1. Morteza Naghavi, M.D. Chairman of Scientific Advisory Board
New Indices of Endothelial Function Measured by Digital Thermal Monitoring of Vascular Reactivity
Presenter:
Morteza Naghavi, M.D. Chairman of Scientific Advisory Board

2. Endothelial Function is disturbed in various diseases.
This slide shows the extent of involvement of endothelial dysfunction in various diseases, much like a high blood pressure measurement or fever that is indicative of different problems. There is a good argument for adopting endothelial function monitoring as part of routine vital sign monitoring along with blood pressure.

3. (S) The vascular endothelium serves multiple functions:
Endothelial cells serve multiple functions.
(S)
The vascular endothelium serves multiple functions:
it regulates fluid and molecule traffic between blood and tissues
it is an anti-coagulant surface
it contributes to vascular homeostasis and repair
it plays a vital role in vascular tone and blood flow regulation ***
Assessing this function is the most practical way of measuring endothelial function.

4. Endothelial and Vascular Dysfunction:
A “Barometer of Cardiovascular Risk”
Marker of the inherent atherosclerotic risk
An integrated index of both the overall CV risk factor burden and the sum of all vasculoprotective factors in an individual.
Aging Diet
Smoking Inactivity
Diabetes ↑ Cholesterol
↑ Blood Pressure Oxidative Stress
Genetics Medications

8. Brachial Artery Ultrasound with FMD
BASELINE
POST OCCLUSION
CP Lerman, A pjs

9. Reactive Hyperemia
Reactive hyperemia is the transient increase in organ blood flow that occurs following a brief period of ischemia (e.g., arterial occlusion).
The left panel shows the effects of a 2 min arterial occlusion on blood flow. In this example, blood flow goes to zero during arterial occlusion. When the occlusion is released, blood flow rapidly increases (i.e., hyperemia occurs) that lasts for several minutes. The hyperemia occurs because during the period of occlusion, tissue hypoxia and a build up of vasodilator metabolites (e.g., adenosine) dilate arterioles and decrease vascular resistance. Then when perfusion pressure is restored (i.e., occlusion released), flow becomes elevated because of the reduced vascular resistance. During the hyperemia, the tissue becomes reoxygenated and vasodilator metabolites are washed out of the tissue. This causes the resistance vessels to regain their normal vascular tone, thereby returning flow to control.

12. Endothelial Function Basic Science to Clinical Practice
Comparison peripheral and coronary endothelial function
Discovery of NO and the role of the endothelium
Endothelial function with exercise and mental stress
Endothelial function and myocardial ischemia
FDA approved device to assess endothelial function
1980
1989
1995
2005
Comparison between the PAT and coronary endothelial function
2006
Coronary endothelial function in clinical practice
Association between endothelial function and CV events
First endothelial function in humans
Noninvasive endothelial function
1986
1992
1996
2005
Clinical practice
Basic science
CP Lerman, A pjs

13. Brachial Artery Ultrasound FMD VENDYS® - Endothelix, Inc.
Moving Endothelial Function Testing out of the Research Lab and into Doctors Offices
Brachial Artery Ultrasound FMD
VENDYS® - Endothelix, Inc.
Ultrasound measurement of brachial artery dilation
15-minute test
Not automated
Requires skilled operator
Fingertip temperature changes
15-minute test
Fully automated
Operator independent

14. What is VENDYS® technology?

15. How does VENDYS® measure vascular function?

16. VENDYS® Vascular Function Monitoring
Blood Pressure “Occluding” Cuff on Right Upper Arm
Fingertip Temperature Sensors on Both Index Fingers

17. VENDYS® Vascular Function Monitoring

19. Inaccurate Individualized Assessment of Cardiovascular Risk
Addressing Problem 1:
Inaccurate Individualized Assessment of Cardiovascular Risk

20. Lower Fingertip Temperature Rebound is Associated with Higher Burden of Cardiovascular Risk Factors Measured by Framingham Risk Score

21. Lower Fingertip Temperature Rebound is Associated with Higher Coronary Plaque Burden

22. The Combination of Low Fingertip Temperature Rebound and High Framingham Risk Score is Associated with High Risk Coronary Artery Calcium Score 22

