sTWEAK is a leukoaraiosis biomarker associated with neurovascular angiopathy

Ann Clin Transl Neurol. 2022 Feb;9(2):171-180. doi: 10.1002/acn3.51502. Epub 2022 Jan 21.

Abstract

Objective: Leukoaraiosis (LA) refers to white matter lesions of undetermined etiology associated with the appearance and worsening of vascular pathologies. The aim is to confirm an increased frequency and intensity of LA in symptomatic patients with neurovascular pathology compared with asymptomatic subjects, and its association with circulating serum levels of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK).

Methods: An observational study was conducted in which two groups of patients were compared. Group I (N = 242) comprised of asymptomatic subjects with arterial hypertension and/or diabetes or with a history of transient ischemic attacks, and Group II (N = 382) comprised patients with lacunar stroke or deep hemispheric intracerebral hemorrhage (ICH) of hypertensive origin. Serum levels of sTWEAK were analyzed and correlated with prevalence and intensity of LA according to the Fazekas scale.

Results: The prevalence of LA was higher in symptomatic (85.1%) versus asymptomatic patients (62.0%). Logistic regression model showed a significant relation of LA with neurovascular pathologies (OR: 2.69, IC 95%: 1.10-6.59, p = 0.003). When stratified according to the Fazekas scale, LA of grade II (OR: 3.53, IC 95%: 1.10-6.59, p = 0.003) and specially grade III (OR: 4.66, 95% CI: 1.09-19.84, p = 0.037) showed correlation with neurovascular pathologies. Increased sTWEAK levels were found in the symptomatic group in all LA grades (p < 0.0001), and associated with 5.06 times more risk of presenting clinical symptoms (OR: 5.06, 95% CI: 2.66-9.75, p < 0.0001).

Interpretation: LA showed a higher prevalence in patients with symptomatic lacunar stroke or deep hemispheric ICH. There is an association between sTWEAK levels and LA degree.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Cerebral Hemorrhage* / blood
  • Cerebral Hemorrhage* / epidemiology
  • Cerebral Hemorrhage* / pathology
  • Comorbidity
  • Cytokine TWEAK / blood*
  • Diabetes Mellitus* / blood
  • Diabetes Mellitus* / epidemiology
  • Diabetes Mellitus* / pathology
  • Female
  • Humans
  • Hypertension* / blood
  • Hypertension* / epidemiology
  • Hypertension* / pathology
  • Ischemic Attack, Transient* / blood
  • Ischemic Attack, Transient* / epidemiology
  • Ischemic Attack, Transient* / pathology
  • Leukoaraiosis* / blood
  • Leukoaraiosis* / epidemiology
  • Leukoaraiosis* / pathology
  • Male
  • Middle Aged
  • Prevalence
  • Registries*
  • Stroke, Lacunar* / blood
  • Stroke, Lacunar* / epidemiology
  • Stroke, Lacunar* / pathology

Substances

  • Biomarkers
  • Cytokine TWEAK
  • TNFSF12 protein, human

Grants and funding

This work was funded by European Regional Development Fund (ERDF) ; European Union, ESF; F. Campos grant CPII19/00020; Instituto de Salud Carlos III grants CD20/00054 and PI17/01103; INTERREG ; INVICTUS grant RD16/0019; Miguel Servet Program; Sara Borrell grant CD20/00054; Spanish Ministry of Economy and Competitiveness grants RTI2018‐102165‐B‐I00 and SAF2017‐84267‐R; Spanish Research Network on Cerebrovascular Diseases RETICS; T. Sobrino grant CPII17/00027; Xunta de Galicia grants IN607A2018/3 and IN607D2020/09; INTERREG V A España Portugal (POCTEP) grant 0624_2IQBIONEURO_6_E.