Use of high-risk coronary atherosclerotic plaque detection for risk stratification of patients with stable chest pain

A secondary analysis of the promise randomized clinical trial

Maros Ferencik, Thomas Mayrhofer, Daniel O. Bittner, Hamed Emami, Stefan B. Puchner, Michael T. Lu, Nandini M. Meyersohn, Alexander V. Ivanov, Elizabeth C. Adami, Manesh R. Patel, Daniel B. Mark, James E. Udelson, Kerry L. Lee, Pamela S. Douglas, Udo Hoffmann

    Research output: Contribution to journalArticle

    40 Citations (Scopus)

    Abstract

    IMPORTANCE Coronary computed tomographic angiography (coronary CTA) can characterize coronary artery disease, including high-risk plaque. A noninvasivemethod of identifying high-risk plaque before major adverse cardiovascular events (MACE) could provide practice-changing optimizations in coronary artery disease care. OBJECTIVE To determine whether high-risk plaque detected by coronary CTA was associated with incident MACE independently of significant stenosis (SS) and cardiovascular risk factors. DESIGN, SETTING, AND PARTICIPANTS This prespecified nested observational cohort study was part of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial. All stable, symptomatic outpatients in this trial who required noninvasive cardiovascular testing and received coronary CTA were included and followed up for a median of 25 months. EXPOSURES Core laboratory assessment of coronary CTA for SS and high-risk plaque (eg, positive remodeling, low computed tomographic attenuation, or napkin-ring sign). MAIN OUTCOMES AND MEASURES The primary end pointwas an adjudicated composite of MACE (defined as death,myocardial infarction, or unstable angina). RESULTS The study included 4415 patients, of whom 2296 (52%) were women, with a mean age of 60.5 years, a median atherosclerotic cardiovascular disease (ASCVD) risk score of 11, and aMACE rate of 3%(131 events). A total of 676 patients (15.3%) had high-risk plaques, and 276 (6.3%) had SS. The presence of high-risk plaque was associated with a higher MACE rate (6.4%vs 2.4%; hazard ratio, 2.73; 95%CI, 1.89-3.93). This association persisted after adjustment for ASCVD risk score and SS (adjusted hazard ratio [aHR], 1.72; 95%CI, 1.13-2.62). Adding high-risk plaque to the ASCVD risk score and SS assessment led to a significant continuous net reclassification improvement (0.34; 95%CI, 0.02-0.51). Presence of high-risk plaque increased MACE risk among patients with nonobstructive coronary artery disease relative to patients without high-risk plaque (aHR, 4.31 vs 2.64; 95%CI, 2.25-8.26 vs 1.49-4.69). There were no significant differences inMACE in patients with SS and high-risk plaque as opposed to those with SS but not high-risk plaque (aHR, 8.68 vs. 9.31; 95%CI, 4.25-17.73 vs 4.21-20.61). High-risk plaque was a stronger predictor of MACE in women (aHR, 2.41; 95%CI, 1.25-4.64) vs men (aHR, 1.40; 95%CI, 0.81-2.39) and younger patients (aHR, 2.33; 95%CI, 1.20-4.51) vs older ones (aHR, 1.36; 95%CI, 0.77-2.39). CONCLUSIONS AND RELEVANCE High-risk plaque found by coronary CTA was associated with a future MACE in a large US population of outpatients with stable chest pain. High-risk plaque may be an additional risk stratification tool, especially in patients with nonobstructive coronary artery disease, younger patients, and women. The importance of findings is limited by low absolute MACE rates and low positive predictive value of high-risk plaque. TRIAL REGISTRATION clinicaltrials.gov Indentifier: NCT01174550.

    Original languageEnglish (US)
    Pages (from-to)144-152
    Number of pages9
    JournalJAMA Cardiology
    Volume3
    Issue number2
    DOIs
    StatePublished - Feb 1 2018

    Fingerprint

    Atherosclerotic Plaques
    Chest Pain
    Randomized Controlled Trials
    Pathologic Constriction
    Angiography
    Coronary Artery Disease
    Cardiovascular Diseases
    Outpatients
    Unstable Angina

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

    Cite this

    Use of high-risk coronary atherosclerotic plaque detection for risk stratification of patients with stable chest pain : A secondary analysis of the promise randomized clinical trial. / Ferencik, Maros; Mayrhofer, Thomas; Bittner, Daniel O.; Emami, Hamed; Puchner, Stefan B.; Lu, Michael T.; Meyersohn, Nandini M.; Ivanov, Alexander V.; Adami, Elizabeth C.; Patel, Manesh R.; Mark, Daniel B.; Udelson, James E.; Lee, Kerry L.; Douglas, Pamela S.; Hoffmann, Udo.

