January 25, 2024Open Access
Proteomics for heart failure risk stratification: a systematic review
Key Result
High-throughput proteomic profiling identified 21 common proteins associated with all-cause death in heart failure with reduced ejection fraction, including WAP four-disulfide core domain protein 2.
Study Design
Type
Systematic Review (n=7,773)
Structured PICO
Does high-throughput proteomics identify protein signatures associated with mortality in patients with heart failure?
P
Population
7,773 adults with heart failure across 9 observational studies followed for 9 to 60 months to evaluate high-throughput proteomic signatures associated with mortality.
E
Exposure
High-throughput proteomics using aptamer or antibody-based affinity platforms on human plasma or serum
O
Outcome
All-cause or cardiovascular deathhard clinical
High-throughput proteomics identifies some common protein signatures associated with heart failure mortality, but significant methodological heterogeneity currently limits broad clinical application.
Limitations
- Considerable heterogeneity across studies in measurement panels, HF definitions, ejection fraction categorization, follow-up duration, and outcome definitions.
- Lack of risk estimates for most protein associations precluded a meta-analysis.
- Antibody-based studies used panels containing only a subset of available proteins, limiting overlap with aptamer studies.
Abstract
BACKGROUND: Heart failure (HF) is a complex clinical syndrome with persistently high mortality. High-throughput proteomic technologies offer new opportunities to improve HF risk stratification, but their contribution remains to be clearly defined. We aimed to systematically review prognostic studies using high-throughput proteomics to identify protein signatures associated with HF mortality. METHODS: We searched four databases and two clinical trial registries for articles published from 2012 to 2023. HF proteomics studies measuring high numbers of proteins using aptamer or antibody-based affinity platforms on human plasma or serum with outcomes of all-cause or cardiovascular death were included. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. A third reviewer resolved conflicts. We assessed the risk of bias using the Risk Of Bias In Non-randomized Studies-of Exposure tool. RESULTS: Out of 5131 unique articles identified, nine articles were included in the review. The nine studies were observational; three used the aptamer platform, and six used the antibody platform. We found considerable heterogeneity across studies in measurement panels, HF definitions, ejection fraction categorization, follow-up duration, and outcome definitions, and a lack of risk estimates for most protein associations. Hence, we proceeded with a systematic review rather than a meta-analysis. In two comparable aptamer studies in patients with HF with reduced ejection fraction, 21 proteins were identified in common for the association with all-cause death. Among these, one protein, WAP four-disulfide core domain protein 2 was also reported in an antibody study on HFrEF and for the association with CV death. We proposed standardized reporting criteria to facilitate the interpretation of future studies. CONCLUSIONS: In this systematic review of nine studies evaluating the association of proteomics with mortality in HF, we identified a limited number of proteins common across several studies. Heterogeneity across studies compromised drawing broad inferences, underscoring the importance of standardized approaches to reporting.
Cite This Study
Kuku et al. (Thu,) conducted a systematic review in Heart failure (n=7,773). High-throughput proteomic profiling was evaluated on All-cause or cardiovascular death. High-throughput proteomic profiling identified 21 common proteins associated with all-cause death in heart failure with reduced ejection fraction, including WAP four-disulfide core domain protein 2.