The Underappreciated Impact of Heart Disease
Emil M. deGoma, MDa,*, Ronald P. Karlsberg, MDb, Debra R. Judelson, MDb, Matthew J. Budoff, MDc
aCardiovascular Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
bCardiovascular Research Foundation of Southern California, Los Angeles, California
cLos Angeles Biomedical Research Institute at Harbor-UCLA, Los Angeles, California
Article history: Received 22 January 2010; Received in revised form 3 May 2010; Accepted 5 May 2010
a b s t r a c t
The 2009 recommendations of the U.S. Preventive Services Task Force regarding mammography have called attention to
the roles of prevention and screening in promoting women’s health. We take this opportunity to raise awareness of
another devastating illness in women, ischemic heart disease, and to suggest that screening for ischemic heart disease,
by providing early detection and identifying women who would benefit most from intensified medical therapy, merits
Copyright ? 2010 by the Jacobs Institute of Women’s Health. Published by Elsevier Inc.
The 2009 recommendations of the U.S. Preventive Services
Task Force regarding mammography have called attention to the
roles of prevention and screening in promoting women’s health
(U.S. PreventiveServicesTask Force, 2009), stimulatinga national
debate over the evidence supporting existing guidelines.
Although breast cancer exacts a terrible toll among women,
ischemic heart disease has an even more devastating impact
(Table 1), warranting considerable public health resources and
novel preventive strategies. Heart disease holds claim as the
leading killer of women (Shaw, Bugiardini, & Merz, 2009),
(Centers for Disease Control and Prevention, 2009). Not simply
a disease of the elderly, heart attacks afflict 1 in 90 women age 45
1 in 240 diagnosed with breast cancer (National Cancer Institute,
2009). Despite these sobering statistics, the burden of ischemic
heart disease in women remains underappreciated. In a 2009
survey of women, approximately half correctly identified
cardiovascular disease as their leading cause of death; 1 in 2
incorrectly reported cancer as their greatest health risk, and only
1 in 6 reported cardiovascular disease as their leading health risk
(Mosca Mochari-Greenberger, Dolor, Newby, & Robb, 2010).
Minimizing the health impact of both ischemic heart disease
and breast cancer relies on risk stratification and matching
intensity of intervention to degree of risk. In patients at high risk
for cardiovascular disease, aggressive preventive measures with
lifestyle modification and pharmacotherapy including aspirin,
statins, and antihypertensive medications are used to improve
outcomes (Redberg et al., 2009; Stampfer, Hu, Manson, Rimm, &
Willett, 2000). Patient symptoms, physical findings, and stan-
dard laboratory testing alone fail to accurately diagnose either
condition; therefore, additional studies can aid in the refinement
of risk. Serial mammography remains the mainstay of early
detection of breast cancer, with one review of randomized
controlled trials demonstrating one breast cancer death averted
for every 1,339 women age 50 years invited to screening (U.S.
Preventive Services Task Force, 2009). For ischemic heart
disease, ‘‘advanced’’ metrics of risk refinement abounddimaging
studies such as coronary artery calcium scoring (CACS), coronary
computed tomography angiography, and carotid ultrasound
evaluation of intima-media thickness (CIMT) and carotid plaque;
inflammatory biomarkers including high-sensitivity C-reactive
protein and lipoprotein-associated phospholipase A2; hemody-
namic testing such as ankle-brachial index, brachial artery flow-
mediated dilatation, and finger plethysmography; and genetic
panels of associated single nucleotide polymorphisms. Welcome
additions to the growing preventive medicine toolset, CACS and
CIMT represent the most studied methods of cardiovascular
risk refinement (Table 2). An exhaustive review lies beyond the
scope of this editorial; selected, representative data from three
landmark, prospective, population-based studies are discussed
Dr. deGoma’s salary is partially funded via NIH National Heart Lung and Blood
Institute grant K12 HL083772-01.
