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Original Investigation
August 18, 2021

Association of Statin Treatment With Progression of Coronary Atherosclerotic Plaque Composition

Author Affiliations
  • 1Department of Radiology, Dalio Institute of Cardiovascular Imaging, NewYork–Presbyterian Hospital and Weill Cornell Medicine, New York
  • 2Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
  • 3Department of Molecular Medicine, Section of Cardiology, University of Pavia, Pavia, Italy
  • 4Department of Healthcare Policy and Research, NewYork–Presbyterian Hospital and Weill Cornell Medical College, New York
  • 5Centro Cardiologico Monzino, IRCCS Milan, Italy
  • 6Houston Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, Texas
  • 7Department of Medicine, Los Angeles Biomedical Research Institute, Torrance, California
  • 8Cardiovascular Imaging Center, SDN IRCCS, Naples, Italy
  • 9Department of Cardiology, William Beaumont Hospital, Royal Oak, Michigan
  • 10Pusan University Hospital, Busan, South Korea
  • 11UNICA, Unit of Cardiovascular Imaging, Hospital da Luz, Lisboa, Portugal
  • 12Department of Radiology, Casa de Saude São Jose, Rio de Janeiro, Brazil
  • 13Department of Radiology and Nuclear Medicine, German Heart Center Munich, Munich, Germany
  • 14Department of Medicine and Radiology, University of British Columbia, Vancouver, British Columbia, Canada
  • 15Department of Radiology, Area Vasta 1/ASUR Marche, Urbino, Italy
  • 16Division of Cardiology, Department of Internal Medicine, Ewha Woman’s University Seoul Hospital, Seoul, Korea
  • 17Department of Internal Medicine, Seoul National University College of Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, South Korea
  • 18Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
  • 19Seoul National University Bundang Hospital, Sungnam, South Korea
  • 20Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea
  • 21Yonsei-Cedars-Sinai Integrative Cardiovascular Imaging Research Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea
  • 22Department of Pathology, CVPath Institute, Gaithersburg, Maryland
  • 23Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia
  • 24Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
  • 25Department of Imaging and Medicine, Cedars Sinai Medical Center, Los Angeles, California
  • 26Icahn School of Medicine at Mount Sinai, Mount Sinai Heart, Zena and Michael A. Wiener Cardiovascular Institute, and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, New York, New York
  • 27Cleerly Inc, New York, New York
  • 28Heart Center, University of Turku and Turku University Hospital, Turku, Finland
  • 29Ontact Health Inc, Seoul, South Korea
JAMA Cardiol. 2021;6(11):1257-1266. doi:10.1001/jamacardio.2021.3055
Key Points

Question  Is statin therapy associated with atherosclerotic plaque progression as assessed across a range of density measurements by coronary computed tomography angiography?

Findings  In this cohort study assessing serial coronary computed tomography angiographic images of 2458 coronary lesions among 857 patients, untreated coronary lesions progressed in volume for all 6 compositional plaque types—low attenuation (−30 to 75 Hounsfield units [HU]), fibro-fatty (76-130 HU), fibrous (131-350 HU), low-density calcium (351-700 HU), high-density calcium (701-1000 HU), and 1K (>1000 HU) plaque—whereas statin therapy was associated with decreases in low-attenuation and fibro-fatty plaque and with greater progression of high-density calcium and 1K plaque. Statin therapy was not associated with a change in calcified plaque but with a transformation toward more dense calcium, which was associated with slower overall plaque progression.

Meaning  These results suggest an association of statin use with greater rates of transformation of coronary atherosclerosis toward high-density calcium, supporting the concept of reduced atherosclerotic risk with increased densification of calcium.

Abstract

Importance  The density of atherosclerotic plaque forms the basis for categorizing calcified and noncalcified morphology of plaques.

Objective  To assess whether alterations in plaque across a range of density measurements provide a more detailed understanding of atherosclerotic disease progression.

Design, Setting, and Participants  This cohort study enrolled 857 patients who underwent serial coronary computed tomography angiography 2 or more years apart and had quantitative measurements of coronary plaques throughout the entire coronary artery tree. The study was conducted from 2013 to 2016 at 13 sites in 7 countries.

Main Outcomes and Measures  The main outcome was progression of plaque composition of individual coronary plaques. Six plaque composition types were defined on a voxel-level basis according to the plaque attenuation (expressed in Hounsfield units [HU]): low attenuation (−30 to 75 HU), fibro-fatty (76-130 HU), fibrous (131-350 HU), low-density calcium (351-700 HU), high-density calcium (701-1000 HU), and 1K (>1000 HU). The progression rates of these 6 compositional plaque types were evaluated according to the interaction between statin use and baseline plaque volume, adjusted for risk factors and time interval between scans. Plaque progression was also examined based on baseline calcium density. Analysis was performed among lesions matched at baseline and follow-up. Data analyses were conducted from August 2019 through March 2020.

Results  In total, 2458 coronary lesions in 857 patients (mean [SD] age, 62.1 [8.7] years; 540 [63.0%] men; 548 [63.9%] received statin therapy) were included. Untreated coronary lesions increased in volume over time for all 6 compositional types. Statin therapy was associated with volume decreases in low-attenuation plaque (β, −0.02; 95% CI, −0.03 to −0.01; P = .001) and fibro-fatty plaque (β, −0.03; 95% CI, −0.04 to −0.02; P < .001) and greater progression of high-density calcium plaque (β, 0.02; 95% CI, 0.01-0.03; P < .001) and 1K plaque (β, 0.02; 95% CI, 0.01-0.03; P < .001). When analyses were restricted to lesions without low-attenuation plaque or fibro-fatty plaque at baseline, statin therapy was not associated with a change in overall calcified plaque volume (β, −0.03; 95% CI, −0.08 to 0.02; P = .24) but was associated with a transformation toward more dense calcium. Interaction analysis between baseline plaque volume and calcium density showed that more dense coronary calcium was associated with less plaque progression.

Conclusions and Relevance  The results suggest an association of statin use with greater rates of transformation of coronary atherosclerosis toward high-density calcium. A pattern of slower overall plaque progression was observed with increasing density. All findings support the concept of reduced atherosclerotic risk with increased densification of calcium.

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    1 Comment for this article
    Transparency of disclosures
    Jon Block, J.D. | Retired attorney
    In a study concluding that statin use is beneficial, and, in which there are a large number of corporate disclosures, it would be more transparent to state whether these companies and/or their subsidiaries manufacture/distribute statin drugs.
    CONFLICT OF INTEREST: None Reported
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