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Investigation of Causal Effects of Protein Biomarkers on Cardiovascular Disease in Persons with HIV

  1. Author:
    Reilly, Cavan S
    Borges, Álvaro H
    Baker, Jason V
    Safo, Sandra E
    Sharma, Shweta
    Polizzotto, Mark N
    Pankow, James S
    Hu, Xiaojun
    Sherman,Brad
    Babiker, Abdel G
    Lundgren, Jens D
    Lane, H Clifford [ORCID]

  2. Author Address

    Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA., Immunology, Statens Serum Institut, Copenhagen, Denmark., HIV Medicine, Infectious Diseases, Hennepin County Medical Center, Minneapolis, MN, USA., Department of Medicine, Australian National University, Canberra, Australia., Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA., Animal and Plant Inspection Service, USDA, Beltsville, MD, USA., Laboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratories, Frederick, MD, USA., Epidemiology and Medical Statistics, University College London, London, United Kingdom., Department of Infectious Diseases, University of Copenhagen, Copenhagen, Denmark., Division of Clinical Research, National Institutes of Allergy and Infectious Diseases, USA.,
    1. Year: 2022
    2. Date: Dec 29
    3. Epub Date: 2022 12 29
  2. Journal: The Journal of Infectious Diseases
  4. Type of Article: Article
  1. Abstract:

    There is an incompletely understood increased risk for cardiovascular disease (CVD) among people living with HIV (PLWH). We investigated if a collection of biomarkers were associated with CVD among PLWH. Mendelian randomization (MR) was used to identify potentially causal associations. Data from follow-up in 4 large trials among PLWH were used to identify 131 incident CVD cases and they were matched to 259 participants without incident CVD (controls). Tests of associations between 460 baseline protein levels and case status were conducted. Univariate analysis found CLEC6A, HGF, IL6, IL10RB, and IGFBP7 as being associated with case status and a multivariate model identified 3 of these: CLEC6A (OR = 1.48, p?=?0.037), HGF (OR = 1.83, p?=?0.012) and IL6 (OR = 1.45, p?=?0.016). MR methods identified 5 significantly associated proteins: AXL, CHI3L1, GAS6, IL6RA, and SCGB3A2. These results implicate inflammatory and fibrotic processes as contributing to CVD. While some of these biomarkers are well established in the general population and in PLWH (IL6 and its receptor), some are novel to PLWH (HGF, AXL and GAS6) and some are novel overall (CLEC6A). Further investigation into; 1.) the uniqueness of these biomarkers in PLWH and 2.) the role of these biomarkers as targets among PLWH, is warranted. © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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  2. DOI: 10.1093/infdis/jiac496
  3. PMID: 36580481
  4. PII : 6965280

Library Notes

  1. Fiscal Year: FY2022-2023
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