Introducing A New Clinical Tool To Assist With Coronary Artery Disease Risk Assessment
The World’s First and Only Non-Invasive Skin Cholesterol Test
PREVU ® HANDHELD SPECTROPHOTOMETER AND POC TEST REAGENT KIT
PreVu® Point of Care Test Benefits
COMPLETELY NON-INVASIVE Utilizes safe reagents
NO BIOHAZARDOUS MATERIALS Protection not required for test operators
CONDUCTED ON THE PALM Patient observes test on the hand
REQUIRES NO OVERNIGHT FASTING Test accurately at any time
ABSOLUTELY PAINLESS No discomfort whatsoever
NO NEEDLE PRICK OR BLOOD DRAW The skin is not punctured
TAKES LESS THAN 5 MINUTES Convenient, rapid and streamlined IMMEDIATE TEST RESULTS No waiting for lab processing
Foreword Dear Colleagues: As you are aware, coronary artery disease (CAD) is one of the leading causes of death in Canada and a highly difficult condition to detect. Evaluation for CAD should ideally begin in a clinical environment where adults would undergo formal risk assessment, including blood cholesterol testing and global risk assessment, under the direction of a healthcare provider. However, many remain unassessed or avoid blood testing entirely. This can result in a potentially dangerous lack of awareness of the significant risk a person may be living with for a coronary event. Consequently, the earlier identification of individuals at risk in the general population, who could benefit from more intensive primary prevention measures to help guard against a first event, is of primary concern. The PreVu® Non-Invasive Skin Cholesterol Point of Care (POC) Test is a Canadian developed, non-invasive risk assessment technology designed to measure epidermal sterol, or skin cholesterol – an emerging biomarker in the risk assessment of CAD. The skin contains 11%, by weight, of total body cholesterol1 and is derived from epithelial steroidogenesis and specific uptake from circulation. Elevated skin cholesterol levels have been shown in clinical studies to be strongly associated with an increased risk of significant CAD as measured by treadmill stress testing2 and coronary angiography3, as well as measured by testing for coronary calcium4, carotid artery thickening5 and carotid artery plaque6. I was involved in early research in this area published in the American Journal of Cardiology in 2002 where skin cholesterol showed significant and positive correlations with systolic blood pressure, LDL-C and the Framingham CAD risk calculation model. We also found that skin cholesterol correlated significantly with inflammatory markers, particularly ICAM-1*.
The following presentation briefly outlines the: • • • • • •
science and technology behind the PreVu POC Test test utility and applications testing procedure step-by-step mechanism of action interpretation of results and correlated CAD risk ratios summary of key clinical references
The PreVu® POC Test does not diagnose the presence or absence of CAD, but has been shown to be effective in helping to identify individuals from the general population who may be at higher, hidden risk for CAD by possessing elevated levels of skin cholesterol. Sincerely,
Dr. G.B. John Mancini, MD, FRCPC, FACP, FACC (Cardiologist) Professor of Medicine University of British Columbia, Department of Medicine, Division of Cardiology Director, Cardiovascular Imaging Research Core Laboratory (CIRCL) University of British Columbia, Department of Medicine Chair, PreVu Medical Advisory Board
Note: References 1-6 appear at end of the booklet *Mancini J, Chan S, Frochlich J, et al. Association of skin cholesterol content, measured by a non-invasive method, with markers of inflammation and Framingham risk prediction. Am J Cardiol 2002;89:1313-16
How the prevu® POC test Works An adhesive foam pad with three wells is placed on the palm of the hand by a test operator. Drops of safe reagent are then placed into the wells in sequence, which first bind with the cholesterol in the skin and then subsequently change color in proportion to the amount of bound cholesterol present. This color change is then read by the PreVu Handheld Spectrophotometer, which is a sophisticated optical reading instrument that also guides the test operator step-by-step through the procedure. The spectrophotometer assigns a numerical value to the color hue and that number places the patient into a range, and accordingly a PreVu risk category (Normal, Borderline, Elevated) based on the clinical data for the biomarker. A PreVu score of 110 or higher (Elevated) may mean an increased risk of coronary artery disease.
Prevu® POC test utility and applications The PreVu® POC Test can quickly identify individuals with hidden, higher levels of risk of CAD by testing their skin cholesterol levels non-invasively and without blood draw, discomfort or fasting. It is ideal for delivery through neighborhood healthcare settings including pharmacies, medical clinics, as well as at cardiovascular screening clinics, where in 5 minutes an individual can receive a ‘preview’ of their possible risk of CAD. Then, if warranted, at risk individuals can start down the path towards formal global risk evaluation, primary prevention and ongoing monitoring of all their relevant risks under their healthcare provider’s direction and guidance. Skin Cholesterol testing is not the same as blood serum cholesterol testing, there is no correlation between the results, and a skin cholesterol test is not a substitute for a blood serum cholesterol test.
PreVu® Poc Test Step-By-Step Step 1: Clean Palm; Apply Foam Pad
Step 2: Add Detector Reagent
Step 3: Add Positive Control Reagent
Step 4: Blot Excess Reagents
Step 5: Add Indicator Reagent
Step 6: Read Degree of Color Hue
PreVu® POC Test Mechanism of Action
This image shows the Mechanism of Action by which the Detector reagent - copolymer of Digitonin conjugated with Horseradish Peroxidaise (HRP) - binds with the cholesterol of the skin and then interacts with the Indicator reagent Tetramethylbenzidine (TMB) to produce a color change, which is then read and quantified by the PreVu Handheld Spectrophotometer.
