Abstract
Biological processes underlying decreased cerebral blood flow (CBF) in patients with cardiovascular disease (CVD) are largely unknown. We hypothesized that identification of protein clusters associated with lower CBF in patients with CVD may explain underlying processes. In 428 participants (74% cardiovascular diseases; 26% reference participants) from the Heart-Brain Connection Study, we assessed the relationship between 92 plasma proteins from the Olink® cardiovascular III panel and normal-appearing grey matter CBF, using affinity propagation and hierarchical clustering algorithms, and generated a Biomarker Compound Score (BCS). The BCS was related to cardiovascular risk and observed cardiovascular events within 2-year follow-up using Spearman correlation and logistic regression. Thirteen proteins were associated with CBF (ρSpearman range: −0.10 to −0.19, pFDR-corrected <0.05), and formed one cluster. The cluster primarily reflected extracellular matrix organization processes. The BCS was higher in patients with CVD compared to reference participants (pFDR-corrected <0.05) and was associated with cardiovascular risk (ρSpearman 0.42, p < 0.001) and cardiovascular events (OR 2.05, p < 0.01). In conclusion, we identified a cluster of plasma proteins related to CBF, reflecting extracellular matrix organization processes, that is also related to future cardiovascular events in patients with CVD, representing potential targets to preserve CBF and mitigate cardiovascular risk in patients with CVD.
| Original language | English |
|---|---|
| Pages (from-to) | 2060-2071 |
| Number of pages | 12 |
| Journal | Journal of Cerebral Blood Flow and Metabolism |
| Volume | 43 |
| Issue number | 12 |
| Early online date | 12 Aug 2023 |
| DOIs | |
| Publication status | Published - Dec 2023 |
Bibliographical note
Funding Information:The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The HBC (Heart-Brain Connection) Consortium is supported by the Netherlands CardioVascular Research Initiative: The Dutch Heart Foundation (CVON 2018-28 & 2012-06 Heart Brain Connection), Dutch Federation of University Medical Centers, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences. J. de Bresser is supported by Alzheimer Nederland (WE.03-2019-08). E.E. Bron is supported by Dutch Heart Foundation (PPP Allowance, 2018B011). G.J. Biessels is supported by ZonMw, The Netherlands, Organization for Health Research and Development VICI Grant 918.16.616). M.J.P. van Osch is supported by the Netherlands Organization for Scientific Research (NOW) (VICI grant 016.160.351). C.E. Teunissen is supported by the European Commission (Marie Curie International Training Network, grant agreement No 860197, Innovative Medicines Initiatives 3TR (Horizon 2020, grant 831434), and JPND (bPRIDE), National MS Society (Progressive MS alliance) and Health Holland, the Dutch Research Council (ZonMW), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands, Alzheimer Association. C.E. Teunissen is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). Acknowledgements
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© The Author(s) 2023.
