Pii: s0002-9149(01)01712-x

Coronary Plaque as a Replacement for
Age as a Risk Factor in Global
Risk Assessment
Risk assessment is assuming an increasing role for iden-
scoring, however, is that age becomes the dominant risk
tification of high-risk persons for intensive medical inter-
factor after age 50. Age is a surrogate for coronary
vention to reduce risk for coronary heart disease (CHD).
atherosclerotic plaque burden, which is the true risk
Of particular importance is the need to identify those
factor. However, for individuals, coronary plaque bur-
persons with CHD risk equivalents who can be managed
den can vary greatly at any given age. For this reason,
with the same intensity as patients with established CHD.
if coronary plaque burden could be measured accu-
For example, the National Cholesterol Education Pro-
rately with noninvasive techniques, the degree of plaque
gram (NCEP) recently classified diabetes as a CHD risk
burden could be used to replace age as a risk factor in
equivalent. The NCEP also recommended use of Fra-
Framingham scoring for risk prediction. This article de-
mingham risk scoring in persons with multiple (2؉) risk
scribes a technique whereby such a replacement can be
factors to uncover others without diabetes who have
made. ᮊ2001 by Excerpta Medica, Inc.
CHD risk equivalents. One limitation of Framingham risk
Am J Cardiol 2001;88(suppl):8E–11E
Advances in preventive cardiovascular medicine years).2,3 The number of people with CHD risk equiv-
make it possible to substantially reduce the risk alents in the general population probably exceeds the for acute coronary syndromes accompanying coronary plaque rupture. These syndromes include unstable an- There are 3 categories of individuals who carry gina and acute myocardial infarction and their com- CHD risk equivalents. First, there is a category of plications. Medical modalities of prevention include individuals with other clinical forms of atherosclerotic several pharmaceutical agents: aspirin, cholesterol- disease—peripheral arterial disease, abdominal aortic lowering drugs, angiotensin-converting enzyme inhib- aneurysm, and symptomatic carotid artery disease.3 itors, and ␤-adrenergic blocking agents (␤-blockers).1 Risk for acute coronary syndromes in such affected Additional risk reduction can be achieved by favor- patients equals that of patients with established CHD.
able changes in life habits—smoking cessation, anti- This high risk for CHD reflects the generalized nature atherogenic diet, weight reduction, and increased of the atherosclerotic process. Second, there is also a physical activity. The combination of these life-habit growing view that persons with diabetes belong in the and drug modalities has been strongly recommended category of CHD risk equivalents.3,4 Diabetes, itself, for patients with established coronary heart disease imparts increased risk for CHD. More importantly, (CHD).1 They also offer similar benefit for persons however, diabetes usually associates with other risk who do not have manifest CHD but who are at high factors that combine to increase risk for CHD. Type 2 risk for developing CHD (high-risk primary preven- diabetes, in particular, is a condition of multiple risk factors. Other factors further contribute to a poor Because of the potential for risk reduction in per- outcome for persons with diabetes. For example, the sons at high risk, the identification of candidates for presence of diabetes increases the likelihood of dying high-risk primary prevention becomes a requirement with acute coronary syndromes; moreover, it worsens for preventive medicine. At highest priority are per- the prognosis in the long term after acute myocardial sons without CHD, whose absolute risk for acute infarction.4 The high risk before onset of CHD and the coronary syndromes is as high as that for patients with poor outcomes after onset combine to raise diabetes to established CHD. Such persons can be said to have CHD risk equivalents. Recent evidence indicates that A third category of CHD risk equivalents includes high absolute risk for myocardial infarction and cor- persons who have the following characteristics: (1) onary deaths (hard CHD), which defines a CHD risk multiple risk factors other than diabetes and (2) a equivalent, is Ͼ2% per year (or Ͼ20% per 10 10-year risk for hard CHD Ͼ20%.2 A challenge forprimary prevention is to reliably identify these high- From the Departments of Clinical Nutrition and Internal Medicine, risk individuals for intensive medical intervention.
