Test-retest reliability of pulse amplitude tonometry measures of vascular endothelial function: implications for clinical trial design

Abstract

Endothelial dysfunction is an important outcome for assessing vascular health in intervention studies. However, reliability of the standard non-invasive method (flow-mediated dilation) is a significant challenge for clinical applications and multicenter trials. We evaluated the repeatability of pulse amplitude tonometry (PAT) to measure change in pulse wave amplitude during reactive hyperemia (Itamar Medical Ltd, Caesarea, Israel). Twenty healthy adults completed two PAT tests (mean interval = 19.5 days) under standardized conditions. PAT-derived measures of endothelial function (reactive hyperemia index, RHI) and arterial stiffness (augmentation index, AI) showed strong repeatability (intra-class correlations = 0.74 and 0.83, respectively). To guide future research, we also analyzed sample size requirements for a range of effect sizes. A crossover design powered at 0.90 requires 28 participants to detect a 15% change in RHI. Our study is the first to show that PAT measurements are repeatable in adults over an interval greater than 1 week.

Figure 1

PAT control and occlusion arm pulse amplitude tonometry recordings and calculation of the reactive hyperemia index (RHI).

Figure 2

PAT reactive hyperemia index (RHI) scores and Framingham reactive hyperemia index (fRHI) scores plotted by visit. (A) Plot of paired measurements of log RHI illustrating a significant correlation (r = 0.68, p < 0.001. (B) Plot of paired measurements of fRHI also demonstrate a significant correlation (r = 0.77, p < 0.0001).