23. VENDYS Improves Risk Stratification of High Risk Patients (CAC ≥ 100) over Traditional Risk Factor Assessment
Variable
AUC ± S.D.
95% CI
P (compared to FRS)
VENDYS + FRS
0.89 (0.02)
0.001
VENDYS
0.79 (0.03)
FRS
0.66 (0.04)
- - -

24. Lower Fingertip Temperature Rebound is Associated with the Presence of Cardiometabolic Disorders

25. Fingertip Temperature Rebound Decreases as the Number of Cardiometabolic Risk Factors Increases

26. VENDYS Improves Identification of High Risk Diabetic Patients (CAC ≥ 100)
DM – Diabetes Mellitus
Variable
AUC ± S.D.
95% CI P
VENDYS + DM
0.91 (0.02)
0.0001
VENDYS
0.79 (0.03) DM
0.70 (0.03)

27. Lower Fingertip Temperature Rebound is Associated with Increased Insulin Resistance, Coronary Calcification, and Framingham Risk Score

28. In Patients with Chest pain, Lower Fingertip Temperature Rebound is Associated with Myocardial Perfusion Defects
Impaired Vascular Reactivity and Endothelial Dysfunction Measured
by Fingertip Thermal Monitoring Correlates with Myocardial Perfusion.
Background: Previous studies have shown that vascular dysfunction measured by Digital Thermal Monitoring (DTM) during an arm-cuff reactive hyperemia procedure correlates with the severity of coronary artery disease measured by coronary artery calcium in asymptomatic patients. Current study investigates the correlation between DTM and abnormal myocardial perfusion imaging (MPI). Methods: 116 consecutive patients with chest discomfort, age 57�10 years, underwent MPI, DTM and Framingham Risk Score (FRS) assessment. Fingertip temperature rebound (TR), DTM index of vascular reactivity, was assessed after a 2-minute arm-cuff reactive hyperemia test. The extent of myocardial perfusion defect was measured by summed stress score (SSS). Results: TR decreased from SSS<4 (1.61�0.15) to 4≤SSS≤8 (0.5�0.22) to 9≤SSS≤13 (0.26�0.15) to SSS>13 (-0.37�0.19) (p=0.0001).After adjusting for cardiac risk factors, the odds ratio of the lowest vs. 2 upper tertiles of TR was 3.93 for SSS≥4 and 9.65 for SSS≥8 compared to SSS<4. TR correlated well with SSS (r= -0.88, p=0.0001). Addition of TR to FRS increased the area under the ROC curve to predict abnormal MPI, SSS≥4, from 0.65 to 0.84 (p<0.05). Conclusion: Vascular dysfunction measured by DTM is associated with the extent of myocardial perfusion defect independent of age, gender and cardiac risk factors.

29. A Combination of VENDYS and Framingham Risk Score May Aid Detection of Vaguely Symptomatic Patients (SSS ≥ 4) with Myocardial Perfusion Defects
Variable
AUC ± S.D.
95% CI P
Comparison with FRS
VENDYS + FRS
0.84 (0.03)
0.0001
0.001
VENDYS¥
0.75 (0.04)
0.04
FRS€
0.65 (0.05)
0.004
- - -
SSS – Summed Stress Score

30. In Patients with Chest Pain, Lower Fingertip Temperature Rebound is Associated with Coronary Artery Disease

31. A Combination of Low Fingertip Temperature Rebound and High Framingham Risk Score is Associated with Obstructive Coronary Artery Disease

32. A Combination of VENDYS and Framingham Risk Score May Aid Clinical Risk Assessment of Vaguely Symptomatic Patients Suspected of having Obstructive Coronary Artery Disease
Variable
AUC ± S.D.
95% CI P
Comparison P with FRS
VENDYS + FRS + CAC
0.94 (0.03)
0.0001
0.001
CACπ
0.84 (0.04)
0.003
VENDYS + FRS
0.79 (0.04)
0.009
VENDYS€
0.74 (0.04)
0.03
FRS¥
0.63 (0.05)
- - -
∏ Coronary Artery Calcium Score: CAC: 0, 1-99, , ≥400
€ Fingertip Temperature Rebound: Tertiles of VENDYS TR
¥ Framingham 10 Year CHD Risk Score (FRS): <10%, 10-20%, >20%

