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IL-6, PF-4, sCD40 L, and homocysteine are associated with the radiological progression of cerebral small-vessel disease: a 2-year follow-up study

Authors Staszewski J, Piusińska-Macoch R, Brodacki B, Skrobowska E, Stępień A

Received 27 February 2018

Accepted for publication 18 April 2018

Published 19 June 2018 Volume 2018:13 Pages 1135—1141


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Richard Walker

Jacek Staszewski,1 Renata Piusińska-Macoch,1 Bogdan Brodacki,1 Ewa Skrobowska,2 Adam Stępień1

1Clinic of Neurology, 2Department of Radiology, Military Institute of Medicine, Warsaw, Poland

Background: Endothelial dysfunction (ED) is involved in the pathogenesis of cerebral small vessel disease (SVD), however, it is not clear if specific biomarkers related to ED are associated with radiological progression of SVD.
Methods: A single-center, prospective cohort study was conducted among consecutive, adult patients with SVD. Logistic regression was used to analyze the association of each baseline biomarker (highest vs lowest tertile) and the MRI radiological outcome after 2 years. The mean Z-score for vascular inflammation (VI) combined soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble platelet selectin (sP-selectin), CD40 ligand (sCD40 L), platelet factor-4 (PF-4) and homocysteine; Z-score for systemic inflammation (SI) combined high-sensitivity C-reactive protein (hsCRP), interleukin-1α and -6 (IL-1α and IL-6, respectively) and tumor necrosis factor-α (TNF-α).
Results: The study group comprised 123 patients (age, mean±SD: 72.2±8 years, 49% females), with lacunar stroke (n=49), vascular dementia (n=48), and vascular parkinsonism (n=26). Moreover, 34.9% patients experienced radiological progression, 43% had progression of isolated white matter lesions (WMLs), 23.2% had new lacunes, and 34.8% had both WMLs progression and new lacunes. After adjustment for confounders (age, sex, blood pressure, MRI lesions load), the PF-4 (OR; 95% CI 5.5; 1.5–21), sCD40L (4.6; 1.1–18.6), IL-6 (7.4; 1.48–37), Z-score for VI (4.5; 1.1–18.6), and, marginally, homocysteine (4.1; 0.99–17) were associated with the risk of any radiological progression; further, homocysteine (2.4; 1.4–14), Z-score for SI (2.1; 1.2–14) and, marginally, IL-6 (6.0; 0.95 -38) were related to the development of new lacunes; PF-4 (7.9; 1.6–38) and, marginally, the Z-score for VI (4.2; 0.9–19.5) were correlated with the risk of WMLs progression. Additional adjustment for clinical SVD manifestations did not significantly alter the results.
Conclusion: The data supports the concept that ED modulates the radiological progression of SVD and WMLs and lacunes are associated with different inflammatory markers.

cerebral small-vessel disease, radiological progression, IL-6, PF-4, sCD40 L, homocysteine

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