Risk Stratification in Coronary Artery Disease: Implications for Stabilization and Prevention

10 Q1997 by Excerpta Medica, Inc. 0002-9149/97/$17.00All rights reserved. PII S0002-9149(97)00380-9

/ 2z0e 7503 Mp 10 Wednesday Jun 25 08:58 AM EL–AJC-S (suppl 7500 ’97) 7503

Risk Stratification in Coronary ArteryDisease: Implications for Stabilization

and PreventionDaniel Berman, MD, Rory Hachamovitch, MD, Howard Lewin, MD, John Friedman, MD,

Leslee Shaw, PhD, and Guido Germano, PhD

Noninvasive nuclear imaging techniques, includingdual-isotope myocardial perfusion single-photon emis-sion computed tomography (SPECT), have been em-ployed in the development of strategies for diagnosisand risk stratification of patients with suspected orknown coronary artery disease. These risk-stratificationstrategies are based on studies in which known outcome

has been linked to diagnostic and prognostic informa-tion provided by myocardial perfusion SPECT. This arti-cle describes a validated dual-isotope exercise protocolfor assessment of perfusion and function and reviewsthe evidence on which a cost-effective risk managementstrategy is based. Q1997 by Excerpta Medica, Inc.

Am J Cardiol 1997;79(12B):10–16

The application of cost-effective strategies for thediagnosis and risk stratification of patients with

coronary artery disease (CAD) is a key issue in thepractice of cardiology today. Although improvedmedical and surgical therapies have led to an overalldecrease in mortality from acute coronary eventssince the 1960s,1 myocardial infarction (MI) remainsthe leading cause of death in the United States.2 Sig-nificantly, 48% of men and 63% of women dyingsuddenly from acute coronary events have not pre-viously been identified as having CAD.2 At the sametime, many patients with clear signs and symptomsof CAD do not go on to experience acute coronaryevents.

These observations suggest that earlier diagnosisand more reliable prognostic information might havea beneficial impact on CAD morbidity and mortalityby allowing accurate stratification of an individualpatient’s cardiac risk. However, the practicing cli-nician is faced with many questions related to theprevention of CAD mortality: (1) which patients willbenefit from early diagnosis and preventive care; (2)which patients should be referred for more extensiveevaluation; and (3) which evaluation strategies pro-vide the most reliable risk-stratification informationin the most cost-effective manner? This investigationdescribes a cost-effective protocol for CAD diag-nosis and risk stratification using myocardial perfu-sion scintigraphy; it also reviews the research uponwhich this risk-stratification strategy is based.

DUAL-ISOTOPE MYOCARDIALSCINTIGRAPHY

Myocardial perfusion scintigraphy performedwith rest thallium-201/exercise technetium-99m (Tc-99m) sestamibi, separate-acquisition, dual-isotopemyocardial perfusion, single-photon emission com-

From the Division of Nuclear Medicine, Cedars–Sinai Medical Cen-ter, Los Angeles, California.

Address for reprints: Daniel Berman, MD, Division of NuclearMedicine Cedars–Sinai Medical Center, 8700 Beverly Boulevard,Los Angeles, California 90048-1865.

puted tomography (SPECT) is an efficient, reliabletechnique for assessment of coronary artery dis-ease.3–5 Briefly, the procedure involves injectingthallium-201 at rest, performing rest thallium-201SPECT 10 minutes after thallium administration, fol-lowed by a symptom-limited exercise treadmill test(ETT) using the standard Bruce protocol.

b-Blocking agents and calcium channel antago-nists are discontinued 48 hours before testing, if pos-sible, and nitrates are discontinued 6 hours beforetesting. Maximal degrees of ST-segment change af-ter the J point on the ECG are measured and assessedas horizontal, upsloping, or downsloping. ExerciseECG responses are considered to be uninterpretableif the patient is taking digoxin, or has indications ofa paced ventricular rhythm or left ventricular hyper-trophy, nonspecific ST-T wave changes, left or rightbundle branch block, or Wolff-Parkinson-White syn-drome. At near maximal exercise, Tc-99m sestamibiis injected, and Tc-99m sestamibi SPECT is per-formed 15–30 minutes later.

