Background. Peripheral arterial tonometry (PAT) is a novel, non-invasive and operator-independent method for simultaneous assessment of endothelial function and arterial stiffness. We examined the repeatability of PAT in females and the influence of the estrous cycle. Methods. In 14 healthy female and five healthy male control subjects, PAT was performed on three separate occasions with 10 days between visits. Reactive hyperemia index (RHI), a measure of endothelial function, and peripheral augmentation index (AIx), a measure of arterial stiffness, were determined with the EndoPAT-2000 system. Intraclass correlation coefficient (ICC) was calculated as a measure of repeatability. Results. In both female and male groups, RHI and AIx did not differ between the three measurements (all n.s. by 1-way ANOVA). In females, reanalyzing the data after taking phase of estrous cycle into account had no effect on the results. Repeatability for RHI and AIx in females (ICC for RHI = 0.43, ICC for AIx = 0.78) was similar to that in male subjects (ICC for RHI = 0.42, ICC for AIx = 0.63). Conclusions. PAT measurements were not affected by the estrous cycle in females, and repeatability was comparable to that in males. This should facilitate inclusion of female subjects into vascular function studies using PAT. 1. Background Endothelial dysfunction is an important mechanism in the initiation and progression of atherosclerotic lesions. By using forearm plethysmography with intra-arterial administration of vasoactive agents, impaired endothelium-dependent vasodilation has been demonstrated in patients with a variety of conditions such as arterial hypertension [1, 2], hypercholesterolemia [3], and diabetes mellitus [4]. Of potential interest for clinical decision making, impaired endothelial function is an independent predictor of future cardiovascular (CV) events [5–7]. Ultrasound-based assessment of flow-mediated vasodilation (FMD) of the brachial artery is a noninvasive alternative method, also predicting future CV events [8, 9]. However, FMD testing requires substantial training. It has been recommended that at least 100 supervised training scans should be performed prior to scanning patients independently, and 100 scans per year are required to maintain competency [10]. Although the prognostic value of endothelial function testing has been recognized, guidelines do not currently recommend testing routinely, as current methods are invasive, laborious, and/or time consuming [11]. Peripheral arterial tonometry (PAT) is a novel method that promises to overcome some of these
References
[1]
J. A. Panza, A. A. Quyyumi, J. E. Brush Jr., and S. E. Epstein, “Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension,” New England Journal of Medicine, vol. 323, no. 1, pp. 22–27, 1990.
[2]
M. P. Schneider, C. Delles, B. M. W. Schmidt et al., “Superoxide scavenging effects of N-acetylcysteine and vitamin C in subjects with essential hypertension,” American Journal of Hypertension, vol. 18, no. 8, pp. 1111–1117, 2005.
[3]
M. A. Creager, J. P. Cooke, M. E. Mendelsohn et al., “Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans,” Journal of Clinical Investigation, vol. 86, no. 1, pp. 228–234, 1990.
[4]
G. E. McVeigh, G. M. Brennan, G. D. Johnston et al., “Impaired endothelium-dependent and independent vasodilation in patients with Type 2 (non-insulin-dependent) diabetes mellitus,” Diabetologia, vol. 35, no. 8, pp. 771–776, 1992.
[5]
F. Perticone, R. Ceravolo, A. Pujia et al., “Prognostic significance of endothelial dysfunction in hypertensive patients,” Circulation, vol. 104, no. 2, pp. 191–196, 2001.
[6]
T. Heitzer, S. Baldus, Y. Von Kodolitsch, V. Rudolph, and T. Meinertz, “Systemic endothelial dysfunction as an early predictor of adverse outcome in heart failure,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 6, pp. 1174–1179, 2005.
[7]
T. Heitzer, T. Schlinzig, K. Krohn, T. Meinertz, and T. Münzel, “Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease,” Circulation, vol. 104, no. 22, pp. 2673–2678, 2001.
[8]
M. Shechter, S. Matetzky, M. Arad, M. S. Feinberg, and D. Freimark, “Vascular endothelial function predicts mortality risk in patients with advanced ischaemic chronic heart failure,” European Journal of Heart Failure, vol. 11, no. 6, pp. 588–593, 2009.
[9]
M. L. Muiesan, M. Salvetti, A. Paini et al., “Prognostic role of flow-mediated dilatation of the brachial artery in hypertensive patients,” Journal of Hypertension, vol. 26, no. 8, pp. 1612–1618, 2008.
[10]
M. C. Corretti, T. J. Anderson, E. J. Benjamin, et al., “Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force,” Journal of the American College of Cardiology, vol. 39, no. 2, pp. 257–265, 2002.
[11]
G. Mancia, G. De Backer, A. Dominiczak et al., “ESH-ESC practice guidelines for the management of arterial hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension,” Journal of Hypertension, vol. 25, no. 9, pp. 1751–1762, 2007.
