Precision Test May Help Diagnose Older Adults With Obstructive CAD


By Marilynn Larkin

NEW YORK (Reuters Health) – A blood-based test incorporating age, sex and gene expression score (ASGES) may be useful in evaluating older outpatients with symptoms indicative of obstructive coronary artery disease (CAD), researchers suggest.

"Physicians usually order a cardiac stress test when seeing patients they suspect of having coronary artery disease, but it misdiagnoses many of these patients because it is not a sensitive test," Dr. Joseph Ladapo of the David Geffen School of Medicine at UCLA told Reuters Health. "These misdiagnosed patients face higher risks of heart attack and death if they are not treated with the right medications."

"The ASGES is a precision medicine test for evaluating these patients, and we have demonstrated that it is more accurate than stress testing for diagnosing coronary artery disease," he said by email. "In this study, we showed that it can be used safely and effectively in older patients, and they are at greatest risk for developing coronary artery disease."

Dr. Ladapo and colleagues analyzed data from a subset of participants in the PRESET registry, a prospective, multicenter observational study that enrolled stable, symptomatic outpatients from 21 U.S. care practices from 2012 to 2014.

Of 566 non-acute outpatients with symptoms suggestive of obstructive CAD, 176 over age 65 (61% women; 92% white) were included in the study and followed for one year. The researchers collected information on demographic characteristics, clinical features, ASGES results, pre- and post-ASGES diagnoses, referral patterns, advanced cardiac testing and major adverse cardiac events (MACEs).

As reported in the Journal of the American Geriatrics Society, online December 6, the median ASGES score was 25 (range: 1-40), and 23% of participants had a low score (15 or lower).

Clinicians referred 12.5% of those with low scores and 49.3% with high scores to cardiology or advanced cardiac testing, a significant difference between the groups after adjustment for demographics and clinical covariates.

Analysis of the ASGES as a continuous variable showed that the rate of cardiac referral increased proportionally with the score. For every 5-point increase in ASGES, the unadjusted odds of referral were 1.40 times higher in a univariate model.

At one-year follow-up, the incidence of a MACE or revascularization was 10% in the high-scoring group and 0% in the low-scoring group.

"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," Dr. Ladapo suggests.

Several cardiologists commented on the findings in emails to Reuters Health. All noted the lack of a control group as a major limitation, and provided additional insights.

Dr. Daniel Edmundowicz, Chief of Cardiology at Temple University Hospital in Philadelphia said, "It is unclear how much value this study brings to the current diagnostic algorithms for diagnosing CAD in the elderly. . . . About half of the (composite) ASGES is derived from the age and sex demographic components, with the gene-expression component generating the other half," he noted.

"It is well known that increasing age and male gender are strong risk factors for the development of CAD," he continued, "so one could question what the additive benefit of the score is over good clinical medicine - i.e., careful history and physical examination and detailed explanation of the differential diagnosis with the patient and their family."

"Not all patients with symptomatic CAD need to be sent for diagnostic testing," he added. "A trial of antianginal medication, along with risk-factor control, can be very safe and as effective as a more invasive approach, which would obviate the risk of further testing (without the need for a risk score)."

Dr. Fred Fefer, chief, division of cardiology at Long Island Jewish Valley Stream Hospital in New York City observed, "Patients who had low scores had no episodes of cardiac complications, but these patients would likely not have required any sort of noninvasive testing even without the additional blood test."

"Patients who did have high composite scores ended up getting either a clinically significant cardiac event or a catheterization, but the study does not separate how many got either," he added. "In fact, putting the two groups together probably allows the study's apparent impact to be larger than it would otherwise be."

"It seems likely that patients who have chronic complaints of chest pain would end up with a revascularization procedure, not for risk stratification, but for alleviation of their symptoms," Dr. Fefer noted. "This issue exists irrespective of their clinical scoring."

Dr. Nieca Goldberg, medical director of the Center for Women's Health at NYU Langone Medical Center in New York City said the ASGES is "a potential tool" for assessing CAD risk in adults 65 or older, but it "is not ready for use in clinical practice. . . . The study compared ASGES to stress testing; we have other tools, such as CT calcium scores, that help to predict risk for heart attacks."

Future studies might compare the ASGES with existing tests used to assess cardiovascular risk, she suggested.

The study was funded by CardioDx, a molecular diagnostics company. Dr. Ladapo and four coauthors have received funding from the company, and three coauthors are company employees.


J Am Geriatr Soc 2017.

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