Prognostic Value of Coronary Artery Calcium in the PROMISE Study (Prospective Multicenter Imaging Study for Evaluation of Chest Pain)

PROMISE Investigators

    Research output: Contribution to journalArticle

    32 Citations (Scopus)

    Abstract

    BACKGROUND: Coronary artery calcium (CAC) is an established predictor of future major adverse atherosclerotic cardiovascular events in asymptomatic individuals. However, limited data exist as to how CAC compares with functional testing (FT) in estimating prognosis in symptomatic patients.

    METHODS: In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain (or dyspnea) and intermediate pretest probability for obstructive coronary artery disease were randomized to FT (exercise electrocardiography, nuclear stress, or stress echocardiography) or anatomic testing. We evaluated those who underwent CAC testing as part of the anatomic evaluation (n=4209) and compared that with results of FT (n=4602). We stratified CAC and FT results as normal or mildly, moderately, or severely abnormal (for CAC: 0, 1-99 Agatston score [AS], 100-400 AS, and >400 AS, respectively; for FT: normal, mild=late positive treadmill, moderate=early positive treadmill or single-vessel ischemia, and severe=large ischemic region abnormality). The primary end point was all-cause death, myocardial infarction, or unstable angina hospitalization over a median follow-up of 26.1 months. Cox regression models were used to calculate hazard ratios (HRs) and C statistics to determine predictive and discriminatory values.

    RESULTS: Overall, the distribution of normal or mildly, moderately, or severely abnormal test results was significantly different between FT and CAC (FT: normal, n=3588 [78.0%]; mild, n=432 [9.4%]; moderate, n=217 [4.7%]; severe, n=365 [7.9%]; CAC: normal, n=1457 [34.6%]; mild, n=1340 [31.8%]; moderate, n=772 [18.3%]; severe, n=640 [15.2%]; P<0.0001). Moderate and severe abnormalities in both arms robustly predicted events (moderate: CAC: HR, 3.14; 95% confidence interval, 1.81-5.44; and FT: HR, 2.65; 95% confidence interval, 1.46-4.83; severe: CAC: HR, 3.56; 95% confidence interval, 1.99-6.36; and FT: HR, 3.88; 95% confidence interval, 2.58-5.85). In the CAC arm, the majority of events (n=112 of 133, 84%) occurred in patients with any positive CAC test (score >0), whereas fewer than half of events occurred in patients with mildly, moderately, or severely abnormal FT (n=57 of 132, 43%; P<0.001). In contrast, any abnormality on FT was significantly more specific for predicting events (78.6% for FT versus 35.2% for CAC; P<0.001). Overall discriminatory ability in predicting the primary end point of mortality, nonfatal myocardial infarction, and unstable angina hospitalization was similar and fair for both CAC and FT (C statistic, 0.67 versus 0.64). Coronary computed tomographic angiography provided significantly better prognostic information compared with FT and CAC testing (C index, 0.72).

    CONCLUSIONS: Among stable outpatients presenting with suspected coronary artery disease, most patients experiencing clinical events have measurable CAC at baseline, and fewer than half have any abnormalities on FT. However, an abnormal FT was more specific for cardiovascular events, leading to overall similarly modest discriminatory abilities of both tests.

    CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01174550.

    Original languageEnglish (US)
    Pages (from-to)1993-2005
    Number of pages13
    JournalCirculation
    Volume136
    Issue number21
    DOIs
    StatePublished - Nov 21 2017

    Fingerprint

    Chest Pain
    Multicenter Studies
    Coronary Vessels
    Prospective Studies
    Calcium
    Unstable Angina
    Coronary Artery Disease
    Hospitalization
    Myocardial Infarction
    Stress Echocardiography
    Normal Distribution
    Proportional Hazards Models
    Dyspnea
    Cause of Death
    Angiography
    Electrocardiography
    Outpatients
    Ischemia
    Clinical Trials
    Exercise

    Keywords

    • calcium
    • coronary artery disease
    • diagnostic tests
    • prognosis
    • routine

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine
    • Physiology (medical)

    Cite this

    Prognostic Value of Coronary Artery Calcium in the PROMISE Study (Prospective Multicenter Imaging Study for Evaluation of Chest Pain). / PROMISE Investigators.

    In: Circulation, Vol. 136, No. 21, 21.11.2017, p. 1993-2005.