33. Digital Thermal Monitoring of Vascular Function is Reproducible
Reproducibility and Variability of Vascular Reactivity Measurement using Digital Thermal Monitoring Background: Previous studies demonstrated that Digital Thermal Monitoring (DTM) of vascular reactivity, a new test for vascular function assessment, is well-correlated with Framingham Risk Score, coronary calcium score and CT angiography. This study evaluates the variability and reproducibility of DTM measurements. We hypothesized that DTM is reproducible and its variability falls within the accepted range of clinical diagnostic tests. A fully automated DTM device (VENDYS, Endothelix Inc., Houston) was used for repeated measurement of vascular reactivity and endothelial function in 18 healthy volunteers (age 35�4 years, 74% male) after 24hours. All subjects underwent overnight fasting, and the test was preceded by 30 minute rest in a supine position inside a dimmed-room with temperature 22�C to 24 �C. The measurements were obtained during and after a 2 minute supra systolic arm-cuff occlusion induced reactive hyperemia procedure. Post cuff-deflation adjusted temperature rebound (TR) and AUC (area under the temperature curve), DTM indices of vascular function, were studied. Day to day coefficient of repeatability was 7.1 % for baseline temperature, 7.5% for mean blood pressure and 10.6% for heart rate. The coefficient of repeatability (CR) of TR and AUC were 2.4% and 2.8%, respectively. In a controlled-environment, the repeatability of DTM is excellent. DTM can be used as a reproducible and operator-independent test for measurement of vascular function in clinical trials and cardiovascular risk assessment clinics.
Variable D
SDD
CV (%)
CR (%)
ICC
P value
Heart Rate
0.47
0.054
11.4
10.6
0.7
0.01
Mean Arterial Pressure
0.44
0.038
8.7
7.5
0.79
0.0005
Start Temperature
0.51
0.036
7.1
0.81
0.0001
DTM (VENDYS®) Indices of Vascular Function
TR (°C)
0.209
0.012
5.7
2.4
0.82
AUC
0.292
0.014
4.8
2.8
0.83
D: mean absolute difference; SDD: SD of mean differences; CV: coefficient of variability [(SDD /D)*100];
CR: coefficient of repeatability [(SDD *1.96)*100)]; ICC: Intra-class Correlation Coefficient.

34. 12-month Treatment with Aged Garlic Extract was Associated with Lower Coronary Calcium Progression and Higher Fingertip Temperature Rebound
Aged garlic extract supplemented with B vitamins, folic acid and L-arginine retards the progression of subclinical atherosclerosis: A randomized clinical trial
Objectives. Previous studies demonstrated that aged garlic extract reduces multiple cardiovascular risk factors. This study was designed to assess whether aged garlic extract therapy with supplements (AGE+S) favorably affects inflammatory and oxidation biomarkers, vascular function and progression of atherosclerosis as compared to placebo.
Methods. In this placebo-controlled, double-blind, randomized trial (conducted 2005�2007), 65 intermediate risk patients (age 60�9 years, 79% male) were treated with a placebo capsule or a capsule containing aged garlic extract (250 mg) plus Vitamin B12 (100 μg), folic acid (300 μg), Vitamin B6 (12.5 mg) and L-arginine (100 mg) given daily for a 1 year. All patients underwent coronary artery calcium scanning (CAC), temperature rebound (TR) as an index of vascular reactivity using Digital Thermal Monitoring (DTM), and measurement of lipid profile, autoantibodies to malondialdehyde (MDA)-LDL, apoB-immune complexes, oxidized phospholipids (OxPL) on apolipoprotein B-100 (OxPL/apoB), lipoprotein (a) [Lp (a)], C-reactive protein (CRP), homocysteine were measured at baseline and 12 months. CAC progression was defined as an increase in CACN15% per year and an increase in TR above baseline was considered a favorable response.
Results. At 1 year, CAC progression was significantly lower and TR significantly higher in the AGE+S compared to the placebo group after adjustment of cardiovascular risk factors (pb0.05). Total cholesterol, LDL-C, homocysteine, IgG and IgM autoantibodies to MDA-LDL and apoB-immune complexes were decreased, whereas HDL, OxPL/apoB, and Lp (a) were significantly increased in AGE+S to placebo.
Conclusion. AGE+S is associated with a favorable improvement in oxidative biomarkers, vascular
function, and reduced progression of atherosclerosis.

