Low Bilirubin Levels Indicate a High Risk of Cerebral Deep White Matter Lesions in Apparently Healthy Subjects

Abstract

Recent studies have reported that deep white matter lesions (DWMLs) on magnetic resonance imaging scans are related to the risk of developing impaired cognitive function in future. Bilirubin exhibits a potent antioxidant effect and an inverse relationship has been reported between bilirubin levels and the risk of several atherosclerotic diseases; however, there is limited evidence with regard to the effect of bilirubin levels on cerebrovascular diseases including DWMLs. This cross-sectional study included 1121 apparently healthy Japanese adults. The subjects were divided into three groups according to their bilirubin levels (low, <0.5 mg/dl; intermediate, ≥0.5 mg/dl and <1.0 mg/dl; and high, ≥1.0 mg/dl). The severity of DWMLs was evaluated according to Fazekas scale and their relation to bilirubin levels was examined. The association between bilirubin levels and the presence of severe DWMLs was assessed using multivariate logistic regression analysis. The analysis revealed that the low- and intermediate bilirubin groups indicated 2.36- and 1.33-fold increase in the prevalence of severe DWMLs compared with the high-bilirubin group, respectively (95% confidence interval (CI): 1.12–4.97 (the low-bilirubin group), 95% CI: 0.85–2.07 (the intermediate-bilirubin group). In conclusion, low total bilirubin levels could be associated with a high prevalence of severe DWMLs in apparent healthy subjects.

Association and genetic overlap between clinical chemistry tests and migraine

“…Padhraig Gormley 1-4,* , Verneri Anttila 2,3,5,* , Bendik S Winsvold [6][7][8] , Priit Palta 9 , Tonu Esko 2,10,11 , Tune H Pers 2,[11][12][13] , Kai-How Farh 2,5,14 , Ester Cuenca-Leon [1][2][3]15 , Mikko Muona 9,[16][17][18] , Nicholas A Furlotte 19 , Tobias Kurth 20,21 , Andres Ingason 22 , George McMahon 23 , Lannie Ligthart 24 , Gisela M Terwindt 25 , Mikko Kallela 26 , Tobias M Freilinger 27,28 , Caroline Ran 29 , Scott G Gordon 30 , Anine H Stam 25 , Stacy Steinberg 22 , Guntram Borck 31 , Markku Koiranen 32 , Lydia Quaye 33 , Hieab H H Adams 34,35 , Terho Lehtim€ aki 36 , Antti-Pekka Sarin 9 , Juho Wedenoja 37 , David A Hinds 19 , Julie E Buring 21,38…”

“…A low level of TB is not a concern for liver disorders, but it is associated with CVD risk factors (32) and stroke (33), which again supports higher risk of CVD among migraineurs. Interestingly, low TB levels are associated with higher risk of deep white matter lesions (34), which are more common among migraine patients (35). Clinically, increased serum level of GGT reflects liver dysfunction but epidemiologically it is associated with higher risk of CVD (36).…”

Heme Oxygenase Dependent Bilirubin Generation in Vascular Cells: A Role in Preventing Endothelial Dysfunction in Local Tissue Microenvironment?

“…Bilirubin has been shown to be protective against the development of ischemic damage associated with ischemic/reperfusion injury and endothelial activation (Yang et al, 2016). A recent cross-sectional study performed on 1121 healthy Japanese demonstrated that low levels of plasma bilirubin are associated with a high prevalence of ischemic modifications in brain white matter (Higuchi et al, 2018). In this context, a recent review form Thakkar et al (2019) rigorously analyzed clinical studies highlighting a relationship between bilirubin levels and cerebral ischemic stroke.…”

Mildly decreased preoperative bilirubin levels are considered as risk factors for periprosthetic joint infection after total hip and knee arthroplasty

“…IL-6), which are in turn responsible for CRP production in the liver tissue [11,12,28]. And other studies with different pathologies such as cardiovascular diseases [29], metabolic syndrome and type 2 diabetes [30], cerebrovascular diseases [31], osteoporosis [32], and even in rheumatoid osteoarthritis [33] also showed negative correlations with bilirubin concentrations. This has also been reported in studies evaluating the association between bilirubin and bacterial infections or associated models such as pathogen exposures including endotoxin, although not all studies show protective effects.…”