Sex Matters in the Diagnostic Performance of Coronary Artery Disease Testing

Patrice Wendling

April 15, 2016

CHICAGO, IL — The relative prognostic value of coronary computed-tomography angiography (CTA) and stress testing varies by sex in patients with suspected coronary artery disease, according to a new analysis of the PROMISE trial[1].

"Women may derive greater positive prognostic value from CTA than from stress testing, while men may derive similar value from both tests," Dr Neha Pagidipati (Duke Clinical Research Institute, Durham, NC) said, presenting the results at the American College of Cardiology (ACC) 2016 Scientific Sessions. The study was simultaneously published April 4, 2016 in the Journal of the American College of Cardiology.

In the overall PROMISE trial, there were no significant differences between anatomic CTA and stress-testing strategies in clinical events (3.3% vs 3.0%) or between sexes in the 10,003 patients.

What that analysis didn't do, however, was to evaluate how likely a positive CTA or stress test is in women or men and, if the test were positive, what kind of outcomes they could expect. To tackle this, multivariable analyses were performed using data from 8966 (90%) PROMISE patients with interpretable results.

A positive CTA was defined as >70% epicardial stenosis or >50% left main stenosis. A stress echo or stress nuclear test was considered positive if there was inducible ischemia in at least one coronary territory or early termination of exercise stress (<3 min) due to ST changes consistent with ischemia, symptom reproduction, arrhythmia, and/or hypotension.

"Overall, what we found is that all of these things; the sex of the patient, the test type, test result, and clinical outcomes are all interlinked in very complex ways," Pagidipati told heartwire from Medscape.

In women, a positive CTA was less likely than a positive stress test (adjusted odds ratio [OR] 0.67; P<0.001), and a positive CTA is more predictive of clinical outcomes (adjusted hazard ratios [HR] 5.86 CTA, HR 2.27 stress test; P=0.028).

In men, a positive CTA is more likely than a positive stress test (adjusted OR 1.23; P=0.019), and positive results were similarly predictive for both tests (adjusted HR 2.80 CTA, HR 4.42 stress test; P=0.168).

Panelist Dr Prediman K Shah (Cedars-Sinai Medical Center, Los Angeles, CA), said, "The message I derive from this study is reconfirmation of the long-standing view that false-positive stress tests are more common in women than in men."

Pagidipati said this is most likely the case but that the excess rate of positive tests compared with clinical events in stress testing may also be "related to microvascular dysfunction that we know is common in women and may be picked up by stress testing and not by CTA."

Dr Michael W Cullen (Mayo Clinic, Rochester, MN), who was not involved in the study, urged caution in viewing the results as confirmation that false-positive stress tests are more common in women. He observed that several factors such as image acquisition, image interpretation, and patient factors go into the interpretation of a stress test. In addition, stress tests provide useful information that can guide management such as hemodynamic and structural data available from stress echocardiography.

"In younger women where you're trying to exclude coronary disease, I think CTA can be a very good test, but you can't neglect the very useful information you can get in both men and women with a standard stress test," Cullen said.

Former ACC president Dr William Zoghbi (Houston Methodist Hospital, TX) told heartwire that CTA may be more definitive in women but that each test has its own advantages and disadvantages that must be put into the context of what the situation is; the pretest likelihood of disease, what the symptoms are, and the patient's overall condition.

"Sex is important to look at in testing, but it really doesn't necessarily point us in the direction that CTA is the test of choice," he said.

During the discussion of the data, the question was raised whether different definitions of test positivity might narrow the gap between men and women.

Pagidipati responded that not all positive tests are the same and that the degree of positivity is very important for an individual. "But on a population level, we're seeing a distinction between positive vs negative results that is very nicely splayed out in the two curves. That may tell us all we need to know," she said.

Pagidipati told heartwire that while patient sex "should probably factor into the decision making of the clinician," prospective data are needed before clinical practice should be changed. The chances of a large prospective randomized trial are relatively low, particularly given the low event rate of just 2% to 3% in PROMISE, but that the question could possibly be examined prospectively through registry-based data, she said.

The research was supported by grants from the National Heart, Lung, and Blood Institute. Pagidipati reported no relevant financial disclosures. Disclosures for the coauthors are listed in the paper. Cullen and Zoghbi report no relevant financial relationships.


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