Endothelial Dysfunction and Hypertension
Cause or Effect?
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Endothelial dysfunction refers to impairment of endothelium-dependent vasodilatation and implies widespread abnormalities in endothelial integrity and homeostasis. The ability to assess endothelial function has been critical to advancing our understanding of the significance of this complex monolayer to cardiovascular (CV) disease. Early human translational approaches required invasive assessments in the coronary and brachial circulatory beds but had limited utility. Popularization of brachial reactivity testing using ultrasound by Celermajer et al,1 better known as flow-mediated dilatation (FMD), allowed more widespread clinical application by providing an estimate of conductance vessel NO bioactivity in response to a fixed hyperemic stimulus.
Although the link between endothelial dysfunction and adverse CV events was first described in studies performed in the human coronary circulation,2 the development of this noninvasive method led to widespread expectations that FMD could be used as a risk prediction tool and as a surrogate end point for novel therapies. Numerous studies demonstrated significant association between impaired FMD and CV risk factors. Although studies in those with CV disease have shown prognostic association with lower FMD predicting worse long-term outcomes,2 the real promise of FMD as a noninvasive tool was in demonstrating predictive use in community-based population cohorts.
In the largest of just 3 studies addressing this question, Yeboah et al3 examined 3026 subjects free of CV disease from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. They demonstrated that, at 5 years, after multivariate analysis, each SD increase in FMD conferred a hazard ratio of 0.84 for incident CV events. Importantly, FMD also improved net reclassification of risk when compared with the Framingham risk score. Two further studies in more selected populations, including the Cardiovascular Health Study of elderly subjects and a study by Rossi et al4 on >2000 postmenopausal women, support these findings by demonstrating significant association …