Introduction
Cardiovascular disease is the leading
cause of mortality for women in the
United States
. Although US men have experienced a decline in CAD deaths,
the number of coronary deaths in women, >240 000 annually,
has remained stable or has increased. CAD,
which increases with advancing age, also is a substantial
cause of morbidity and disability for US women. Women, in
particular young women (<55 years), have a worse
prognosis from acute MI than their male counterparts,
with a greater recurrence of MI and higher mortality. Furthermore,
women have less favorable near-term outcomes after
myocardial revascularization procedures than do their male
peers. An effective diagnostic
strategy is critical in women at risk because up to 40% of
initial cardiac events are fatal.
A consistent body of evidence documents
that women are less likely than age-matched men to have
obstructive CAD; in particular, triple-vessel or left main
CAD is more common in men, even though more women than men
die from CAD. The high
prevalence of nonobstructive CAD and single-vessel disease in
women results in an observed decreased diagnostic accuracy
and higher false-positive rate for noninvasive testing in
women versus men. Physicians
may choose from a wide range of diagnostic modalities, but
the accuracy and limitations of stress testing in women
patients remains an area of significant confusion.
Role of CT Measurements of Coronary
Calcification in the Diagnosis and Risk Assessment of Women With
Suspected CAD
Coronary CT
detects and quantifies the amount of
coronary artery calcium (CAC), a marker of
atherosclerotic disease burden, via either electron beam
tomography (EBT) or multidetector CT (MDCT). However
some limitations remain for MDCT (including slower speed
of the acquisition [EBT 50 to 100 ms, MDCT 200 to 330 ms],
higher radiation dose [EBT dose 0.7 mSv, MDCT dose 1.5 to 1.8
mSv], and possibly greater interscan variability of measurement [EBT
11% to 16%, MDCT 23% to 35%]).
Calcification does not occur in a normal
vessel wall, thus signifying the presence of atherosclerosis;
however, it is not specific for luminal obstruction. CAC
scores approximate the total atherosclerotic plaque burden.
Data specific to symptomatic women include a report on a
cohort including 539 women (mean age 60±16 years) undergoing
clinically indicated angiography. Among the 220 (41%) women
with a normal coronary arteriogram, none had detectable CAC,
yielding a
negative predictive
value of 100%. In contrast, women with moderate (
100)
or higher (400)
CAC scores had a greater prevalence of obstructive coronary
disease.
Sex and age distributions of the presence
and severity of CAC have been published. For women, the
prevalence of CAC is low premenopausally, but in general,
across age deciles,
prevalence
lags by
10
years when compared with their male counterparts.
Risk
Assessment
The greatest potential for CAC detection could be as a marker for
CAD prognosis in asymptomatic women, beyond the prognostic information
supplied by conventional coronary risk factors. Since the
2000 ACC/AHA expert consensus document on EBT noted inconclusive
risk-stratification evidence on CAC scanning, a number of
studies primarily composed of men have reported that the
presence and severity of CAC has independent and incremental value
when added to clinical or historical data in the estimation of
death or nonfatal MI. Included
among these is one study estimating total mortality that is
notable for the inclusion of a large number of women. In a
cohort of 10 377 asymptomatic individuals (including >4000
women) undergoing CAC measurement with EBT (with a mean
follow-up of 5.0 years), the extent of
CAC
was an independent and incremental estimator of
all-cause mortality over and above an estimate of the FRS determined
by patient history without measurement of lipids or glucose.
For women, risk-adjusted relative risk ratios for all-cause
mortality were elevated
2.5-,
3.7-, 6.3-, and 12.3-fold for calcium scores of 11 to
100, 101 to 400, 401 to 1000, and >1000, respectively
(P<0.0001), as compared with a score of
10.
Importantly, for a given CAC score, mortality rates in this
study were
3- to 5-fold higher for women than they were for men.
