CVD Risk Assessment and Stroke Risk Assessment: Noninvasive Testing and a Point-of-Care Test

Tuesday, June 25, 2013

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Atherosclerosis is the fundamental process behind coronary artery disease, stroke, and many other vascular diseases. Although the rates of death associated with cardiovascular disease (CVD) and stroke have decreased in the United States, the burden of these diseases remains high. The total direct and indirect cost of CVD and stroke in 2009 was estimated to be over $312 billion.1

The atherosclerotic process begins in childhood, with the development of more advanced lesions starting at about 25 years of age. Clinical manifestations generally appear in patients aged 40 years or older. Identifying people at imminent risk for complications is important, since medication and lifestyle modifications can reduce risk. Well-established risk factors include hypertension, serum cholesterol and lipid levels, diabetes, obesity, metabolic syndrome, diet, tobacco use, and a sedentary lifestyle. Serum levels of homocystine and C-reactive protein may also predict risk. Carotid artery intima-media thickness (CIMT) and the brachial artery reactivity test (BART), which are both obtained by ultrasound, have been found to be independent risk factors. In addition, there is a skin sterol test that has promise as a convenient, noninvasive, point-of-care assay.

At the root of atherosclerosis is a disturbance within the inner (intimal) wall of the artery. The mechanisms are still unclear. Vasomotor function, damage to the blood vessel wall leading to clot formation, the activation state of the coagulation cascade, the fibrinolytic system, the activity of smooth muscle cells, and cellular inflammation are interrelated and complex factors involved in atherogenesis and the development of atherosclerotic plaques. These plaques accumulate over time, narrow the lumen of the artery, and limit blood flow to distal structures, including the myocardium and brain. Pieces of ruptured plaque may block distal arterial branches. The final common pathway is insufficient blood supply to an end organ, which may be acute or chronic.

Despite the central role of the artery in coronary and cerebrovascular disease, it has not been practical to screen every patient by direct assessment of arteries. Evaluation using carotid ultrasound, coronary angiography, computed tomography angiography (CTA), and magnetic resonance angiography (MRA) is usually reserved for patients believed to have significant disease. Some of these techniques are invasive, many are expensive, and all are labor-intensive.

CIMT Test, Endothelial Function Test, and POC Test for Skin Cholesterol

There are now some noninvasive tests for screening and monitoring patients respectively at risk for or with atherosclerosis:

  • Medical Technologies International, Inc. (Palm Desert, CA) offers the FDA-cleared ArterioVision™ Carotid Intima Media Thickness test. The technology is based on standardized B-mode ultrasound image-acquisition methodology and proprietary ultrasound image-processing software. The company says that it is a painless and precise technique for measuring the combined thickness of the intimal and medial layers of the walls of the carotid artery. In addition to utility as a screening test, it can be used to monitor treatment efficacy. The test is most appropriate for people with traditional factors for heart disease. Computed tomography coronary calcium scoring (CACS) has also been used to evaluate subclinical atherosclerosis. The Multi-Ethnic Study of Atherosclerosis evaluated CAC and CIMT for predicting subsequent cardiovascular disease events, and found that CAC was better at predicting risk for coronary heart disease outcomes and that CIMT was better at predicting the risk for stroke.2 The CIMT test also remains controversial as a predictor of cardiovascular outcomes.3
  • BART is a noninvasive test that looks at endothelial function using high-resolution ultrasound. The brachial artery is scanned before and after a blood pressure cuff is inflated to occlude the artery, and the diameter of the artery is measured before and at a precise time after stimulus to determine the degree of vasodilatation in response to the increased blood flow after the blood pressure cuff is deflated. After a 10-min rest period, the patient is administered nitroglycerin and the diameter of the artery is again measured to assess endothelium-independent vasodilatation. This test is highly operator-dependent, requiring an experienced ultrasonographer.
  • Miraculins Inc. (Winnipeg, Manitoba, Canada) is commercializing the PreVu® Non-Invasive Skin Cholesterol Point of Care (POC) Test, an FDA-cleared, CLIA-exempt noninvasive point-of care measurement of skin cholesterol. The test also has regulatory approval for sale in Canada and Europe. The company describes this test as a novel technology for the risk assessment of coronary artery disease (CAD). It measures epidermal cholesterol, which the company considers to be a new biomarker. According to the company, elevated skin cholesterol has been shown in clinical trials to be strongly associated with significant CAD. The test consists of the PreVu Handheld Spectrophotometer, and a 40-unit test kit containing Detector reagent, Indicator reagent, Positive Control reagent, medical adhesive foam pads, capillary blotting sticks, Wet-Naps® moist towelettes, and alcohol swabs. The simple test is performed by placing a drop of digitonin solution, which binds selectively to the cholesterol in the skin, on the palm of the hand. The digitonin is conjugated to horseradish peroxidase (HPO) by a copolymer. After a 1-min incubation period, the area is blotted dry to remove any unbound digitonin solution. A second drop of the reagent containing HPO substrate is then added, and a blue color change occurs in direct proportion to the amount of digitonin that is bound to skin cholesterol. Two minutes later, a handheld spectrophotometer is placed over the drop to quantify the cholesterol present in the skin. Negative and positive procedural controls are also applied to monitor test performance. For information on marketing and distribution, contact the Miraculins business development team at [email protected].

References

  1. Go, A.S.; Mozaffarian, D. et al. Heart disease and stroke statistics—2013 update. A report from the American Heart Association. Circulation  2013, 127, e6–e245.
  2. Folsom, A.R.; Kronmal, R.A. et al. Coronary artery calcification compared with carotid intima-media thickness in the prediction of cardiovascular disease incidence: The Multi-Ethnic Study of Atherosclerosis. Arch. Intern. Med. 2008, 168, 1333–9.
  3. Medscape Cardiology, May 10, 2013. Et Tu, Olive Oil? Fats and endothelial function. Henry R. Black, M.D.; Robert Vogel, M.D.

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