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

Angela Lowenstern, Karen P. Alexander, C. Larry Hill, Brooke Alhanti, Patricia A. Pellikka, Michael G. Nanna, Rajendra H. Mehta, Lawton S. Cooper, Renee P. Bullock-Palmer, Udo Hoffmann, Pamela S. Douglas

Research output: Contribution to journalArticle

Abstract

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 10003 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.

Original languageEnglish (US)
JournalJAMA cardiology
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Chest Pain
Multicenter Studies
Coronary Artery Disease
Myocardial Infarction
Coronary Vessels
Odds Ratio
Calcium
Random Allocation
North America
Angiography
Outpatients
Cardiovascular Diseases
Age Groups
Outcome Assessment (Health Care)
Morbidity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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. / Lowenstern, Angela; Alexander, Karen P.; Hill, C. Larry; Alhanti, Brooke; Pellikka, Patricia A.; Nanna, Michael G.; Mehta, Rajendra H.; Cooper, Lawton S.; Bullock-Palmer, Renee P.; Hoffmann, Udo; Douglas, Pamela S.

In: JAMA cardiology, 01.01.2019.

Research output: Contribution to journalArticle

Lowenstern, Angela ; Alexander, Karen P. ; Hill, C. Larry ; Alhanti, Brooke ; Pellikka, Patricia A. ; Nanna, Michael G. ; Mehta, Rajendra H. ; Cooper, Lawton S. ; Bullock-Palmer, Renee P. ; Hoffmann, Udo ; Douglas, Pamela S. / 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. In: JAMA cardiology. 2019.
@article{8a92830df8bc450daa8d28228a4ddc38,
title = "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",
abstract = "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 10003 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.",
author = "Angela Lowenstern and Alexander, {Karen P.} and Hill, {C. Larry} and Brooke Alhanti and Pellikka, {Patricia A.} and Nanna, {Michael G.} and Mehta, {Rajendra H.} and Cooper, {Lawton S.} and Bullock-Palmer, {Renee P.} and Udo Hoffmann and Douglas, {Pamela S.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1001/jamacardio.2019.4973",
language = "English (US)",
journal = "JAMA Cardiology",
issn = "2380-6583",
publisher = "American Medical Association",

}

TY - JOUR

T1 - Age-Related Differences in the Noninvasive Evaluation for Possible Coronary Artery Disease

T2 - Insights from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) Trial

AU - Lowenstern, Angela

AU - Alexander, Karen P.

AU - Hill, C. Larry

AU - Alhanti, Brooke

AU - Pellikka, Patricia A.

AU - Nanna, Michael G.

AU - Mehta, Rajendra H.

AU - Cooper, Lawton S.

AU - Bullock-Palmer, Renee P.

AU - Hoffmann, Udo

AU - Douglas, Pamela S.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 10003 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.

AB - 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 10003 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.

UR - http://www.scopus.com/inward/record.url?scp=85075249592&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85075249592&partnerID=8YFLogxK

U2 - 10.1001/jamacardio.2019.4973

DO - 10.1001/jamacardio.2019.4973

M3 - Article

C2 - 31738382

AN - SCOPUS:85075249592

JO - JAMA Cardiology

JF - JAMA Cardiology

SN - 2380-6583

ER -