Identifying obstructive coronary artery disease in women: an interview with Dr. Ladapo, NYU School of Medicine

insights from industryDr. Joseph A. Ladapo, MD, PhDAssistant Professor of Population Health and Medicine at
NYU School of Medicine and cares for hospitalized patients
at NYU Langone Medical Center.

A recent study presented at the American College of Cardiology 64th Annual Scientific Meeting evaluated the impact of an age, sex, and gene expression score on clinical decision-making and the rate of further cardiac evaluation in symptomatic female patients suggestive of CAD in the outpatient setting. The study was an aggregated analysis of female cohorts from the IMPACT-PCP and REGISTRY I studies. The study was published, ahead of the print issue, online on Menopause: The Journal of The North American Menopause Society in April 2015.

Please can you outline the current testing approaches for identifying obstructive coronary artery disease (CAD)?

Current guidelines for the assessment of obstructive coronary artery disease (CAD) recommend using exercise electrocardiogram (ECG) as the first-line diagnostic test in the evaluation of most women presenting with non-acute symptoms suggestive of obstructive CAD.

This may be followed by non-invasive cardiac imaging, like nuclear stress testing or stress echocardiography. More invasive and surgical procedures may come into play when these tests alone do not provide enough information about a patient’s health or when they indicate a patient has a major cardiovascular problem.

What are the main limitations of these tests?

Most traditional tests for obstructive CAD, including nuclear stress testing and exercise treadmill tests, perform less well in women than men, and a growing body of evidence suggests that they fail to detect obstructive CAD frequently.

The radiation exposure from one nuclear stress test alone can be equivalent to 39 mammograms, or approximately 13.6 years-worth of natural radiation.

Also, invasive procedures, like heart catheterizations and surgery, can expose patients to procedural complications and the risk of adverse events.

With more women and men undergoing unnecessary diagnostic testing, our current standard CAD testing approach is not optimal. More effective diagnostic methods are needed to evaluate women, in particular, with symptoms suggestive of obstructive CAD.

We have scientific evidence, including evidence from this study, that a blood test that incorporates age, sex and gene expression to generate a score that corresponds to a patient’s likelihood of obstructive CAD may improve medical decision-making in the primary care setting.

What prompted you to examine the effect of the use of an age, sex and gene expression score as part of the clinical assessment?

Better approaches are needed to evaluate women during mid-life and beyond with chest pain and related atypical symptoms suggestive of obstructive CAD presenting to primary care physicians. The blood test we studied incorporates age, sex and gene expression measurements into a single score that indicates the likelihood of obstructive CAD.

As the only sex-specific test for the evaluation of obstructive CAD, the test has shown a 96% negative predictive value in a combined population of men and women in determining a patient’s current likelihood of obstructive CAD.

We hypothesized that the age, sex and gene expression score (Corus® CAD test, CardioDx, Inc, Redwood City, CA) could be incorporated into medical decision-making, and influence the rate of patient referrals for further cardiac evaluation.

Given its high negative predictive value and sensitivity, we hypothesized that the test could help clinicians exclude patients with low scores (and whose symptoms are most likely not due to obstructive CAD) from having to undergo further cardiac testing.

Why did you focus this study analysis on women only?

As I mentioned earlier, the current approach to women’s diagnostic testing in CAD is not optimized. Women often present with atypical symptoms that are less predictive of significant coronary obstruction.

Typical symptoms of CAD, such as chest pain, are more likely to have non-cardiac etiologies in women compared to men, resulting in a lower prevalence of obstructive CAD as confirmed by invasive coronary angiography.

Thus, there is a challenge for primary care physicians when treating women, especially those who are middle-aged and beyond, because their risk of CAD increases with age.

Since 1980, patients in the U.S. have experienced a six-fold increase in radiation exposure from medical imaging. Nearly 40% of this exposure (excluding radiotherapy) is related to cardiovascular imaging and cardiovascular interventions.

Because of this increase, the American Heart Association (AHA) issued a scientific statement in September 2014 advising healthcare providers to discuss the diagnostic accuracy, cost, availability, convenience, and risks of each testing option they may suggest for their patients.  

Women already receive imaging involving radiation as part of their general health screening, so additional radiation increases their risk of cancer.

Please can you describe the Corus CAD test that was used in your study? Why did you choose this test?