* Correspondence to: Dr. Emil M. deGoma, 3400 Spruce Street, Penn Tower,
6th Floor Philadelphia, PA 19104.
E-mail address: Emil.deGoma@uphs.upenn.edu (E.M. deGoma).
1049-3867/$ – see front matter Copyright ? 2010 by the Jacobs Institute of Women’s Health. Published by Elsevier Inc.
Women’s Health Issues 20-5 (2010) 299–303
Both CACS and CIMT have consistently shown a positive asso-
ciation with coronary heart disease (CHD) risk. In the St. Francis
Heart Study of 4,613 healthy subjects (35% women) followed for
unadjusted relative risk of 10.2 for CHD events compared with
those with a CAC of 0 (Cook, 2007). The Atherosclerosis Risk in
CHD at baseline over a median of 5.2 years. Among the 7,289
with a relative risk for CHD events of 5.1 compared with a CIMT
below1 mm,adjustedforage andrace.Inananalysis of the Multi-
Ethnic Study of Atherosclerosis (MESA), which involved 6,698
healthy individuals (53% women) followed for a median of 3.9
years, CACS and CIMT were evaluated in the same cohort,
2.3 and per 1 standard deviation maximal CIMT was 1.1 (Folsom
et al., 2008). The results may underestimate the predictive utility
number of cardiovascular events, and the absence of plaque
the standardized protocol which increases the sensitivity and
specificity of testing (Stein et al., 2008). Among low-risk women
(10-year CHD risk <10%), an analysis of MESA further demon-
stratedthatCACSwashighlyassociated withCHDevents, yielding
an adjusted hazard ratio of 8.3 and an absolute annual risk of 1.8%
among women with a CAC above 300 (Lakoski et al., 2007).
CACS and CIMT improve discrimination for CHD above and
beyond traditional risk factors, effecting statistically significant
discrimination that fails to improve even with incorporation of
several accepted traditional risk factors (Cook, 2007). Adding
0.79 (p ¼ .0006) and from0.79 to 0.83 (p ¼ .006) in the St. Francis
MESA (Folsom et al., 2008), respectively. Incorporation of CIMT
and carotid plaque assessment increased the AUC, as well, in the
ARIC study. Among7,463 women followed fora mean of 15 years,
the AUC increased from 0.76 with traditional risk factors alone to
0.77 with the addition of CIMT and carotid plaque assessment
(95% CI for change þ0.005 to þ0.017; Nambi et al., 2010).
CACS and CIMT reclassify a substantial proportion of patients
tested, particularly among intermediate-risk patients. In other
patients between clinical risk categories, thereby suggesting
a change in management for a significant population. In MESA,
the net reclassification index with CACS was 26% in the overall
cohort and 55% among intermediate-risk subjects (5-year CHD
risk 3%–10%; Polonsky et al., 2010). Among intermediate-risk
patients, 39% were classified as low risk (<3%) and 16% were
classified as high risk (>10%). In the ARIC study, using four risk
>20%), the net reclassification index with CIMT and plaque
assessment was 9.8% in the overall female cohort and 25.4%
among intermediate-risk women (10-year Framingham CHD risk
5%–20%; Nambi et al., 2010). Among intermediate-risk women,
Through CHD risk refinement, preliminary data suggest CACS
improves the direction of efficient population-based care. The
randomized clinical trial of the St. Francis Heart Study (n ¼ 1,005;
27% women) concluded that statin therapy administered to
patients with a CAC over 400 leads to a relative risk reduction of
42% and an absolute risk reduction of 6.3% in coronary death,
procedures, ischemic stroke, and peripheral revascularization
procedures (p < .05; Arad, Spadaro, Roth, Newstein, & Guerci,
2005). This yielded a number needed to treat (NNT) with sta-
tins of 16 patients over 4 years to avoid a cardiovascular event in
1 patient, a notably lower NNT than previously reported figures
in the primary prevention literature for statin therapy (NNT 50–
70) and antihypertensive therapy (NNT 80–160) over a longer,
The Burden of Ischemic Heart Disease and Breast Cancer in Women
E.M. deGoma et al. / Women’s Health Issues 20-5 (2010) 299–303300
5-year period (Ridker et al., 2009). A similar randomized trial
employed CIMT as a criterion for enrollment, using a threshold
of modest thickening (maximum CIMT 1.2–3.5 mm), although
hard outcomes were not evaluated. In the Measuring Effects
on Intima-Media Thickness: An Evaluation of Rosuvastatin study,
984 low to intermediate Framingham risk participants (40%
women) were randomized to rosuvastatin 40 mg daily or
placebo and followed for 2 years (Crouse et al., 2007). Subjects
assignedto rosuvastatinexhibitedsignificantlyless progressionof
CIMT compared with placebo. Importantly, the magnitude of the
CIMT difference between groups was similar to that observed in
with a reduction in coronary events (Espeland et al., 2005).