35. Comparison with Competitor
VENDYS® - Endothelix, Inc.
EndoPAT® - Itamar Medical Inc.
Fingertip temperature changes
15-minute test
Fully automated
Fingertip pressure changes
15-minute test
Not automated

37. Infrared Imaging
Cuff inflated Post cuff deflation

38. To schedule a free demo or learn more, send an email to info@endothelix.com.

39. VENDYS® Portable
A complete system to perform automated, vascular function studies
Cuff management module (CMM)
Digital thermal monitoring (DTM) module
VENDYS® fingertip probes
Laptop computer with pre-installed software
Data acquisition
Report generation and data tabulation

40. Software Screenshots
The VENDYS Report

41. Software Screenshots
Report Viewer

42. The VENDYS® Report Temperature Curves Vascular Reactivity Gauge
Red = right finger
Blue = left finger
Vascular Reactivity Gauge
Green = Good
Yellow = Intermediate
Red = Poor
Flags help to notify user of conditions that may affect the technical quality of the study.
A summary of VENDYS indices is shown here.
aTR is the primary vascular reactivity index.
Ambient room temperature is recorded throughout the study.

43. Sample Report Screen: “Intermediate” Vascular Reactivity

44. Sample Report Screen: “Poor” Vascular Reactivity

45. Digital Thermal Monitoring of Vascular Function is Reproducible
Reproducibility and Variability of Vascular Reactivity Measurement using Digital Thermal Monitoring Background: Previous studies demonstrated that Digital Thermal Monitoring (DTM) of vascular reactivity, a new test for vascular function assessment, is well-correlated with Framingham Risk Score, coronary calcium score and CT angiography. This study evaluates the variability and reproducibility of DTM measurements. We hypothesized that DTM is reproducible and its variability falls within the accepted range of clinical diagnostic tests. A fully automated DTM device (VENDYS, Endothelix Inc., Houston) was used for repeated measurement of vascular reactivity and endothelial function in 18 healthy volunteers (age 35�4 years, 74% male) after 24hours. All subjects underwent overnight fasting, and the test was preceded by 30 minute rest in a supine position inside a dimmed-room with temperature 22�C to 24 �C. The measurements were obtained during and after a 2 minute supra systolic arm-cuff occlusion induced reactive hyperemia procedure. Post cuff-deflation adjusted temperature rebound (TR) and AUC (area under the temperature curve), DTM indices of vascular function, were studied. Day to day coefficient of repeatability was 7.1 % for baseline temperature, 7.5% for mean blood pressure and 10.6% for heart rate. The coefficient of repeatability (CR) of TR and AUC were 2.4% and 2.8%, respectively. In a controlled-environment, the repeatability of DTM is excellent. DTM can be used as a reproducible and operator-independent test for measurement of vascular function in clinical trials and cardiovascular risk assessment clinics.
Variable D
SDD
CV (%)
CR (%)
ICC
P value
Heart Rate
0.47
0.054
11.4
10.6
0.7
0.01
Mean Arterial Pressure
0.44
0.038
8.7
7.5
0.79
0.0005
Start Temperature
0.51
0.036
7.1
0.81
0.0001
DTM (VENDYS®) Indices of Vascular Function
TR (°C)
0.209
0.012
5.7
2.4
0.82
AUC
0.292
0.014
4.8
2.8
0.83
D: mean absolute difference; SDD: SD of mean differences; CV: coefficient of variability [(SDD /D)*100];
CR: coefficient of repeatability [(SDD *1.96)*100)]; ICC: Intra-class Correlation Coefficient.

