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Q1.
What does VENDYS® measure?
Q2.
What is “vascular reactivity”?
Q3.
What is the definition of
“macrovascular” and “microvascular”?
Q4.
What is the relationship between
“vascular reactivity” and “endothelial function”?
Q5.
How does VENDYS® measure
vascular reactivity?
Q6.
Does VENDYS® temperature
rebound (TR) change in the presence of nitric oxide (NO)
inhibitors?
Q7.
How does the VENDYS® method
compare to laser Doppler flowmetry (LDF)?
Q8.
How does the VENDYS® method
compare to Doppler ultrasound flow velocity measurement?
Q9.
What is the correlation between VENDYS®
and other vascular function tests?
Q10.
How does the VENDYS® method
compare to EndoPAT®
peripheral artery tonometry?
Q11.
How well does VENDYS®
correlate with conventional cardiovascular risk factors
(Framingham Risk Score), subclinical atherosclerosis
(coronary calcium score), and obstructive coronary artery
disease (coronary angiography and myocardial perfusion)?
Q12.
How reproducible are VENDYS®
results? (Intra-individual and inter-observer variability)
Q13.
What is “hot finger”, and how does
diurnal variation in fingertip temperature affect VENDYS®
test results?
Q14.
What is “cold finger”, and what should
be done about it?
Q15.
What are the recommended test
conditions?
Q16.
How often can VENDYS® tests
be performed?
Q17.
What is the second temperature probe
used for?
Q18.
How long is cuff occlusion?
Q19.
Does 5-minute cuff occlusion pose any
risk to the subject?
Q20.
In what format are VENDYS®
data files stored? Can the data be exported to data analysis
software?
Q21.
How long does the VENDYS®
test take to complete?
Q22.
What does Advanced VENDYS®
Analysis Software provide?
Q23.
What is adjusted Temperature Rebound
(aTR), and what is the unit of measurement, °Celsius or
°Fahrenheit?
Q24.
What are suggested topics for future
VENDYS®
research studies?
Q1. What does VENDYS®
measure?
A1. In simple terms, VENDYS® measures vascular
reactivity.
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Q2. What is
“vascular reactivity”?
A2. Vascular reactivity is a vital component of vascular
function that enables the circulatory system to respond to
physiologic and pharmacologic stimuli that require
adjustments of blood flow and alterations of vessel tone and
diameter. Vascular reactivity occurs in two forms –
vasoconstrictive and vasodilative – and can be exhibited at
both the macrovascular and microvascular levels.
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Q3.
What is the definition of “macrovascular” and
“microvascular”?
A3. “Macrovascular” pertains to large, conduit arteries with
an internal diameter greater than 100 microns.
“Microvascular” refers to small, resistance vessels
(pre-capillary arterioles) with an internal diameter of less
than 100 microns. It is estimated that the microvasculature
accounts for over 95% of the total body vasculature.
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Q4.
What is the relationship between “vascular reactivity” and
“endothelial function”?
A4. Microvascular reactivity (here,vasodilative reactivity)
causes reactive hyperemia (increased blood flow in response
to ischemia or similar pharmacologic stimuli), whereas
macrovascular reactivity (flow mediated dilatation, or FMD)
results from reactive hyperemia. Both macro- and
microvascular reactivity are governed by multiple
physiologic (endothelium-dependent and –independent)
regulatory mechanisms and are mediated by a number of
biochemical agents, such as nitric oxide (NO),
prostaglandins, adenosine, bradykinin, histamine, and other
vasoactive substances. It is believed that macrovascular
reactivity is predominantly mediated by endothelium-derived
NO, whereas microvascular reactivity is only partially
mediated by NO. Traditionally, assessment of macrovascular
reactivity (FMD) at the brachial artery level by high
resolution ultrasound imaging has been described as an
endothelial function test. However, some key opinion leaders
believe that “endothelial function” is a misnomer because
endothelial cells have numerous functions. Moreover,
endothelial cells exist in all vascular beds and play
critical roles at both macro- and microvascular levels.
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Q5.
How
does VENDYS® measure vascular reactivity?
A5. VENDYS® monitors, records, and analyzes
fingertip temperature, which serves as a surrogate marker of
blood flow changes that result from vascular reactivity. The
VENDYS® test begins with an automated blood
pressure measurement in the left arm, followed by a period
of suprasystolic cuff occlusion of the right arm (usually 5
minutes). During the cuff occlusion, fingertip temperature
in the right hand falls because of the absence of warm
circulating blood. The occlusion of blood flow elicits a
vasodilatory response in the ischemic area. Once the cuff is
released, blood flow rushes into the forearm and hand,
causing a temperature rebound (TR) in the fingertip which is
directly proportional to the reactive hyperemia response.
