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

Reilly, Cavan S; Borges, Álvaro H; Baker, Jason V; Safo, Sandra E; Sharma, Shweta; Polizzotto, Mark N; Pankow, James S; ... Lane, H Clifford; + view all (2023) Investigation of Causal Effects of Protein Biomarkers on Cardiovascular Disease in Persons with HIV. The Journal of Infectious Diseases , 227 (8) pp. 951-960. 10.1093/infdis/jiac496. Green open access

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Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. 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 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.

Type: Article
Title: Investigation of Causal Effects of Protein Biomarkers on Cardiovascular Disease in Persons with HIV
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/infdis/jiac496
Publisher version: https://doi.org/10.1093/infdis/jiac496
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Mendelian randomization, fibrosis, inflammation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10162692
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