Lee Stoner, PhD and Gabriel Zieff, MA present a complete, in-depth overview of their research involving Pulse Wave Velocity (PWV) in a variety of different applications and a deep dive into the methods they use to record high-quality, repeatable data. Arguably, the “gold-standard” method for noninvasive assessment of cardiovascular disease risk is pulse wave velocity. The PWV is widely used in both epidemiological and physiological studies to assess arterial stiffness, a construct dependent on the functional and structural characteristics of a vessel. PWV is calculated by measuring the transit time of the arterial waveform between two points of a measured distance. The most widely studied path is between the carotid and femoral arteries, which represents the aorto-illiac pathway. Traditionally, these measurements are made using tonometers, which are highly sensitive pressure transducers. However, alternative approaches to tonometry are available, and pathways other than the aorta can be measured. These alternative approaches may be better suited for use with certain populations or study designs. The focus of the presentation is to assist the audience in identifying the correct research tool for their particular research paradigm. Specifically, these experts outline the theoretical principles underlying PWV, as well as the importance of this measure to both epidemiological and physiological studies. Subsequently, they highlight some of the different approaches for measuring PWV, including technical considerations. This is followed by discussion pertaining to the identification of the appropriate PWV measure for the specific study design and populations of interest. This includes consideration of internal and external validity. They end the session by providing some tips to facilitate high-quality PWV assessments. Key Topics Include: - Meaning and clinical importance of pulse wave velocity - How to measure and interpret pulse wave velocity - Considerations for internal- and external-validity - Considerations for the measurement of pulse wave velocity of various study designs and populations

1. Pulse Wave Velocity:
Theory, Applications,
Methods, & Future Directions
Gabriel Zieff, MA
Doctoral Candidate
Exercise and Sport Science
University of North Carolina at Chapel Hill
Lee Stoner, PhD, MPH
Assistant Professor
Exercise and Sport Science
University of North Carolina at Chapel Hill

2. Experts present an in-depth overview of their
research involving Pulse Wave Velocity (PWV)
in a variety of different applications and a
deep dive into the methods they use to
record high-quality, repeatable data.
Pulse Wave Velocity:
Theory, Applications,
Methods, & Future Directions

3. Pulse Wave Velocity:
Theory, Applications,
Methods, & Future Directions
Copyright 2021 L. Stoner, G. Zieff and InsideScientific. All Rights Reserved.
Gabriel Zieff, MA
Doctoral Candidate
Exercise and Sport Science
University of North Carolina at Chapel Hill
Lee Stoner, PhD, MPH
Assistant Professor
Exercise and Sport Science
University of North Carolina at Chapel Hill

4. What is PWV?
• PWV = pulse wave velocity
–Speed of forward pressure between sites
• AS reflects:
–Structure
–Function
• Not homogenous along arterial tree
• Most common: aorta
–Carotid-femoral

5. PTT = t2 – t1
PWV (m/s) = D / PTT
carotid
femoral
t2
t1
D

6. Contents
• What is PWV?
• Importance
• Measurement Approaches
• PWV Selection Considerations
• Tips for High Quality Measurements

7. Importance
• Why is AS important?
• Overview of vascular system
• Clinical Importance

8. What is AS?
• AS reflects:
–Function
• Endothelial function
–Structure
• Vessel wall extracellular
matrix

9. Importance
• Why is AS important?
• Overview of vascular system
• Clinical Importance

10. Vascular Anatomy
• Intima
–Endothelium cells
• Medial
–Smooth muscle cells
–Controls tone
• Adventitial (Externa)
–Connective tissue
–Maintains shape
–Numerous nerves

11. Arterial Tree
11

12. Aorta

13. Aorta = Elastic Arteries
13
• Thin walls relative to diameter
–Well defined connective tissue
• Many elastic fibers
– Elastic lamellae
• Pressure Reservoir
• Propels blood forward
–Stretches
–Mechanical energy stored
–Recoils

14. Why is AS Important?
• Vasculature gradually stiffens
from ascending aorta to
periphery

15. Why is AS Important?
• Vasculature gradually stiffens
from ascending aorta to
periphery
• Importance
– Consistent blood flow – inc.
diastole
– Attenuates forward travelling
pressure waves
– Moderate wave reflection
• London 2010. Nephrol Dial
Transplant;25(12):3815-23

