Inflammatory biomarkers and cerebral small vessel disease: a community-based cohort study

Abstract

Background and purposeAlthough inflammation has been proposed to be a candidate risk factor for cerebral small vessel disease (CSVD), previous findings remain largely inconclusive and vary according to disease status and study designs. The present study aimed to investigate possible associations between inflammatory biomarkers and MRI markers of CSVD.MethodsA group of 15 serum inflammatory biomarkers representing a variety of those putatively involved in the inflammatory cascade was grouped and assessed in a cross-sectional study involving 960 stroke-free subjects. The biomarker panel was grouped as follows: systemic inflammation (high-sensitivity C reactive protein (hsCRP), interleukin 6 and tumour necrosis factor α), endothelial-related inflammation (E-selectin, P-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1), CD40 ligand, lipoprotein-associated phospholipase A2, chitinase-3-like-1 protein and total homocysteine (tHCY)) and media-related inflammation (matrix metalloproteinases 2, 3 and 9, and osteopontin). The association(s) between different inflammatory groups and white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs), enlarged perivascular space (PVS) and the number of deep medullary veins (DMVs) were investigated.ResultsHigh levels of serum endothelial-related inflammatory biomarkers were associated with both increased WMH volume (R2=0.435, p=0.015) and the presence of lacunes (R2=0.254, p=0.027). Backward stepwise elimination of individual inflammatory biomarkers for endothelial-related biomarkers revealed that VCAM-1 was significant for WMH (β=0.063, p=0.005) and tHCY was significant for lacunes (β=0.069, p<0.001). There was no association between any group of inflammatory biomarkers and CMBs or PVS. Systemic inflammatory biomarkers were associated with fewer DMVs (R2=0.032, p=0.006), and backward stepwise elimination of individual systemic-related inflammatory biomarkers revealed that hsCRP (β=−0.162, p=0.007) was significant.ConclusionWMH and lacunes were associated with endothelial-related inflammatory biomarkers, and fewer DMVs were associated with systemic inflammation, thus suggesting different underlying inflammatory processes and mechanisms.

Serum YKL-40 Levels and White Matter Hyperintensities in Patients with Acute Ischemic Stroke

“… 30 A recently published community-based study with 960 Chinese stroke-free participants observed a significant association between elevated levels of endothelial-related inflammatory biomarkers including YKL-40 and increased WMH volume. 9 In another study with 42 sporadic CSVD patients, CSF levels of YKL-40 were positively correlated with the WMH load. 31 The results of our study suggested that serum YKL-40 levels at baseline, in AIS patients remained significantly associated with PV-WMH after adjusting for potential confounding risk factors, which has never been reported to our knowledge.…”

“… 26 , 27 In recent years, increasing evidence indicates an extraordinarily critical role of inflammation in the progression of WMH. 9 , 24 , 28 , 29 As a glycoprotein mediating inflammation, YKL-40 has been reported to correlated with pulmonary diseases, diabetes mellitus, coronary heart disease, Alzheimer’s disease and stroke. 10 , 11 , 14 However, evidence for the correlation between YKL-40 and CSVD is limited.…”

“… 6 , 7 Several inflammatory biomarkers have been identified as candidate risk factors for WMH, such as vascular cell adhesion molecule-1, lipoprotein-associated phospholipase A2, and so on. 8 , 9 YKL-40, also called chitinase-3-like-1 protein (CHI3L1) or breast regression protein 39 (BRP-39), is a novel biomarker of inflammation and plays a crucial role in angiogenesis, tissue fibrosis, inflammation, oxidative tissue injury, and extracellular remodeling responses. 10 , 11 Elevated YKL-40 levels have been reported to be associated with atherosclerosis, 12 cardiovascular disease 13 and cerebrovascular disease.…”

Association between Serum Amyloid A Level and White Matter Hyperintensity Burden: a Cross-Sectional Analysis in Patients with Acute Ischemic Stroke

“…The current investigation found that higher SAA levels were independently associated with total WMH, implying that dysregulated SAA may play a role in the etiology of overall WMH. However, the bulk of prior investigations has focused on the association of other plasma inflammatory markers [including, total homocysteine (tHcy), hypersensitive-C reactive protein (hs-CRP), vascular cell adhesion molecule-1 (VCAM-1), E-selection, and P-selection] with total WMH burden [26][27][28]. Few researchers have focused on the impact of different variables on PVWHM and DWMH.…”

Implication of heart rate variability on cerebral small vessel disease: A potential therapeutic target

“…Typical neuroimaging features of CSVD on magnetic resonance imaging (MRI) include white matter hyperintensity (WMH), lacunes, enlarged perivascular spaces (EPVS), cerebral microbleeds (CMBs), and brain atrophy (BA) 3 . Previous studies have identified a spectrum of traditional vascular risk factors and blood‐based biomarkers for CSVD 4–7 . However, despite abundant literature on this subject, these is insufficient explanation regarding the biological processes of CSVD.…”