The higher the temperature rebound, the better the vascular
reactivity.
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Q6.
Does VENDYS® temperature rebound (TR) change in
the presence of nitric oxide (NO) inhibitors?
A6. Studies have shown that cutaneous microvascular
reactivity, measured by laser Doppler flowmetry (LDF, the
current, standard method of measuring skin blood flow), is
blunted by NO synthase inhibitors. Similar studies using
VENDYS® are underway. These studies not only
investigate the effect of an eNOS (endothelial NO synthase)
inhibitor on fingertip temperature reactivity in the
occluded arm, but also aim to test the hypothesis that
increased temperature in the contralateral finger during
cuff occlusion is partly effected by eNOS and nNOS (neuronal
NO synthase).
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Q7.
How does the VENDYS® method compare to laser
Doppler flowmetry (LDF)?
A7. Several studies have shown that skin temperature
correlates strongly with skin blood flow measured by LDF.
However, unlike LDF, which is sensitive to red blood cell
motion only at the skin level (1-2 mm depth), VENDYS®
temperature signals can reflect blood flow changes in both
skin and subcutaneous tissues simply because the heat from
the inrush of warm blood travels from deep tissues to the
skin surface. Also, LDF is markedly sensitive to any
movement at the measurement site, whereas VENDYS®
is not affected by finger motion.
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Q8.
How does the VENDYS® method compare to Doppler
ultrasound flow velocity measurement?
A8. Our studies have demonstrated a direct relationship
between VENDYS® parameters and flow velocity
changes in the radial and ulnar arteries at the wrist level.
In most circumstances, fingertip temperature changes
appeared to reflect changes in Doppler blood flow
velocities, but with dampened amplitudes as well as lower
noise. Unlike Doppler ultrasound, which is reliant on proper
probe placement and handling by the operator, VENDYS®
temperature recording is automated and does not require
probe handling. Our studies have also shown a disparity
between Doppler velocity measurements and VENDYS®
parameters when the fingertip temperature approaches (>35°C)
body core temperature (37°C).
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Q9.
What is the correlation between VENDYS® and other
vascular function tests?
A9. VENDYS® has been studied in relation to
FMD-BAUS (flow mediated dilatation-brachial artery
ultrasound), Doppler flow velocity, LDF (laser Doppler
flowmetry), and PAT (peripheral arterial tonometry-EndoPAT).
In summary, VENDYS®
exhibited modest correlations with these methods. We believe
that VENDYS®, by reflecting both cutaneous and
deep tissue vascular reactivity, introduces a new angle to
vascular function assessment and does not equate with any of
the above techniques; in fact, based on our preliminary
studies, VENDYS® is a very sensitive marker of
vascular (and neurovascular) reactivity and may prove to be
the most useful and cost effective clinical tool for
monitoring vascular function.
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Q10.
How does the VENDYS® method compare to EndoPAT®
peripheral artery tonometry?
A10. Although both EndoPAT® and VENDYS®
measure vascular reactivity at the fingertip and employ a
similar cuff-induced reactive hyperemia procedure, the
EndoPAT®
probe includes a fingertip cuff that obstructs
microvasculature at the point of measurement; therefore,
EndoPAT® may not be able to accurately evaluate
microvascular reactivity at the fingertip. Studies have
shown a modest correlation (r=0.29, p=0.01) between EndoPAT®
reactive hyperemia index (RHI) and VENDYS®
temperature rebound (TR).
[top]
Q11.
How well does VENDYS® correlate with conventional
cardiovascular risk factors (Framingham Risk Score),
subclinical atherosclerosis (coronary calcium score), and
obstructive coronary artery disease (coronary angiography
and myocardial perfusion)?
A11. Our studies have clearly demonstrated that lower VENDYS®
fingertip temperature rebound (TR) is associated with
increased Framingham Risk Score (FRS) and higher coronary
calcium score (CAC). More importantly, TR has been shown to
significantly improve the predictive value of FRS in the
detection of high-risk, subclinical atherosclerosis
(CAC>100) in asymptomatic population. Similarly, we have
also found that a combination of TR and FRS has shown a
higher predictive power in the identification of obstructive
coronary artery disease (diagnosed by coronary angiography
and myocardial perfusion imaging) in vaguely symptomatic
patients. These data suggest a potential clinical utility
for VENDYS® as a complementary, non-invasive,
non-imaging, inexpensive test for cardiovascular risk
assessment in asymptomatic and vaguely symptomatic
populations. For more information, please see the
Clinical Findings Section.
