Risk Factors For Intracranial Atherosclerosis:A Systematic Review And Meta-Analysis

Background: As one of the most common causes of ischemic stroke throughout world,intracranial atherosclerosis(ICAS)accounts for about 30-50% of ischemic stroke or transient ischemic attacks in Asia,15–29% in Africa,and 5-10% in Europe or North America.Twenty to 40 per 100000 people worldwide are estimated prone to an ICAS related ischemic event.The high incidence,disability and mortality of ischemic stroke impose a heavy economic burden on society and families,prevention and evaluation of ICAS is particularly important for the prevention and treatment of ischemic stroke.And for the early prevention and management of identifying the target populations,determining risk factors for ICAS is an urgent problem to be solved at preventive medicine levels.Due to the variety of risk profiles and uneven quality of studies,there is still a lack of systematic and reliable evidence of evidence-based medicine.An increasing number of studies on possible risk factors for ICAS,such as age,ethnicity,hypertension,diabetes mellitus,smoking status and dyslipidemia,yielded inconsistent conclusions for diverse study populations and different imaging modalities of intracranial arteries.We assume there might be several factors associated only with ICAS or stroke although they could all be affected by similar factors.Thus,we performed this comprehensive systematic review and meta-analysis to summarize the non-modifiable and modifiable risk factors for ICAS identified in previous reports.Methods: The Pub Med and EMBASE were searched(1995-May to 2018-May)to enroll cross-sectional and longitudinal studies exploring risk factors for ICAS.The risk estimates and 95% confidence interval(CI)in multivariate analysis were aggregated using random-effect models and heterogeneity was assessed with Cochran's Q test and I2 statistic.Subgroup analyses and meta-regression analyses were performed to explore the source of heterogeneity.Sensitivity analyses were performed to examine the robustness of the pooled resultsResults: Thirty-four studies comprising 59,736 subjects,included two longitudinal studies and thirty-two studies cross-sectional studies,met the inclusion criteria for the systematic review involving thirty-one risk or protective factors,twenty-four studies were included in quantitative analysis.As for study populations,twenty studies recruited community-dwelling population,and fourteen studies recruited stroke patients.Seven factors were associated with ICAS suggested by meta-analysis,including advanced age(odds ratio(OR)1.05,95% CI 1.03-1.08),metabolic syndrome(OR 2.13,95% CI 1.35-3.37),diabetes mellitus(OR 1.98,95% CI 1.69-2.31),hypertension(OR 1.97,95% CI 1.69-2.31),dyslipidemia(OR 1.29,95% CI 1.04-1.59),high levels of low-density lipoprotein cholesterol(OR 1.06,95% CI 1.00-1.12)and high levels of apolipoprotein A1(OR 0.34,95% CI 0.15-0.75).The subgroup analysis for study populations indicated advanced age,metabolic syndrome,diabetes mellitus and hypertension elevated risk of ICAS among community subjects and stroke patients;according to the subgroup analysis for ethnicity,those similar associations remained in Asians,but only metabolic syndrome and diabetes mellitus were correlated with ICAS in Caucasians.Conclusions: Individuals with advanced age,metabolic syndrome,diabetes mellitus,hypertension and dyslipidemia might have higher risk of ICAS,whereas high levels of apolipoprotein A1 might render protection against ICAS.The current review also revealed several less well-established factors that might be associated with ICAS,which warrants further large and prospective research into the associations and the underlying mechanisms for the links.Further relevant research will help establish more effective prevention strategy for intracranial atherosclerosis and subsequent stroke.