A cluster of blood-based protein biomarkers reflecting coagulation relates to the burden of cerebral small vessel disease

Kuipers, Sanne; Overmars, L. Malin; Es, Bram van; Bresser, Jeroen de; Bron, Esther E.; Hoefer, Imo E.; Kappelle, L. Jaap; Teunissen, Charlotte E.; Biessels, Geert Jan; Haitjema, Saskia

doi:10.1177/0271678x221077339

Cited by 14 publications

(21 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the authors found a mediation effect of the biomarker cluster on the relation between age and WMH ratio (proportion mediated 17%), and hypertension and WMH volume (proportion mediated 21%). Therefore, the authors suggested the involvement of coagulation abnormalities in the etiology of CSVD 135 . In conclusion, these studies suggest that the composite measures of multiple functional‐interrelated biomarkers may be more relevant to CSVD than individual biomarkers.…”

Section: Resultsmentioning

confidence: 90%

See 1 more Smart Citation

Plasma inflammatory biomarkers in cerebral small vessel disease: A review

et al. 2022

View full text Add to dashboard Cite

Cerebral small vessel disease (CSVD) is a group of pathological processes affecting small arteries, arterioles, capillaries, and small veins of the brain. It is one of the most common subtypes of cerebrovascular diseases, especially highly prevalent in elderly populations, and is associated with stroke occurrence and recurrence, cognitive impairment, gait disorders, psychological disturbance, and dysuria. Its diagnosis mainly depends on MRI, characterized by recent small subcortical infarcts, lacunes, white matter hyperintensities (WMHs), enlarged perivascular spaces (EPVS), cerebral microbleeds (CMBs), and brain atrophy. While the pathophysiological processes of CSVD are not fully understood at present, inflammation is noticed as playing an important role. Herein, we aimed to review the relationship between plasma inflammatory biomarkers and the MRI features of CSVD, to provide background for further research.

show abstract

Section: Resultsmentioning

confidence: 90%

“…Therefore, the authors suggested the involvement of coagulation abnormalities in the etiology of CSVD. 135 In conclusion, these studies suggest that the composite measures of multiple functional-interrelated biomarkers may be more relevant to CSVD than individual biomarkers.…”

Section: Ta B L E 3 Associations Of Hemostasis Factors With Mri Featu...mentioning

confidence: 75%

Plasma inflammatory biomarkers in cerebral small vessel disease: A review

et al. 2022

View full text Add to dashboard Cite

show abstract

“…7 Since not all existing proteinprotein interactions are already known, we used both prior knowledge and data-driven cluster analyses based on our Olink V R data to suggest novel protein-protein interactions. This combination of prior knowledge and data-driven cluster analyses also proved effective in previous studies, such as in cerebral small vessel disease, 7 diabetes, 26 heart failure, 27,28 and cancer. 6,29 Of note, the mean differences in CBF between patients and controls were modest and the relationship between lower CBF and MACE was not statistically significant.…”

Section: Discussionmentioning

confidence: 99%

A cluster of blood-based protein biomarkers associated with decreased cerebral blood flow relates to future cardiovascular events in patients with cardiovascular disease

Overmars

Kuipers

et al. 2023

J Cereb Blood Flow Metab

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Typical neuroimaging features of CSVD on magnetic resonance imaging (MRI) include white matter hyperintensity (WMH), lacunes, enlarged perivascular spaces (EPVS), cerebral microbleeds (CMBs), and brain atrophy (BA) 3 . Previous studies have identified a spectrum of traditional vascular risk factors and blood‐based biomarkers for CSVD 4–7 . However, despite abundant literature on this subject, these is insufficient explanation regarding the biological processes of CSVD.…”

Section: Introductionmentioning

confidence: 99%

“… 3 Previous studies have identified a spectrum of traditional vascular risk factors and blood‐based biomarkers for CSVD. 4 , 5 , 6 , 7 However, despite abundant literature on this subject, these is insufficient explanation regarding the biological processes of CSVD. Therefore, identifying novel biomarkers for a better understanding of CSVD may provide a strong foundation for advances in knowledge and clinical management.…”

Section: Introductionmentioning

confidence: 99%