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

Abstract

Background:

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.

Aims:

This study investigated the association of VCAM-1 and ICAM-1 with the presence of CSVD and CSVD burden.

Methods:

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 four grades. Presence of CSVD was defined as CSVD burden score ⩾ 1.

Results:

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: odds ratio (OR) = 1.16, 95% confidence interval (CI): 1.06–1.26, P = 0.001), higher CSVD burden (Wardlaw: common OR (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 the presence of CSVD (Rothwell) and cognition-impaired CSVD (Rothwell). However, ICAM-1 was not associated with CSVD and did not improve prediction of CSVD.

Conclusion:

Endothelial inflammation, especially VCAM-1, was associated with the presence of CSVD and higher CSVD burden.

Graphical abstract