Center for Human Nutrition, University of Texas Southwestern Medical The most widely used method of detection is “global” Center at Dallas, Dallas, Texas, USA.
risk assessment. This assessment uses risk-scoring Address for reprints: Scott M. Grundy, MD, PhD, Center for tables based on multiple risk factors to determine Human Nutrition, Departments of Clinical Nutrition and Internal Med- absolute risk for CHD in the short term (ie, icine, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9052. E-mail: years). Researchers for the Framingham Heart Study5 and the Prospective Cardiovascular Mu¨nster (PRO- CAM) study6 developed 2 sets of risk tables for esti- than is given by age alone. Development of methods mating absolute risk. The defining risk factors for for estimating coronary plaque burden thus offers the Framingham risk scores are (1) age, (2) cigarette possibility of replacing age as a risk factor with a smoking, (3) blood pressure, (4) total cholesterol, (5) measure of plaque burden.12 This measure could be high-density lipoprotein cholesterol, and (6) diabetes.5 incorporated into Framingham risk scores in place of Diabetes can be removed from this list because it age. Risk prediction should then be improved.
already constitutes a CHD risk equivalent. Currently Several methods are available for estimating coro- available Framingham algorithms5 relate risk factors nary plaque burden. One approach is to detect myo- to “total” CHD, which includes angina pectoris as an cardial ischemia resulting from advanced coronary endpoint in addition to hard CHD endpoints. A Fra- atherosclerosis.13 Ischemia can be identified by stan- mingham scoring table that uses hard CHD as an dard exercise electrocardiogram. Predictive power is outcome is needed to define a CHD risk equivalent in highest in middle-aged men who have risk factors. It persons with multiple risk factors. Modified risk scor- is less reliable for young adults without risk factors ing for hard CHD based on Framingham data has been and for women. A positive exercise test in a middle- aged man carries a 12-fold increase in risk for devel- (AHA),7 and more recently by the National Choles- opment of angina pectoris and a 4-fold increase in risk terol Education Program.3 In fact, Framingham scor- for acute myocardial infarction, compared with a neg- ing for hard CHD has recently been shown to be ative test. This risk is so high that it equates to a CHD “transportable” to other populations in the United risk equivalent, independently of particular risk fac- States.8 Thus, Framingham scoring can be accepted tors. A more sensitive indicator of myocardial isch- for global risk assessment to identify CHD risk equiv- emia is stress myocardial perfusion imaging (single- alents in most populations in the United States. Al- photon emission computed tomography). A positive though new Framingham algorithms for risk assess- test likewise denotes high risk for major coronary ment are currently under development, those reported events. Thus, detection of myocardial ischemia by any for hard CHD by the AHA7 can be used for present type of stress testing justifies a diagnosis of CHD risk equivalent and calls forth the need for intensive med- One of the more prominent features of Framing- ical intervention to reduce risk. Although detection of ham scoring is the increase of risk with advancing myocardial ischemia is a robust approach to detection age.5 Indeed, after 50 years, age becomes the predom- of high-risk patients, it has 2 major limitations: (1) inant risk factor. Although several factors contribute only the limited number of asymptomatic persons with to higher risk for acute coronary syndromes in older very advanced plaque burden are detected, and (2) persons, the major factor almost certainly is an in- detection by the most sensitive method, myocardial creasing coronary plaque burden with advancing age.
perfusion imaging, is unduly expensive for routine Coronary atherosclerosis develops slowly but progres- sively throughout life. Many older individuals have Another approach to estimating coronary plaque accumulated a considerable plaque burden by the time burden is indirect (ie, detection of atherosclerosis in they reach later middle age. Men develop coronary other arterial beds). Advanced atherosclerosis in pe- atherosclerosis more rapidly than women, but after ripheral arteries can be identified by the ankle– bra- menopause, women, too, begin to accumulate substan- chial blood pressure index.14 When the ratio of blood pressure measurements at the ankle over the brachial The likelihood of developing acute coronary syn- artery is Ͻ0.9 in either leg, advanced peripheral ath- dromes correlates with the severity of coronary plaque erosclerosis is usually present. A low ankle– brachial burden. Much of the plaque that develops throughout index typically correlates strongly with advanced cor- life becomes covered with a thick fibrous cap. This onary atherosclerosis and is a powerful predictor of thick cap protects the plaque against rupture. None- acute coronary syndrome. In fact, a low ankle– bra- theless, advanced plaques often contain regions vul- chial index warrants the diagnosis of CHD risk equiv- nerable to rupture.9 These are regions where the fi- alent and thus overrides Framingham risk scoring.
brous cap is thin and covers a lipid-rich zone. Here, Another way to estimate coronary plaque burden the fibrous cap is prone to rupture. When rupture indirectly is by measurement of carotid intimal-medial occurs, it precipitates thrombosis in the coronary lu- thickness (IMT) with B-mode sonography.14 In- men, and depending on the degree of resulting occlu- creased IMT denotes carotid atherosclerosis and cor- sion, unstable angina or myocardial infarction results.
