EPMA J. 2025 Sep 28;16(4):773-783. doi: 10.1007/s13167-025-00421-8. eCollection 2025 Dec.
ABSTRACT
OBJECTIVE: Hypertension management remains challenging due to coexisting insulin resistance (IR) and arterial stiffness-two silent yet synergistic drivers of atherosclerotic cardiovascular disease (ASCVD). This study aimed to evaluate their joint impact on ASCVD risk and assess their utility in predictive, preventive, and personalized strategies.
METHODS: In this prospective cohort study of 30,094 adults with hypertension, IR was assessed using the triglyceride-glucose (TyG) index (calculated as ln [TG (mg/dL) × FBG (mg/dL)/2]) and arterial stiffness via brachial-ankle pulse wave velocity (baPWV). Time-to-event analyses examined their individual and combined associations with ASCVD incidence.
RESULTS: Over a median 5.6-year follow-up, 1655 ASCVD cases occurred. TyG exhibited a dose-response relationship with ASCVD across baPWV strata. Each 1-SD increase in TyG was associated with a higher ASCVD risk in the elevated baPWV subgroup (HR: 1.17, 95% CI: 1.07-1.27) than in the normal baPWV subgroup (HR: 1.11, 95% CI: 1.02-1.21). A significant additive interaction was observed: individuals with both elevated TyG and baPWV had the highest ASCVD risk (HR: 1.93, 95% CI: 1.66-2.25), with 33.4% of the joint risk attributable to their interaction. Adding both biomarkers to traditional models improved discrimination (C-index: 0.66 to 0.68) and reclassification (NRI: 18.63%, P < 0.001).
CONCLUSIONS: This study reveals a synergistic effect of IR and arterial stiffness on ASCVD risk and provides strong support for their integration into predictive models. This dual-biomarker approach enables early identification of high-risk hypertensive phenotypes and aligns with the predictive, preventive, and personalized medicine (PPPM) paradigm to optimize cardiovascular outcomes through tailored intervention.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-025-00421-8.
PMID:41311992 | PMC:PMC12647484 | DOI:10.1007/s13167-025-00421-8