Review Article
Assessment of Endothelial Function Using Digital Pulse Amplitude Tonometry☆,☆☆

https://doi.org/10.1016/j.tcm.2009.03.001Get rights and content

The importance of endothelial dysfunction in the development and clinical expression of cardiovascular disease is well recognized. Impaired endothelial function has been associated with an increased risk of cardiovascular events. Endothelial function may be evaluated in humans by assessing vasodilation in response to stimuli known to induce the release of nitric oxide. A novel pulse amplitude tonometry device noninvasively measures vasodilator function in the microcirculation of the finger. This article reviews the recent studies that support the utility of digital pulse amplitude tonometry as a relevant test of peripheral endothelial function.

Introduction

The significance of endothelial dysfunction in cardiovascular disease is well established (Widlansky et al. 2003). In the healthy state, the endothelium produces a number of factors including nitric oxide that are essential for maintaining vascular homeostasis. Systemic risk factors damage endothelial cells lowering nitric oxide (NO) bioavailability. Endothelial dysfunction facilitates atherogenesis by promoting inflammation, thrombosis and cellular adhesion. Recent studies demonstrate higher risk of cardiovascular events in individuals with impaired endothelial function (Yeboah et al. 2007).

Since the initial identification of NO, several techniques have been employed to investigate endothelial vasomotor function in humans (McMackin and Vita 2005). Endothelial function assessment has not yet been incorporated into routine risk stratification in part owing to technical and logistical limitations. The use of a novel digital pulse amplitude tonometry (PAT) device to measure endothelial function offers the possibility of an easily performed, rapid assessment of vascular function (Celermajer 2008). The current article reviews the use of digital PAT as an indicator of endothelial function.

Section snippets

Testing of Endothelial Function in Cardiovascular Disease

Endothelial health can be assessed by measuring vasodilator responses to interventions known to stimulate endothelial release of NO. Endothelial function testing has many potential applications in both research and clinical practice that are outlined in Table 1. Several methodologies have been developed to measure endothelial vasomotor function in humans, and these have been the subject of recent reviews (Barac et al., 2007, Deanfield et al., 2007, McMackin and Vita, 2005).

The most frequently

Measurement of Endothelial Function with the Use of Digital PAT

Emerging evidence supports the assessment of digital PAT as a measure of endothelial function. Assessment of vascular function with PAT involves measuring pulse amplitude in the fingertip at rest and following the induction of reactive hyperemia. The EndoPAT device (Itamar Medical, Caesarea, Israel) is a Federal Drug Administration–approved, commercially available system, consisting of a fingertip plethysmograph capable of sensing volume changes in the digit with each arterial pulsation. The

Clinical Studies Measuring Endothelial Function with Digital PAT

Investigators have developed evidence supporting the clinical relevance of the PAT hyperemic response. Selected studies measuring PAT hyperemic responses are summarized in Table 2. Multiple studies have examined the relation of PAT hyperemia to established measures of endothelial function. In addition, studies have examined the associations between traditional and novel cardiovascular risk factors and digital vascular function. Finally, investigators have measured the changes in the PAT

Limitations of Digital PAT

There are several limitations to digital vascular function testing as a measure of endothelial function. First, few studies have reported the PAT response to a direct vasodilator such as nitroglycerin; thus, the relative importance of endothelium-dependent and independent vasodilation in the PAT hyperemic response has not been defined in patients with risk factors or in disease states. Second, published studies reporting digital vascular responses have primarily included individuals of European

Research Directions

Several important questions require further investigation in order to define the clinical relevance and research utility of PAT for cardiovascular disease. The overall association of digital vascular function with cardiovascular risk factors in the Framingham Heart Study was modest at 16% and the contribution of individual risk factors was small. Thus, the determinants of digital vascular function remain incompletely defined. Future studies will define the heritability and relation of genetic

Summary and Conclusions

There is abundant evidence linking endothelial dysfunction to atherosclerosis and to an increased risk of cardiovascular events. Thus, a simple and accurate endothelial function test is an attractive, noninvasive addition to cardiovascular risk stratification tools. There is considerable interest in developing the test of digital vascular function using PAT as a method for evaluating endothelial function. The advantages of this technique include ease of administration and an automated analysis

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    ☆

    Dr Hamburg is supported by National Institutes of Health grant HL083781. Dr Benjamin receives support from RO1 HL076784, 1R01 AG028321, RO1 HL70100, and N01-HC 25195.

    ☆☆

    Dr Benjamin has received an unrestricted research grant from Itamar Medical (Caesarea, Israel), the manufacturer of the PAT device.

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