Associations between endothelial inflammatory markers and cerebral small vessel disease in a community-based population

Endothelial inflammation is involved in cerebral small vessel disease (CSVD) pathogenesis. Vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) are biomarkers of endothelial inflammation. This study investigated association of VCAM-1 and ICAM-1 with presence of CSVD and CSVD burden. This cross-sectional study included community residents from the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study. Fasting venous blood was drawn to assay VCAM-1 and ICAM-1. Cognition was assessed by the Montreal Cognitive Assessment (MoCA). Cognitive impairment was defined as MoCA scores <26. White matter hyperintensity, lacunes, cerebral microbleeds, and enlarged perivascular spaces were evaluated in a 3.0T MRI scanner. CSVD burden was rated according to the criteria of Wardlaw's (score 0-4) and Rothwell's (score 0-6) and classified into 4 grades. Presence of CSVD was defined as CSVD burden score ≥1. This study included 2596 participants with a mean age of 61.2 ± 6.7 years and 50.9% of males. Elevated VCAM-1 was associated with increased odds of presence of CSVD (Rothwell: OR=1.16, 95%CI: 1.06-1.26, P=0.001), higher CSVD burden (Wardlaw: cOR=1.11, 95%CI: 1.02-1.21, P=0.02; Rothwell: cOR=1.16, 95%CI: 1.07-1.25, P<0.001), and presence of cognition-impaired CSVD (Rothwell: OR=1.15, 95%CI: 1.05-1.25, P=0.003). VCAM-1 improved net reclassification index and integrated discrimination improvement for presence of CSVD (Rothwell) and cognition-impaired CSVD (Rothwell). However, ICAM-1 was not associated with CSVD and did not improve prediction of CSVD. Endothelial inflammation, especially VCAM-1, was associated with presence of CSVD and higher CSVD burden.