Our SPECT studies are performed with a scintil-lation camera/computer system equipped with ahigh-resolution collimator. Two energy windows(30% centered on 68–80 keV; 10% centered on 167keV are used for thallium-201; 1 energy window(15% centered on 140 keV) is used for Tc-99m ses-tamibi; details of this procedure have been previ-ously described, as have quality control measures.5

For optimal assessment of myocardial viability inpatients with resting thallium-201 SPECT defects,thallium-201 SPECT is repeated prior to exercise at4 hours after rest injection, or 24 hours after exer-cise.4 Approximately 2 years ago, we incorporatedthe routine use of gating into our myocardial perfu-sion protocol (we obtain 8 frames per cardiac cycle).The gated studies add information on left ventricularejection fraction6 and regional wall motion.7

Semiquantitative visual image interpretation ofmyocardial perfusion is performed using short-axis,and vertical and horizontal long-axis tomograms thatare displayed on transparency film at 2-pixel thick-ness with staggered summation.3 As shown in Figure

A SYMPOSIUM: NEW PERSPECTIVES ON PREVENTION AND STABILIZATION OF CORONARY SYNDROMES 11


TABLE I Common Conditions Associated With an IntermediateLikelihood of Coronary Artery Disease*

j Asymptomatic patients with positive stress electrocardiogram(ECG)

j Nonanginal chest pain patients with positive or nondiagnosticstress tests

j Atypical chest pain patients regardless of stress ECGj Typical angina patient with negative stress ECG

*Likelihood: 10–90%Reprinted with permission from Am J Cardiol.10

1, short- and long-axis tomograms are divided into20 segments for assessment.8 Uptake at stress and atrest in each segment is scored on a scale of 0–4(where 0 Å normal uptake and 4 Å absent uptake).Scans with only scores of 0 are normal; scans withstress/rest scores of 1/1 are called probably normal.Scans with multiple-segments with stress/rest scoresof 1/0, or scores with a single-segment stress scoreof 2, are classified as equivocal; scans with 2 seg-ments with a stress score of 2 are classified as prob-ably abnormal; those with ú2 stress segments witha score of 2, or ¢1 segment with a score of 3 areclassified as definitely abnormal.

Summed stress and rest scores—defined as thetotal of stress and rest scores for all 20 segments—are also calculated.9 The summed stress score, whichreflects the extent of severity of perfusion defects,follows a 4-step rating scale: normal or equivocal(õ4); mildly abnormal (4–8); moderately abnormal(9–13); and severely abnormal (ú13). The degreeof reversibility of the perfusion abnormality is indi-cated by calculating the differences between thesummed stress and rest scores, yielding the summeddifference score. Quantitative methods for objective,reproducible assessment of the extent, severity, andreversibility of Tc-99m exercise myocardial perfu-sion SPECT have also been developed and validatedin our laboratory.10

CAD DIAGNOSISWhen considered in the context of clinical and

historical findings, data from exercise nuclear testingcan be applied to a practical strategy for the identi-fication and confirmation of CAD.10 In patients withno previous history of CAD, MI, or revascularizationprocedures, the first step is to assess the likelihoodthat the patient has CAD. Patients with a low prob-ability (õ0.15) of having angiographically signifi-cant (ú50% stenosis) CAD can be identified, evenbefore standard ETT is performed. Several ap-proaches may be used, including the validated CA-DENZA computer algorithm12—a method that de-termines CAD likelihood based on age, sex,symptom classification, and conventional cardiacrisk factors (resting systolic blood pressure, smokinghistory, glucose intolerance, resting ECG ST-seg-ment abnormalities).

Patients with a low pre-ETT likelihood of CADdo not require further diagnostic testing, althoughcontinued medical follow-up or a ‘‘watchful wait-ing’’ approach is recommended.

Patients with a low-intermediate pre-ETT likeli-hood of CAD (ú0.15 to õ0.50) should undergostandard ETT as the next diagnostic step.8,11,13–15

Those who continue to have an intermediate likeli-hood of CAD after ETT (or those with an indeter-minate ETT) and those whose pre-ETT likelihood ofCAD was in the 0.50–0.90 range (in these patientseven a negative ETT would not result in a low like-lihood of CAD) will benefit from exercise nucleartesting. The most common conditions associated

with an intermediate likelihood of CAD are shownin Table I.11,16–18

Patients with a high pre-ETT likelihood of CAD(ú0.90) are generally considered to have an estab-lished diagnosis of CAD. Thus, nuclear stress testingis typically not needed for diagnostic purposes. Nev-ertheless, these noninvasive procedures may be veryeffective in risk stratification of such patients.11,16–18

