Vascular Phenotyping Across the CKM Syndrome: Arterial Stiffness and Endothelial Function Testing, Prognostic Value...

Cardiovascular-kidney-metabolic (CKM) syndrome represents a continuum of metabolic, renal, and cardiovascular abnormalities in which vascular dysfunction may develop before clinically overt cardiovascular disease. Endothelial dysfunction, arterial stiffness, microvascular abnormalities, and structural vascular damage may therefore provide complementary information regarding vascular injury across CKM stages. This narrative review synthesizes current evidence on the pathophysiological basis, non-invasive assessment, prognostic value, and clinical implementation of vascular phenotyping across the CKM spectrum, with particular emphasis on arterial stiffness and endothelial function. The principal approaches discussed include carotid-femoral pulse wave velocity (cfPWV), brachial-ankle pulse wave velocity, flow-mediated dilation (FMD), peripheral arterial tonometry, microvascular techniques, and structural markers such as coronary artery calcium (CAC) and carotid plaque, considered in the context of contemporary CKM staging and PREVENT-based risk assessment. Among functional vascular measures, cfPWV remains the best-validated non-invasive marker of aortic stiffness and is independently associated with cardiovascular and renal outcomes, whereas FMD provides complementary information on conduit-artery endothelial function but is limited by technical requirements and inconsistent incremental predictive value. Microvascular and glycocalyx-based techniques remain less standardized, while structural phenotyping, particularly CAC and carotid plaque assessment, has stronger evidence for risk reclassification in selected populations. Vascular phenotyping should therefore be regarded as a selective, risk-adapted strategy rather than a universal screening approach. Its greatest potential may lie in integrating vascular measures with CKM stage, PREVENT estimates, kidney and cardiac biomarkers, and structural imaging to identify disproportionate or subclinical vascular injury, particularly during progression from CKM stage 2 to stage 3. Prospective studies are needed to determine whether such multimodal phenotyping improves therapeutic decision-making and cardiovascular and kidney outcomes.