title: Inflammatory biomarkers, cerebral microbleeds, and small vessel disease: Framingham Heart Study.
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 α, 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.
authors: From McMaster University (A.S.), Hamilton, Canada; Harvard Medical School (A.S.), Boston; Boston University School of Public Health (S.R.P., A.S.B.); Boston University School of Medicine (A.S.B., R.S.V., E.J.B., C.S.K., P.A.W., J.R.R., S.S.), MA; and University of California (C.D.), Davis School of Medicine, Sacramento. ashkan.shoamanesh@phri.ca.
authors: Ashkan
authors: A
authors: Shoamanesh
authors: From McMaster University (A.S.), Hamilton, Canada; Harvard Medical School (A.S.), Boston; Boston University School of Public Health (S.R.P., A.S.B.); Boston University School of Medicine (A.S.B., R.S.V., E.J.B., C.S.K., P.A.W., J.R.R., S.S.), MA; and University of California (C.D.), Davis School of Medicine, Sacramento.
authors: Sarah R
authors: SR
authors: Preis
authors: From McMaster University (A.S.), Hamilton, Canada; Harvard Medical School (A.S.), Boston; Boston University School of Public Health (S.R.P., A.S.B.); Boston University School of Medicine (A.S.B., R.S.V., E.J.B., C.S.K., P.A.W., J.R.R., S.S.), MA; and University of California (C.D.), Davis School of Medicine, Sacramento.
authors: Alexa S
authors: AS
authors: Beiser
authors: From McMaster University (A.S.), Hamilton, Canada; Harvard Medical School (A.S.), Boston; Boston University School of Public Health (S.R.P., A.S.B.); Boston University School of Medicine (A.S.B., R.S.V., E.J.B., C.S.K., P.A.W., J.R.R., S.S.), MA; and University of California (C.D.), Davis School of Medicine, Sacramento.
authors: Ramachandran S
authors: RS
authors: Vasan
authors: From McMaster University (A.S.), Hamilton, Canada; Harvard Medical School (A.S.), Boston; Boston University School of Public Health (S.R.P., A.S.B.); Boston University School of Medicine (A.S.B., R.S.V., E.J.B., C.S.K., P.A.W., J.R.R., S.S.), MA; and University of California (C.D.), Davis School of Medicine, Sacramento.
authors: Emelia J
authors: EJ
authors: Benjamin
authors: From McMaster University (A.S.), Hamilton, Canada; Harvard Medical School (A.S.), Boston; Boston University School of Public Health (S.R.P., A.S.B.); Boston University School of Medicine (A.S.B., R.S.V., E.J.B., C.S.K., P.A.W., J.R.R., S.S.), MA; and University of California (C.D.), Davis School of Medicine, Sacramento.
authors: Carlos S
authors: CS
authors: Kase
authors: From McMaster University (A.S.), Hamilton, Canada; Harvard Medical School (A.S.), Boston; Boston University School of Public Health (S.R.P., A.S.B.); Boston University School of Medicine (A.S.B., R.S.V., E.J.B., C.S.K., P.A.W., J.R.R., S.S.), MA; and University of California (C.D.), Davis School of Medicine, Sacramento.
authors: Philip A
authors: PA
authors: Wolf
authors: From McMaster University (A.S.), Hamilton, Canada; Harvard Medical School (A.S.), Boston; Boston University School of Public Health (S.R.P., A.S.B.); Boston University School of Medicine (A.S.B., R.S.V., E.J.B., C.S.K., P.A.W., J.R.R., S.S.), MA; and University of California (C.D.), Davis School of Medicine, Sacramento.
authors: Charles
authors: C
authors: DeCarli
authors: From McMaster University (A.S.), Hamilton, Canada; Harvard Medical School (A.S.), Boston; Boston University School of Public Health (S.R.P., A.S.B.); Boston University School of Medicine (A.S.B., R.S.V., E.J.B., C.S.K., P.A.W., J.R.R., S.S.), MA; and University of California (C.D.), Davis School of Medicine, Sacramento.
authors: Jose R
authors: JR
authors: Romero
authors: From McMaster University (A.S.), Hamilton, Canada; Harvard Medical School (A.S.), Boston; Boston University School of Public Health (S.R.P., A.S.B.); Boston University School of Medicine (A.S.B., R.S.V., E.J.B., C.S.K., P.A.W., J.R.R., S.S.), MA; and University of California (C.D.), Davis School of Medicine, Sacramento.
authors: Sudha
authors: S
authors: Seshadri
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002543:Cerebral Hemorrhage / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D059345:Cerebral Small Vessel Diseases / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators
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