The test is a simple sex-specific blood draw that can be performed in a clinician’s office. As stated previously, this test incorporates the measurement of age, sex, and gene expression into a score to help clinicians safely and efficiently rule-out a narrowing or blockage in the heart arteries in symptomatic patients. It is a decision-making tool that can help identify patients unlikely to have obstructive CAD and help clinicians determine appropriate next steps for patient management.

We chose the age, sex and gene expression score for this study because it is the only sex-specific test available that takes into account cardiovascular differences between men and women, making it especially suitable for women who may experience symptoms differently than men.

What were the main findings of the study?

This was a subgroup analysis of women from two clinical utility studies focusing on primary care clinicians, IMPACT-PCP and REGISTRY I. In these studies, the age, sex and gene expression score was incorporated into medical decision-making and helped PCPs rule-out obstructive CAD among symptomatic women who were unlikely to benefit from further cardiac testing.

The recently reported results showed that the referral rate for further cardiac evaluation was 4.0% (10/248) for women with low test scores versus 83.3% (60/72) for women with elevated test scores, with an overall follow-up MACE/revascularization rate of 1.2%.

After adjusting for common clinical covariates, women with low age, sex and gene expression scores (≤15) were significantly less likely to be referred for further cardiac evaluation (odds ratio 0.013, p<0.0001) by their primary care clinicians within 45 days of follow-up.

What impact do you think this study will have?

We believe this study will help clinicians comfortably integrate the age, sex and gene expression score into their practices, resulting in fewer women being sent on for unnecessary cardiac imaging or invasive cardiac procedures. We expect this will lead to better management of healthcare resources and improved patient care.

Please can you outline the PROMISE trial?

An important study, the PROMISE trial, which was presented at the American College of Cardiology meeting this year and published online in the New England Journal of Medicine, examined whether an initial strategy of coronary CT angiography or functional testing yields better clinical outcomes in newly symptomatic, stable patients, without a previous diagnosis of CAD.

This study found that CT angiography is no better than functional testing as a first-line strategy in the evaluation of patients presenting with symptoms suggestive of significant CAD. Importantly, while the Diamond and Forrester pretest probability for patients overall was 53%, only ~6% of patients were actually found to have obstructive CAD after testing.

The PROMISE trial and our study both underscore how important it is for physicians to evaluate the best testing options for symptomatic women and overcome CAD diagnostic challenges that contribute to over-testing of low-risk patients.

Where can readers find more information?

Readers can learn more about the study by downloading the publication at http://journals.lww.com/menopausejournal/Abstract/publishahead/Use_of_a_blood_test_incorporating_age,_sex,_and.98193.aspx.

To learn more about the Corus CAD test, visit www.cardiodx.com.

About Dr. Ladapo

Joseph A. Ladapo, MD, PhD, is a physician and health policy researcher whose primary research interests include assessing the cost-effectiveness of diagnostic technologies and reducing the population burden of cardiovascular disease.

He is Assistant Professor of Population Health and Medicine at NYU School of Medicine and cares for hospitalized patients at NYU Langone Medical Center. He previously served as a Staff Fellow at the Food and Drug Administration.

His research program, funded by the National Heart, Lung, and Blood Institute, focuses on patient-centered approaches to improving the health of individuals evaluated for coronary artery disease.

He also leads the health economic and quality of life evaluation of multiple NIH-funded randomized trials focused on cardiovascular disease and tobacco cessation.

His national honors include the Daniel Ford Award for health services and outcomes research, and he was also a regular columnist for the Harvard Focus during medical school and residency, where he discussed his experiences on the medical wards and perspectives on health policy issues.

Dr. Ladapo graduated from Wake Forest University and received his MD from Harvard Medical School and his PhD in Health Policy from Harvard Graduate School of Arts and Sciences. He completed his clinical training in internal medicine at the Beth Israel Deaconess Medical Center.

April Cashin-Garbutt

Written by

April Cashin-Garbutt

April graduated with a first-class honours degree in Natural Sciences from Pembroke College, University of Cambridge. During her time as Editor-in-Chief, News-Medical (2012-2017), she kickstarted the content production process and helped to grow the website readership to over 60 million visitors per year. Through interviewing global thought leaders in medicine and life sciences, including Nobel laureates, April developed a passion for neuroscience and now works at the Sainsbury Wellcome Centre for Neural Circuits and Behaviour, located within UCL.

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