46. 12-month Treatment with Aged Garlic Extract was Associated with Lower Coronary Calcium Progression and Higher Fingertip Temperature Rebound
Aged garlic extract supplemented with B vitamins, folic acid and L-arginine retards the progression of subclinical atherosclerosis: A randomized clinical trial
Objectives. Previous studies demonstrated that aged garlic extract reduces multiple cardiovascular risk factors. This study was designed to assess whether aged garlic extract therapy with supplements (AGE+S) favorably affects inflammatory and oxidation biomarkers, vascular function and progression of atherosclerosis as compared to placebo.
Methods. In this placebo-controlled, double-blind, randomized trial (conducted 2005�2007), 65 intermediate risk patients (age 60�9 years, 79% male) were treated with a placebo capsule or a capsule containing aged garlic extract (250 mg) plus Vitamin B12 (100 μg), folic acid (300 μg), Vitamin B6 (12.5 mg) and L-arginine (100 mg) given daily for a 1 year. All patients underwent coronary artery calcium scanning (CAC), temperature rebound (TR) as an index of vascular reactivity using Digital Thermal Monitoring (DTM), and measurement of lipid profile, autoantibodies to malondialdehyde (MDA)-LDL, apoB-immune complexes, oxidized phospholipids (OxPL) on apolipoprotein B-100 (OxPL/apoB), lipoprotein (a) [Lp (a)], C-reactive protein (CRP), homocysteine were measured at baseline and 12 months. CAC progression was defined as an increase in CACN15% per year and an increase in TR above baseline was considered a favorable response.
Results. At 1 year, CAC progression was significantly lower and TR significantly higher in the AGE+S compared to the placebo group after adjustment of cardiovascular risk factors (pb0.05). Total cholesterol, LDL-C, homocysteine, IgG and IgM autoantibodies to MDA-LDL and apoB-immune complexes were decreased, whereas HDL, OxPL/apoB, and Lp (a) were significantly increased in AGE+S to placebo.
Conclusion. AGE+S is associated with a favorable improvement in oxidative biomarkers, vascular
function, and reduced progression of atherosclerosis.

47. Comparison with Competitor
VENDYS® - Endothelix, Inc.
EndoPAT® - Itamar Medical Inc.
Fingertip temperature changes
15-minute test
Fully automated
Fingertip pressure changes
15-minute test
Not automated

50. 1 Figure 1: Patient Setup and Sample VENDYS DTM Report
(Above) Illustration of patient setup, with temperature sensors affixed to both index fingers and blood pressure cuffs on both arms.
(Below left) A sample report screen displays a right finger temperature curve (red), a left finger temperature curve (blue), and a Zero Reactivity Curve (green).
(Below right) The software-generated, vascular reactivity curve is shown. The vascular reactivity index (VRI) is taken as the maximum value of this temperature curve during the reactive hyperemic period.

51. 2A Figure 2A: Distribution of Vascular Reactivity Index (VRI)
A histogram and cumulative percentage curve are shown.

52. 2B
Women
Men
≥ 2
Figure 2B: Distribution of Vascular Reactivity Index (VRI) by Gender
The percent of DTM tests falling into categories of poor, intermediate, and good vascular reactivity is shown for men (solid fill) and women (hatch fill).

53. 3 Figure 2C: Vascular Reactivity Index (VRI) and Age
A scatter plot, trend line, and Pearson’s r coefficient are shown. VRI was mildly and inversely correlated with age.

54. 4A Figure 2D: Prevalence of Poor VRI in Different Age Groups ≥ 70
The frequency of having a poor VRI score (VRI <1.0) is shown for the three age categories of age < 50y, age 50-70y, and age >=70y.

55. 4B
Figure 2E: Distribution of Vascular Reactivity Index (VRI) in Oldest Age Group
The percent of tests falling into categories of poor, intermediate, and good vascular reactivity is shown for patients age >= 70 years.

