Flow-mediated dilation (FMD)

Flow-mediated dilation (FMD) is a non-invasive ultrasound measure of endothelial function, quantifying the percentage increase in brachial artery diameter in response to a reactive hyperemia stimulus. The standard protocol involves inflating a blood pressure cuff on the forearm to supra-systolic pressure for five minutes, then releasing it; the resulting surge in blood flow imposes shear stress on the endothelium, triggering endothelial nitric oxide synthase (eNOS) to release nitric oxide (NO), which relaxes vascular smooth muscle and causes transient vasodilation measurable by high-resolution duplex ultrasound. FMD declines with age as eNOS activity diminishes, oxidative stress increases, and NO bioavailability falls, making it a sensitive readout of vascular aging. A meta-analysis by Ras et al. (2013) pooling data from prospective cohorts found that each 1% higher FMD was associated with approximately 8% lower cardiovascular event risk (RR 0.92; 95% CI 0.88–0.95), establishing FMD as an independent predictor beyond traditional risk factors. Despite this prognostic signal, FMD has not been adopted into standard clinical cardiovascular risk guidelines, partly because the measurement is operator-dependent, universal reference ranges remain undefined, and debate persists over whether cuff position fully isolates NO-dependent vasodilation from other mediators (Green et al., 2011).