CAD RISK STRATIFICATION WITHDUAL-ISOTOPE SPECT

Diagnosis of CAD is only the first step in cost-effective clinical management. Subsequent therapeu-tic decisions may require prognostic information, orrisk stratification.16,17 In general, for purposes of riskstratification, CAD patients, whose annual risk ofcardiac death or MI is õ1%, require only medicalmanagement and do not need further risk stratifica-tion. Patients whose annual risk is ú5% are gener-ally considered candidates for revascularization andundergo catheterization (also without further riskstratification). Patients whose annual risk is in theintermediate range (1–5%) are appropriate candi-dates for noninvasive risk stratification.8,11

The prognostic value of exercise dual-isotopeSPECT scans in CAD risk stratification was dem-onstrated in an analysis of follow-up data from aconsecutive series of 2,149 patients referred for nu-clear stress testing.8 After eliminating patients lost tofollow-up, those with inadequate scan data, or thosewith percutaneous angioplasty or coronary bypasssurgery within 60 days of testing, data from 1,702patients were available for analysis. Patients weredivided into 3 groups according to prescan likelihoodof CAD—low (õ0.15); intermediate (0.15–0.85);or high (ú0.85).8

Each group was then subdivided into those withnormal or abnormal scan results. Analysis of therates of cardiac events (cardiac death or nonfatal MI)throughout a 20-month follow-up period revealed ahighly significant difference (põ0.001) between thenormal (normal, probably normal, and equivocal)and abnormal (probably or definitely abnormal) scangroups. Only 1 cardiac death and 1 nonfatal MI oc-curred among the 1,131 patients with normal scans(0.25% event rate), while 17 cardiac deaths and 26nonfatal MIs were reported in the 571 patients withabnormal scans (7.5% event rate).8 As Figure 2 il-lustrates, the SPECT results accurately predicted therisk of coronary events during the study’s 20-month

12 THE AMERICAN JOURNAL OF CARDIOLOGYT VOL. 79 (12B) JUNE 26, 1997


FIGURE 1. Assignment of myocardial regions for single-photon emission computed tomo-graphic (SPECT) images. Classification of images is described in the text. (Reprinted with per-mission from J Am Coll Cardiol.8)

FIGURE 2. Rate of cardiac events (cardiac death or nonfatal MI) throughout the follow-upperiod (¢20 { 5 months) as a function of SPECT results and prescan likelihood of coronaryartery disease (õ0.15 Å low likelihood; 0.15–0.85 Å intermediate likelihood; ú0.85 Åhigh likelihood). Solid bars Å abnormal scan results; hatched bars Å normal scan results.(Adapted with permission from J Am Coll Cardiol.8)

follow-up period.8 One notable finding was that theevent rate for patients with normal scans was low forall levels of prescan likelihood of CAD. Further-more, none of the patients with the highest prescanlikelihood of CAD had a subsequent cardiac eventduring the study period if their scan results were nor-mal.30

A subsequent analysis, in which the number ofpatients in the prescan high-likelihood group was in-creased by a factor of 5 (n Å 425), revealed that theevent rate among patients with normal scans re-mained low (0.70% per year).18 In addition, myo-cardial perfusion SPECT added significant stratifi-cation information about patients with low andintermediate risk as indicated by prescan likelihoodof CAD.17

Potential cost savings: Although the cost of usingscintigraphy as a prognostic tool for all patients atrisk for CAD would be prohibitive, dual-isotopemyocardial perfusion SPECT can be cost effective

in selected subsets of patients at intermediate risk ofcoronary events. The cost–benefit of nuclear testingwas evaluated using the 1995 Medicare reimburse-ment rates of $840 for nuclear costs and $2,800 forcatheterization costs.8

Figures 3A and B illustrate patient outcomes andcosts per cardiac event as categorized by the inter-pretability of exercise ECG responses. Assuming allpatients with abnormal scans are referred for cathe-terization, the cost of each event detected by the test-ing strategy in the prescan low-likelihood of CADgroup would be in the range of $100,000–200,000.The cost per event detected in patients in the prescanintermediate-to-high-likelihood of CAD groups(about $50,000) would be quite acceptable, however(even in today’s cost-restrictive environment), par-ticularly because not all patients with abnormal scansrequire catheterization.

