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    Original Investigation
    Cardiology
    July 24, 2020

    Association of Cardiovascular Disease Risk Factor Burden With Progression of Coronary Atherosclerosis Assessed by Serial Coronary Computed Tomographic Angiography

    Author Affiliations
    • 1Department of Imaging and Medicine, Cedars-Sinai Medical Center, Los Angeles, California
    • 2Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea
    • 3Department of Cardiac Sciences, University of Calgary, Calgary, Alberta, Canada
    • 4Centro Cardiologico Monzino, Institute for Research, Hospitalization and Healthcare (IRCCS), Milan, Italy
    • 5Department of Medicine, Los Angeles Biomedical Research Institute, Torrance, California
    • 6Cardiovascular Imaging Center, SDN Institute, Institute for Research, Hospitalization and Healthcare (IRCCS), Naples, Italy
    • 7Department of Cardiology, William Beaumont Hospital, Royal Oak, Michigan
    • 8Pusan National University Hospital, Busan, South Korea
    • 9UNICA, Unit of Cardiovascular Imaging, Hospital da Luz, Lisbon, Portugal
    • 10Department of Radiology, Casa de Saúde São José, Rio de Janeiro, Brazil
    • 11Department of Radiology and Nuclear Medicine, German Heart Center Munich, Munich, Germany
    • 12Department of Medicine and Radiology, University of British Columbia, Vancouver, British Columbia, Canada
    • 13Department of Radiology, Area Vasta 1–ASUR Marche, Urbino, Italy
    • 14Ewha Womans University Seoul Hospital, Seoul, South Korea
    • 15Seoul National University Hospital, Seoul, South Korea
    • 16Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
    • 17Seoul National University Bundang Hospital, Sungnam, South Korea
    • 18Department of Pathology, CVPath Institute, Gaithersburg, Maryland
    • 19Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia
    • 20Cardiovascular Division, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts
    • 21Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, Mount Sinai Heart, New York, New York
    • 22Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, New York, New York
    • 23Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
    • 24Department of Radiology, New York–Presbyterian Hospital and Weill Cornell Medicine, New York, New York
    • 25Cleerly, Inc, New York, New York
    JAMA Netw Open. 2020;3(7):e2011444. doi:10.1001/jamanetworkopen.2020.11444
    Key Points español 中文 (chinese)

    Question  Is the risk factor burden of cardiovascular disease, as assessed by atherosclerotic cardiovascular disease risk score, associated with coronary plaque progression and the development of adverse plaque characteristics?

    Findings  In this cohort study of 1005 adult patients from an international multicenter registry who underwent serial coronary computed tomographic angiography, the progression of coronary atherosclerotic plaque volume and the development of adverse plaque characteristics was greater in patients with a high atherosclerotic cardiovascular disease risk score.

    Meaning  The study findings suggest that the overall cardiovascular disease risk burden is associated with the progression of coronary atherosclerosis; the progression of fibrofatty plaque and low-attenuation plaque and the development of adverse plaque characteristics appear to be accelerated in patients with a high risk of atherosclerotic cardiovascular disease.

    Abstract

    Importance  Several studies have reported that the progression of coronary atherosclerosis, as measured by serial coronary computed tomographic (CT) angiography, is associated with the risk of future cardiovascular events. However, the cumulative consequences of multiple risk factors for plaque progression and the development of adverse plaque characteristics have not been well characterized.

    Objectives  To examine the association of cardiovascular risk factor burden, as assessed by atherosclerotic cardiovascular disease (ASCVD) risk score, with the progression of coronary atherosclerosis and the development of adverse plaque characteristics.

    Design, Setting, and Participants  This cohort study is a subgroup analysis of participant data from the prospective observational Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) study, which evaluated the association between serial coronary CT angiography findings and clinical presentation. The PARADIGM international multicenter registry, which includes 13 centers in 7 countries (Brazil, Canada, Germany, Italy, Portugal, South Korea, and the US), was used to identify 1005 adult patients without known coronary artery disease who underwent serial coronary CT angiography scans (median interscan interval, 3.3 years; interquartile range [IQR], 2.6-4.8 years) between December 24, 2003, and December 16, 2015. Based on the 10-year ASCVD risk score, the cardiovascular risk factor burden was classified as low (<7.5%), intermediate (7.5%-20.0%), or high (>20.0%). Data were analyzed from February 8, 2019, to April 17, 2020.

    Exposures  Association of baseline ASCVD risk burden with plaque progression.

    Main Outcomes and Measures  Noncalcified plaque, calcified plaque, and total plaque volumes (mm3) were measured. Noncalcified plaque was subclassified using predefined Hounsfield unit thresholds for fibrous, fibrofatty, and low-attenuation plaque. The percent atheroma volume (PAV) was defined as plaque volume divided by vessel volume. Adverse plaque characteristics were defined as the presence of positive remodeling, low-attenuation plaque, or spotty calcification.

    Results  In total, 1005 patients (mean [SD] age, 60 [8] years; 575 men [57.2%]) were included in the analysis. Of those, 463 patients (46.1%) had a low 10-year ASCVD risk score (low-risk group), 373 patients (37.1%) had an intermediate ASCVD risk score (intermediate-risk group), and 169 patients (16.8%) had a high ASCVD risk score (high-risk group). The annualized progression rate of PAV for total plaque, calcified plaque, and noncalcified plaque was associated with increasing ASCVD risk (r = 0.26 for total plaque, r = 0.23 for calcified plaque, and r = 0.11 for noncalcified plaque; P < .001). The annualized PAV progression of total plaque, calcified plaque, and noncalcified plaque was significantly greater in the high-risk group compared with the low-risk and intermediate-risk groups (for total plaque, 0.99% vs 0.45% and 0.58%, respectively; P < .001; for calcified plaque, 0.61% vs 0.23% and 0.36%; P < .001; and for noncalcified plaque, 0.38%vs 0.22% and 0.23%; P = .01). When further subclassified by noncalcified plaque type, the annualized PAV progression of fibrofatty and low-attenuation plaque was greater in the high-risk group (0.09% and 0.02%, respectively) compared with the low- to intermediate-risk group (n = 836; 0.02% [P = .02] and 0.001% [P = .008], respectively). The interval development of adverse plaque characteristics was greater in the high-risk group compared with the low-risk and intermediate-risk groups (for new positive remodeling, 73 patients [43.2%] vs 151 patients [32.6%] and 133 patients [35.7%], respectively; P = .02; for new low-attenuation plaque, 26 patients [15.4%] vs 44 patients [9.5%] and 35 patients [9.4%]; P = .02; and for new spotty calcification, 37 patients [21.9%] vs 52 patients [11.2%] and 54 patients [14.5%]; P = .002). The progression of noncalcified plaque subclasses and the interval development of adverse plaque characteristics did not significantly differ between the low-risk and intermediate-risk groups.

    Conclusions and Relevance  Progression of coronary atherosclerosis occurred across all ASCVD risk groups and was associated with an increase in 10-year ASCVD risk. The progression of fibrofatty and low-attenuation plaques and the development of adverse plaque characteristics was greater in patients with a high risk of ASCVD.

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