Unfortunately for women, advanced testing, and imaging for
atherosclerosis in particular, remains an underappreciated,
underrecognized, and often unreimbursed opportunity to iden-
tify ischemic heart disease risk. Critics cite the absence of
randomized, controlled trials comparing the clinical outcomes of
further risk refinement with traditional clinical (e.g., Framing-
ham) assessment. Although these studies are indeed critical, it is
important to acknowledge that 1) the current clinical standard
has never passed such rigorous scrutiny (Cooney, Dudina, &
Graham, 2009), 2) the fundamental tenet of cardiovascular
disease prevention has been matching intensity of therapy to
individual patient risk (Pasternak et al., 2003), and 3) proposals
for CACS and CIMT trials have previously been put forward but
deemed too expensive to fund (Kaul & Douglas, 2009). Mean-
while, expert guidelines already support selective use of CACS or
CIMT among patients at intermediate risk (Table 2). Among
patients with a Framingham risk score of 6% to 20% (risk of fatal
Screening Tests for Ischemic Heart Disease and Breast Cancer
Coronary Artery Calcium ScanCarotid UltrasoundMammography
American Heart Association and American
College of Cardiology 2007 (Greenland et al.,
It may be reasonable to consider use of CACS
in intermediate risk patients based on
available evidence that demonstrates
incremental risk prediction information in
this selected patient group. This conclu-
sion is based on the possibility that such
patients might be reclassified to a higher
risk status based on high CAC score, and
subsequent patient management may be
American Heart Association 2006 (Budoff et al.,
Witha prior probability of a coronary event in
the intermediate range, a calcium score of
>100 would yield a posttest probability of
>2% per year in the majority of patients,
within the range of a CHD risk equivalent
population and within a level requiring
secondary prevention strategies.
National Cholesterol Education Program Adult
Treatment Panel III 2001 (National
Cholesterol Education Program, 2001)
In persons with multiple risk factors, a high
coronary calcium score denotes advanced
coronary atherosclerosis and provides
a rationale for intensified LDL-lowering
CACS resulted in net reclassification indices of
25% and 55% among the overall cohort and
among intermediate-risk patients, respec-
tively (Polonsky et al.).
Among patients with a CAC>400, only 16
patients need to be treated with statins over 4
years to avoid a cardiovascular event (Arad
et al., 2005b), the lowest figure yet described
in the primary prevention literature (Ridker
et al., 2009)
American Society of Echocardiography 2008
(Stein et al., 2008)
Measuring CIMT and identifying carotid pla-
que can be useful for refining cardiovas-
cular risk assessment in patients at
National Cholesterol Education Program Adult
Treatment Panel III 2001 (National
Cholesterol Education Program, 2001)
The finding of an elevated carotid IMT (>75th
percentile for age and sex) could elevate
a person with multiple risk factors to
a higher risk category.
