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Clinical Research and Public HealthIn-Press PreviewAIDS/HIVCardiologyInflammation Open Access | 10.1172/JCI196021

Statin-dependent and -independent pathways are associated with major adverse cardiovascular events in people with HIV

Márton Kolossváry,1 Irini Sereti,2 Markella V. Zanni,1 Carl J. Fichtenbaum,3 Judith A Aberg,4 Gerald S. Bloomfield,5 Carlos D. Malvestutto,6 Judith S. Currier,7 Sarah M. Chu,1 Marissa R. Diggs,1 Alex B. Lu,1 Christopher deFilippi,8 Borek Foldyna,9 Sara McCallum,1 Craig A. Sponseller,10 Michael T. Lu,9 Pamela S. Douglas,11 Heather J. Ribaudo,12 and Steven K. Grinspoon1

1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

Find articles by Kolossváry, M. in: PubMed | Google Scholar

1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, United States of America

4Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Department of Medicine, Duke Global Health Institute and Duke Clinical Rese, Duke University School of Medicine, Durham, United States of America

6Division of Infectious Diseases, Ohio State University Medical Center, Columbus, United States of America

7Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, United States of America

8Inova Schar Heart and Vascular, Falls Church, United States of America

9Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

10Kowa Pharmaceuticals America Inc., Montgomery, United States of America

11Duke Clinical Research Institute, Duke University School of Medicine, Durham, United States of America

12Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, United States of America

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Published September 9, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI196021.
Copyright © 2025, Kolossváry et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published September 9, 2025 - Version history
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Abstract

Background. Statin therapy lowers the risk of major adverse cardiovascular events (MACE) among people with HIV (PWH). Residual risk pathways contributing to excess MACE beyond low-density lipoprotein cholesterol (LDL-C) are not well understood. Our objective was to evaluate the association of statin responsive and other inflammatory and metabolic pathways to MACE in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE).

Methods. Cox proportional hazards models were used to assess the relationship between MACE and proteomic measurements at study entry and year 2 adjusting for time-updated statin use and baseline 10-year atherosclerotic cardiovascular disease risk score. We built a machine learning (ML) model to predict MACE using baseline proteins values with significant associations.

Results. In 765 individuals (age: 50.8±5.9 years, 82% males) among 7 proteins changing with statin vs. placebo, angiopoietin-related protein 3 (ANGPTL3) related most strongly to MACE (aHR: 2.31 per 2-fold higher levels; 95%CI: 1.11-4.80; p=0.03), such that lower levels of ANGPTL3 achieved with statin therapy were associated with lower MACE risk. Among 248 proteins not changing in response to statin therapy, 26 were associated with MACE at FDR<0.05. These proteins represented predominantly humoral immune response, leukocyte chemotaxis, and cytokine pathways. Our proteomic ML model achieved a 10-fold cross-validated c-index of 0.74±0.11 to predict MACE, improving on models using traditional risk prediction scores only (c-index: 0.61±0.18).

Conclusions. ANGPTL3, as well as key inflammatory pathways may contribute to residual risk of MACE among PWH, beyond LDL-C.

Trial registration. ClinicalTrials.gov: NCT02344290.

Funding. NIH, Kowa, Gilead Sciences, ViiV.

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Version history
  • Version 1 (September 9, 2025): In-Press Preview
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