Epilogue: What Do Clinicians Expect From Imagers?
Eugene Braunwald, MD, MACC*
TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Manuscript received June 17, 2005;
accepted October 11, 2005.
* Reprint requests and correspondence: Dr. Eugene Braunwald, TIMI Study Group, Brigham and Women’s Hospital, 350 Longwood Avenue, First Floor Offices, Boston, Massachusetts 02115 (Email: ebraunwald{at}partners.org).
Although the expectations of clinicians caring for patients with coronary artery disease from imagers are enormous, they are fairly straightforward. Clinicians need assistance in the identification of patients who are at very high risk of developing acute coronary events. In a large proportion of previously asymptomatic individuals, sudden coronary death or acute myocardial infarction occurs as the first manifestation of coronary atherosclerosis. Therefore, treating such events is analogous to locking the barn door after the horse has been stolen. Although such acute events were accepted as natural but unavoidable manifestations of coronary atherosclerosis in the past, it is now increasingly clear that patients experiencing these events may have subclinical disease and usually exhibit classical or novel risk factors. Clearly, the prevention of such events is now a very important goal.
Hypercholesterolemia, hypertension, cigarette smoking, and diabetes mellitus were identified as risk factors for coronary disease about 50 years ago. The modern integration of these risk factors together with age and gender into the Framingham risk score allows classification of patients into low-, intermediate-, and high-risk categories for the likelihood of development of acute coronary events (1) (Fig. 1).
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Figure 1 Risk stratification in coronary disease. The standard risk stratification allocates subjects to low-, intermediate-, and high-risk categories. High risk is traditionally considered to be >2% per year. However, since such patients may also include those at very high annual risk (>15%), the latter deserve to be placed into a separate category. Identification of a very-high-risk category will require development of imaging techniques aimed at the detection of unstable coronary plaques.
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Individuals with a risk of developing an acute coronary event over the next decade of up to approximately 5%, or <0.5% per year, are arbitrarily considered to be at "low" risk. Those who carry a risk of 5% to 20% over a 10-year period (0.5% to 2% per year) are at "intermediate" risk. And those with an acute coronary event rate of more than 20% over a decade (>2% per year) are generally considered to be at "high" risk (2).
Almost half of the adult population in the U.S. and Western Europe belongs to the low-risk group. A common example of a low-risk person would be a 40-year-old woman without any detectable risk factors. Such individuals should receive lifestyle advice and serial follow-up. Because of the great prevalence of this low-risk population, the total number of actual coronary events in them is high and a variety of genomic and proteomic approaches to further risk stratify this group are now under intense investigation.
Approximately 40% of the population is at intermediate risk. A typical individual in this category would be a 55-year-old man with hypertension who is a nonsmoker and does not have hypercholesterolemia, diabetes, or a family history of coronary disease. In such individuals, additional testing may be helpful to aid in further risk stratification (Fig. 2). For example, determining the high-sensitivity C-reactive protein (hsCRP) level is a simple inexpensive test that is helpful in this regard (3). The ankle-brachial index also is a relatively inexpensive test and is not time or labor intensive and can add further information (4). Such additional testing may allow reclassification of intermediate-risk patients into either low- or high-risk categories. For instance, if the hypertensive man described above exhibits a low hsCRP concentration, <1 mg/l, he may be reclassified as low risk and be a candidate for control of hypertension and follow-up, whereas if his hsCRP is elevated, >3 mg/l, this would place him into a higher risk category. Ultrasonographic measurement of the carotid artery intimal-medial wall thickness (5), the "coronary calcium score" derived from electron-beam computerized tomography (6), or magnetic resonance imaging of the thoracic aorta and the walls of the carotid arteries and the proximal coronary arteries (7,8) also may be useful. However, the accuracy and cost-effectiveness of these more expensive imaging tests in large populations has yet to be determined.
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Figure 2 Proposed algorithm for the detection of plaques likely to result in acute coronary syndromes. After the initial stratification into low-, intermediate-, and high-risk categories, using the Framingham risk score (FRS) and defined by the estimated event rate per year, identification of patients at very high risk will need development of tests that characterize vessel wall and identification of vulnerable plaques (VP), not simply luminal obstruction. Inter = intermediate; F/U = follow-up; V. = very; New Rx = new treatment modes.
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The high-risk category includes the remaining one-sixth of the adult population. Such individuals are known to have coronary, cerebral, or peripheral vascular disease or to suffer from diabetes mellitus or renal dysfunction. This category may also include patients upgraded from intermediate risk by additional testing. Patients identified as being at high risk should receive intense global risk factor reduction. In addition, these patients need further stratification to identify those with vulnerable plaques who are at very high risk (>15% acute coronary events per year). Identification of these "accidents waiting to happen" is a key goal for coronary artery imaging.
A number of new potent agents to suppress the inflammation that leads to rupture of vulnerable coronary plaques are now on the horizon, but it is unlikely that their systemic administration will be free of risk and therefore they will have to be used selectively. Other radical strategies to protect "vulnerable patients" could involve the implantation of multiple drug-eluting stents, or even coronary surgery to bypass multiple unstable plaques in the proximal coronary arterial tree. Obviously, careful risk-benefit analyses will need to be carried out with these therapeutic approaches. In the near term, imaging to identify multiple high-risk vulnerable plaques will require an invasive approach to be incorporated into the coronary arteriographic examination. Given the multicentricity of vulnerable plaques (9), the proximal segments of all three major coronary arteries will have to be examined. This accomplishment appears to be within reach using the technology discussed in this Supplement. The ultimate goal, however, will be to identify such plaques by noninvasive imaging. Such an achievement, which still seems far off, could be the real solution to this critical medical problem. Thus, clinicians’ expectations of the imagers are very high indeed; close collaboration of these two groups to reach this important goal is of the utmost importance.
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References
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1. Wilson PW, D’Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories Circulation 1998;97:1837-1847.[Abstract/Free Full Text]2. Wood D, De Backer G, Faergeman O, et al. Prevention of coronary heart disease in clinical practicerecommendations of the Second Joint Task Force of European and Other Societies on Coronary Prevention. Eur Heart J 1998;19:1434-1503.[Free Full Text] 3. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention Circulation 2003;107:363.[Free Full Text] 4. McDermott MM, Greenland P, Liu K, et al. The ankle brachial index is associated with leg function and physical activity. The Walking and Leg Circulation Study Ann Intern Med 2002;136:873.[Abstract/Free Full Text] 5. O’Leary DH, Polak JF, Kronmal RA, et al. Cardiovascular Health Study Collaborative Research group Carotid artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults N Engl J Med 1999;340:14.[Abstract/Free Full Text] 6. Keelan PC, Bielak LF, Ashai K, et al. Long term prognostic value of coronary calcification detected by electron-beam computed tomography in patients undergoing coronary angiography Circulation 2001;104:412.[Abstract/Free Full Text] 7. Stuber M, Botnar RM, Fischer SE, et al. Preliminary report on in vivo coronary MRA at 3 Tesla in humans Magn Reson Med 2002;48:425.[CrossRef][Web of Science][Medline] 8. Fayad ZA, Fuster V. Clinical imaging of the high-risk or vulnerable atherosclerotic plaque Circ Res 2001;89:305-316.[Abstract/Free Full Text] 9. Rioufol G, Finet G, Ginon I, et al. Multiple atherosclerotic plaque rupture in acute coronary syndromea three-vessel intravascular ultrasound study. Circulation 2002;106:804-808.[Abstract/Free Full Text]
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