Redox-Driven Precision Medicine for Life-Course Prevention of Cardiovascular-Kidney-Metabolic Syndrome.

Accumulating evidence recognizes cardiovascular-kidney-metabolic syndrome (CKMS) as a life-course disorder arising from dynamic and maladaptive interactions among the heart, vasculature, kidneys, liver, and pancreas. Beyond a late-onset clinical entity, CKMS susceptibility is increasingly understood to be programmed during critical developmental periods. Redox imbalance has emerged as a central integrative mechanism in this process, functioning as a mechanistic interface through which adverse early-life environments translate into persistent multi-organ vulnerability. Perturbation of the reactive oxygen species-nitric oxide axis during development disrupts organogenesis, vascular maturation, and metabolic regulation, resulting in enduring structural and functional alterations that predispose individuals to hypertension, metabolic dysfunction, and chronic kidney disease. These insights position redox biology not merely as a pathogenic mechanism but as a strategic entry point for precision intervention. Addressing the escalating global burden of CKMS requires a paradigm shift toward redox-driven precision medicine. This framework integrates biologically informed phenotyping, life-course-based risk stratification, early precision prevention through developmental reprogramming, and phenotype-guided therapeutics to stabilize interconnected organ networks. Transitioning from reactive, fragmented care to a proactive, systems-oriented approach offers a transformative opportunity to interrupt intergenerational risk transmission and achieve durable improvements in cardiovascular-kidney-metabolic health across the lifespan.