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Leo
P. Lawler, MD, FRCR1
1The
Russell H. Morgan Department of Radiology and Radiological
Science,
Johns Hopkins Medical Institutions,
600 N. Caroline Street,
Baltimore,
Maryland, MD 21231
Introduction
Coronary
artery disease remains one of the leading causes of mortality
and morbidity for women in the western world. In recent
decades there has been significant progress in the therapies
aimed at the limitation of ischaemic insults and the salvage
of function in infarcted myocardial tissues. Most people
accept that it is preferable to arrest the atherosclerotic
process before it gets to this point of vascular compromise.
Fifty percent of those who suffer a myocardial infarction
(MI) have no prior history of cardiac disease and conventional
risk factors fail to predict one third of those who subsequently
suffer a cardiac event. Coronary calcium is specific for
atherosclerotic plaque and can be detected with high sensitivity
and accurately quantified by computed tomography (CT) to
help predict future cardiac events related to coronary artery
disease. This article will discuss the evolution of coronary
artery calcium imaging as it pertains to atherosclerotic
heart disease in women.
Keywords. Coronary,
calcification, computed tomography, scoring.
Women
and coronary artery disease
Many
of the theories and therapies of coronary artery disease
may be applied equally to men and women. However one must
bear in mind that gender differences in pathophysiology
may influence the distribution of disease among the sexes,
its detection and the response to therapy. The leading cause
of death in U.S. women is cardiovascular disease with 500,000
dying annually and 250,000 of these deaths are ascribed
to myocardial infarction (MI) . Between 35 and 64 years
of age only 0.2% of women will have experienced a non-fatal
myocardial infarction but by age 70, 15-20% of women will
have experienced a manifestation of coronary artery disease
. The average age for female MI is 10 years later than for
men but after age 60 one in four of each group will die
of such a cardiac event. The rate of decline of MI mortality
is falling less for women and they undergo less evaluation
and treatment than men with similar or less symptoms. It
has been suggested women may not have benefited from all
the recent advances in detection and management of coronary
artery disease [1, 6].
Diet,
weight, activity, diabetes, hypertension and dyslipedaemia
behave as similar modifiable risk factors in both sexes.
Relative estrogen deficiency is a risk factor specific to
women. Post-menopausal women lose a protective effect from
circulating estrogens and an up to 50 percent reduction
in the risk of coronary artery disease has been recognized
in healthy post-menopausal women with of oral estrogen replacement
. Smoking is one of the leading identifiable risk factors
for CAD and is more hazardous to women but their cessation
has been less than men with women more likely switch to
'low yield' brands rather than stop altogether. Smoking
is higher in female adolescents and is increasing among
young and disadvantaged females.
The
significance of cornary artery calcification
Coronary
arteries become calcified in an active and regulated process
only in those areas that are atherosclerotic. The amount
of calcium present correlates highly with histomorphometric
measurements of calcium crystals deposited . Calcification
is present in 50% of those 40-49 years and 80% of those
60-69 years though the numbers are higher in symptomatic
individuals. Crystalline calcium is deposited in fatty streaks
and in greater quantity in older people and those with advanced
lesions. In a non-linear way the amount of calcium correlates
with the amount of atherosclerosis. Though there may be
a correlation with vessel lumen compromise or plaque instability
the exact relationship is hard to define . Conversely the
absence of coronary calcification can reliably exclude the
presence of significant atherosclerotic disease and vessel
narrowing though it does not exclude the presence of fatty
streaks or non-calcified plaque. Fallavollita showed a 95%
negative predictive value for significant atherosclerotic
disease with a CT demonstrating no calcium and the predictive
values are similar in men and women. Coronary artery calcification
may be present in small lesions and its population prevalence
is higher than the expected incidence of coronary artery
disease implying there may be a threshold quantity that
represents clinical significance.
The
CT detection of coronary artery calcification
Chest
radiographs and fluoroscopy have been explored as easy and
inexpensive modalities to detect coronary calcium but both
are insensitive for detection and inaccurate in quantification.
CT, not surprisingly, has been shown to be highly sensitive
and specific in detection of coronary calcium(Figs. 1A-D).
CT
must have temporal resolution values that approximate the
40ms R-R interval of the cardiac cycle to accurately image
and quantify coronary artery calcium without motion artifact.
