Increased visceral fat accumulation modifies the effect of insulin resistance on arterial stiffness and hypertension risk

Abstract Background and Aims Both insulin resistance (IR) and visceral adipose tissue (VAT) are related cardiometabolic risk factors, nevertheless its joint effect on endothelial functionality are controversial. To evaluate the joint effect of IR and VAT on endothelial functionality using the pulse-waveform analysis; explore the mediating role of VAT on the effect of IR on arterial pressure, arterial stiffness and incident arterial hypertension. Methods and Results We measured VAT (n=586) using two methods: dual energy X-ray absorptiometry and a clinical surrogate, arterial stiffness (with pulse-waveform velocity) and insulin resistance (using three methods: HOMA2-IR (n=586), a frequently-sampled intravenous glucose tolerance test (n=131) and euglycemic hyperinsulinemic clamping (n=97) to confirm the mediator effect of IR on VAT. Incidence of arterial hypertension attributable to the mediating effect of IR related to VAT was evaluated using a prospective cohort (n= 6,850). Adjusted linear regression models, causal mediation analysis, and Cox-proportional hazard risk regression models were performed to test our objective. IR and VAT led to increased arterial stiffness and increased blood pressure; the combination of both further worsened vascular parameters. Nearly, 57% (ΔE→MY 95% CI: 31.7-100.0) of the effect of IR on altered PWV was mediated through VAT. Moreover, VAT acts as a mediator of the effect of IR on increased mean arterial pressure (ΔE→MY 35.7%, 95% CI: 23.8-59) and increased hypertension risk (ΔE→MY 69.1%, 95% CI: 46.1-78.8). Conclusion VAT acts as a mediator of IR in promoting arterial stiffness and arterial hypertension. Both phenomena should be targeted to ameliorate cardiometabolic risk.