Large Artery Stiffness, Microvascular Function, and Cardiovascular Risk.

Large artery stiffness is an important mediator of cardiovascular disease. Aortic stiffening causally contributes to isolated systolic hypertension1 and increases left ventricular pulsatile hydraulic load,2,3 which is important in conditions such as heart failure, hypertensive heart disease, and valvular heart disease (particularly aortic stenosis). In addition, there is increasing recognition of the role of arterial stiffness on microvascular disease, which is relevant for the damage of target organs such as the brain and the kidney.3,4 See Article by Cooper et al Consistent with the important role of arterial stiffness in cardiovascular health, measures of large artery stiffness have been shown to independently predict the risk of incident cardiovascular events in both clinical and community-based cohorts.5–8 However, the degree to which the relationship between large artery stiffness and incident cardiovascular disease is mediated by microvascular dysfunction is unclear. In this issue of Circulation: Cardiovascular Imaging , Cooper et al9 report the results of a large prospective cohort study that advances our understanding of this issue. The authors measured carotid–femoral pulse wave velocity (a measure of large artery stiffness) and brachial artery hyperemic mean Doppler flow velocity after an ischemic forearm occlusion (an index of microvascular function), among 4547 Framingham Heart Study participants. They performed analyses to relate individual measures of vascular function to incident cardiovascular disease, and subsequent mediation analyses to assess the degree to which prevalent microvascular dysfunction at baseline accounts for the prediction of cardiovascular events provided by carotid–femoral pulse wave velocity. Their results demonstrate that both higher carotid–femoral pulse wave velocity and lower hyperemic mean flow velocity were independently associated with incident cardiovascular disease. In mediation analyses, 8% to 13% of the relationship between aortic stiffness and cardiovascular events was explained by hyperemic mean flow velocity. The …