Thus, in 2000, the ACC/AHA
issued a joint statement that advocated the use of CAC testing as a
screening procedure for CAD risk in
selected clinically referred individuals with intermediate
clinical risk. Since then, on the basis of the evolving
literature, other guidelines and expert consensus documents
have extended this recommendation to suggest its use, or the
use of other tests of atherosclerosis burden, in
clinically
selected intermediate-CAD risk patients (eg, those with a
10% to 20% Framinghamc
10-year risk estimate) to refine
clinical risk prediction and to select patients for altered
targets for lipid-lowering therapies. Consistent with
these statements, the recent US Preventive Services Task Force
recommends against EBT scanning for either the presence of
severe coronary artery stenosis or for prediction of CAD events
in adults at low risk for CAD events.
Summary
Given the evolving literature since the last ACC/AHA Expert
Consensus statement, current data indicate that CAD risk
stratification is possible in women. Specifically, low CAC
scores are associated with a low adverse event risk, and high
CAC scores are associated with a worse event-free survival. Additional
high-quality data are needed from larger cohorts that
specifically address CAD outcomes in women to more precisely
establish female-specific CAC risk cut points and to more
precisely quantify the incremental prognostic value beyond
the measurement of conventional coronary risk factors.
Until then, consistent with recent consensus statements, CAC
testing for CAD risk detection should be limited to clinically selected
women at intermediate risk.
Beyond Secondary Prevention : Identifying the High-Risk Patient for Primary
Prevention : Executive Summary
Introduction
This conference, "Beyond Secondary Prevention: Identifying the High-Risk
Patient for Primary Prevention," which was the fifth in a series
of prevention conferences sponsored by the American Heart Association
(AHA), was held October 26–28, 1998, in San Francisco, Calif. The
need for this conference was precipitated by the remarkable advances in
medical therapies for the prevention of coronary heart disease (CHD).
The AHA has already set forth guidelines for aggressive medical
therapy in patients with established CHD (secondary prevention). The
major issue under consideration at this conference was the development
of strategies to identify high-risk patients without established CHD
who are candidates for aggressive medical therapies for primary prevention.
Therefore, a central theme for the conference was the emphasis on
establishing a prognosis for high-risk patients without clinical
evidence of CHD. Three writing groups were established to report on
the following areas: (1) medical office assessment, (2) tests for
silent and inducible ischemia, and (3) noninvasive tests of
atherosclerotic burden. Each working group reviewed research on
existing risk-assessment strategies relevant to the prediction of
risk in patients without clinical evidence of CHD.
Writing Group II Summary
The purpose of noninvasive testing for subclinical myocardial ischemia is
to detect patients who have been found to be at intermediate risk by
office-based risk assessment and identify those who are candidates
for more aggressive risk-reduction therapies. Several studies in
middle-aged men in this category have documented that exercise ECG
has independent power for predicting major coronary events and may be
a useful adjunct in identifying high-risk patients who otherwise
would be classified as being at intermediate risk. On the other
hand, exercise ECG has little use in the routine screening of young
adults who as a group are at low risk for developing CHD in the next
decade. Furthermore, its predictive power in older men (>75 years)
and women is uncertain. Ambulatory ECG apparently is less
sensitive than exercise ECG for detecting myocardial ischemia, and
its use for risk adjustment cannot be recommended at this time. SE
appears to add little prognostic/diagnostic information to exercise
ECG in middle-aged men but may have utility for adjusting risk
assessment in women and older men (>75 years), in whom the
predictive power of exercise ECG is uncertain. The same can be said
regarding myocardial perfusion imaging. PET scanning may detect
myocardial ischemia in the presence of less severe degrees of
coronary atherosclerosis than can be detected by exercise ECG;
however, its lack of availability and high cost seemingly do not
justify PET scanning of intermediate-risk patients whose exercise
ECGs are normal.
