MedicalResearch.com Interview with:
Joseph A. Ladapo, MD, PhD
Principal Substudy Investigator, PRESET Registry
Subgroup Analysis, Elderly Patients
Associate Professor, Division of General Internal Medicine and Health Services Research
David Geffen School of Medicine
University of California, Los Angeles
MedicalResearch.com: What is the background for this study?
Response: The mapping of the Human Genome 14 years ago ushered in a new era of precision medicine. Many people are familiar with advances in oncology using precision medicine, but recently, new developments in precision medicine in cardiology have allowed us to develop a tool to differentiate patients likely to have obstructive coronary artery (CAD) from those who have non-cardiac causes of their symptoms.
Diagnosing CAD in the elderly is challenging. Aging individuals often present with atypical symptoms of CAD which can complicate the evaluation process. The typical diagnostic pathway for possible CAD often starts with less invasive testing and progresses to invasive testing, especially in older patients. Invasive procedures pose greater risk in the elderly population than they do in younger patients because of the higher risk of side effects, including bleeding, vascular complications and kidney injury.
Elderly adults evaluated for CAD have a higher pretest probability of CAD and are also at higher risk of experiencing procedure-related complications during their evaluation.[i],[ii] It is also important to note that elderly patients are often underrepresented in clinical trials and other types of comparative effectiveness research.[iii],[iv] For example, the 2013 American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease Risk Algorithm is only formally approved to be used in individuals up to the age of 75, despite the fact that individuals exceeding this threshold in age experience higher rates of adverse cardiovascular events.[v]
All of this means that the elderly population may have the most to gain from timely and accurate determination of their currently likelihood of obstructive CAD.
This precision medicine tool, the age, sex and gene expression score (ASGES), and its clinical utility in the elderly population is the focus of this study. It was based on patient data from the PRESET Registry, a prospective, multicenter, observational study enrolling stable, symptomatic outpatients from 21 U.S. primary care practices from August 2012 to August 2014.
MedicalResearch.com: What are the main findings?
Response: Of the individuals within the PRESET Registry, 176 were aged 65 and older. We used the community-based registry to examine the clinical utility of the ASGES and its effects on medical decision-making, with an emphasis on referrals to cardiology or advanced cardiac testing.[vi]
This subgroup analysis examined the use of the ASGES to help augment current diagnostic tools with the hopes of redefining the CAD evaluation paradigm for eldering patients. ASGES is a quantitative, simple blood test that incorporates age, sex and gene expression levels into an algorithmic score to assess the current likelihood of obstructive CAD, defined as at least one atherosclerotic plaque causing 50% or more luminal diameter stenosis in a major coronary artery (≥1.5mm lumen diameter).[vii],[viii],[ix]
The main findings of this analysis show the potential clinical utility of the ASGES in the evaluation of elderly patients with stable symptoms suggestive of CAD. Using the ASGES as a first-line diagnostic tool in these patients may reduce unnecessary referrals and the risk of procedure-related complications in individuals with low ASGES (≤15 on a scale of 1 to 40). The use of the ASGES can help identify patients unlikely to benefit from further testing as well as patients who may benefit from further cardiac evaluation. For more information about the ASGES, visit www.coruscad.com.
MedicalResearch.com: What should readers take away from your report?
Response: The main takeaway points are summed up as follows:
1. Elderly patients are more susceptible to complications from invasive cardiac tests.
2. Studies of patients with suspected CAD often underrepresent the elderly population, which means we cannot be sure conventional diagnostic pathways are the most appropriate way to manage these older patients.
3. The ASGES is a precision medicine tool that can replace the current paradigms for diagnosing CAD, particularly in elderly populations.
4. The ASGES is a more accurate, less invasive, cost-effective tool for evaluating patients with suspected CAD[x]
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Physicians should consider using this precision medicine test when they see their patients with chest pain or similar symptoms prior to ordering conventional cardiac stress tests. It is more accurate than stress testing for diagnosing coronary artery disease, which has much lower sensitivity than most physicians and patients think.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
J Am Geriatr Soc. 2017 Dec 6. doi: 10.1111/jgs.15215. [Epub ahead of print]
Utility of a Precision Medicine Test in Elderly Adults with Symptoms Suggestive of Coronary Artery Disease.
Ladapo JA1, Budoff MJ2, Sharp D3, Kuo JZ4, Huang L4, Maniet B5, Herman L6, Monane M4.
[i] Song W, Zhang T, Pu J et al. Incidence and risk of developing contrastinduced acute kidney injury following intravascular contrast administration in elderly patients. Clin Interv Aging. 2014;9:85–93.
[ii] Ahmed B, Piper WD, Malenka D et al. Signiﬁcantly improved vascular complications among women undergoing percutaneous coronary intervention: A report from the Northern New England Percutaneous Coronary Intervention Registry. Circ Cardiovasc Interv. 2009;2:423–429.
[iii] Sardar MR, Badri M, Prince CT et al. Underrepresentation of women, elderly patients, and racial minorities in the randomized trials used for cardiovascular guidelines. JAMA Intern Med. 2014;174:1868–1870.
[iv] Murthy VH, Krumholz HM, Gross CP. Participation in cancer clinical trials: Race-, sex-, and age-based disparities. JAMA.2004;291:2720–2726.
[v] Goff DC Jr, Lloyd-Jones DM, Bennett G et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S49–S73.
[vi] Ladapo JA, Budoff M, Sharp D et al. Clinical utility of a precision medicine test evaluating outpatients with suspected obstructive coronary artery disease. Am J Med. 2017;130:482.e411–482.e417.
[vii] Wingrove JA, Daniels SE, Sehnert AJ et al. Correlation of peripheral-blood gene expression with the extent of coronary artery stenosis. Circ Cardiovasc Genet. 2008;1:31–38.
[viii] Elashoff MR, Wingrove JA, Beineke P et al. Development of a blood-based gene expression algorithm for assessment of obstructive coronary artery disease in non-diabetic patients. BMC Med Genomics. 2011;4:26.
[ix] Rosenberg S, Elashoff MR, Beineke P et al. Multicenter validation of the diagnostic accuracy of a blood-based gene expression test for assessing obstructive coronary artery disease in nondiabetic patients. Ann Intern Med. 2010;153:425–434.
[x] Phelps CE, O’Sullivan AK, Ladapo JA et al. Cost effectiveness of a gene expression score and myocardial perfusion imaging for diagnosis of coronary artery disease. Am Heart J. 2014;167:697.e692–706.e692.
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