A Retrospective Analysis Of Risk Factors Of Cerebral Microbleeds In Small Vessel Disease

Research backgroundCerebral small vessel disease(CSVD)refers to a series of clinical,imaging and pathological syndromes caused by intracranial small perforating arteries and arterioles,capillaries and venules.CSVD accounts for approximately 20%of all strokes and it is the major reason of cognitive decline and dementia in the elderly.The main imaging findings were recent small subcortical infarction,presumed vasogenic lacunar foci,presumed vasogenic white matter hyperintensity,perivascular space,cerebral microbleeds(CMBs),and cerebral atrophy.CMBs is one of the imaging features of CSVD that has been widely studied in recent years.Its pathological essence is increased vascular wall permeability or vascular rupture,extravasation of red blood cells into perivascular brain tissue,and perivascular deposits of fresh red blood cells or hemosiderin particles,or phagocytosis of hemosiderin-containing macrophages.The risk factors of CMBs are complex and varied.At present,the recognized risk factors are age and hypertension,while other risk factors(including inflammation/immunity,blood lipid levels,chronic kidney disease,the use of statins,antiplatelet and anticoagulant drug,etc.)are still controversial and need to be confirmed by further studies.ObjectiveThis study retrospectively analyzed the demographic characteristics,traditional risk factors,the presence of systemic autoimmune connective tissue disease,imaging and laboratory examination results of patients with CSVD.The purpose of this study is to explore the independent risk factors of CMBs,reveal the potential mechanism of CMBs,improve the prediction of the occurrence of CMBs and search strategies for the prevention and treatment of CMBs.Materials and methods1.Retrospectively collected 225 patients with CSVD imaging diagnosis.The general clinical data,laboratory examination results and craniocerebral magnetic resonance imaging(MRI)results were collected.2.All enrolled patients were divided into immune mediated CSVD group and non-immune mediated CSVD group(patients with genetic CSVD were excluded)according to relevant systemic autoimmune connective tissue disease,then patients in each group were divided into CMBs group and non-CMBs group.SPSS 21.0 software was used for statistical analysis.First,the Chi-square test was used to analyze the differences of CMBs between the immune mediated CSVD group and non-immune mediated CSVD group,the counting data were expressed as percentage(%).Secondly,the Chi-square test was used to analyze the differences of the number grading and location distribution of CMBs between the immune mediated CSVD group and non-immune mediated CSVD group,the counting data were expressed as percentage(%).Finally,independent risk factors for CMBs in the non-immune mediated CSVD group were further analyzed.(1)To analyze the differences of general clinical data and traditional risk factors between the two subgroups of non-immune mediated CSVD group.The differences of continuous measurement data between the two groups were performed by t-test,expressed as mean±standard deviation(SD).The Chi-square test was used to analyze the differences of the counting data between the two groups,expressed as percentage(%).(2)Binary logistic regression analyze was conducted for the indicators with significant differences in above analysis to determine the independent risk factors of CMBs.(3)Then patients in the non-immune mediated CMBs group were grouped according to the site of CMBs(the cerebral lobe,deep and mixed site CMBs group),and graded according to the severity of CMBs(the mild,moderate and severe CMBs group).The Chi-square test and kruskal-wallis H were used to test whether there were significant differences in the regional distribution of CMBs between independent risk factors.The Spearman correlation analysis was used to explore the relationship between the severity of CMBs and the independent risk factors.P<0.05 is considered statistically significant.Results1.The proportion of CMBs in the immune mediated CSVD group was higher than that in the non-immune mediated CSVD group(P<0.05).2.The number grading of CMBs in the immune mediated CSVD group was higher than that in the non-immune mediated CSVD group(P<0.05).3.The proportion of patients with hypertension and white matter hyperintensities in the non-immune mediated CMBs group was higher than that in the non-CMBs group(P<0.05).Compared to the non-CMBs group,the levels of high sensitivity c-reactive protein,homocysteine,cystatin C and lipoprotein a were higher in the non-immune mediated CMBs group(P<0.05),and the low density lipoprotein cholesterol level was lower in the non-immune mediated CMBs group(P<0.05).4.Binary logistic regression analysis showed that hypertension,white matter hyperintensities,high sensitivity c-reactive protein,homocysteine,low density lipoprotein cholesterol and lipoprotein a were independently correlated with non-immune mediated CMBs(P<0.05).5.In the non-immune mediated CMBs group,the proportion of hypertension in the deep CMBs group was higher than that in the lobar CMBs group(Bonferroni corrected chi-square test,P<0.01 7),the difference was statistically significant.6.In the non-immune mediated CMBs group,the number of CMBs has a mildly positive correlation with the level of high sensitivity c-reactive protein(P<0.05,r=0.395),and a moderately positive correlation with the level of homocysteine(P<0.05,r=0.534).Conclusion1.Systemic autoimmune connective tissue disease may be a risk factor of CMBs.2.Hypertension,white matter hyperintensities,high sensitivity c-reactive protein,homocysteine,lipoprotein a are independent risk factors of CMBs,and low density lipoprotein cholesterol is a protective factor of CMBs.3.Compared to the cerebral lobe CMBs,hypertension is more likely to cause deep CMBs.4.The severity of non-immune mediated CMBs was positively correlated with the levels of high sensitivity c-reactive protein and homocysteine.