Inspection of Figures 3A and B reveals that acost-effective strategy for prognostic testing is one



FIGURE 3. Outcomes in patients with interpretable (A) or uninterpretable (B) exercise ECGresponses. LK Å likelihood, INT–HIGH Å intermediate-to-high. Events Å myocardial infarc-tion or cardiac death (frequency). Costs listed per event detected using nuclear testing withineach patient subset. (Modified with permission from J Am Coll Cardiol.8)

in which the risk of events is evaluated before test-ing. Patients with a low likelihood of CAD(õ0.15) are at low risk and do not require furthertesting. Some patients at high risk clinically maybe considered for direct cardiac catheterization;and patients with intermediate risk need further as-sessment.

Thus, a practical strategy for cost-effective prog-nostic evaluation employing SPECT must first iden-tify patients with a low pre-ETT likelihood of CAD;as noted earlier, nuclear testing is of little prognosticvalue in this group.11,12,15 Patients with an interme-diate-to-high prescan likelihood of CAD can then bedivided into 2 groups, according to whether or nottheir resting ECG results would be interpretable dur-ing ETT. Nuclear studies should clearly be consid-ered in intermediate-to-high–likelihood patientswith uninterpretable ECGs (Figure 3B). ETT studiesmay be used for initial risk stratification of patients

with interpretable rest ECGs (Figure 3A). Then thosepatients with a low post-ETT likelihood of CAD donot require further testing for prognostic purposesbecause of their low event rate (1.7% throughout thefollow-up period or õ1% per year). Nuclear testing,however, is cost-effective in the subgroup of patientswith intermediate-to-high likelihood of CAD afterETT. As noted above, patients in whom clinical as-sessment clearly reveals high risk or those with med-ically refractory angina would be directly referredfor angiography.

The cost-effective strategy discussed here wastested in both men and women. While the categoriesare the same in women and men, abnormal scanshave greater impact in women.9,19

Stratification by risk of cardiac death vs MI: Prelimi-nary data suggest that it may be possible to differ-entiate risks of MI and death, allowing preventivetherapy to be tailored to the patient’s specific risk for



FIGURE 4. Event rate (myocardial infarction or cardiac death) inwomen (A) or men (B) with low or high pre-scan likelihood ofCAD as stratified by nuclear scan. *p õ0.0002, chi-square 14 vsnormal scan results; †p õ0.0001, chi-square 58 vs normal scanresults; ‡p õ0.00001, chi-square 20 vs normal scan results.19

each event. Patients with moderately or severely ab-normal scan results are at intermediate-to-high riskfor both cardiac death and MI; these patients shouldbe considered for referral for catheterization becauserevascularization could decrease their risk of death.20

In contrast, patients with normal scan results are notcandidates for catheterization because their rates forboth events are low.

Patients with only mildly abnormal scans have alow rate of subsequent mortality (0.8% per year)and an intermediate rate of MI (2.7% per year).20

Since revascularization has not been shown in anyrandomized trial to reduce the rate of nonfatal MIit is appropriate to consider management of thesepatients with prophylactic medical treatment (lipid-lowering agents, aspirin, angiotensin-converting-enzyme inhibitors, b-blockers, and so forth); theydo not necessarily need to be referred directly forcatheterization. Of course, patients with refractoryor persisting symptoms should be referred for cath-eterization.

DUAL-ISOTOPE SPECT: PROGNOSTICVALUE IN POPULATION SUBGROUPS

The prognostic value of dual-isotope SPECT hasalso been evaluated in selected population sub-groups.

Women: Sex-related differences in the prognosticvalue of SPECT evaluation have been assessed in alarge series of patients referred for nuclear testing.19

The final study group (after exclusions for patientslost to follow-up, those with missing data, and thosewith revascularization within 60 days of testing) in-cluded 2,949 men and 1,457 women.

As Figures 4A and B show, nuclear scan datawere useful in stratifying event rates in both men andwomen, but the value of risk stratification with nu-clear testing was even more pronounced amongwomen.19 The added benefit of nuclear testing wasespecially notable among women with a prescanlikelihood of CAD ú0.15. The event rates for car-diac death or MI in women with definitely abnormalscans were significantly higher than those in men (põ0.001). Furthermore, although nuclear scan dataadded significant prognostic value to the clinical andexercise data in both men and women (p õ0.0001compared to prognostic information without nuclearvariables), stratification by nuclear testing was evenmore effective in women than in men.

