Endothelial function assessed by peripheral arterial tonometry is not related to cardiovascular risk score in healthy subjects

Ylfa Rún Sigurðardóttir, Bylgja Rún Stefánsdóttir, Thor Aspelund, Thorgeirsson Guðmundur, Linda Björk Kristinsdóttir, Vilmundur Gudnason, Karl Andersen


Background: The majority of first cases of myocardial infarction stem from those classified as intermediate- or low-risk in CV risk prediction calculators. Risk prediction models need to be refined in their capacity to discriminate high-risk from low-risk. Peripheral arterial tonometry (PAT) is a non-invasive method to assess peripheral endothelial function that could potentially improve primary prevention of CVD. We investigated the relation of PAT results to CV risk factors and risk score in a healthy cohort.

Methods: PAT measurements were performed on 102 individuals, with no previous history of CAD, attending a Risk Preventive Clinic. Traditional CV risk factors were evaluated and integrated into a CV risk score calculator. Outcome was expressed as absolute and relative 10-year risk of developing CVD.

Results: PAT results of reactive hyperemia index (RHI) and augmentation index (AI) had no statistically significant relation to risk score while baseline pulse amplitude was positively correlated with both absolute (p = 0.02) and relative (p = 0.02) 10-year risk of developing CVD. Among CV risk factors only heart rate was significantly associated with RHI (r = - 0.24, R2 = 0.06, p = 0.01). AI and baseline pulse amplitude both correlated with several risk factors.

Conclusions: Endothelial dysfunction, as measured by PAT, was not associated with an increased 10-year risk of developing CVD. The relation between endothelial dysfunction and established CV risk factors was limited. Further clinical end point studies are needed to fully comprehend the diagnostic and predictive value of PAT measurements in healthy subjects.


Cardiovascular prevention; Endothelial function; Peripheral artery tonometry; Reactive hyperemia index; Coronary risk score

Full Text:



World Health Organization. World Health Organization. Global Health Estimates 2014 Summary Tables: Death by cause, age and sex, by WHO region, 2000-2012. Geneva, Switzerland: Geneva, WHO, 2014.

Rose G. Sick individuals and sick populations. Int J Epidemiol. 2001; 30: 427-32; discussion 33-4. http://dx.doi.org/10.1093/ije/30.3.427

Behrendt D,Ganz P. Endothelial function: From vascular biology to clinical applications. The American Journal of Cardiology. 2002; 90: L40-L8. http://dx.doi.org/10.1016/S0002-9149(02)02963-6

Bonetti PO, Pumper GM, Higano ST et al. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. Journal of the American College of Cardiology. 2004; 44: 2137-41. http://dx.doi.org/10.1016/j.jacc.2004.08.062

Kuvin JT, Mammen A, Mooney P et al. Assessment of peripheral vascular endothelial function in the ambulatory setting. Vascular medicine (London, England). 2007; 12: 13-6. http://dx.doi.org/10.1177/1358863X06076227

Hamburg NM, Keyes MJ, Larson MG, et al. Cross-sectional relations of digital vascular function to cardiovascular risk factors in the Framingham Heart Study. Circulation. 2008; 117: 2467-74. http://dx.doi.org/10.1161/CIRCULATIONAHA.107.748574

Konttinen J, Lindholm H, Sinisalo J, et al. Association between lowered endothelial function measured by peripheral arterial tonometry and cardio-metabolic risk factors - a cross-sectional study of Finnish municipal workers at risk of diabetes and cardiovascular disease. BMC Cardiovasc Disord. 2013; 13: 83. http://dx.doi.org/10.1186/1471-2261-13-83

Okumura K, Takahashi R, Taguchi N, et al. Small low-density lipoprotein cholesterol concentration is a determinant of endothelial dysfunction by peripheral artery tonometry in men. Journal of atherosclerosis and thrombosis. 2012; 19: 897-903. http://dx.doi.org/10.5551/jat.13243

Schnabel RB, Schulz A, Wild PS, et al. Noninvasive vascular function measurement in the community: cross-sectional relations and comparison of methods. Circ Cardiovasc Imaging. 2011; 4: 371-80. http://dx.doi.org/10.1161/CIRCIMAGING.110.961557

World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013; 310: 2191-4. http://dx.doi.org/10.1001/jama.2013.281053

Aspelund T, Thorgeirsson G, Sigurdsson G et al. Estimation of 10-year risk of fatal cardiovascular disease and coronary heart disease in Iceland with results comparable with those of the Systematic Coronary Risk Evaluation project. European journal of cardiovascular prevention and rehabilitation. 2007; 14: 761-8. http://dx.doi.org/10.1097/HJR.0b013e32825fea6d

Itamar Medical. EndoPAT 2000 Device User Manual. 2014.

Nohria A, Gerhard-Herman M, Creager MA, et al. Role of nitric oxide in the regulation of digital pulse volume amplitude in humans. Journal of applied physiology (Bethesda, Md : 1985). 2006; 101: 545-8. http://dx.doi.org/10.1152/japplphysiol.01285.2005

Hedetoft M, Olsen NV. Evaluation of endothelial function by peripheral arterial tonometry and relation with the nitric oxide pathway. Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society. 2014; 42: 1-8. http://dx.doi.org/10.1016/j.niox.2014.07.003

Moerland M, Kales AJ, Schrier L, et al. Evaluation of the EndoPAT as a Tool to Assess Endothelial Function. International journal of vascular medicine. 2012; 2012: http://dx.doi.org/10.1155/2012/904141.

