Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Reilly CS

PROVIDER: S-EPMC10319949 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Reilly Cavan S CS Borges Álvaro H ÁH Baker Jason V JV Safo Sandra E SE Sharma Shweta S Polizzotto Mark N MN Pankow James S JS Hu Xiaojun X Sherman Brad T BT Babiker Abdel G AG Lundgren Jens D JD Lane H Clifford HC

The Journal of infectious diseases 20230401 8

<h4>Background</h4>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.<h4>Methods</h4>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 association ...[more]

PMID: 36580481

Similar Datasets

Project description:BackgroundThe discovery of novel and highly predictive biomarkers of cardiovascular disease (CVD) has the potential to improve risk-stratification methods and may be informative regarding biological pathways contributing to disease.Methods and resultsWe used a discovery proteomic platform that targeted high-value proteins for CVD to ascertain 85 circulating protein biomarkers in 3523 Framingham Heart Study participants (mean age, 62 years; 53% women). Using multivariable-adjusted Cox models to account for clinical variables, we found 8 biomarkers associated with incident atherosclerotic CVD, 18 with incident heart failure, 38 with all-cause mortality, and 35 with CVD death (false discovery rate, q<0.05 for all; P-value ranges, 9.8×10-34 to 3.6×10-2). Notably, a number of regulators of metabolic and adipocyte homeostasis were associated with cardiovascular events, including insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 1 (IGFBP1), insulin-like growth factor binding protein 2 (IGFBP2), leptin, and adipsin. In a multimarker approach that accounted for clinical factors, growth differentiation factor 15 (GDF15) was associated with all outcomes. In addition, N-terminal pro-b-type natriuretic peptide, C-reactive protein, and leptin were associated with incident heart failure, and C-type lectin domain family 3 member B (CLEC3B; tetranectin), N-terminal pro-b-type natriuretic peptide, arabinogalactan protein 1 (AGP1), soluble receptor for advanced glycation end products (sRAGE), peripheral myelin protein 2 (PMP2), uncarboxylated matrix Gla protein (UCMGP), kallikrein B1 (KLKB1), IGFBP2, IGF1, leptin receptor, and cystatin-C were associated with all-cause mortality in a multimarker model.ConclusionsWe identified numerous protein biomarkers that predicted cardiovascular outcomes and all-cause mortality, including biomarkers representing regulators of metabolic homeostasis and inflammatory pathways. Further studies are needed to validate our findings and define clinical utility, with the ultimate goal of improving strategies for CVD prevention.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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