Patients without known CAD: The effect of SPECTtesting on patient management has been demon-strated by an evaluation of the rates of cardiac eventsand of cardiac catheterization among patients with-out known CAD.9,20,21 In 3 studies, a low rate of cath-eterization was observed in patients after normalSPECT studies. In a Cedars–Sinai Medical Centerstudy,9 õ2% of patients with normal scan resultswere referred for catheterization within 60 days afternuclear exercise testing. Given the very low eventrate in this group, the low catheterization rate is con-sidered to be an appropriate use of prognostic infor-mation. Of patients proceeding to catheterization,16% with mildly abnormal scans and 40% with se-verely abnormal scans underwent early catheteriza-tion. In general, the catheterization rates appropri-ately paralleled the cardiac event rates. However,this study also showed that event rates rose moresharply with increasing scan abnormality in womenthan in men—although the catheterization referralrate was not significantly different between men andwomen, suggesting that women with abnormal scansare not referred to catheterization as frequently asthey should be, given their risk of events.9 Howeverit still remains undetermined whether this reflectsoveruse of catheterization in men or underuse inwomen.

The prognostic value of myocardial perfusionSPECT has been compared recently in patients withsuspected CAD but without symptoms and in thosewith symptomatic ischemia. In a population of 8,228patients, of whom 4,369 were asymptomatic or hadnonanginal chest pain, those without anginal symp-toms tended to have a lower cardiac event rate thanthose with symptoms (mean follow-up, 1.9 { 5years). However, the rates of cardiac death and myo-cardial infarction were still substantial in the asymp-tomatic patient group. Furthermore, it was demon-strated that myocardial perfusion SPECT addedincremental prognostic value over clinical and ETT



assessment in patients without anginal symptoms,and that SPECT added significant information to riskstratification in all clinical risk subsets in asympto-matic patients.23

The cost effectiveness of risk stratification bySPECT in asymptomatic patients needs to be eval-uated, as it has been in symptomatic patients. Suchan evaluation will probably result in reservation ofthis application to patients who have a high prescanlikelihood of CAD on the basis of risk factor andETT assessments. In contrast, SPECT has beenshown to be cost effective for risk stratification inthe symptomatic patient with an intermediate as wellas for a high prescan likelihood of CAD.

Post-MI patients: Both low-level exercise thallium-201 scintigraphy24 and dipyridamole–thallium scin-tigraphy25 have been shown to be effective in iden-tifying the risk of subsequent MI or cardiac death inpost-MI patients before hospital discharge. Theseobservations, made more than one decade ago, havebeen confirmed more recently in a study employingadenosine–thallium SPECT.26 Recent studies havealso confirmed the application of pharmacologicstress Tc-99m sestamibi myocardial perfusionSPECT in patients after myocardial infarction. Ingeneral, it has been established that risk stratificationof patients with clinically uncomplicated myocardialinfarction can be effectively performed with myo-cardial perfusion SPECT. Patients with very smallmyocardial perfusion defects and little evidence ofdefect reversibility are characterized as being at lowrisk of subsequent cardiac events. These patients donot require further invasive management. Patientswith perfusion defects, whether reversible or non-reversible, that include ú20% of the myocardium,are at such high risk that they are likely to benefitfrom early catheterization and consideration of re-vascularization.

The benefits of catheterization are not clearly de-fined in patients with an intermediate extent of isch-emia—for example, those with ischemia that affects10–20% of the myocardium. In this subgroup, Mah-marian et al26 demonstrated that resting left ventric-ular ejection fraction could be used to define patientsat high risk for subsequent MI or death. Those withischemia in 10–20% of the myocardium and a rest-ing left ventricular ejection fraction of õ40% wereshown to be at high risk, whereas the risk of suchpatients was much lower when left ventricular ejec-tion fraction was ú40%.

Gated SPECT is a particularly effective risk-strat-ification tool in post-MI patients in this subgroupbecause it can be used not only to measure myocar-dial perfusion defects and their reversibility, but alsoto provide an automated measure of ejection frac-tion.6 The ejection-fraction measurements producedin this way are highly correlated with those obtainedby first-pass data (rÅ 0.909, põ0.001, SEEÅ 6.87).It is now possible with a rest/stress gated SPECTstudy to routinely evaluate resting ventricular func-tion, the extent of infarcted myocardium, and the ex-tent of jeopardized myocardium in patients in the

early postinfarction period since post-MI left ven-tricular ejection fraction is an important determinantof prognosis and subsequent treatment, the utility ofan easily acquired gated image may have a profoundimpact in the early triage of MI.