relates with increased coronary atherosclerosis.15 In Follow-up monitoring of patients who have undergone fact, carotid IMT predicts major coronary events in- coronary angiography reveals that the likelihood of dependently of other risk factors.16 Hence, elevated having an acute coronary syndrome is proportionate to IMT, theoretically, could replace age as a risk factor in the extent of coronary plaque burden.10,11 Because older persons usually have a greater plaque burden A more direct measure of coronary plaque burden than younger people, older persons are more likely to is coronary calcium. Electron-beam computed tomog- experience acute coronary syndromes.
raphy (EBCT) or spiral computed tomography can If the coronary plaque burden could be accurately detect and measure coronary calcium. Most experi- measured, it should provide a better indicator of the ence has been accrued with EBCT, whereas spiral probability of developing an acute coronary syndrome computed tomography is still under investigation. The A SYMPOSIUM: FIRST INTERNATIONAL SAI MEETING TABLE 1 Replacement of Framingham Risk Points for Age with Coronary Calcium Scores for Men and Women
extent of coronary calcium correlates with the severity factors were identified and quantified at the beginning of coronary atherosclerosis. Both autopsy studies and and were left untreated over the duration of study.
angiographic measurements indicate that coronary Unfortunately, any prospective study that adds coro- calcium scores are a reliable indicator of coronary nary calcium scores to the mix of predictive risk plaque burden.17–19 This allows coronary calcium to factors is no longer feasible. First, major coronary risk be used to replace age as a risk factor in Framingham factors cannot ethically be left untreated for long periods. For this reason, long-term effects of each risk In recent years, coronary calcium scores have been factor on CHD risk can no longer be determined.
measured in a large number of men and women with- Second, many investigators believe it is not ethical to out CHD. These scores can be arranged in percentiles withhold coronary calcium scores from study partici- according to age and sex.20 Depending on the percen- pants. Although the morality of this position can be tile, the coronary calcium score can variably replace debated, once people learn their coronary calcium age points in Framingham scoring. Table 1 illustrates scores, they often take steps to modify their risk. This a method for making this transformation. In the gen- action will ruin a prospective study. A good solution eral US population, mean coronary calcium scores to the problem of integrating coronary calcium scores shift upward by about 1 quartile for every decade Ͼ50 with risk factor in risk assessment is to replace age as years of age. This allows replacement of Framingham a risk factor with coronary calcium scores. This con- age points3 according to the percentile of coronary servative approach takes advantage of the weakness of age as a risk factor and makes use of a more robust Replacement of age as a risk factor should be particularly valuable in older persons. Although risk There is a growing consensus that “quantitative” increases progressively as plaque burden accumulates, risk assessment based on global risk equations, such rates of accumulation vary greatly from person to as those developed by Framingham, improves the person. Thus, assigning the same number of Framing- selection of patients for intensive medical interven- ham risk points to all individuals of the same chrono- tion. The use of coronary calcium scores represents an logic age ignores the great variation in plaque burden attractive addition to global risk assessment for this at a given age. Coronary calcium scores help to cor- purpose. This approach was examined in detail by the rect for this variation. More accurate estimates of Prevention V Conference of the AHA.25 The confer- plaque burden using coronary calcium scores should ence examined a variety of methods for noninvasive therefore improve risk prediction in older persons. An assessment of coronary plaque burden to improve risk improvement in risk prediction in older persons would prediction. It identified coronary calcium scores as a be particularly valuable in view of evidence from promising method. The summary of the conference recent clinical trials that medical intervention reduces stressed the need to integrate coronary calcium scores risk for acute coronary syndromes in older persons as with other risk factors in predicting global risk.25 It well as in middle-aged individuals.21–23 further emphasized that coronary calcium scores Some investigators have expressed skepticism should be prescribed exclusively by physicians as a about the utility of coronary calcium scores in risk component of total risk assessment. This physician- prediction, and especially whether they provide pre- based approach should be distinguished from “coro- dictive power independently of the major risk fac- nary calcium screening,” which may lead to interven- tors.24 The claim is made that what is needed is a new tion strategies that fail to appropriately match intensity Framingham Heart Study in which coronary calcium scores are included in a prospective study along with Recently the American College of Cardiology26 other major risk factors. The Framingham Heart Study evaluated the role of coronary calcium scores in the was carried out over a period of many years; risk diagnosis and treatment of CHD. The major conclu- 10E THE AMERICAN JOURNAL OF CARDIOLOGYா
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A SYMPOSIUM: FIRST INTERNATIONAL SAI MEETING

Source: http://www.ctmrvoitsberg.at/heartrisk/programm/Vati.pdf