[12]
P. O. Bonetti, G. M. Pumper, S. T. Higano, D. R. Holmes Jr., J. T. Kuvin, and A. Lerman, “Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia,” Journal of the American College of Cardiology, vol. 44, no. 11, pp. 2137–2141, 2004.
[13]
A. Nohria, M. Gerhard-Herman, M. A. Creager, S. Hurley, D. Mitra, and P. Ganz, “Role of nitric oxide in the regulation of digital pulse volume amplitude in humans,” Journal of Applied Physiology, vol. 101, no. 2, pp. 545–548, 2006.
[14]
M. Dhindsa, S. M. Sommerlad, A. E. DeVan et al., “Interrelationships among noninvasive measures of postischemic macro- and microvascular reactivity,” Journal of Applied Physiology, vol. 105, no. 2, pp. 427–432, 2008.
[15]
J. T. Kuvin, A. Mammen, P. Mooney, A. A. Alsheikh-Ali, and R. H. Karas, “Assessment of peripheral vascular endothelial function in the ambulatory setting,” Vascular Medicine, vol. 12, no. 1, pp. 13–16, 2007.
[16]
J. T. Kuvin, A. R. Patel, K. A. Sliney et al., “Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude,” American Heart Journal, vol. 146, no. 1, pp. 168–174, 2003.
[17]
N. M. Hamburg, M. J. Keyes, M. G. Larson et al., “Cross-sectional relations of digital vascular function to cardiovascular risk factors in the Framingham heart study,” Circulation, vol. 117, no. 19, pp. 2467–2474, 2008.
[18]
R. B. Schnabel, A. Schulz, P. S. Wild et al., “Noninvasive vascular function measurement in the community cross-sectional relations and comparison of methods,” Circulation, vol. 4, no. 4, pp. 371–380, 2011.
[19]
N. M. Hamburg, J. Palmisano, M. G. Larson et al., “Relation of brachial and digital measures of vascular function in the community: the framingham heart study,” Hypertension, vol. 57, no. 3, pp. 390–396, 2011.
[20]
R. Rubinshtein, J. T. Kuvin, M. Soffler et al., “Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events,” European Heart Journal, vol. 31, no. 9, pp. 1142–1148, 2010.
[21]
G. M. London, J. Blacher, B. Pannier, A. P. Guérin, S. J. Marchais, and M. E. Safar, “Arterial wave reflections and survival in end-stage renal failure,” Hypertension, vol. 38, no. 3, pp. 434–438, 2001.
[22]
C. Vlachopoulos, K. Aznaouridis, M. F. O'Rourke, M. E. Safar, K. Baou, and C. Stefanadis, “Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis,” European Heart Journal, vol. 31, no. 15, pp. 1865–1871, 2010.
[23]
J. A. Chirinos, J. P. Zambrano, S. Chakko et al., “Aortic pressure augmentation predicts adverse cardiovascular events in patients with established coronary artery disease,” Hypertension, vol. 45, no. 5, pp. 980–985, 2005.
[24]
E. Patvardhan, K. S. Heffernan, J. Ruan et al., “Augmentation index derived from peripheral arterial tonometry correlates with cardiovascular risk factors,” Cardiology Research and Practice, vol. 2011, Article ID 253758, 6 pages, 2011.
[25]
N. Ounis-Skali, G. F. Mitchell, C. G. Solomon, S. D. Solomon, and E. W. Seely, “Changes in central arterial pressure waveforms during the normal menstrual cycle,” Journal of Investigative Medicine, vol. 54, no. 6, pp. 321–326, 2006.
[26]
L. Bowyer, M. A. Brown, and M. Jones, “Vascular reactivity in men and women of reproductive age,” American Journal of Obstetrics and Gynecology, vol. 185, no. 1, pp. 88–96, 2001.
[27]
J. Liu, J. Wang, Y. Jin, H. J. Roethig, and M. Unverdorben, “Variability of peripheral arterial tonometry in the measurement of endothelial function in healthy men,” Clinical Cardiology, vol. 32, no. 12, pp. 700–704, 2009.
[28]
E. S. Selamet Tierney, J. W. Newburger, K. Gauvreau et al., “Endothelial pulse amplitude testing: feasibility and reproducibility in adolescents,” Journal of Pediatrics, vol. 154, no. 6, pp. 901–905, 2009.
[29]
J. M. Bland and D. G. Altman, “Measurement error,” British Medical Journal, vol. 313, no. 7059, article744, 1996.
[30]
C. E. McCrea, A. C. Skulas-Ray, M. Chow, and S. G. West, “Test-retest reliability of pulse amplitude tonometry measures of vascular endothelial function: implications for clinical trial design,” Vascular Medicine, vol. 17, no. 1, pp. 29–36, 2012.
[31]
S. John, M. P. Schneider, C. Delles, J. Jacobi, and R. E. Schmieder, “Lipid-independent effects of statins on endothelial function and bioavailability of nitric oxide in hypercholesterolemic patients,” American Heart Journal, vol. 149, no. 3, p. 473, 2005.