American Heart Association 2000 (Smith et al.,
In asymptomatic individuals older than 45
years of age, carefully performed carotid
ultrasound examination with IMT
measurement can add incremental infor-
mation to traditional risk factor
American Cancer Society 2009 (American Cancer
Annual screening mammography is
recommended beginning at age 40.
U.S. Preventive Services Task Force 2009 (U.S.
Preventive Services Task Force, 2009)
Screening mammography is recommended
every 2 years for women between the ages
of 50 and 74 years. Routine screening
mammography is not recommended in
women aged 40-49 years.
Among women, CIMT and carotid plaque
assessment yielded an overall net reclassifi-
cation index of 8% and a net reclassification
index among intermediate risk patients of
21% (Nambi et al.).
Framingham low- to intermediate-risk patients
with moderately thickened CIMT (maximum
CIMT 1.2 to 3.5 mm) demonstrated signifi-
cantly less CIMT progression with statin
treatment compared with placebo. Between-
group differences were similar to those
observed in secondary prevention statin trials
associated with CHD event reduction
(Espeland et al., 2005).
Breast cancer death is averted in 1 of every 1,339
women age 50 years invited to screening
with serial mammography over a 10-year
period (U.S. Preventive Services Task Force,
0.9 mSv (Rumberger, 2008)None0.7 mSv (Pisano et al., 2005)
$300–$600 (Kaul & Douglas, 2009)$200–$300 (Kaul & Douglas, 2009)$100–$150 (Trivedi et al., 2008)
E.M. deGoma et al. / Women’s Health Issues 20-5 (2010) 299–303301
or nonfatal myocardial infarction at 10 years), ‘‘a calcium score of
>100 would yield a post-test probability >2% per year in the
majority of patients, within the range of a CHD risk equivalent
population and within a level requiring secondary prevention
strategies (Budoff et al., 2006; Greenland et al., 2001).’’
Recent controversy over routine mammography for women
younger than 50 years of age has reignited the debate over
appropriate early detection strategies for breast cancer. Although
the final outcome on women’s health care policy remains
unknown, and the conclusion may ultimately be to restrict
population-wide screening to women over the age of 50, it is
nonetheless encouraging that both supporting and dissenting
parties have been actively engaged, national attention has
intensified its focus on a critical women’s health issue, and
regardless of the decision, serial mammography will remain
a widely available, integral component of preventive care for
women age 50 years and above. Given the lives at risk, the accu-
mulated evidence to date supporting the ability of CIMT and in
particular CACS to refine risk, and the availability of effective
primary prevention measures, early detection of ischemic heart
for breast cancer. Assessment of CAC or CIMT will better identify
those women who would benefit most from intensified medical
therapy to prevent the sequelae of ischemic heart disease. At
a minimum, it behooves us to elevate the discussion regarding
heart disease screening to a national level for a passionate debate
stated by the National Heart, Lung, and Blood Institute’s ‘‘The
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Emil M. deGoma, MD, is a preventive cardiovascular medicine specialist at the
University of Pennsylvania. His clinical areas of focus include premature and
familial atherosclerotic disease, complex dyslipidemias, complex hypertension, and
Ronald P. Karlsberg, MD, is a Cedars Sinai Heart Institute Cardiologist. As a founder
of one of the first office-based advanced imaging centers he is recognized for his
publications, research and leadership in the field. He teaches an acclaimed training
program for cardiac CT.
Debra Judelson, MD, is a cardiologist and Director of the Women’s Heart Institute at
Cardiovascular Medical Group of Southern California. She is a member of Cedars-
Sinai Heart Institute, Cardiovascular Research Foundation, and past President of the
American Medical Women’s Association.
Matthew J. Budoff, MD, is a professor of medicine at the David Geffen School of
Medicine at UCLA and the director of cardiac CT at the Los Angeles Biomedical
E.M. deGoma et al. / Women’s Health Issues 20-5 (2010) 299–303303