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. 2023 Feb 3;15(3):781.
doi: 10.3390/nu15030781.

Proteomic Mediators of Overall Cardiovascular Health on All-Cause Mortality

Toshiko Tanaka  1 , Sameera A Talegawkar  2 , Yichen Jin  2 , Julián Candia  1 , Giovanna Fantoni  1 , Stefania Bandinelli  3 , Luigi Ferrucci  2
Affiliations

Proteomic Mediators of Overall Cardiovascular Health on All-Cause Mortality

Toshiko Tanaka et al. Nutrients. .

Abstract

Measures of cardiovascular health (CVH) assessed by a combination of behavioral and biological factors has shown protective associations with all-cause mortality. The mechanisms underlying these associations have not been fully elucidated. In this study, we characterized the plasma proteomics profile of CVH and tested whether specific proteins mediated the associations between CVH and all-cause mortality in participants of the InCHIANTI study. Of the 1301 proteins tested, 92 proteins were associated with CVH (22 positively, 70 negatively). Proteins most strongly associated with CVH included leptin (LEP), fatty acid binding protein 3 (FABP3), Angiopoietin-2 (ANGPT2), and growth-differential factor 15 (GDF15). Of the 92 CVH-associated proteins, 33 proteins significantly mediated the associations between CVH and all-cause mortality, with percent mediation ranging from 5 to 30%. The most significant mediating proteins were GDF15 and insulin-like growth factor 2 (IGFBP2). Proteins associated with better CVH were enriched for proteins that reflect the suppression of the complement coagulation and GH/IGF pathways.

Keywords: all-cause mortality; cardiovascular health; mediation; proteomics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Heatmap displaying the associations between plasma proteins with cardiovascular health (CVH) and individual components of CVH: smoking, physical activity, smoking, blood pressure, total cholesterol, fasting glucose, and body mass index (BMI). None of the CVH associated proteins were associated with dietary intake component.
Figure 2
Figure 2
The mediating effect of individual plasma protein on the relationship between CVH and all-cause mortality. Higher CVH was negatively associated with all-cause mortality (white circle). Inclusion of individual plasma proteins significantly changed the magnitude of association (black circle), reflecting the mediation effect. Of the 92 CVH associated proteins, 33 proteins significantly mediated the relationship between CVH and all-cause mortality.
See this image and copyright information in PMC

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