Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Dec 7;10(23):e023330.
doi: 10.1161/JAHA.121.023330. Epub 2021 Nov 30.

Large-Scale Plasma Protein Profiling of Incident Myocardial Infarction, Ischemic Stroke, and Heart Failure

Lars Lind  1 , Daniela Zanetti  2 , Martin Ingelsson  3 , Stefan Gustafsson  1 , Johan Ärnlöv  4   5 , Themistocles L Assimes  2   6
Affiliations

Large-Scale Plasma Protein Profiling of Incident Myocardial Infarction, Ischemic Stroke, and Heart Failure

Lars Lind et al. J Am Heart Assoc. .

Abstract

Background We recently reported a link between plasma levels of 2 of 84 cardiovascular disease (CVD)-related proteins and the 3 major CVDs, myocardial infarction, ischemic stroke, and heart failure. The present study investigated whether measurement of almost 10 times the number of proteins could lead to discovery of additional risk markers for CVD. Methods and Results We measured 742 proteins using the proximity extension assay in 826 male participants of ULSAM (Uppsala Longitudinal Study of Adult Men) who were free from CVD at the age of 70 years. Cox proportional hazards models were adjusted for age only, as well as all traditional risk factors. During a 12.5-year median follow-up (maximal, 22.0 years), 283 incident CVDs occurred. Forty-one proteins were significantly (false discovery rate <0.05) related to the combined end point of incident CVD, with N-terminal pro-brain natriuretic peptide as the top finding, while 53 proteins were related to incident myocardial infarction. A total of 13 and 16 proteins were significantly related to incident ischemic stroke and heart failure, respectively. Growth differentiation factor 15, 4-disulfide core domain protein 2, and kidney injury molecule were related to all of the 3 major CVD outcomes. A lasso selection of 11 proteins improved discrimination of incident CVD by 5.0% (P=0.0038). Conclusions Large-scale proteomics seem useful for the discovery of new risk markers for CVD and to improve risk prediction in an elderly population of men. Further studies are needed to replicate the findings in independent samples of both men and women of different ages.

Keywords: cardiovascular disease; heart failure; myocardial infarction; proteomics; stroke.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Pairwise correlations between the 742 proteins used in the analyses.
The correlation coefficients are given by the color‐coding at the right. The names of the individual proteins cannot be given in the figure because of limitation in space, therefore the figure gives only an overview of the correlation matrix of the measured proteins.
Figure 2
Figure 2. Overview of relationships between protein associations and the 3 different cardiovascular diseases.
The table to the right gives the proteins related to myocardial infarction (MI) only. HF indicates heart failure.
See this image and copyright information in PMC

References

    1. Van der Harst P, Verweij N. Identification of 64 novel genetic loci provides an expanded view on the genetic architecture of coronary artery disease. Circ Res. 2018;122:433–443. doi: 10.1161/CIRCRESAHA.117.312086 - DOI - PMC - PubMed
    1. Malik R, Chauhan G, Traylor M, Sargurupremraj M, Okada Y, Mishra A, Rutten‐Jacobs L, Giese AK, van der Laan SW, Gretarsdottir S, et al. Multiancestry genome‐wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat Genet. 2018;50:524–537. doi: 10.1038/s41588-018-0058-3 - DOI - PMC - PubMed
    1. Shah S, Henry A, Roselli C, Lin H, Sveinbjörnsson G, Fatemifar G, Hedman ÅK, Wilk JB, Morley MP, Chaffin MD, et al. Genome‐wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Nat Commun. 2020;11:163. doi: 10.1038/s41467-019-13690-5 - DOI - PMC - PubMed
    1. Lind L, Gigante B, Borné Y, Feldreich T, Leppert J, Hedberg P, Östgren CJ, Nyström FH, Sundström J, Ärnlöv J, et al. Plasma protein profile of carotid artery atherosclerosis and atherosclerotic outcomes: meta‐analyses and mendelian randomization analyses. Arterioscler Thromb Vasc Biol. 2021;41:1777–1788. doi: 10.1161/ATVBAHA.120.315597 - DOI - PMC - PubMed
    1. Zheng J, Haberland V, Baird D, Walker V, Haycock PC, Hurle MR, Gutteridge A, Erola P, Liu Y, Luo S, et al. Phenome‐wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases. Nat Genet. 2020;52:1122–1131. doi: 10.1038/s41588-020-0682-6 - DOI - PMC - PubMed

Publication types