Genetic Testing for Early Detection of Individuals at Risk of Coronary Heart Disease and Monitoring Response to Therapy: Challenges and Promises

Current Atherosclerosis Reports, Aug 2011

Coronary heart disease (CHD) often presents suddenly with little warning. Traditional risk factors are inadequate to identify the asymptomatic high-risk individuals. Early identification of patients with subclinical coronary artery disease using noninvasive imaging modalities would allow the early adoption of aggressive preventative interventions. Currently, it is impractical to screen the entire population with noninvasive coronary imaging tools. The use of relatively simple and inexpensive genetic markers of increased CHD risk can identify a population subgroup in which benefit of atherosclerotic imaging modalities would be increased despite nominal cost and radiation exposure. Additionally, genetic markers are fixed and need only be measured once in a patient’s lifetime, can help guide therapy selection, and may be of utility in family counseling.

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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 0 2 3 Robert Roberts 0 2 3 Arthur Agatston 0 2 3 Stephen Frohwein 0 2 3 Jason S. Reingold 0 2 3 Thomas J. White 0 2 3 John J. Sninsky 0 2 3 Basil Margolis 0 2 3 Kathryn M. Momary 0 2 3 Brenda C. Garrett 0 2 3 Spencer B. King III 0 2 3 J. S. Reingold e-mail: 0 2 3 K. M. Momary e-mail: 0 2 3 S. B. King III e-mail: 0 2 3 0 S. B. King III Emory University , Atlanta, GA, USA 1 500, Miami Beach, FL 33139, USA 2 A. Agatston South Beach Preventive Cardiology, 1691 Michigan Ave 3 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: - 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)


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H. Robert Superko, Robert Roberts, Arthur Agatston, Stephen Frohwein, Jason S. Reingold, Thomas J. White, John J. Sninsky, Basil Margolis, Kathryn M. Momary, Brenda C. Garrett, Spencer B. King. Genetic Testing for Early Detection of Individuals at Risk of Coronary Heart Disease and Monitoring Response to Therapy: Challenges and Promises, Current Atherosclerosis Reports, 2011, pp. 396, Volume 13, Issue 5, DOI: 10.1007/s11883-011-0198-8