We cannot, as yet, image the motionless heart but the accepted
gold standard at present is electron beam CT (EBCT) with
a temporal resolution of 100ms. Most of the current principles
of imaging and clinical application of scoring relate to
the original EBCT work which was shown to be reproducible
. However EBCT is expensive and limited in availability
making it of less utility for common clinical use and an
unlikely candidate for future population screening. Single
detector sequential CT scanning with a gantry rotation time
of 1 second lacks the temporal resolution required. With
the advent of slip ring technology single, dual and multi-detector
row helical scanners with partial reconstruction algorithms
can now give up to 500ms gantry rotation times and temporal
resolution of up to 250ms. Prospective or retrospective
gating is used to image the heart in the phase of end-diastole
with least motion. We know that we can obtain reproducible
results with these non-EBCT methods [13-16] but since much
of the data to date relates to EBCT the exact meaning of
these measurements for clinical use is still a matter of
debate. It is hoped that with the constant progress in helical
scanning technology we may have a widely available tool
for routine coronary calcium imaging but standardize protocols
and techniques remain elusive.
The
CT quantification of coronary artery calcium
Plaque
histomorphometry , severity , progression and response to
therapy may be indexed to attenuation value [8, 11] but
quantification of this calcium is no simple matter. The
actual coronary artery calcium score has evolved from the
original description by Agatston et al. . After the images
are sent to a workstation regions of interest are drawn
over foci of high density, deemed to be in the coronary
arteries. A calcification is defined as a focus with a Houndsfield
unit measurement over 130 and occupying over 1mm2
or three pixels. The density is assigned a value based on
an arbitrary severity scale and is multiplied by the total
area involved. The final score for the epicardial coronary
arteries is tabulated based on a summation of all the regions
of interest over all the vessels. Scoring mechanisms have
been refined and modified and conversion equations for different
types of scanners have been developed. Some authors have
suggested other methods such as volume measurements may
be superior for calcium quantification. Consensus
on the actual scoring methods has yet to be obtained and
this is compounded by rapidly changing CT scanners and techniques.
What
do CT coronary calcium scores mean?
As
previously mentioned it is believed there is a threshold
of calcium and score that is of clinical significance. The
scores are thought to identify those at higher than expected
risk for future coronary events . Though many practice with
a philosophy that a threshold score around 100 is of significance
others believe ranges of values should be ultilized. Similarly
it is likely that similar scores in different patient populations
based on age and gender may have different significance.
For example a lower score in a young woman may imply severe
disease whereas a similar value in an older man may not
reach significance. Further studies are required to interpret
the significance of score changes over time to assess progression
or response to therapy.
Women
tend to have low scores or negative scans before the menopause.
Under 50 years of age scores over 10 are extremely uncommon
but are seen in 25% of such men. In women 50-59 years old
their scores remain significantly lower than men. From 60-69
women have scores equivalent to men 10 years younger. A
study of women 60-76 years showed that the absence of coronary
calcium was predictive of angiographically normal arteries
with sensitivity 61%, specificity 100% and 85% accuracy
. In general terms high scores are predictive of moderate
risk over the next 2-5 years of a morbid cardiovascular
event and low scores imply low risk of such an event in
a similar time period .
The
roles suggested for coronary artery calcium scoring at present
include management of acute chest pain syndrome, screening
of asymptomatic patients for risk factor assessment and
follow-up of disease progression after risk factor modification.
For the patient in the emergency room with chest pain high
calclium scores do predict the likelihood of significant
stenosis and these patients have a four fold risk of death
of infarction compared to those free of calcium . However
scoring is not recommended instead of conventional methods
of stress testing or nuclear imaging. The absence of coronary
calcium on CT has a high negative predictive value for significant
luminal narrowing and it has been suggested as a useful
tool for triage of the patient with atypical chest pain
and low pre-test probability for the presence of disease.
In screening of low-risk asymptomatic patients the role
of coronary calcium scoring is not defined but it may be
considered in association with conventional risk factors.
Ususpected high calcium scores may precipitate either more
aggressive risk factor modification or more directed pharmacologic
therapies such as cholesterol lowering medication.
Conclusion
Coronary
artery calcium scoring will be with us for the foreseeable
future. It clearly bears a relationship to the pathophysiology
of coronary artery disease and its sequelae and it is likely
that CT will continue to be the easiest way to detect and
quantify it. There are many implications for women’s cardiovascular
health and for the practice of radiology. However before
it is embraced uniformly in patient care there are questions
still to be answered. Which scanner and what scoring method
is to be the universal standard ? Is population screening
to be recommended? What are the ethical and clinical guidelines
for patients who self-refer for scoring? What are the issues
relating to radiation exposure and the discovery of incidental
findings such as lung nodules? How are the professional
and financial interests of radiologists and cardiologists
to be reconciled? The final, consensus driven application
of this tool has yet to be defined for its potentially large
contribution to be realized.
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