Inflammatory biomarkers, cerebral microbleeds, and small vessel disease: Framingham heart study

Ashkan Shoamanesh, Sarah R. Preis, Alexa S. Beiser, Ramachandran S. Vasan, Emelia J. Benjamin, Carlos S. Kase, Philip A. Wolf, Charles DeCarli, Jose R. Romero, Sudha Seshadri

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

Objective: We investigated the association between circulating biomarkers of inflammation and MRI markers of small vessel disease. Methods: We performed a cross-sectional study relating a panel of 15 biomarkers, representing systemic inflammation (high-sensitivity C-reactive protein, interleukin-6, monocyte chemotactic protein-1, tumor necrosis factor, tumor necrosis factor receptor 2, osteoprotegerin, and fibrinogen), vascular inflammation (intercellular adhesion molecule 1, CD40 ligand, P-selectin, lipoprotein-associated phospholipase A2 mass and activity, total homocysteine, and vascular endothelial growth factor), and oxidative stress (myeloperoxidase) to ischemic (white matter hyperintensities/silent cerebral infarcts) and hemorrhagic (cerebral microbleeds) markers of cerebral small vessel disease (CSVD) on MRI in 1,763 stroke-free Framingham offspring (mean age 60.2 ± 9.1 years, 53.7% women). Results: We observed higher levels of circulating tumor necrosis factor receptor 2 and myeloperoxidase in the presence of cerebral microbleed (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.1-4.1 and OR 1.5, 95% CI 1.1-2.0, respectively), higher levels of osteoprotegerin (OR 1.1, 95% CI 1.0-1.2), intercellular adhesion molecule 1 (OR 1.7, 95% CI 1.1-2.5), and lipoprotein-associated phospholipase A2 mass (OR 1.5, 95% CI 1.1-2.1), and lower myeloperoxidase (OR 0.8, 95% CI 0.7-1.0) in participants with greater white matter hyperintensity volumes and silent cerebral infarcts. Conclusions: Our study supports a possible role for inflammation in the pathogenesis of CSVD, but suggests that differing inflammatory pathways may underlie ischemic and hemorrhagic subtypes. If validated in other samples, these biomarkers may improve stroke risk prognostication and point to novel therapeutic targets to combat CSVD.

Original languageEnglish (US)
Pages (from-to)825-832
Number of pages8
JournalNeurology
Volume84
Issue number8
DOIs
StatePublished - Feb 24 2015
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology

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    Shoamanesh, A., Preis, S. R., Beiser, A. S., Vasan, R. S., Benjamin, E. J., Kase, C. S., Wolf, P. A., DeCarli, C., Romero, J. R., & Seshadri, S. (2015). Inflammatory biomarkers, cerebral microbleeds, and small vessel disease: Framingham heart study. Neurology, 84(8), 825-832. https://doi.org/10.1212/WNL.0000000000001279