17. Importance
• Why is AS important?
• Overview of vascular system
• Clinical Importance

18. Clinical Importance
• Early in disease progression
• Predicts CVD
• Normative data

19. Progression of CVD
Ter Avest, et al. Clin Sci (Lond); 112, 2007
What is the role of non-invasive
measurements of atherosclerosis in
individual cardiovascular risk
prediction?
Ewoud Ter Avest , Anton F H
Stalenhoef, Jacqueline de Graaf

20. Predicts CVD
• Predicts CV events in a range of patients
• Carotid-Femoral Pulse Wave Velocity
–Gold standard
–1 m/s = 15%↑CVD risk
Prediction of cardiovascular events and all-cause mortality with
arterial stiffness: a systematic review and meta-analysis
Charalambos Vlachopoulos , Konstantinos Aznaouridis, Christodoulos Stefanadis
Vlachopoulos, Charalambos et al. JACC; 1318-27, 2010

21. Normative Data
• Adults
• Children
• VascAgeNet

22. • ↑0.2 - 0.7 m/s
every 5 y
Determinants of Vascular Age:
An Epidemiological Perspective
Anna M Kucharska-Newton, Lee
Stoner, Michelle L Meyer
https://doi.org/10.1373/clinchem.2018.287623

23. Cardiometabolic Health and Carotid-Femoral Pulse Wave Velocity in Children:
A Systematic Review and Meta-Regression
Lee Stoner, PhD , Anna Kucharska-Newton, PhD, Michelle L. Meyer, PhD
https://doi.org/10.1016/j.jpeds.2019.10.065

24. Endothelium function
dependence of acute
changes in pulse wave
velocity and flow-mediated
slowing
Lee Stoner, Keeron Stone,
Gabriel Zieff, Jade Blackwell,
Jake Diana, Daniel P Credeur,
Craig Paterson, Simon Fryer
https://doi.org/10.1177/1358863x20926588

25. Contents
• What is PWV?
• Importance
• Measurement Approaches
• PWV Selection Considerations
• Tips for High Quality Measurements

26. Devices
• Tonometry
• Oscillometry
• Ultrasound
• Electrocardiogram
• Photoplethysmography
• Transcranial doppler
• Magnetic resonance imaging

27. Tonometry

28. Tonometry
SphygmoCor Complior

29. Vicorder
Oscillometry

30. Combination
Tonometer
Cuff
SphygmoCor

31. Ultrasound
Validity and reliability of lower-limb pulse-wave velocity
assessments using an oscillometric technique
Keeron Stone, Simon Fryer, Elizabeth Kelsch, Kathryn Burnet, Gabriel Zieff, James
Faulkner, Daniel Credeur, Danielle Lambrick, Erik D Hanson, Lee Stoner

32. Photoplethysmography (PPG)

33. Heart to Toe PPG

34. Measurement Path
• From carotid to:
–Femoral
–Ankle
–Radial
–CAVI
• From brachial to
–Femoral
–Ankle
• From ECG to:
–Carotid
–Femoral
–Middle cerebral

35. Carotid vs. Brachial
• Carotid-femoral
–“Gold-standard”
–Normative data
• Brachial-femoral
–Signal : noise
–Ease of use

36. Central pulse wave velocity in neonates: feasibility and comparison to
normative data
Patricia Pagan Lassalle, Michelle L. Meyer, Kim. A. Boggess & Lee Stoner
https://doi.org/10.1038/s41440-020-0489-y

37. Brain Pulse Wave Velocity

38. Contents
• What is PWV?
• Importance
• Measurement Approaches
• PWV Selection Considerations
• Tips for High Quality Measurements

39. Which PWV Tool?
• Internal vs. External Validity
• Study Design
• Special Populations

40. Internal vs. External Validity
• Internal
–Degree Δ in DV ascribed to Δ in IV(s)
–Treatment → Outcome
• External
–Generalizability to pop. across setting and time

