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Genetic Testing for Early Detection of Individuals at Risk of Coronary Heart Disease and Monitoring Response to Therapy: Challenges and Promises
H. Robert Superko
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Robert Roberts
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Arthur Agatston
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Stephen Frohwein
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Jason S. Reingold
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Thomas J. White
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John J. Sninsky
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Basil Margolis
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Kathryn M. Momary
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Brenda C. Garrett
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Spencer B. King III
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J. S. Reingold e-mail:
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K. M. Momary e-mail:
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S. B. King III e-mail:
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S. B. King III Emory University
,
Atlanta, GA, USA
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500, Miami Beach,
FL 33139, USA
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A. Agatston South Beach Preventive Cardiology, 1691 Michigan Ave
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R. Roberts Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute
, 40 Ruskin Street,
Ottawa
, ON K1Y 4W7,
Canada
Coronary heart disease (CHD) often presents suddenly with little warning. Traditional risk factors are tions. Currently, it is impractical to screen the entire population with noninvasive coronary imaging tools. The use of relatively inadequate to identify the asymptomatic high-risk individuals. simple and inexpensive genetic markers of increased CHD risk Early identification of patients with subclinical coronary artery disease using noninvasive imaging modalities would can identify a population subgroup in which benefit of atherosclerotic imaging modalities would be increased despite allow the early adoption of aggressive preventative intervennominal cost and radiation exposure. Additionally, genetic B. Margolis e-amail:
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markers are fixed and need only be measured once in a
patients lifetime, can help guide therapy selection, and may be
of utility in family counseling.
The genetic revolution for some individuals has yet to
begin whereas for others it came and was a disappointment.
Although such a statement may be a clich, it does not
reflect the recent genetic efforts of the scientific community.
The quest to elucidate the genetic factors predisposing to
common diseases is based on well-founded progress. The
revolution did not gain momentum until 2005, and in
6 years the progress has been nothing short of remarkable.
The high-throughput microarray platforms employed to
perform genome-wide association studies (GWAS) have
already provided more data than can be currently appraised
or applied [1]. Nearly 1000 loci have been shown to
associate with common diseases [2]. The critics are quick to
indicate the effect of any one locus is small and unlikely to
revolutionize therapy or usher in the era of personalized
medicine. Cholesterol has been known to be a risk factor
for coronary artery disease (CAD) since the 1950s. The first
specific drugs to lower cholesterol were produced in 1987,
yet we are still working to overcome barriers that prevent
such testing and therapy for primary and secondary
prevention. This is just the beginning of the genetic
revolution and its success is likely to inspire and accelerate
future efforts. First, in regard to heart disease, GWAS have
revealed that there are many mechanisms inducing CAD
and myocardial infarction (MI) independent of known
traditional risk factors [3]. Second, there are many more
genetic factors yet to be identified for heart disease and
other common diseases. Third, we can expect new drugs to
be developed as a result of targeting these new mechanisms.
Fourth, now is the time to acquire the education and
infrastructure to properly apply genetic testing and prevention.
It has been stated that heart disease can be eliminated in
this century [4]. This exuberant statement was stimulated
by the observation that most types of heart disease are
preventable. Clinical trials have shown that modulating
current risk factors prevents 30% to 40% of heart disease
[5]. Epidemiology and family studies have long
documented that approximately 50% of susceptibility for heart
disease is genetic [6]. We should hope and prepare for the
day when these genetic factors are elucidated.
Comprehensive prevention and treatment will be possible only if we
know the genetic predisposition [7]. There are currently
over 30 loci proven to be associated with increased risk for
CAD [8]. While caution is advised, there are costs to
delaying the implementation of genetic testing and it may
be productive to consider provisional approaches [9]. There
are some benefits to be derived currently from testing for
genetic predisposition. This review is a description of
examples illustrating this benefit.
Atherosclerosis is often a slow-moving and silent disease
until the eventual development of a sudden coronary event
or the appearance of symptoms of myocardial ischemia.
Sixty-seven percent of out-of-hospital emergency medical
servicestreated cardiac arrests have no symptoms within 1
hour of death [10]. However, many individuals develop
coronary atherosclerosis and lead active lives, eventually
succumbing to a fatal disorder not necessarily related to
coronary atherosclerosis. The relatively recent concept of
plaque instability as the acute etiology of a clinical event is
now embraced by the medical community and highlights
the important difference between the presence (...truncated)