56. Table 1: Selected Patient and Test Characteristics
Variable
Mean ± SD or %(n)
Mean ± SD or %
Age (y)
65.5 ± 13.7
Cold Finger
5.8% (n=353)
Male / Female
54% / 46%
Sympathetic Response
4.8% (n=294)
Systolic blood pressure (mmHg)
138 ± 20
VRI score, overall
1.53 ± 0.53
Diastolic blood pressure (mmHg)
77 ± 12
VRI score, women
1.56 ± 0.58
Heart rate (bpm)
70 ± 13
VRI score, men
1.50 ± 0.49
Right finger t300 (°C)
32.1 ± 2.7
Left finger t300 (°C)
31.9 ± 2.8
Ambient temperature (°C)
24.3 ± 1.9
Table 1:  Selected Patient and Test Characteristics
Finger t300 = finger temperature at the onset of cuff occlusion (time300s); VRI = vascular reactivity index; NVRI = neurovascular reactivity index; Cold Finger = a flagged condition in which right finger t300 is equal to or less than 27°C; Sympathetic Response = a flagged condition in which left finger temperature continuously declines after right arm cuff occlusion

57. Table 2: Multiple Linear Regression – Models for VRI, SBP, and DBP
VRI (Dependent)
R Square = 0.06, SE = 0.52 β
p-value
Intercept
< 0.001
Age
DBP
0.002
Male sex
SBP (Dependent)
R Square = 0.02, SE = 20.36 β
p-value
Intercept
< 0.001
VRI
0.001
Age HR
0.018
Male sex
0.560
DBP (Dependent)
R Square = 0.10, SE = 11.78
Results are shown for four separate multiple linear regression models: VRI (vascular reactivity index), SBP (systolic blood pressure) and DBP (diastolic blood pressure). β = β coefficient; R Square = R2; SE = standard error. Units for variables were as follows: Age (y), HR (bpm), Sex (male = 1, female = 0), SBP and DBP (mm Hg).

58. Table 3: Comparison between CVD Risk Assessment Methods
Type (Structural, Functional, Risk Factors)
Independen t of Age
Predictive Value
Response to Therapy
Ease of Use and Applicability in Primary Care Setting
Intra- and Inter - Observer Reproducibility
Self-Monitoring by Patients at Home
Coronary Artery Calcium
Structural -
+++ +
Carotid IMT and Plaque ++
Ankle Brachial Index
Arterial Stiffness (e.g., PWV, AI, C1/C2)
Structural/
Functional
Risk Factor- Based Risk Calculators (e.g.,FRS, SCORE, QRISK2)
Risk Factors
n/a
FMD
PAT (RHI)
PPG (RI)
DTM (VRI)
Table 3: Comparison between CVD Risk Assessment Methods
Carotid IMT = carotid intima-media thickness; PWV = pulse wave velocity; AI = augmentation index; C1/C2 = indices of large and small artery compliance (elasticity); FRS = Framingham Risk Score; SCORE = Systematic Coronary Risk Evaluation risk score system published by The European Society of Cardiology; QRISK2 = risk calculator developed by UK National Health Service; FMD = flow mediated dilatation; PAT = peripheral arterial tonometry; RHI = reactive hyperemia index; PPG = photoplethysmography for digital pulse waveform analysis; RI = reflection index; DTM = digital thermal monitoring; VRI = vascular reactivity

59. VENDYS Publications DTM Clinical Papers:
DTM Clinical Papers:
Association of coronary artery calcium score and vascular dysfunction in long-term hemodialysis patients. Hemodialysis International, International Society for Hemodialysis (2013). PDF
Beneficial effects of aged garlic extract and coenzyme Q10 on vascular elasticity and endothelial function: The FAITH randomized clinical trial Nutrition / Elsevier (2013). PDF  
Evaluation of Digital Thermal Monitoring as a Tool to Assess Perioperative Vascular Reactivity J Atheroscler Thromb (2013). PDF  
A Novel Technique for the Assessment of Preoperative Cardiovascular Risk: Reactive Hyperemic Response to Short-Term Exercise BioMed Research International (2013). PDF  
Fingertip Digital Thermal Monitoring: A Fingerprint for Cardiovascular Disease? Int J Cardiovasc Imaging (2010). PDF  
Aged garlic extract supplemented with B vitamins, folic acid and L-arginine retards the progression of subclinical atherosclerosis: A randomized clinical trial. Preventive Medicine (2009). PDF  
Low fingertip temperature rebound measured by digital thermal monitoring strongly correlates with the presence and extent of coronary artery disease diagnosed by 64-slice multi-detector computed tomography. Int. J Cardiovasc Imaging (2009). PDF  Accompanying Editorial: Digital thermal monitoring of vascular function: a novel tool to improve cardiovascular risk assessment. Vascular Medicine (2009). PDF
Concomitant insulin resistance and impaired vascular function is associated with increased coronary artery calcification. Int. Journal of Cardiology (2009). PDF  
Vascular dysfunction measured by fingertip thermal monitoring is associated with the extent of myocardial perfusion defect. JNC (2009). PDF  
Vascular function measured by fingertip thermal reactivity is impaired in patients with metabolic syndrome and diabetes. J Clin Hypertens (2009). PDF  
Relations between digital thermal monitoring of vascular function, the Framingham risk score, and coronary artery calcium score. JCCT (2008). PDF  Accompanying Editorial: Anatomy, physiology, or epidemiology: Which is the best target for assessing vascular health? JCCT (2008). Abstract  
Flow mediated change of finger tip temperature in patients with high cardiovascular risk. Cardiologia Hungarica (2005). PDF English summary PDF Graphical Data  
Post-Exercise Reactive Hyperemia: A Novel Preoperative Risk Assessment Tool Poster Abstract  
Digital Thermal Monitoring: Non-Invasive Assessment of Perioperative Microvascular Function Poster Abstract

