Coronary Plaque, Inflammation, Subclinical Myocardial Injury, and Major Adverse Cardiovascular Events in the REPRIEVE Substudy

Michael T. Lu, MD, MPH; Heather J. Ribaudo, PhD; Sara McCallum, MPH; Markella V. Zanni, MD; Christopher deFilippi, MD; Jana Taron, MD; Julia Karady, MD, PhD, MPH; Borek Foldyna, MD, PhD; Kayla Paradis, MBA; Sarah M. Chu, MSN; Marissa R. Diggs, BA; Tricia H. Burdo, PhD; Judith S. Currier, MD; Gerald S. Bloomfield, MD, MPH; Carl J. Fichtenbaum, MD; Carlos D. Malvestutto, MD, MPH; Judith A. Aberg, MD; Thomas Mayrhofer, PhD; Pamela S. Douglas, MD; Steven K. Grinspoon, MD

doi:10.1016/j.jacadv.2025.101781

JACC: Advances (Jun 2025)

Coronary Plaque, Inflammation, Subclinical Myocardial Injury, and Major Adverse Cardiovascular Events in the REPRIEVE Substudy

Michael T. Lu, MD, MPH,
Heather J. Ribaudo, PhD,
Sara McCallum, MPH,
Markella V. Zanni, MD,
Christopher deFilippi, MD,
Jana Taron, MD,
Julia Karady, MD, PhD, MPH,
Borek Foldyna, MD, PhD,
Kayla Paradis, MBA,
Sarah M. Chu, MSN,
Marissa R. Diggs, BA,
Tricia H. Burdo, PhD,
Judith S. Currier, MD,
Gerald S. Bloomfield, MD, MPH,
Carl J. Fichtenbaum, MD,
Carlos D. Malvestutto, MD, MPH,
Judith A. Aberg, MD,
Thomas Mayrhofer, PhD,
Pamela S. Douglas, MD,
Steven K. Grinspoon, MD

Affiliations

Michael T. Lu, MD, MPH: Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Address for correspondence: Dr Michael T. Lu, Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 165 Cambridge Street, Ste 400, Boston, Massachusetts 02114, USA.
Heather J. Ribaudo, PhD: Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
Sara McCallum, MPH: Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
Markella V. Zanni, MD: Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
Christopher deFilippi, MD: Inova Schar Heart and Vascular, Falls Church, Virginia, USA
Jana Taron, MD: Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Radiology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany
Julia Karady, MD, PhD, MPH: Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
Borek Foldyna, MD, PhD: Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
Kayla Paradis, MBA: Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
Sarah M. Chu, MSN: Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
Marissa R. Diggs, BA: Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
Tricia H. Burdo, PhD: Department of Medicine, Rutgers Institute of Translational Medicine and Science, Robert Wood Johnson Medical School, Rutgers, The University of New Jersey, New Brunswick, New Jersey, USA
Judith S. Currier, MD: Division of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
Gerald S. Bloomfield, MD, MPH: Department of Medicine, Duke Global Health Institute and Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
Carl J. Fichtenbaum, MD: Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Carlos D. Malvestutto, MD, MPH: Division of Infectious Diseases, Ohio State University Medical Center, Columbus, Ohio, USA
Judith A. Aberg, MD: Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Thomas Mayrhofer, PhD: Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Center for Preventive Medicine and Digital Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Pamela S. Douglas, MD: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
Steven K. Grinspoon, MD: Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Dr Steven K. Grinspoon, Metabolism Unit, Massachusetts General Hospital, 50 Staniford Street, Room 768, Boston, Massachusetts 02114, USA.

DOI: https://doi.org/10.1016/j.jacadv.2025.101781
Journal volume & issue: Vol. 4, no. 6
p. 101781

Abstract

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Background: In REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV), pitavastatin prevented major adverse cardiovascular events (MACE) and reduced noncalcified coronary plaque (NCP) among people with HIV and low-to-moderate traditional cardiovascular disease (CVD) risk. Objectives: The purpose of this study was to assess the relationship of coronary plaque, inflammation, and subclinical myocardial injury with MACE. Methods: 804 REPRIEVE Mechanistic Substudy participants enrolled from April 2015 to February 2018 at 31 U.S. sites, randomized to pitavastatin 4 mg/day or placebo, and followed for incident MACE (median 6.2 years [Q1-Q3 5.4-7.1]), were assessed for relationships of baseline NCP, markers of inflammation (high-sensitivity C-reactive protein [hs-CRP], interleukin (IL)-6, oxidized low-density lipoprotein, and lipoproprotein-associated phospholipase A2), and subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT]) with MACE. Results: Among enrolled participants (17% female [139/804], 47% non-White [379/804], median age 51 years, median low-density lipoprotein 105 mg/dL, 10-year atherosclerotic CVD [ASCVD] risk 4.6%, 40% [299/755] with noncalcified plaque), MACE incidence was 7.26/1,000 (95% CI: 4.51-11.7) person-years (17 events) for pitavastatin and 9.15/1,000 person-years (95% CI: 5.97-14.0) (21 events) for placebo. The hazard of MACE was greater in those with (vs without) noncalcified plaque (HR: 2.5; [95% CI: 1.3-4.8]; P = 0.008), with higher levels of hs-CRP (P = 0.049), IL-6 (P = 0.033), and hs-cTnT (P = 0.003) at study entry, persisting after ASCVD risk adjustment. In exploratory prediction modeling, adding hs-CRP, IL-6, and hs-cTnT to ASCVD risk increased the integrated area under the curve to 0.72 and C-statistic to 0.73 (0.62-0.84) vs 0.58 and 0.56 (0.45-0.67) compared to ASCVD risk alone. Conclusions: NCP and higher hs-CRP, IL-6, and hs-cTnT were associated with MACE and improved risk prediction over traditional risk factors in people with HIV without cardiac symptoms and low-to-moderate ASCVD risk. (Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults [REPRIEVE]; NCT02344290)

Published in JACC: Advances

ISSN: 2772-963X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system; Medicine: Internal medicine: Medical emergencies. Critical care. Intensive care. First aid
Website: https://www.sciencedirect.com/journal/jacc-advances

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