Ambulatory ECG monitoring and low-level ECG test-ing post-MI: The utility of ambulatory ECG monitor-ing has also been assessed in the coronary care unitfor its value in determining prognosis in the post-MIpatient. In a trial of 48-hour ambulatory ECG mon-itoring performed 5–7 days post-MI, 406 patientsunderwent ECG ambulatory monitoring as well assubmaximal ETT before discharge; left ventricularejection fractions were measured within 28 days af-ter discharge. Among the 23% of patients with isch-emia on ambulatory monitoring, the mortality rate at1 year post-MI was 12%, while among the 77% ofpatients without ischemia, mortality was only 3.9%(p õ0.009).27

Nonmaximal exercise testing did not distinguishsubgroups; however, those patients who were notable to perform the exercise test had a significantlyhigher mortality rate (16% vs 4% [positive test] vs3% [negative test]; p õ0.001). Ejection-fraction de-termination showed that patients with an ejectionfraction õ35% were significantly more likely to dieduring the first year after MI (p õ0.001). None ofthese nonnuclear post-MI tests added significantprognostic information when cardiac mortality wasthe only outcome. When nonfatal MI and unstableangina were included as outcomes in the multiplelogistic regression analysis, only ambulatory moni-toring added significant prognostic information.27

SUMMARY AND CONCLUSIONSMyocardial perfusion scintigraphy has many use-

ful applications in diagnosis and risk stratification inpatients at risk for CAD or with suspected or knownCAD. In particular, the dual-isotope (rest thallium-201/exercise Tc-99m sestamibi) SPECT described inthis review provides cost-effective diagnostic andprognostic information in certain subsets of patientswith CAD. For diagnostic purposes, nuclear testingis best reserved for patients with a low-to-interme-diate likelihood (0.15–0.50) of CAD after ETT withan ECG interpretable for ETT or before ETT withan uninterpretable ECG. In the higher range of in-termediate likelihood (0.50–0.85), direct nucleartesting may be warranted even in patients with aninterpretable rest ECG. For purely diagnostic appli-cations, patients with a high prescan likelihood ofCAD (ú0.85) are already considered to have CAD.For purposes of risk stratification, a cost-effectivestrategy that is very similar to the diagnostic strategydescribed above, has been developed. For this pur-pose, even patients with a high prescan likelihood ofCAD can benefit from testing. Those with normal ormildly abnormal scan results may be defined as hav-ing CAD that requires medical management ratherthan consideration of revascularization. Myocardialperfusion SPECT may also provide valuable prog-nostic information in subgroups of patients with



known CAD, including those who are recoveringfrom acute MI, as well as in several other subsets ofcoronary disease not described here. In general,myocardial perfusion SPECT studies are effective infurther definition of coronary event risk in patientswho have an intermediate risk of a cardiac event onthe basis of all available clinical information.

Currently, the evidence strongly supports the useof SPECT to determine prognosis in patients with anintermediate-to-high prescan risk of CAD.8,11,18 Pa-tients with normal scans are generally at low risk ofcoronary events; for these patients, risk-factor mod-ification is appropriate. For those with mildly ab-normal scans, who have a low risk of cardiac mor-tality but a somewhat higher risk of MI, aggressiverisk-factor modification might be recommended.20

Those with moderately or severely abnormal scansshould be strongly considered for referral to cathe-terization for further evaluation and appropriatetreatment.

In clinical practice, referral for cardiac catheter-ization or revascularization is influenced not only byscan results and pre- and post-ETT CAD likelihood,but also by presence of anginal symptoms at time ofevaluation and by the sex of the patient. The currentdata indicate that risk is similar in subgroups with orwithout anginal symptoms, although the presence ofanginal symptoms may double referral rates in allscan categories.23

It is also important to consider the relative risk ofCAD and the enhanced prognostic value of nucleartesting in women. Although an equal percentage ofmen and women with severely abnormal scans arereferred to catheterization or revascularization,9

these rates may represent relative underreferral. Inview of the higher risk for adverse outcomes amongwomen with severely abnormal scans,19 a more ag-gressive approach to catheterization may be war-ranted in this subgroup.

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Risk Stratification in Coronary Artery Disease: Implications for Stabilization and Prevention