Atherosclerosis is the fundamental process in coronary artery disease, stroke, and many other vascular diseases. It is responsible for more than half of the disease burden of the United States, with an annual cost of over $100 billion. This includes over 1.5 million myocardial infarctions annually. Atherosclerosis technically occurs in everyone 25 and over, but most remain asymptomatic for decades. This underscores the need to identify people at imminent risk for complications, since medication and lifestyle modification can reduce that risk. Well-established risk factors include hypertension, serum cholesterol and lipid levels, diabetes, obesity, diet, tobacco use, and a sedentary lifestyle. Serum levels of homocystine and C-reactive protein also predict risk. More recently, carotid intima-media thickness (CIMT) and the brachial artery reactivity test (BART), both obtained by ultrasound, have been shown to be powerful independent risk factors. Meanwhile, a skin sterol test called PREVU(x) provides a convenient, non-invasive, Point-of-Care assay.
At the root of atherosclerosis is a disturbance of the inner (intimal) wall of the artery. The process is complex, but one component is usually hypertension, which contributes to turbulent blood flow that traumatizes the intimal surface. Another component is inflammation, which combines with lipid, cholesterol, and calcium deposition to form plaques. These plaques accumulate over time, narrow the lumen inside the artery, and limit blood flow to distal structures such as the myocardium and brain. A plaque may also break and liberate pieces that block distal arterial branches. The final common pathway is insufficient blood supply to end organs, 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 directly assessing the arteries. Direct assays such as carotid ultrasound, coronary angiography, computed tomography angiography (CTA), and magnetic resonance angiography (MRA) are usually reserved for patients believed to have significant disease. Some of these techniques are invasive, many are expensive, and all are labor-intensive.
A new method, CIMT uses ultrasound to measure the combined thickness of the intimal and medial layers of the carotid artery walls. OLeary and coworkers (New Engl. J. Med. 1999;340:14-22) tested CIMT in a sample of adults with no prior history of atherosclerotic complications and then followed them for a mean of 6 years. Compared to those in the lowest CIMT quintile, patients in the highest quintile had almost a 4-fold risk of myocardial infarction and stroke. This risk was similar even when statistical analysis controlled for the vascular risk factors mentioned above. In a complementary study, Raitakari and coworkers (JAMA. 2003;290:2277-228) followed adolescents 12-18 years old and found that conventional atherosclerotic risk factors predicted elevated CIMT as adults.
Another new and non-invasive modality is BART, which measures flow-dependent vasodilation in an arm artery Like CIMT, BART has demonstrated usefulness for prospective risk stratification of coronary artery disease (Schroeder S et al. Am Heart J. 1999;138:731-9). Both CIMT and BART have yet to enter routine use, but with their wider availability more patients may be screened. Both techniques require special ultrasound equipment and an experienced operator.
Amidst the new non-invasive methods, the PREVU(x) skin sterol tests holds special promise for Point-of-Care use. The concept behind this test is that cholesterol slowly accumulates in skin tissue, paralleling the buildup of cholesterol on arterial walls. The test provides an independent predictor of coronary artery disease. It has been shown to correlate with coronary angiography, stress testing, and a history of heart attack. Tzou and coworkers (Am Heart J. 2005;150:1135-9) recently tested the ability of the PREVU(x) test to predict CIMT. They found that CIMT was indeed highest among individuals in the highest quartile of skin cholesterol levels. The correlation held up even when statistical analysis controlled for other risk factors.
The PREVU(x) test requires only two drops of solution placed on the palm of the hand. The first, digitonin, binds to skin cholesterol. The second contains an enzyme substrate that allows readout with a spectrophotometer. The test can be performed in minutes. PREVU(x) is marketed by McNeil Consumer Healthcare and approved for use in North America and Europe. The manufacturer has also announced plans for a quantitative laboratory-based version and a semiquantitative home-based version.
All of these new, noninvasive tests for atherosclerosis risk will make it easier, and hopefully more cost-effective, to anticipate and intervene upon one of the worlds most prevalent disease processes.
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