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

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

Research output: Contribution to journalArticlepeer-review


Background: There is an incompletely understood increased risk for cardiovascular disease (CVD) among people with HIV (PWH). We investigated if a collection of biomarkers were associated with CVD among PWH. Mendelian randomization (MR) was used to identify potentially causal associations. Methods: Data from follow-up in 4 large trials among PWH 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. Results: Univariate analysis found CLEC6A, HGF, IL-6, IL-10RB, and IGFBP7 as being associated with case status and a multivariate model identified 3 of these: CLEC6A (odds ratio [OR] = 1.48, P =. 037), HGF (OR = 1.83, P =. 012), and IL-6 (OR = 1.45, P =. 016). MR methods identified 5 significantly associated proteins: AXL, CHI3L1, GAS6, IL-6RA, and SCGB3A2. Conclusions: 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 PWH (IL-6 and its receptor), some are novel to PWH (HGF, AXL, and GAS6) and some are novel overall (CLEC6A). Further investigation into the uniqueness of these biomarkers in PWH and the role of these biomarkers as targets among PWH is warranted.

Original languageEnglish (US)
Pages (from-to)951-960
Number of pages10
JournalJournal of Infectious Diseases
Issue number8
StatePublished - Apr 15 2023

Bibliographical note

Funding Information:
Financial support . This work was supported by the National Institutes of Health (grant number HHSN261200800001E).

Publisher Copyright:
© 2022 The Author(s).


  • fibrosis
  • inflammation
  • mendelian randomization

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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