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Q12.
How reproducible are VENDYS® results?
(Intra-individual and inter-observer variability)
A12. Our intra-individual repeatability studies (24-hour
interval) in apparently healthy individuals have shown that
VENDYS® parameters, TR (temperature rebound) and
AUC (Area Under Curve), are reproducible when performed
under the recommended standard test conditions (see below).
The coefficient of variation (CV) was 5.7% for temperature
rebound (TR), 8.7% for mean arterial pressure (MAP), and
11.4% for heart rate (HR). These data indicate that TR
reproducibility fits within the accepted reproducibility
range for methods that have been widely adopted in clinical
practice, namely MAP and HR.
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It is important to realize that
VENDYS®, like other cardiovascular physiologic
markers (e.g., blood pressure and heart rate), is sensitive
to factors such as autonomic nervous system activity and
postprandial metabolic changes. Therefore, for maximum
reproducibility, VENDYS® tests should be
performed under optimum conditions with minimum disturbing
factors that would influence the cardiovascular system.
Recommended subject and testing conditions are listed in the
International Brachial Artery Reactivity Task Force
guidelines (J Am Coll Cardiol 2002 Jan;39(2):257-65.) and in
the VENDYS® Operating Manual.
The VENDYS® testing procedure (temperature
measurement, thermal analysis, report generation) is
completely automated. Therefore, inter-observer variability
is not an issue.
Q13.
What is “hot finger”, and how does diurnal variation in
fingertip temperature affect VENDYS® test
results?
A13. Studies have shown that resting fingertip temperature
usually ranges from 27°C to 33°C (average 30°C) and is
primarily affected by mental stress, physical activity, and
thermoregulatory mechanisms (in response to ambient
temperature and metabolic activity). It is well known that
fingertip temperature varies with the status of autonomic
nervous system activity in such a way that the higher the
sympathetic activity, the lower the fingertip temperature.
Also, temperature rebound (TR) appears to be inversely
correlated with the starting fingertip temperature. As the
starting temperature increases above 33°C (and approaches
core body temperature, 37°C), the magnitude of temperature
rebound appears to be artificially reduced in such a way
that the higher the starting temperature, the lower the TR
(possibly resulting in a negative TR). This effect occurs
because maximum fingertip temperature usually does not
exceed core body temperature. To address this issue,
Advanced VENDYS® Analysis Software provides
normalized TR and other VENDYS® indices, such as
area under the curve (AUC), slope of temperature recovery
(SLP), and bioheat vascular reactivity index. However, in
our initial clinical studies, we chose TR because it was the
simplest index of thermal reactivity. Despite the apparent
“dampening effect” of high starting temperatures on
temperature rebound, unadjusted TR has demonstrated strong
predictive value in multiple clinical studies, as shown in
the Clinical Findings section. (See VENDYS®
Operating Manual for additional information.)
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Q14.
What is “cold finger”, and what should be done about it?
A14. We define “cold finger” as a baseline fingertip
temperature below 27°C. This situation is usually indicative
of heightened, sympathetic nervous system activity (from
mental stress, anxiety, pain, etc.), although it may also
result from vasospasm (e.g., Raynaud’s phenomenon) or cold
ambient temperature. As stated in the International Brachial
Artery Reactivity Task Force guidelines, these situations
are sub-optimal for vascular function measurement and must
be addressed by reducing mental stress, warming the
subject’s hands (preferably with dry heat), and increasing
the room temperature. If all attempts to relax the subject
and increase the fingertip temperature fail, it is
recommended that VENDYS® testing be rescheduled.
N.B. Despite the apparent noise effect of “cold finger” and
fingertip vasoconstriction on temperature response curves,
our preliminary investigations have suggested that
sympathetic overactivity during performance of the VENDYS®
test may be an indication of abnormal neurovascular response
and signals a higher cardiovascular risk.
[top]
Q15.
What are the recommended test conditions?
A15. The optimum conditions for VENDYS® testing
are similar to optimum conditions for measuring blood
pressure and other vascular function and reactivity tests. A
comprehensive list of such conditions has been outlined by
the International Brachial Artery Reactivity Task Force and
is included in the VENDYS® Operating Manual.