60. Review Articles about Vascular/Endothelial Dysfunction Measurement:
DTM Technical Papers:
Reproducibility and variability of digital thermal monitoring of vascular reactivity. Clin Physiol Funct Imaging (2011). PDF  
Use of temperature alterations to characterize vascular reactivity. Clin Physiol Funct Imaging (2011). PDF  
Sensitivity of Digital Thermal Monitoring Parameters to Reactive Hyperemia. Journal of Biomechanical Engineering, ASME (2010). PDF   
Digital Thermal Monitoring (DTM) of Vascular Reactivity Closely Correlates with Doppler Flow Velocity. Conf Proc IEEE Eng Med Biol Soc (2009). PDF  
Lumped parameter thermal model for the study of vascular reactivity in the fingertip. J Biomech Eng (2008). Abstract  
Interrelationships among noninvasive measures of postischemic macro- and microvascular reactivity J Appl Physiol (2008). PDF
Review Articles about Vascular/Endothelial Dysfunction Measurement:
Endothelial dysfunction over the course of coronary artery disease. Eur Heart J (2013). PDF  
The Assessment of Endothelial Function: From Research Into Clinical Practice. Circulation (2012). PDF  
The Endothelial Cell in Health and Disease: Its Function, Dysfunction, Measurement and Therapy. Int J Impot Res (2010). PDF  
Endothelial function as a functional expression of cardiovascular risk factors. Biomark Med (2010). PDF  

61. Additional Publications
1. Schier R, Hinkelbein J, Marcus H, Smallwood A, Correa AM, Mehran R, El-Zein R, Riedel B. A novel technique for the assessment of preoperative cardiovascular risk: reactive hyperemic response to short-term exercise. Biomed Res Int. 2013;2013: PMID:
2. Schier R, Marcus HE, Mansur E, Lei X, El-Zein R, Mehran R, Purugganan R, Heir JS, Riedel B, Gottumukkala V. Evaluation of digital thermal monitoring as a tool to assess perioperative vascular reactivity J Atheroscler Thromb. 2013;20(3): PMID:
3. Ahmadi N, McQuilkin GL, Akhtar MW, Hajsadeghi F, Kleis SJ, Hecht H, Naghavi M, Budoff M. Reproducibility and variability of digital thermal monitoring of vascular reactivity. Clin Physiol Funct Imaging Nov;31(6): PMID:
4. Akhtar MW, Kleis SJ, Metcalfe RW, Naghavi M. Sensitivity of digital thermal monitoring parameters to reactive hyperemia. J Biomech Eng May;132(5): PMID:
5. Schwartz BG, Economides C, Mayeda GS, Burstein S, Kloner RA. The endothelial cell in health and disease: its function, dysfunction, measurement and therapy. Int J Impot Res Mar-Apr;22(2): Review. PMID:
6. van der Wall EE, Schuijf JD, Bax JJ, Jukema JW, Schalij MJ. Fingertip digital thermal monitoring: a fingerprint for cardiovascular disease? Int J Cardiovasc Imaging Feb;26(2): PMID:

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