Writing Group III: Noninvasive Tests of
Atherosclerotic Burden
Writing Group III examined techniques used to estimate atherosclerotic burden
for the purpose of risk prognostication. The ankle/brachial blood
pressure index (ABI) emerged as a powerful, independent predictor of
future coronary events. Several reports further indicate that
measures of carotid intimal-medial thickness (IMT) by B-mode
sonography provide an independent assessment of coronary risk.
Finally,
measures of coronary calcium by computerized tomography (CT) show a
high correlation with extent of coronary atherosclerosis.
Furthermore, preliminary studies suggest that coronary calcium scores
provide an independent estimate of future coronary events; however,
available studies are insufficient to define the magnitude of
independent prediction. Overall, noninvasive procedures for
assessing myocardial ischemia and atherosclerotic burden promise to
improve the accuracy of risk prognostication for patients found to be
at intermediate risk by office-based assessment.
Pathology studies document that the levels of "traditional" risk
factors are associated with the extent and severity of atherosclerosis. However,
at every level of risk factor exposure, there is substantial variation
in the amount of the atherosclerosis. Thus, subclinical disease
measurements, representing the end result of risk exposures, may be
useful in improving CHD risk prediction.
Coronary Calcium Scores in CAD Risk Assessment
Calcification within the coronary arterial wall is a recognized marker
of atherosclerosis. EBCT and helical CT are highly sensitive means of
detecting coronary calcium and are being intensively evaluated as
noninvasive means of defining coronary atherosclerotic disease and
identifying the asymptomatic but high-risk CAD patient. There
are, however, relatively few prospective data linking coronary
calcium scores with risk of subsequent CHD events. Data concerning
risk prediction with EBCT in asymptomatic people (the primary focus
of the Prevention V conference) are sparse.
Conclusions
The presence of coronary calcium correlates strongly with coronary atherosclerosis.
Because the severity of coronary atherosclerosis (from pathological
or angiographic studies) is well known to be associated with risk of
coronary events, coronary calcium scores likewise should correlate
with risk for coronary events. However, the extent to which
coronary calcium scores predict coronary events independently of the
traditional coronary risk factors needs additional study. This latter
uncertainty must be weighed against the costs of measurement and the
risk that the results of the tests may create enough concern for
patients and their physicians to lead to inappropriate and invasive
coronary evaluation. Because of these uncertainties and concerns, the
writing group was reluctant to advocate the use of EBCT for routine
risk assessment in spite of the promise of the technique. The
greatest potential for coronary calcium scores would appear to be in
the detection of advanced coronary atherosclerosis in patients at
apparently intermediate risk. Conversely, low or absent coronary
calcium scores may prove valuable in determining a low CAD event
risk. Some clinicians and researchers currently recommend use of the
coronary calcium score in risk assessment in these ways. Selected
use of coronary calcium scores when a physician is faced with a
patient with intermediate coronary disease risk may be appropriate.
MRI and Atherosclerotic Disease
There has been increasing awareness of the importance of composition of
atherosclerotic plaque as a major risk factor for acute coronary syndromes.
MRI has been shown to characterize tissue noninvasively in many
different study systems. Therefore, research has begun to focus on
the use of in vivo MRI to evaluate the vessel wall in several animal
models and in humans.
Conclusions
MRI is a promising research tool, but its use appears limited to only
a small number of research laboratories at this time. The writing
group concluded that MRI is not ready for application in the
identification of patients at high risk for CAD.
Prevention V Conference Writing Group Members
Sidney C. Smith, Jr, Prevention V Conference Chair
Writing Group III: Philip Greenland, Chair; Jonathan Abrams, Gerard
P. Aurigemma, M. Gene Bond, Michael H. Criqui, Luther T. Clark, John
R. Crouse, Lawrence Friedman, Valentin Fuster, David M. Herrington,
Lewis H. Kuller, Paul M. Ridker, William C. Roberts, William
Stanford, Neil Stone, H. Jeremy Swan, Kathryn A. Taubert, Lewis
Wexler.