41. Internal vs. External Validity

44. Threat to internal validity
Internal Validity Consideration
Regression
When subjects have been selected on the basis of extreme scores, because extreme (low and
high) scores in a distribution tend to move closer to the mean (i.e., regress) in repeated testing
Treatment randomization How the intervention is given from one participant to the next
Treatment Implementation Not standardizing how the intervention is give from one participant to the next
Diffusion or Imitation of Treatment Cross-talk b/w exp and con groups
Selection What should be the appropriate control group condition?
History Changes over time with longitudinal studies. Is there a carry-over effect?
Drop-outs Are those who remain different?
Pre-assessment control Prior physical activity & sleep, caffeine, medications & supplements
During assessment control
Thermo-neutral, noise, meal consumption, fluid replacement, non-stimulatory documentary,
movement
Instrumentation
Precision, accuracy, single-observer, measurement posture, signal interpretation, covariates,
repeated testing

45. Precision vs
Accuracy?

46. Measurement Posture
• Algorithm validated in supine posture
• During orthostasis:
–Blood pools
–Less venous return
–Baroreceptors detect ↓ BP
–↑ systemic vascular resistance
–No longer examining just arterial stiffness!!!

47. Why Important?
• Garbage in = garbage out
• Human participants
–Ethical & moral considerations

48. Which Tool?
• Internal vs. External Validity
• Study Design
• Special Populations

49. Study Design
• Observational
• Parallel
• RCT
• Cross-over
• Quasi-experimental

50. Major Considerations
Consideration Example
Research question Will the tools answer your question?
Level of
invasiveness
Invasive measurements may arouse the participant
Subject burden Too many measurements will arouse the participant
Measurement time How long will each measurement take?
Measurement
frequency
Too frequent measurement may act as a stimulus
Measurement
posture
Are the measurements validated for use in the
measurement posture

51. Which Tool?
• Internal vs. External Validity
• Study Design
• Special Populations

52. Special Population
• Women
–Pregnant
• Certain chronic diseases
–Obesity
–Stroke
–Cancer
• Ambulation impaired
–Spinal cord injury

53. Pregnant Women
• Major source of error = path length
• Measurement of pulse distance
–Difficult if significant body contours
–Vessel tortuosity not accounted

54. Caliper

55. Stroke

56. Associations between carotid-femoral and heart-femoral pulse wave velocity in older
adults: the Atherosclerosis Risk In Communities study
Lee Stoner, Michelle L Meyer, Anna Kucharska-Newton, Keeron Stone, Gabriel Zieff, Gaurav Dave, Simon Fryer,
Daniel Credeur, James Faulkner, Kunihiro Matsushita, Timothy M Hughes, Hirofumi Tanaka
https://doi.org/10.1097/hjh.0000000000002449

57. Contents
• What is PWV?
• Importance
• Measurement Approaches
• PWV Selection Considerations
• Tips for High Quality Measurements

58. High Quality Measurements
• Theoretical
• Practical
• Device

59. Theoretical
• Good research question
• Know your confounders
• Theoretical model

60. High Quality Measurements
• Theoretical
• Practical
• Device

61. Practical
• Data collection sheet
• Know your anatomy
• Quality waveforms

62. Tonometry

63. Quality Data
1. Signal strength
2. Clear upstroke
3. Detection of foot

64. High Quality Measurements
• Theoretical
• Practical
• Device

65. Device
• Practice, practice, practice
• Know device assumptions
• Training

66. Training
• Within-day reliability
–Acceptable = >0.90
• Between-day reliability
–Acceptable = >0.75
• Between-observer reliability
–Acceptable = >0.75

67. Quality Control
• Initial
–Review first 4 PWV records
–Quality grading score & feedback
–Will not be inc. if quality subpar
• Ongoing
–Random sample of 20 scored per month
–Re-training if ≥2 low records

68. Summary: Quality
• Theoretical
–Research question
–Theoretical model
–Confounders
• Practical
–Data collection sheet
–Know your anatomy
–Quality waveforms
• Device
–Path length
–Device assumptions
–Training

69. What Did We Learn?
• What is PWV?
• Importance
• Measurement Approaches
• PWV Selection Considerations
• Tips for High Quality Measurements

70. Thank you!
Stoner: stonerl@email.unc.edu
Zieff: gzieff@live.unc.edu
Lab: unc-cml.weebly.com
RG: researchgate.net/lab/UNC-Cardiometabolic-Lab-Lee-Stoner

71. Gabriel Zieff, MA
Doctoral Candidate
Exercise and Sport Science
University of North Carolina at Chapel Hill
Lee Stoner, PhD, MPH
Assistant Professor
Exercise and Sport Science
University of North Carolina at Chapel Hill
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