Risk factors for cardiovascular disease mediate their effects by altering the structure and function of wall and endothelial components of arterial blood vessels. Pathological change in the microcirculation plays a pivotal role in promoting end-organ dysfunction that not only predisposes to further organ damage but also increases the risk for future macrovascular events. The microcirculation is recognised as the site where the earliest manifestations of cardiovascular disease occur that may play a pivotal role in driving the atherosclerotic process in conduit vessels(1). Ultrasound and the Doppler effect have been long used to measure blood velocity and its temporal and spatial variation within the vascular tree in order to diagnose and monitor vascular disease. Changes in morphology of the linear flow velocity spectral envelope is not representative of any single vessel but is determined by changes in the properties and total cross-sectional area of downstream vascular networks(2). Quantitative analysis of Doppler-time velocity waveforms that reflect measures of flow pulsatility (eg resistive index, pulsatility index) can mirror changes in downstream vascular resistance and may predict future adverse clinical outcomes(3). In a series of studies in different patient groups we have shown these derived indices often provide misleading information in relation to the haemodynamic actions of drug interventions and are not sensitive in detecting early microvascular dysfunction in different vascular beds in humans(4,5). Novel algorithms that enable quantitative analysis of the Doppler velocity spectral envelope over the duration of the cardiac cycle provides more sensitive information in relation to the haemodynamic action of drugs and identification of early microvascular abnormalities in humans. Data will be presented showing the superiority of this approach in identifying early microvascular abnormalities in waveforms obtained from different arterial territories in different disease states associated with increased cardiovascular risk. Techniques capable of detecting microvascular damage and monitoring response to therapeutic interventions, especially in vulnerable target organs of interest, may improve risk stratification and could represent a valuable surrogate for future cardiovascular outcome.