    Research output: Contribution to journalArticle

    @article{271bcf2c5c064ca781784d1c0d972ac8,
    title = "Prognostic Value of Coronary Artery Calcium in the PROMISE Study (Prospective Multicenter Imaging Study for Evaluation of Chest Pain)",
    abstract = "BACKGROUND: Coronary artery calcium (CAC) is an established predictor of future major adverse atherosclerotic cardiovascular events in asymptomatic individuals. However, limited data exist as to how CAC compares with functional testing (FT) in estimating prognosis in symptomatic patients.METHODS: In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain (or dyspnea) and intermediate pretest probability for obstructive coronary artery disease were randomized to FT (exercise electrocardiography, nuclear stress, or stress echocardiography) or anatomic testing. We evaluated those who underwent CAC testing as part of the anatomic evaluation (n=4209) and compared that with results of FT (n=4602). We stratified CAC and FT results as normal or mildly, moderately, or severely abnormal (for CAC: 0, 1-99 Agatston score [AS], 100-400 AS, and >400 AS, respectively; for FT: normal, mild=late positive treadmill, moderate=early positive treadmill or single-vessel ischemia, and severe=large ischemic region abnormality). The primary end point was all-cause death, myocardial infarction, or unstable angina hospitalization over a median follow-up of 26.1 months. Cox regression models were used to calculate hazard ratios (HRs) and C statistics to determine predictive and discriminatory values.RESULTS: Overall, the distribution of normal or mildly, moderately, or severely abnormal test results was significantly different between FT and CAC (FT: normal, n=3588 [78.0{\%}]; mild, n=432 [9.4{\%}]; moderate, n=217 [4.7{\%}]; severe, n=365 [7.9{\%}]; CAC: normal, n=1457 [34.6{\%}]; mild, n=1340 [31.8{\%}]; moderate, n=772 [18.3{\%}]; severe, n=640 [15.2{\%}]; P<0.0001). Moderate and severe abnormalities in both arms robustly predicted events (moderate: CAC: HR, 3.14; 95{\%} confidence interval, 1.81-5.44; and FT: HR, 2.65; 95{\%} confidence interval, 1.46-4.83; severe: CAC: HR, 3.56; 95{\%} confidence interval, 1.99-6.36; and FT: HR, 3.88; 95{\%} confidence interval, 2.58-5.85). In the CAC arm, the majority of events (n=112 of 133, 84{\%}) occurred in patients with any positive CAC test (score >0), whereas fewer than half of events occurred in patients with mildly, moderately, or severely abnormal FT (n=57 of 132, 43{\%}; P<0.001). In contrast, any abnormality on FT was significantly more specific for predicting events (78.6{\%} for FT versus 35.2{\%} for CAC; P<0.001). Overall discriminatory ability in predicting the primary end point of mortality, nonfatal myocardial infarction, and unstable angina hospitalization was similar and fair for both CAC and FT (C statistic, 0.67 versus 0.64). Coronary computed tomographic angiography provided significantly better prognostic information compared with FT and CAC testing (C index, 0.72).CONCLUSIONS: Among stable outpatients presenting with suspected coronary artery disease, most patients experiencing clinical events have measurable CAC at baseline, and fewer than half have any abnormalities on FT. However, an abnormal FT was more specific for cardiovascular events, leading to overall similarly modest discriminatory abilities of both tests.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01174550.",
    keywords = "calcium, coronary artery disease, diagnostic tests, prognosis, routine",
    author = "{PROMISE Investigators} and Budoff, {Matthew J.} and Thomas Mayrhofer and Maros Ferencik and Daniel Bittner and Lee, {Kerry L.} and Lu, {Michael T.} and Adrian Coles and James Jang and Mayil Krishnam and Douglas, {Pamela S.} and Udo Hoffmann",
    year = "2017",
    month = "11",
    day = "21",
    doi = "10.1161/CIRCULATIONAHA.117.030578",
    language = "English (US)",
    volume = "136",
    pages = "1993--2005",
    journal = "Circulation",
    issn = "0009-7322",
    publisher = "Lippincott Williams and Wilkins",
    number = "21",

    }

    TY - JOUR

    T1 - Prognostic Value of Coronary Artery Calcium in the PROMISE Study (Prospective Multicenter Imaging Study for Evaluation of Chest Pain)

    AU - PROMISE Investigators

    AU - Budoff, Matthew J.

    AU - Mayrhofer, Thomas

    AU - Ferencik, Maros

    AU - Bittner, Daniel

    AU - Lee, Kerry L.

    AU - Lu, Michael T.

    AU - Coles, Adrian

    AU - Jang, James

    AU - Krishnam, Mayil

    AU - Douglas, Pamela S.