[top]
Q16.
How often can VENDYS® tests be performed?
A16. The answer is not quite clear. However, research
studies have suggested that 5 minute cuff occlusion creates
a “vascular memory” effect that may require 30 minutes, or
more, to reset. Therefore, cuff reactive hyperemia studies,
such as the VENDYS® test, should be performed at
least 30 minutes apart.
[top]
Q17.
What
is the second temperature probe used for?
A17. The second probe monitors fingertip temperature changes
on the contralateral, non-occluded hand. Temperature data
from the second probe were originally intended to serve as a
relatively stable, reference curve. However, recent studies
have revealed that temperature changes in the non-occluded
hand may provide additional insight into the subject’s
vascular function. It is hypothesized that increased
fingertip temperature in the contralateral hand is a
physiologic, neurally-mediated, systemic response to the
ischemic stimulus. It is further hypothesized that this
response would be vasodilatory in healthy individuals and
hampered in individuals with cardiovascular risk factors and
sympathetic overactivity. For more information, please see
“Page 25 – Latest Findings.”
[top]
Q18. How long is
cuff occlusion?
A18. Traditionally, reactive hyperemia tests have been
performed using a 5-minute protocol because flow-mediated
dilatation of the brachial artery has been found to plateau
after 5 minutes cuff occlusion. However, our preliminary
studies have shown that fingertip temperature rebound after
a shorter period of cuff occlusion (as short as 2 minutes)
can distinguish individuals with increased cardiovascular
risk (higher Framingham Risk Score, higher coronary calcium
score, abnormal myocardial perfusion, and obstructive
coronary artery disease). Note that observed temperature
rebound values will be higher with 2 minute cuff occlusion
than with 5 minute occlusion, simply because the fingertip
temperature will fall further during a longer period of cuff
occlusion. It is recommended that VENDYS® users
choose and utilize a consistent duration of cuff occlusion
if they wish to compare TR values.
[top]
Q19.
Does 5-minute cuff occlusion pose any risk to the subject?
A19. Numerous studies have used 5-minute cuff occlusion and
reported no significant problems. However, it is recommended
that VENDYS® testing be aborted if the subject
complains of excessive pain or discomfort. In our studies
involving over 1500 subjects, only one subject experienced
this problem. In some subjects, mild skin bruising occurs at
the cuff site.
[top]
Q20.
In what format are VENDYS® data files stored? Can
the data be exported to data analysis software?
A20. In addition to showing a real-time, graphical display
and saving the test results in the VENDYS®
database (SQL), the raw data can be exported in .CSV and
.XML formats to other databases.
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Q21.
How long does the VENDYS® test take to complete?
A21. The entire test procedure can usually be completed in
15 minutes. Details are provided in the VENDYS®
Operating Manual.
[top]
Q22.
What does Advanced VENDYS® Analysis Software
provide?
A22. The software performs an extensive analysis of
temperature data obtained from both fingers and generates a
detailed report of multiple parameters, including
temperature rebound (TR), area under the curve (AUC), slope
of temperature fall and recovery, and parameters obtained
using advanced bioheat algorithms. Also included are
adjusted values for TR and AUC, based on various starting
fingertip temperatures.
[top]
Q23.
What is adjusted Temperature Rebound (aTR), and what is the
unit of measurement, °Celsius or °Fahrenheit?
A23. The VENDYS® software utilizes a proprietary
method to calculate what the fingertip temperature rebound
curve would look like if no vascular reactivity were
present, taking into account the starting fingertip
temperature and the amount of temperature fall during cuff
occlusion. The difference between this “zero reactivity
curve” and the actual observed temperature curve is used to
determine the adjusted temperature rebound (aTR) presented
in the VENDYS®
test report. Consequently, aTR is a dimensionless number
whose magnitude directly correlates with the extent of the
subject’s vascular reactivity. The higher the aTR, the
higher the vascular reactivity, the better the vascular
function…[top]
Q24.
What are suggested topics for future VENDYS®
research studies?
A24.
We encourage our colleagues to investigate the following:
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VENDYS®
for monitoring response to non-pharmacologic therapies
(diet, exercise, smoking cessation, stress reduction,
etc.)
Other important topics are welcomed. Endothelix®
provides special offers to investigators whose areas of
research overlap with any the topics listed above.
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