Review ArticleAssessment of Endothelial Function Using Digital Pulse Amplitude Tonometry☆,☆☆
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
References (32)
- et al.
Enhanced external counterpulsation improves endothelial function in patients with symptomatic coronary artery disease
J Am Coll Cardiol
(2003) - et al.
Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia
J Am Coll Cardiol
(2004) - et al.
The effects of 1-year treatment with a Herbst mandibular advancement splint on obstructive sleep apnea, oxidative stress, and endothelial function
Chest
(2007) - et al.
Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude
Am Heart J
(2003) - et al.
Evaluation of endothelial function in women with polycystic ovary syndrome
Eur J Obstet Gynecol Reprod Biol
(2007) - et al.
Impaired endothelial function in adolescents with type 1 diabetes mellitus
J Pediatr
(2008) - et al.
Update on nitric oxide-dependent vasodilation in human subjects
Methods Enzymol
(2005) - et al.
The clinical implications of endothelial dysfunction
J Am Coll Cardiol
(2003) - et al.
Chronic administration of Sildenafil improves markers of endothelial function in men with type 2 diabetes
Diabet Med
(2008) - et al.
Methods for evaluating endothelial function in humans
Hypertension
(2007)
Potential benefits on impairment of endothelial function after a high-fat meal of 4 weeks of flavonoid supplementation
Evid Based Complement Alternat Med
Indoor particles affect vascular function in the aged: an air filtration-based intervention study
Am J Respir Crit Care Med
Reliable endothelial function testing: at our fingertips?
Circulation
Post-challenge hyperglycemia in older adults is associated with increased cardiovascular risk profile
J Clin Endocrinol Metab
Endothelial function and dysfunction: testing and clinical relevance
Circulation
Interrelationships among noninvasive measures of postischemic macro- and microvascular reactivity
J Appl Physiol
Cited by (0)
- ☆
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.