem cells bearing somatic mutations in the absence of overt hematological malignancy. Emerging evidence suggests that CHIP is not merely a marker of aging, but an active driver of metainflammation, a chronic systemic inflammatory state arising from metabolic dysregulation. Indeed, several studies have linked CHIP with an increased risk of cardiovascular, renal, and hepatic diseases, which are known to be driven by inflammation. CHIP also appears to be associated with upstream metabolic precursors such as obesity and type 2 diabetes, suggesting its involvement across the cardiometabolic disease continuum. Importantly, this relationship may be bidirectional: systemic inflammation promotes CHIP expansion, whereas CHIP mutations further fuel inflammation. Thus, anti-inflammatory agents that mitigate CHIP-driven inflammation may have a future therapeutic role in cardiometabolic diseases. Furthermore, gene-based therapies offer exciting opportunities for precision approaches in CHIP. This review aims to synthesize emerging evidence that links CHIP with cardiovascular, renal, and hepatic diseases, emphasizing shared inflammatory pathways. Moreover, the review aims to highlight current knowledge gaps, including the need to establish causality between CHIP and cardiometabolic diseases. Furthermore, it emphasizes the need for future research in both human populations and preclinical models to elucidate the underlying mechanisms that could ultimately position CHIP at the forefront of cardiometabolic medicine.