Background and purpose Although 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 a...Background and purpose Although 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.Methods A 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 factorα),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.Results High levels of serum endothelial-related inflammatory biomarkers were associated with both increased WMH volume(R^(2)=0.435,p=0.015)and the presence of lacunes(R^(2)=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(R^(2)=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.Conclusion WMH 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.展开更多
We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospectiv...We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospective population-based Shunyi Study,1,082 stroke-free participants aged 55.9±9.1 years were included.Participants were followed for incident stroke throughout the study period(2013-2019).Total small vessel disease score was used to measure CSVD burden.Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound.We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models.During a mean follow-up of 4.2 years,34 participants(3.1%)experienced at least one ischemic stroke.Severe LAS(≥50% stenosis versus no stenosis:HR=3.27(95%CI:1.31-8.18))and high CSVD burden(total small vessel disease score 2-4 versus 0 point:HR=12.73(4.83-33.53))were associated with increased stroke risk independently.In multivariate models,CSVD burden(7.72%)explained a larger portion of the variation in stroke risk than severity of LAS(3.49%).Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects,while those with high CSVD burden deserve more attention in primary prevention of stroke.展开更多
Background and purpose This study aimed to investigate the association of metabolic syndrome(MetS)with both intracranial atherosclerotic stenosis(ICAS)and imaging markers of cerebral small vessel disease(CSVD)in a com...Background and purpose This study aimed to investigate the association of metabolic syndrome(MetS)with both intracranial atherosclerotic stenosis(ICAS)and imaging markers of cerebral small vessel disease(CSVD)in a community-based sample.Methods This study included 943 participants(aged 55.6±9.2 years,36.1%male)from the community-based Shunyi cohort study.MetS was defined according to the joint interim criteria and quantified by the MetS severity Z-score.ICAS was evaluated by brain magnetic resonance angiography.The MRI markers of CSVD,including white matter hyperintensities(WMHs),lacunes,cerebral microbleeds(CMBs)and enlarged perivascular spaces(EPVS),were assessed.Multiple regression models were used to investigate the association of MetS severity Z-score with ICAS and these CSVD markers.Results We found that risk of ICAS(OR=1.75,95%CI 1.39 to 2.21,p<0.001)increased consistently with MetS severity.MetS severity was significantly associated with higher risks of WMH volume(β=0.11,95%CI 0.01 to 0.20,p=0.02)and lacunes(OR=1.28,95%CI 1.03 to 1.59,p=0.03)but not the presence of CMBs(OR=0.93,95%CI 0.74 to 1.16,p=0.51)and PVS severity(EPVS in basal ganglia:OR=0.96,95%CI 0.84 to 1.09,p=0.51 and EPVS in white matter:OR=1.09,95%CI 0.96 to 1.23,p=0.21).Conclusions Our findings suggest that WMH and lacunes share risk factors with atherosclerosis of the cerebral artery,whereas the impact of glucose and lipid metabolic disorder to CMB or EPVS might be weak.展开更多
基金funded by the National Key Research and Development Program of China(grant number:2016YFC0901004)National Natural Science Foundation of China(grant number:81971138)+1 种基金the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(grant number:2017-I2M 3-008)the Strategic Priority Research Program,‘Biological Basis of Aging and Therapeutic Strategies'of the Chinese Academy of Sciences(grant number:XDB39040300).
文摘Background and purpose Although 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.Methods A 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 factorα),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.Results High levels of serum endothelial-related inflammatory biomarkers were associated with both increased WMH volume(R^(2)=0.435,p=0.015)and the presence of lacunes(R^(2)=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(R^(2)=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.Conclusion WMH 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.
基金supported by the National Key Research and Development Program of China(2016YFB1001402)National Natural Science Foundation of China(81971138)+2 种基金Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS)(2017-I2M-3-008)Strategic Priority Research Program(Pilot study)“Biological basis of aging and therapeutic strategies”of the Chinese Academy of Sciences(XDPB10)Research Foundation for Young Scholars of Peking Union Medical College Hospital(PUMCH201911275)。
文摘We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospective population-based Shunyi Study,1,082 stroke-free participants aged 55.9±9.1 years were included.Participants were followed for incident stroke throughout the study period(2013-2019).Total small vessel disease score was used to measure CSVD burden.Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound.We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models.During a mean follow-up of 4.2 years,34 participants(3.1%)experienced at least one ischemic stroke.Severe LAS(≥50% stenosis versus no stenosis:HR=3.27(95%CI:1.31-8.18))and high CSVD burden(total small vessel disease score 2-4 versus 0 point:HR=12.73(4.83-33.53))were associated with increased stroke risk independently.In multivariate models,CSVD burden(7.72%)explained a larger portion of the variation in stroke risk than severity of LAS(3.49%).Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects,while those with high CSVD burden deserve more attention in primary prevention of stroke.
基金The study was funded by the'13th Five-Year'National Science and Technology Major Project for New Drugs(grant number:2019ZX09734001)National Natural Science Foundation of China(grant number:81971138)the Strategic Priority Research Program“Biological basis of aging and therapeutic strategies”of the Chinese Academy of Sciences(grant number:XDB39040300).
文摘Background and purpose This study aimed to investigate the association of metabolic syndrome(MetS)with both intracranial atherosclerotic stenosis(ICAS)and imaging markers of cerebral small vessel disease(CSVD)in a community-based sample.Methods This study included 943 participants(aged 55.6±9.2 years,36.1%male)from the community-based Shunyi cohort study.MetS was defined according to the joint interim criteria and quantified by the MetS severity Z-score.ICAS was evaluated by brain magnetic resonance angiography.The MRI markers of CSVD,including white matter hyperintensities(WMHs),lacunes,cerebral microbleeds(CMBs)and enlarged perivascular spaces(EPVS),were assessed.Multiple regression models were used to investigate the association of MetS severity Z-score with ICAS and these CSVD markers.Results We found that risk of ICAS(OR=1.75,95%CI 1.39 to 2.21,p<0.001)increased consistently with MetS severity.MetS severity was significantly associated with higher risks of WMH volume(β=0.11,95%CI 0.01 to 0.20,p=0.02)and lacunes(OR=1.28,95%CI 1.03 to 1.59,p=0.03)but not the presence of CMBs(OR=0.93,95%CI 0.74 to 1.16,p=0.51)and PVS severity(EPVS in basal ganglia:OR=0.96,95%CI 0.84 to 1.09,p=0.51 and EPVS in white matter:OR=1.09,95%CI 0.96 to 1.23,p=0.21).Conclusions Our findings suggest that WMH and lacunes share risk factors with atherosclerosis of the cerebral artery,whereas the impact of glucose and lipid metabolic disorder to CMB or EPVS might be weak.
