Abstract
Biological processes underlying cerebral small vessel disease (cSVD) are largely unknown. We hypothesized that identification of clusters of inter-related bood-based biomarkers that are associated with the burden of cSVD provides leads on underlying biological processes. In 494 participants (mean age 67.6 ± 8.7 years; 36% female; 75% cardiovascular diseases; 25% reference participants) we assessed the relation between 92 blood-based biomarkers from the OLINK cardiovascular III panel and cSVD, using cluster-based analyses. We focused particularly on white matter hyperintensities (WMH). Nineteen biomarkers individually correlated with WMH ratio (r range: 0.16–0.27, Bonferroni corrected p-values <0.05), of which sixteen biomarkers formed one biomarker cluster. Pathway analysis showed that this biomarker cluster predominantly reflected coagulation processes. This cluster related also significantly to other cSVD manifestations (lacunar infarcts, microbleeds, and enlarged perivascular spaces), which supports generalizability beyond WMHs. To study possible causal effects of biological processes reflected by the cluster we performed a mediation analysis that showed a mediation effect of the cluster on the relation between age and WMH ratio (proportion mediated 17%), and hypertension and WMH-volume (proportion mediated 21%). In conclusion, we identified a cluster of blood-based biomarkers reflecting coagulation, that is related to manifestations of cSVD, corroborating involvement of coagulation abnormalities in the etiology of cSVD.
| Original language | English |
|---|---|
| Pages (from-to) | 1282-1293 |
| Number of pages | 12 |
| Journal | Journal of Cerebral Blood Flow and Metabolism |
| Volume | 42 |
| Issue number | 7 |
| Early online date | 27 Jan 2022 |
| DOIs | |
| Publication status | Published - Jul 2022 |
Bibliographical note
Funding Information:We gratefully acknowledge the contribution of researchers and participants of the HBC (Heart-Brain Connection) Consortium. 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). GJ Biessels is supported by ZonMw, The Netherlands, Organization for Health Research and Development Vici Grant 918.16.616).
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). GJ Biessels is supported by ZonMw, The Netherlands, Organization for Health Research and Development Vici Grant 918.16.616). Acknowledgements
Publisher Copyright:
© The Author(s) 2022.