    In: JAMA Cardiology, Vol. 3, No. 2, 01.02.2018, p. 144-152.

    Research output: Contribution to journalArticle

    Ferencik, M, Mayrhofer, T, Bittner, DO, Emami, H, Puchner, SB, Lu, MT, Meyersohn, NM, Ivanov, AV, Adami, EC, Patel, MR, Mark, DB, Udelson, JE, Lee, KL, Douglas, PS & Hoffmann, U 2018, 'Use of high-risk coronary atherosclerotic plaque detection for risk stratification of patients with stable chest pain: A secondary analysis of the promise randomized clinical trial', JAMA Cardiology, vol. 3, no. 2, pp. 144-152. https://doi.org/10.1001/jamacardio.2017.4973
    Ferencik, Maros ; Mayrhofer, Thomas ; Bittner, Daniel O. ; Emami, Hamed ; Puchner, Stefan B. ; Lu, Michael T. ; Meyersohn, Nandini M. ; Ivanov, Alexander V. ; Adami, Elizabeth C. ; Patel, Manesh R. ; Mark, Daniel B. ; Udelson, James E. ; Lee, Kerry L. ; Douglas, Pamela S. ; Hoffmann, Udo. / Use of high-risk coronary atherosclerotic plaque detection for risk stratification of patients with stable chest pain : A secondary analysis of the promise randomized clinical trial. In: JAMA Cardiology. 2018 ; Vol. 3, No. 2. pp. 144-152.
    @article{e674f37892b543a7af1517c36d347385,
    title = "Use of high-risk coronary atherosclerotic plaque detection for risk stratification of patients with stable chest pain: A secondary analysis of the promise randomized clinical trial",
    abstract = "IMPORTANCE Coronary computed tomographic angiography (coronary CTA) can characterize coronary artery disease, including high-risk plaque. A noninvasivemethod of identifying high-risk plaque before major adverse cardiovascular events (MACE) could provide practice-changing optimizations in coronary artery disease care. OBJECTIVE To determine whether high-risk plaque detected by coronary CTA was associated with incident MACE independently of significant stenosis (SS) and cardiovascular risk factors. DESIGN, SETTING, AND PARTICIPANTS This prespecified nested observational cohort study was part of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial. All stable, symptomatic outpatients in this trial who required noninvasive cardiovascular testing and received coronary CTA were included and followed up for a median of 25 months. EXPOSURES Core laboratory assessment of coronary CTA for SS and high-risk plaque (eg, positive remodeling, low computed tomographic attenuation, or napkin-ring sign). MAIN OUTCOMES AND MEASURES The primary end pointwas an adjudicated composite of MACE (defined as death,myocardial infarction, or unstable angina). RESULTS The study included 4415 patients, of whom 2296 (52{\%}) were women, with a mean age of 60.5 years, a median atherosclerotic cardiovascular disease (ASCVD) risk score of 11, and aMACE rate of 3{\%}(131 events). A total of 676 patients (15.3{\%}) had high-risk plaques, and 276 (6.3{\%}) had SS. The presence of high-risk plaque was associated with a higher MACE rate (6.4{\%}vs 2.4{\%}; hazard ratio, 2.73; 95{\%}CI, 1.89-3.93). This association persisted after adjustment for ASCVD risk score and SS (adjusted hazard ratio [aHR], 1.72; 95{\%}CI, 1.13-2.62). Adding high-risk plaque to the ASCVD risk score and SS assessment led to a significant continuous net reclassification improvement (0.34; 95{\%}CI, 0.02-0.51). Presence of high-risk plaque increased MACE risk among patients with nonobstructive coronary artery disease relative to patients without high-risk plaque (aHR, 4.31 vs 2.64; 95{\%}CI, 2.25-8.26 vs 1.49-4.69). There were no significant differences inMACE in patients with SS and high-risk plaque as opposed to those with SS but not high-risk plaque (aHR, 8.68 vs. 9.31; 95{\%}CI, 4.25-17.73 vs 4.21-20.61). High-risk plaque was a stronger predictor of MACE in women (aHR, 2.41; 95{\%}CI, 1.25-4.64) vs men (aHR, 1.40; 95{\%}CI, 0.81-2.39) and younger patients (aHR, 2.33; 95{\%}CI, 1.20-4.51) vs older ones (aHR, 1.36; 95{\%}CI, 0.77-2.39). CONCLUSIONS AND RELEVANCE High-risk plaque found by coronary CTA was associated with a future MACE in a large US population of outpatients with stable chest pain. High-risk plaque may be an additional risk stratification tool, especially in patients with nonobstructive coronary artery disease, younger patients, and women. The importance of findings is limited by low absolute MACE rates and low positive predictive value of high-risk plaque. TRIAL REGISTRATION clinicaltrials.gov Indentifier: NCT01174550.",
    author = "Maros Ferencik and Thomas Mayrhofer and Bittner, {Daniel O.} and Hamed Emami and Puchner, {Stefan B.} and Lu, {Michael T.} and Meyersohn, {Nandini M.} and Ivanov, {Alexander V.} and Adami, {Elizabeth C.} and Patel, {Manesh R.} and Mark, {Daniel B.} and Udelson, {James E.} and Lee, {Kerry L.} and Douglas, {Pamela S.} and Udo Hoffmann",
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    T1 - Use of high-risk coronary atherosclerotic plaque detection for risk stratification of patients with stable chest pain

