Circulating inflammatory biomarkers are related to cerebrovascular disease in older adults

Neurol Neuroimmunol Neuroinflamm. 2018 Nov 14;6(1):e521. doi: 10.1212/NXI.0000000000000521. eCollection 2019 Jan.

Abstract

Objective: This investigation aimed at examining whether circulating inflammatory biomarkers C-reactive protein (CRP), interleukin-6 (IL6), and alpha 1-antichymotrypsin (ACT) were related to cerebrovascular disease (CVD) assessed by MRI.

Methods: The study included nondemented elderly participants of a community-based, multiethnic cohort, who received baseline MRI scans and had CRP (n = 508), ACT (435), and IL6 (N = 357) measured by ELISA. Silent brain infarcts and white matter hyperintensities (WMH) were derived from all available MRI scans at baseline, approximately 4.4 years after blood sample collection for inflammatory biomarkers. Repeated assessments of infarcts and WMH, as well as microbleeds assessment, were performed at follow-up MRI visits around 4.5 years later. Cross-sectional and longitudinal relationship between inflammatory biomarkers and CVD were analyzed using appropriate logistic regression models, generalized linear models, or COX models.

Results: After adjusting for age, sex, ethnicity, education, APOE genotype, and intracranial volume, 1 SD increase in log10IL6 was associated with infarcts on MRI {odds ratio [OR] (95% confidence interval [CI]) = 1.28 [1.02-1.60], p = 0.033}, and 1 SD increase in log10CRP and log10ACT was associated with microbleeds (OR [95% CI] = 1.46 [1.02-2.09], p = 0.041; and 1.65 [1.11-2.46], p = 0.013; respectively). One SD increase in log10ACT was also associated with larger WMH at the follow-up MRI (b = 0.103, p = 0.012) and increased accumulation of WMH volume (b = 0.062, p = 0.041) during follow-up. The associations remained significant after additional adjustment of vascular risk factors and excluding participants with clinical stroke.

Conclusions: Among older adults, increased circulating inflammatory biomarkers were associated with the presence of infarcts and microbleeds, WMH burden, and progression of WMH.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Cerebrovascular Disorders / blood*
  • Cerebrovascular Disorders / complications
  • Cerebrovascular Disorders / diagnosis*
  • Cohort Studies
  • Disease Progression
  • Female
  • Humans
  • Inflammation / blood*
  • Inflammation / complications
  • Inflammation / diagnosis*
  • Inflammation Mediators / blood*
  • Interleukin-6 / blood
  • Male
  • alpha 1-Antichymotrypsin / blood

Substances

  • Biomarkers
  • Inflammation Mediators
  • Interleukin-6
  • alpha 1-Antichymotrypsin
  • C-Reactive Protein