3,3’,5,5’- Tetramethylbenzidine (TMB) H3C
Specificity based on the affinity of Digitonin for the 3b-hydroxy ring structure of cholesterol. The reporter molecule is HRP. The oxidized product of TMB has a deep blue color. The intensity of the blue color - the hue of the TMB solution - is measured directly off the hand by the PreVu Handheld Spectrophotometer.
Interpretation of prevu® poc Test Results Elevated Skin Cholesterol Level PreVu® Score 110 or higher Elevation correlates with an increased risk of Coronary Artery Disease
Borderline Skin Cholesterol Level PreVu® Score between 100 – 109
Normal Skin Cholesterol Level PreVu® Score below 100 Skin Cholesterol risk marker is within normal range
Discuss this test result with your healthcare provider. Formal risk assessment is warranted, including blood cholesterol testing and global risk assessment, under the direction of a healthcare provider.
Discuss this test result with your healthcare provider. Due to test variability of approximately 10%, formal risk assessment, including blood cholesterol testing and global risk assessment under the direction of a healthcare provider, should also be considered for patients with a borderline skin cholesterol reading. You do not have abnormal skin cholesterol. Further concerns about cardiovascular health related to risk factors such as a family history of cardiovascular disease or high blood cholesterol, being personally overweight, having diabetes, being a smoker, living a sedentary lifestyle or having high blood pressure, should be discussed by the patient with a healthcare provider. Note: The PreVu® POC test score does not correlate with blood serum cholesterol testing and is not a replacement for blood serum cholesterol testing.
ELEVATED SKIN CHOLESTEROL AND RISK OF CORONARY ARTERY DISEASE Individuals with elevated skin cholesterol levels as measured by the PreVu® POC Test, have been shown toRISK have OF a much greater risk ofCARDIOVASCULAR scoring an abnormal resultTESTS in the clinical ABNORMAL WITHcardiovascular tests listed below: ELEVATED SKIN CHOLESTEROL AS MEASURED BY THE PREVU® POC TEST RISK OF ABNORMAL CLINICAL CARDIOVASCULAR TEST WITH ELEVATED SKIN CHOLESTEROL
IF TEST RESULT ABNORMAL
2.6 times greater risk of abnormal Treadmill Stress Test2
Functional cardiovascular disease
Possible coronary artery disease
1.4 times greater risk of abnormal Coronary Angiography3
Coronary artery atherosclerosis
Blockage of coronary arteries
3.0 times greater risk of abnormal Coronary Calcium4
Calcified coronary plaque
Higher risk of future cardiac events
2.0 times greater risk of abnormal Carotid Ultrasound5 (IMT)
Carotid artery atherosclerosis
Increased risk of heart attack and stroke
3.0 times greater risk of abnormal Carotid Ultrasound6 (Plaque)
Carotid artery atherosclerosis
Increased risk of heart attack and stroke
Note: Clinical study references appear at the end of the booklet.
Clinical References The specific clinical references made in this booklet appear below in their order of presentation: (1) (2) (3) (4) (5) (6)
Sabine, JR (1977) Cholesterol, New York: Marcel Dekkar. Zawydiwski R, Sprecher DL, Evelegh MJ, et al. A novel test for the measurement of Skin Cholesterol. Clinical Chemistry 2001;47:1302-4. Sprecher DL, Goodman SG, Kannampuzha P, et al. Skin Tissue Cholesterol (Skin Tc) is related to angiographically-defined cardiovascular disease. Atherosclerosis 2003;171:255-258. Vaidya D, Ding J, Hill JG, et al. Skin Tissue Cholesterol assay correlates with presence of coronary calcium. Atherosclerosis 2005;181:167-73. Tzou WS, Mays ME, Korcarz CE, et al. Skin Cholesterol Content Identifies Increased Carotid Intima-Media Thickness in Asymptomatic Adults. Am Heart J 2005;150:1135-39. Stein JH, Tzou WS, DeCara JM, et al. Usefulness of increased Skin Cholesterol to identify individuals at increased cardiovascular risk (from the Predictor of Advanced Subclinical Atherosclerosis Study). Am J Cardiol 2008;101:986-991.
Since 1999, there have been multiple studies, publications, scientific presentations, and abstracts and posters related to skin cholesterol and the PreVu® technology developed to measure it, that have been conducted, submitted, prepared and delivered by respected researchers from leading North American institutions in cardiovascular research including: •
University of Wisconsin, School of Medicine
The Cleveland Clinic Foundation
The Johns Hopkins School of Medicine
University of Pennsylvania, Department of Experimental Therapeutics
Much of this clinical data has been published in prestigious peer reviewed journals that include: •
The American Journal of Cardiology
The American Heart Journal
Corresponding presentations have been made at some of the most important conferences and meetings in the clinical world including: •
Annual American Association of Clinical Chemistry Meeting
American Heart Association Scientific Sessions
Canadian Cardiovascular Congress
Annual Scientific Session of the American College of Cardiology
The Endocrine Society Annual Meeting
American Heart Association Conference on Arteriosclerosis, Thrombosis and Vascular Biology
For further clinical evidence please visit www.prevu.com.
For further information on the science of skin cholesterol, the PreVu technology and the clinical applications of both in risk assessment of coronary artery disease, please visit www.prevu.com For further information on distributing the PreVu® POC Test technology in your community, please contact: Paul J. Moreau Vice President, Sales and Marketing Miraculins Inc. T. 204.478.5603 • F. 204.453.1546 email@example.com
Copyright © 2013 by Miraculins Inc. All Rights Reserved. Unauthorized distribution, transmission or republication is strictly prohibited. PreVu® is a Registered Trademark of Miraculins Inc. All Rights Reserved. 2013. by
Printed in Canada.
Miraculins Inc. - PreVu Non-Invasive Skin Cholesterol Clinical Brochure