    T2 - A secondary analysis of the promise randomized clinical trial

    AU - Ferencik, Maros

    AU - Mayrhofer, Thomas

    AU - Bittner, Daniel O.

    AU - Emami, Hamed

    AU - Puchner, Stefan B.

    AU - Lu, Michael T.

    AU - Meyersohn, Nandini M.

    AU - Ivanov, Alexander V.

    AU - Adami, Elizabeth C.

    AU - Patel, Manesh R.

    AU - Mark, Daniel B.

    AU - Udelson, James E.

    AU - Lee, Kerry L.

    AU - Douglas, Pamela S.

    AU - Hoffmann, Udo

    PY - 2018/2/1

    Y1 - 2018/2/1

    N2 - IMPORTANCE Coronary computed tomographic angiography (coronary CTA) can characterize coronary artery disease, including high-risk plaque. A noninvasivemethod of identifying high-risk plaque before major adverse cardiovascular events (MACE) could provide practice-changing optimizations in coronary artery disease care. OBJECTIVE To determine whether high-risk plaque detected by coronary CTA was associated with incident MACE independently of significant stenosis (SS) and cardiovascular risk factors. DESIGN, SETTING, AND PARTICIPANTS This prespecified nested observational cohort study was part of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial. All stable, symptomatic outpatients in this trial who required noninvasive cardiovascular testing and received coronary CTA were included and followed up for a median of 25 months. EXPOSURES Core laboratory assessment of coronary CTA for SS and high-risk plaque (eg, positive remodeling, low computed tomographic attenuation, or napkin-ring sign). MAIN OUTCOMES AND MEASURES The primary end pointwas an adjudicated composite of MACE (defined as death,myocardial infarction, or unstable angina). RESULTS The study included 4415 patients, of whom 2296 (52%) were women, with a mean age of 60.5 years, a median atherosclerotic cardiovascular disease (ASCVD) risk score of 11, and aMACE rate of 3%(131 events). A total of 676 patients (15.3%) had high-risk plaques, and 276 (6.3%) had SS. The presence of high-risk plaque was associated with a higher MACE rate (6.4%vs 2.4%; hazard ratio, 2.73; 95%CI, 1.89-3.93). This association persisted after adjustment for ASCVD risk score and SS (adjusted hazard ratio [aHR], 1.72; 95%CI, 1.13-2.62). Adding high-risk plaque to the ASCVD risk score and SS assessment led to a significant continuous net reclassification improvement (0.34; 95%CI, 0.02-0.51). Presence of high-risk plaque increased MACE risk among patients with nonobstructive coronary artery disease relative to patients without high-risk plaque (aHR, 4.31 vs 2.64; 95%CI, 2.25-8.26 vs 1.49-4.69). There were no significant differences inMACE in patients with SS and high-risk plaque as opposed to those with SS but not high-risk plaque (aHR, 8.68 vs. 9.31; 95%CI, 4.25-17.73 vs 4.21-20.61). High-risk plaque was a stronger predictor of MACE in women (aHR, 2.41; 95%CI, 1.25-4.64) vs men (aHR, 1.40; 95%CI, 0.81-2.39) and younger patients (aHR, 2.33; 95%CI, 1.20-4.51) vs older ones (aHR, 1.36; 95%CI, 0.77-2.39). CONCLUSIONS AND RELEVANCE High-risk plaque found by coronary CTA was associated with a future MACE in a large US population of outpatients with stable chest pain. High-risk plaque may be an additional risk stratification tool, especially in patients with nonobstructive coronary artery disease, younger patients, and women. The importance of findings is limited by low absolute MACE rates and low positive predictive value of high-risk plaque. TRIAL REGISTRATION clinicaltrials.gov Indentifier: NCT01174550.

