Impact of peripheral microvascular endothelial dysfunction on white matter hyperintensity

Takumi Toya, Jaskanwal D. Sara, Eugene L. Scharf, Ali Ahmad, Valentina Nardi, Ilke Ozcan, Lilach O. Lerman, Amir Lerman

Research output: Contribution to journalArticlepeer-review


BACKGROUND: White matter hyperintensity (WMH), characterized by hyperintensities on T2-weighted fluid-attenuated inversion recovery brain magnetic resonance imaging, has been linked to an increased risk of ischemic stroke (IS). Endothelial dysfunction is an indicator of vascular dysfunction, predicting the risk of IS. This study aimed to investigate the association between endothelial dysfunction and regional WMH, and its impact on future risk of IS. METHODS AND RESULTS: We enrolled 219 patients (mean age, 53.1±14.1 years; 34.7% men) who underwent peripheral endothelial function assessment using reactive hyperemia peripheral arterial tonometry and brain magnetic resonance imaging without any history of IS. Volumetric WMH segmentation was automatically extrapolated using a validated automated digital tool. Total and juxtacortical WMH volume/intracranial volume (%) increased with aging and became more prominent in patients aged >50 years (n=131) than those aged ≤50 years (n=88) (total WMH: ≤50 years, Pearson r=0.24, P=0.03; >50 years, Pearson r=0.62, P<0.0001; juxtacortical WMH: ≤50 years, Pearson r=0.09, P=0.40; >50 years, Pearson r=0.55, P<0.0001). Reactive hyperemia peripheral arterial tonometry index was negatively associated with total and juxtacortical WMH volume/ intracranial volume (%) in patients aged >50 years after adjustment for other covariates (reactive hyperemia peripheral arterial tonometry index, standardized β coefficient −0.17, P=0.04). Juxtacortical WMH volume/intracranial volume (%) was associated with an increased risk of IS during median follow-up of 6.5 years (hazard ratio, 1.47; 95% CI, 1.05–1.92; P=0.03). CONCLUSIONS: Peripheral endothelial dysfunction is associated with an increased volume of juxtacortical WMH in patients aged >50 years, which is a potential marker to predict future risk of IS.

Original languageEnglish (US)
Article numbere021066
JournalJournal of the American Heart Association
Issue number20
StatePublished - Oct 19 2021


  • Endothelial dysfunction
  • Ischemic stroke
  • Reactive hyperemia peripheral arterial tonometry
  • White matter disease

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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