    AU - Hoffmann, Udo

    PY - 2017/11/21

    Y1 - 2017/11/21

    N2 - BACKGROUND: Coronary artery calcium (CAC) is an established predictor of future major adverse atherosclerotic cardiovascular events in asymptomatic individuals. However, limited data exist as to how CAC compares with functional testing (FT) in estimating prognosis in symptomatic patients.METHODS: In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain (or dyspnea) and intermediate pretest probability for obstructive coronary artery disease were randomized to FT (exercise electrocardiography, nuclear stress, or stress echocardiography) or anatomic testing. We evaluated those who underwent CAC testing as part of the anatomic evaluation (n=4209) and compared that with results of FT (n=4602). We stratified CAC and FT results as normal or mildly, moderately, or severely abnormal (for CAC: 0, 1-99 Agatston score [AS], 100-400 AS, and >400 AS, respectively; for FT: normal, mild=late positive treadmill, moderate=early positive treadmill or single-vessel ischemia, and severe=large ischemic region abnormality). The primary end point was all-cause death, myocardial infarction, or unstable angina hospitalization over a median follow-up of 26.1 months. Cox regression models were used to calculate hazard ratios (HRs) and C statistics to determine predictive and discriminatory values.RESULTS: Overall, the distribution of normal or mildly, moderately, or severely abnormal test results was significantly different between FT and CAC (FT: normal, n=3588 [78.0%]; mild, n=432 [9.4%]; moderate, n=217 [4.7%]; severe, n=365 [7.9%]; CAC: normal, n=1457 [34.6%]; mild, n=1340 [31.8%]; moderate, n=772 [18.3%]; severe, n=640 [15.2%]; P<0.0001). Moderate and severe abnormalities in both arms robustly predicted events (moderate: CAC: HR, 3.14; 95% confidence interval, 1.81-5.44; and FT: HR, 2.65; 95% confidence interval, 1.46-4.83; severe: CAC: HR, 3.56; 95% confidence interval, 1.99-6.36; and FT: HR, 3.88; 95% confidence interval, 2.58-5.85). In the CAC arm, the majority of events (n=112 of 133, 84%) occurred in patients with any positive CAC test (score >0), whereas fewer than half of events occurred in patients with mildly, moderately, or severely abnormal FT (n=57 of 132, 43%; P<0.001). In contrast, any abnormality on FT was significantly more specific for predicting events (78.6% for FT versus 35.2% for CAC; P<0.001). Overall discriminatory ability in predicting the primary end point of mortality, nonfatal myocardial infarction, and unstable angina hospitalization was similar and fair for both CAC and FT (C statistic, 0.67 versus 0.64). Coronary computed tomographic angiography provided significantly better prognostic information compared with FT and CAC testing (C index, 0.72).CONCLUSIONS: Among stable outpatients presenting with suspected coronary artery disease, most patients experiencing clinical events have measurable CAC at baseline, and fewer than half have any abnormalities on FT. However, an abnormal FT was more specific for cardiovascular events, leading to overall similarly modest discriminatory abilities of both tests.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01174550.

    AB - BACKGROUND: Coronary artery calcium (CAC) is an established predictor of future major adverse atherosclerotic cardiovascular events in asymptomatic individuals. However, limited data exist as to how CAC compares with functional testing (FT) in estimating prognosis in symptomatic patients.METHODS: In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain (or dyspnea) and intermediate pretest probability for obstructive coronary artery disease were randomized to FT (exercise electrocardiography, nuclear stress, or stress echocardiography) or anatomic testing. We evaluated those who underwent CAC testing as part of the anatomic evaluation (n=4209) and compared that with results of FT (n=4602). We stratified CAC and FT results as normal or mildly, moderately, or severely abnormal (for CAC: 0, 1-99 Agatston score [AS], 100-400 AS, and >400 AS, respectively; for FT: normal, mild=late positive treadmill, moderate=early positive treadmill or single-vessel ischemia, and severe=large ischemic region abnormality). The primary end point was all-cause death, myocardial infarction, or unstable angina hospitalization over a median follow-up of 26.1 months. Cox regression models were used to calculate hazard ratios (HRs) and C statistics to determine predictive and discriminatory values.RESULTS: Overall, the distribution of normal or mildly, moderately, or severely abnormal test results was significantly different between FT and CAC (FT: normal, n=3588 [78.0%]; mild, n=432 [9.4%]; moderate, n=217 [4.7%]; severe, n=365 [7.9%]; CAC: normal, n=1457 [34.6%]; mild, n=1340 [31.8%]; moderate, n=772 [18.3%]; severe, n=640 [15.2%]; P<0.0001). Moderate and severe abnormalities in both arms robustly predicted events (moderate: CAC: HR, 3.14; 95% confidence interval, 1.81-5.44; and FT: HR, 2.65; 95% confidence interval, 1.46-4.83; severe: CAC: HR, 3.56; 95% confidence interval, 1.99-6.36; and FT: HR, 3.88; 95% confidence interval, 2.58-5.85). In the CAC arm, the majority of events (n=112 of 133, 84%) occurred in patients with any positive CAC test (score >0), whereas fewer than half of events occurred in patients with mildly, moderately, or severely abnormal FT (n=57 of 132, 43%; P<0.001). In contrast, any abnormality on FT was significantly more specific for predicting events (78.6% for FT versus 35.2% for CAC; P<0.001). Overall discriminatory ability in predicting the primary end point of mortality, nonfatal myocardial infarction, and unstable angina hospitalization was similar and fair for both CAC and FT (C statistic, 0.67 versus 0.64). Coronary computed tomographic angiography provided significantly better prognostic information compared with FT and CAC testing (C index, 0.72).CONCLUSIONS: Among stable outpatients presenting with suspected coronary artery disease, most patients experiencing clinical events have measurable CAC at baseline, and fewer than half have any abnormalities on FT. However, an abnormal FT was more specific for cardiovascular events, leading to overall similarly modest discriminatory abilities of both tests.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01174550.

    KW - calcium

    KW - coronary artery disease

    KW - diagnostic tests

    KW - prognosis

    KW - routine

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    U2 - 10.1161/CIRCULATIONAHA.117.030578

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    SP - 1993

    EP - 2005

    JO - Circulation

    JF - Circulation

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