    AB - IMPORTANCE Coronary computed tomographic angiography (coronary CTA) can characterize coronary artery disease, including high-risk plaque. A noninvasivemethod of identifying high-risk plaque before major adverse cardiovascular events (MACE) could provide practice-changing optimizations in coronary artery disease care. OBJECTIVE To determine whether high-risk plaque detected by coronary CTA was associated with incident MACE independently of significant stenosis (SS) and cardiovascular risk factors. DESIGN, SETTING, AND PARTICIPANTS This prespecified nested observational cohort study was part of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial. All stable, symptomatic outpatients in this trial who required noninvasive cardiovascular testing and received coronary CTA were included and followed up for a median of 25 months. EXPOSURES Core laboratory assessment of coronary CTA for SS and high-risk plaque (eg, positive remodeling, low computed tomographic attenuation, or napkin-ring sign). MAIN OUTCOMES AND MEASURES The primary end pointwas an adjudicated composite of MACE (defined as death,myocardial infarction, or unstable angina). RESULTS The study included 4415 patients, of whom 2296 (52%) were women, with a mean age of 60.5 years, a median atherosclerotic cardiovascular disease (ASCVD) risk score of 11, and aMACE rate of 3%(131 events). A total of 676 patients (15.3%) had high-risk plaques, and 276 (6.3%) had SS. The presence of high-risk plaque was associated with a higher MACE rate (6.4%vs 2.4%; hazard ratio, 2.73; 95%CI, 1.89-3.93). This association persisted after adjustment for ASCVD risk score and SS (adjusted hazard ratio [aHR], 1.72; 95%CI, 1.13-2.62). Adding high-risk plaque to the ASCVD risk score and SS assessment led to a significant continuous net reclassification improvement (0.34; 95%CI, 0.02-0.51). Presence of high-risk plaque increased MACE risk among patients with nonobstructive coronary artery disease relative to patients without high-risk plaque (aHR, 4.31 vs 2.64; 95%CI, 2.25-8.26 vs 1.49-4.69). There were no significant differences inMACE in patients with SS and high-risk plaque as opposed to those with SS but not high-risk plaque (aHR, 8.68 vs. 9.31; 95%CI, 4.25-17.73 vs 4.21-20.61). High-risk plaque was a stronger predictor of MACE in women (aHR, 2.41; 95%CI, 1.25-4.64) vs men (aHR, 1.40; 95%CI, 0.81-2.39) and younger patients (aHR, 2.33; 95%CI, 1.20-4.51) vs older ones (aHR, 1.36; 95%CI, 0.77-2.39). CONCLUSIONS AND RELEVANCE High-risk plaque found by coronary CTA was associated with a future MACE in a large US population of outpatients with stable chest pain. High-risk plaque may be an additional risk stratification tool, especially in patients with nonobstructive coronary artery disease, younger patients, and women. The importance of findings is limited by low absolute MACE rates and low positive predictive value of high-risk plaque. TRIAL REGISTRATION clinicaltrials.gov Indentifier: NCT01174550.

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