Table 2.

Longitudinal studies investigating the association between biologic endothelial markers and chronic SVD.

Ref.	Circulating markers	Study design	MRI markers	Investigated associations	Results
Markus et al.85	ICAM-1, TM, TFPI, F 1 + 2, DD	Population based. Austrian Stroke prevention study. Individuals randomly selected from a community register: n = 267 (free of stroke and dementia; Mean age: 60 years) 3 and 6 years MRI available	WMH	Plasma markers of endothelial function and WMH progression	ICAM associated with WMH lesion progression at both 3 and 6 years (adjusting for demographics, and vascular RF)
Satizabal et al.60	IL-6, CRP	Population based. 3C Dijon study. Community-dwelling elderly free of dementia: n = 1,841 (mean age 72.5 years) Subjects with new MRI after 4 years: n = 1,341	WMH (volume) divided in WMH total, PV and deep, SBI, brain volume	IL-6 and CRP levels and progression of SVD MRI markers	No significant associations between baseline IL-6 and CRP levels and MRI changes progression over 4 years
Van Dijk et al.61	CRP	Population based. Rotterdam Scan Study At baseline nondemented pts: n = 1,033 (mean age 72 years) Subjects with new MRI: n = 636 (mean age 71 years; Mean follow-up period from 1st to 2nd: 3.3 years)	WMH progression (PV and deep) LI	CRP levels and progression of WMH volume and incidence of new LI	Progression of periventricular WMH greater among subjects with high CRP levels compared with subjects with low CRP levels (adjusting for demographics and vascular RF, carotid plaques and IMT).

Abbreviations: CRP, C-reactive protein; DD, D-dimer; F1 + 2, prothrombin fragment 1 + 2; ICAM-1, intercellular adhesion molecule-1; IMT, intima media thickness; LI, lacunar infarct; pts, patients; PV, periventricular; SBI, subcortical brain infarct; TFPI, tissue factor pathway inhibitor; TM, thrombomodulin; WMH, white-matter hyperintensities.