Sauder KA, West SG, McCrea CE, et al. Test-retest reliability of peripheral arterial tonometry in the metabolic syndrome. Diabetes & vascular disease research : official journal of the International Society of Diabetes and Vascular Disease. 2014; 11: 201-7. http://dx.doi.org/10.1177/1479164114525971

Wilkinson IB, MacCallum H, Flint L, et al. The influence of heart rate on augmentation index and central arterial pressure in humans. J Physiol. 2000; 525 Pt 1: 263-70. http://dx.doi.org/10.1111/j.1469-7793.2000.t01-1-00263.x

Syvanen K, Korhonen P, Partanen A, et al. Endothelial function in a cardiovascular risk population with borderline ankle-brachial index. Vascular health and risk management. 2011; 7: 97-101. http://dx.doi.org/10.2147/VHRM.S17249

Toggweiler S, Schoenenberger A, Urbanek N, et al. The prevalence of endothelial dysfunction in patients with and without coronary artery disease. Clin Cardiol. 2010; 33: 746-52. http://dx.doi.org/10.1002/clc.20836

Lind L. Relationships between three different tests to evaluate endothelium-dependent vasodilation and cardiovascular risk in a middle-aged sample. J Hypertens. 2013; 31: 1570-4. http://dx.doi.org/10.1097/HJH.0b013e3283619d50

Ferre R, Aragones G, Plana N, et al. High-density lipoprotein cholesterol and apolipoprotein A1 levels strongly influence the reactivity of small peripheral arteries. Atherosclerosis. 2011; 216: 115-9. http://dx.doi.org/10.1016/j.atherosclerosis.2011.01.039

Mulukutla SR, Venkitachalam L, Bambs C, et al. Black race is associated with digital artery endothelial dysfunction: results from the Heart SCORE study. European heart journal. 2010; 31: 2808-15. http://dx.doi.org/10.1093/eurheartj/ehq295

Fitch KV, Stavrou E, Looby SE, et al. Associations of cardiovascular risk factors with two surrogate markers of subclinical atherosclerosis: endothelial function and carotid intima media thickness. Atherosclerosis. 2011; 217: 437-40. http://dx.doi.org/10.1016/j.atherosclerosis.2011.04.009

Kuvin JT, Patel AR, Sliney KA, et al. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. American heart journal. 2003; 146: 168-74. http://dx.doi.org/10.1016/S0002-8703(03)00094-2

Truschel E, Jarczok MN, Fischer JE, et al. High-throughput ambulatory assessment of digital reactive hyperemia: concurrent validity with known cardiovascular risk factors and potential confounding. Prev Med. 2009; 49: 468-72. http://dx.doi.org/10.1016/j.ypmed.2009.09.019

Fischer-Rasokat U, Spyridopoulos I, Walter J, et al. Microvascular dysfunction and pulse wave reflection characterize different vascular pathologies in patients at cardiovascular risk. Vasa. 2012; 41: 192-9. http://dx.doi.org/10.1024/0301-1526/a000185

Heffernan KS, Patvardhan EA, Kapur NK, et al. Peripheral augmentation index as a biomarker of vascular aging: an invasive hemodynamics approach. Eur J Appl Physiol. 2012; 112: 2871-9. http://dx.doi.org/10.1007/s00421-011-2255-y

Patvardhan E, Heffernan KS, Ruan J, et al. Augmentation index derived from peripheral arterial tonometry correlates with cardiovascular risk factors. Cardiology research and practice. 2011; 2011: http://dx.doi.org/10.4061/2011/253758.

Yang WI, Park S, Youn JC, et al. Augmentation index association with reactive hyperemia as assessed by peripheral arterial tonometry in hypertension. Am J Hypertens. 2011; 24: 1234-8. http://dx.doi.org/10.1038/ajh.2011.132

Matsuzawa Y, Sugiyama S, Sumida H, et al. Peripheral endothelial function and cardiovascular events in high-risk patients. J Am Heart Assoc. 2013; 2: http://dx.doi.org/10.1161/JAHA.113.000426.

Rubinshtein R, Kuvin JT, Soffler M, et al. Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. European heart journal. 2010; 31: 1142-8.

Dorresteijn JA, Visseren FL, Wassink AM, et al. Development and validation of a prediction rule for recurrent vascular events based on a cohort study of patients with arterial disease: the SMART risk score. Heart. 2013; 99: 866-72. http://dx.doi.org/10.1136/heartjnl-2013-303640

Dhindsa M, Sommerlad SM, DeVan AE, et al. Interrelationships among noninvasive measures of postischemic macro- and microvascular reactivity. Journal of applied physiology (Bethesda, Md : 1985). 2008; 105: 427-32. http://dx.doi.org/10.1152/japplphysiol.90431.2008

Shewan LG, Coats AJS, Henein M. Requirements for ethical publishing in biomedical journals. International Cardiovascular Forum Journal 2015;2:2 DOI: 10.17987/icfj.v2i1.4

DOI: https://doi.org/10.17987/icfj.v9i0.385

Copyright (c) 2017 Ylfa Rún Sigurðardóttir, Bylgja Rún Stefánsdóttir, Thor Aspelund, Thorgeirsson Guðmundur, Linda Björk Kristinsdóttir, Vilmundur Gudnason, Karl Andersen

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.