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Original Investigation
November 18, 2019

Age-Related Differences in the Noninvasive Evaluation for Possible Coronary Artery Disease: Insights From the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) Trial

Author Affiliations
  • 1Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
  • 2Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
  • 3National Heart, Lung, and Blood Institute, Bethesda, Maryland
  • 4Deborah Heart and Lung Center, Browns Mills, New Jersey
  • 5Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
JAMA Cardiol. Published online November 18, 2019. doi:https://doi.org/10.1001/jamacardio.2019.4973
Key Points

Question  Among patients in the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial, did age affect the likelihood of a positive test result for coronary artery disease and its prognostic value, and did this differ according to type of test (anatomic vs functional test)?

Findings  In this prespecified PROMISE trial substudy, test result positivity increased with age regardless of the noninvasive test completed. However, among patients younger than 65 years, anatomic testing provided better prognostic discrimination, whereas among patients 65 years and older, functional testing was able to distinguish future risk, with a significant interaction between age, test type, and prognosis.

Meaning  Positive functional test results vs anatomic test results differ in their association with cardiovascular death or myocardial infarction across patient age. Age-specific approaches to the noninvasive evaluation of coronary artery disease should be further explored.


Importance  Although cardiovascular (CV) disease represents the leading cause of morbidity and mortality that increases with age, the best noninvasive test to identify older patients at risk for CV events remains unknown.

Objective  To determine whether the prognostic utility of anatomic vs functional testing varies based on patient age.

Design, Setting, and Participants  Prespecified analysis of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) study, which used a pragmatic comparative effectiveness design. Participants were enrolled from 193 sites across North America and comprised outpatients without known coronary artery disease (CAD) but with symptoms suggestive of CAD. Data were analyzed between October 2018 and April 2019.

Interventions  Randomization to noninvasive testing with coronary computed tomographic angiography or functional testing.

Main Outcomes and Measures  The composite of CV death/myocardial infarction (MI) over a median follow-up of 25 months.

Results  Among 10 003 PROMISE patients, we included the 8966 who received the noninvasive test to which they were randomized and had interpretable results; 6378 (71.1%) were younger than 65 years, 2062 (23.0%) were between ages 65 and 74 years, and 526 (5.9%) were 75 years and older. More than half of participants were women (4720 of 8966 [52.6%]). Only a minority of patients were of nonwhite race/ethnicity, a proportion that was lower among the older age groups (1071 of 6378 [16.8%] for <65 years; 258 of 2062 [12.5%] for age 65-74 years; 41 of 526 [7.8%] for ≥75 years). Compared with patients younger than 65 years, older patients were more likely to have a positive test result (age 65-74 years: odds ratio, 1.65; 95% CI, 1.42-1.91; age ≥75 years: odds ratio, 2.32; 95% CI, 1.83-2.95), regardless of noninvasive test completed. A positive functional test result was not associated with CV death/MI in patients younger than 65 years (hazard ratio [HR], 1.09; 95% CI, 0.43-2.82) but it was among older patients (age 65-74 years: HR, 3.18; 95% CI, 1.44-7.01; age ≥75 years: HR, 6.55; 95% CI, 1.46-29.35). Conversely, a positive anatomic test result was associated with CV death/MI among patients younger than 65 years (HR, 3.04; 95% CI, 1.46-6.34) but not among older patients (age, 65-74 years: HR, 0.67; 95% CI, 0.15-2.94; age ≥75 years: HR, 1.07; 95% CI, 0.22-5.34; P for interaction = .01). An elevated coronary artery calcium score was predictive of events in patients younger than 65 years (HR, 2.73; 95% CI, 1.31-5.69) but not for older patients (age 65-74 years: HR, 0.44; 95% CI, 0.14-1.42; age ≥75 years: HR, 1.31; 95% CI, 0.25-6.88).

Conclusions and Relevance  Older patients with stable symptoms suggestive of CAD are more likely to have a positive noninvasive test result and more coronary artery calcium. However, only a positive functional test result was associated with risk of CV death/MI. Age-specific approaches to noninvasive evaluation of CAD should be further examined.

Trial Registration  ClinicalTrials.gov identifier: NCT01174550