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Derivation of a Protein Risk Score for Cardiovascular Disease Among a Multiracial and Multiethnic HIV+ Cohort

Safo, Sandra E; Haine, Lillian; Baker, Jason; Reilly, Cavan; Duprez, Daniel; Neaton, James D; Jain, Mamta K; ... ESPRIT, INSIGHT FIRST, SMART and START study groups; + view all (2023) Derivation of a Protein Risk Score for Cardiovascular Disease Among a Multiracial and Multiethnic HIV+ Cohort. Journal of the American Heart Association , 12 , Article e027273. 10.1161/JAHA.122.027273. Green open access

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Abstract

Background Cardiovascular disease risk prediction models underestimate CVD risk in people living with HIV (PLWH). Our goal is to derive a risk score based on protein biomarkers that could be used to predict CVD in PLWH. Methods and Results In a matched case-control study, we analyzed normalized protein expression data for participants enrolled in 1 of 4 trials conducted by INSIGHT (International Network for Strategic Initiatives in Global HIV Trials). We used dimension reduction, variable selection and resampling methods, and multivariable conditional logistic regression models to determine candidate protein biomarkers and to generate a protein score for predicting CVD in PLWH. We internally validated our findings using bootstrap. A protein score that was derived from 8 proteins (including HGF [hepatocyte growth factor] and interleukin-6) was found to be associated with an increased risk of CVD after adjustment for CVD and HIV factors (odds ratio: 2.17 [95% CI: 1.58-2.99]). The protein score improved CVD prediction when compared with predicting CVD risk using the individual proteins that comprised the protein score. Individuals with a protein score above the median score were 3.10 (95% CI, 1.83-5.41) times more likely to develop CVD than those with a protein score below the median score. Conclusions A panel of blood biomarkers may help identify PLWH at a high risk for developing CVD. If validated, such a score could be used in conjunction with established factors to identify CVD at-risk individuals who might benefit from aggressive risk reduction, ultimately shedding light on CVD pathogenesis in PLWH.

Type: Article
Title: Derivation of a Protein Risk Score for Cardiovascular Disease Among a Multiracial and Multiethnic HIV+ Cohort
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/JAHA.122.027273
Publisher version: https://doi.org/10.1161/JAHA.122.027273
Language: English
Additional information: Copyright © 2023 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Keywords: HIV, Olink, cardiovascular disease, protein biomarkers, proteomics
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 > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health
URI: https://discovery.ucl.ac.uk/id/eprint/10172656
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