Journal of Applied Physiology http://www.adinstruments.com/labchart/faseb
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 103: 1108, 2007; doi:10.1152/japplphysiol.00518.2007
8750-7587/07 $8.00
This Article
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Harris, R. A.
Right arrow Articles by Padilla, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Harris, R. A.
Right arrow Articles by Padilla, J.

LETTER TO THE EDITOR

Proper "normalization" of flow-mediated dilation for shear

To the Editor: Established in 1992 by Celermajer and colleagues (1), the measurement of brachial artery flow-mediated dilation (FMD) is the most used noninvasive assessment of endothelial function. In an effort to standardize the FMD measurement among researchers, guidelines for the ultrasonic assessment of brachial artery FMD (2) were published in 2002. Since then, additional work has been conducted to create an even more reliable and accurate measurement of endothelial function.

The shear produced by hyperemic blood flow is proposed to be the most important mechanical stimuli that evokes the vasodilatory response (4). Given that the magnitude of the shear stimulus generated with reactive hyperemia is influenced by several factors and may vary among subjects, correcting (normalizing) the FMD for shear is imperative. Recently, Pyke and Tschakovsky (5) investigated the independent contributions of the shear stress profile following cuff release and proposed that the shear stimulus area under the curve (AUC) is the determinant of the peak FMD response. In essence, normalization of FMD to shear is accomplished by dividing FMD by shear (in this case shear AUC). For all intents and purposes this correction 1) is simple, 2) provides an arbitrary unit of measurement, 3) converts the endpoint value to a different scale that may be difficult to interpret, and 4) may not be the most appropriate method to control for the shear stress stimuli.

It is no surprise that there is a strong association between the shear stimulus and the vasodilatory response. In statistical terms, the ancillary information provided by shear is known as a concomitant variable or covariate. If in fact there is a modest correlation between the dependent variable (FMD) and the covariate (shear), the proper method to control FMD for shear is through an analysis of covariance (ANCOVA; Ref. 6). The three main uses of ANCOVA are to 1) lessen the effects of the covariate despite losing a statistical degree of freedom, 2) reduce the unexplained variability in the experimental design, and 3) improve power by incorporating the relationship of the dependent variable and the covariate (3), in this case FMD and shear, respectively. Specifically, the ANCOVA tests the differences in regression equations among levels of the independent variable (group and/or time). If either the slope or intercept of the general linear model are different among levels, the adjusted means will reflect the statistical removal of the covariate's (shear) influence on the dependent variable (FMD). Providing ANCOVA statistically controls for the shear effect on FMD, it may be the proper technique to normalize FMD for shear.

In conclusion, given that both FMD and shear stress data are routinely collected and that there undoubtedly exists a correlation between the two, we encourage investigators to, at the minimum, compare normalization of FMD (dividing by shear) vs. ANCOVA when performing FMD comparisons. As different interpretations of the data will arise between the two statistical solutions and since an abundance of studies use FMD, it is imperative at this time to understand this measurement dilemma.

FOOTNOTES


Address for reprint requests and other correspondence: R. A. Harris, Indiana Univ., Dept. of Kinesiology, School of Health Physical Education and Recreation Rm. 070, 1025 E. 7th St., Bloomington, IN 47404 (e-mail: harrisra{at}indiana.edu)

REFERENCES

  1. Celermajer DS, Sorensen KE, Gooch VM. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340: 1111–1115, 1992.[CrossRef][ISI][Medline]
  2. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gehard-Herman M, Herrington D, Vallance P, Vita J, Vogel R. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery. J Am Coll Cardiol 39: 257–265, 2002.[Abstract/Free Full Text]
  3. Keppel G, Wickens TD. Design and Analysis: A Researchers Handbook. Pearson Prentice Hall, 2004.
  4. Pyke KE, Dwyer EM, Tschakovsky ME. Impact of controlling shear rate on flow-mediated dilation responses in the brachial artery of humans. J Appl Physiol 97: 499–508, 2004.[Abstract/Free Full Text]
  5. Pyke KE, Tschakovsky ME. Peak vs. total reactive hyperemia: which determines the magnitude of flow-mediated dilation? J Appl Physiol 102: 1510–1519, 2007.[Abstract/Free Full Text]
  6. Tabachnick BG, Fidell LS. Using Multivariate Statistics. Pearson Education Company, 2001.

Ryan A. Harris
Jaume Padilla
 Clinical Exercise Physiology Laboratory, School of Health, Physical Education and Recreation, Department of Kinesiology, Indiana University, Bloomington, Indiana





This Article
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Harris, R. A.
Right arrow Articles by Padilla, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Harris, R. A.
Right arrow Articles by Padilla, J.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.