The Risk Of Thromboembolic Events In Antineutrophil Cytoplasmic Antibody Associated Vasculitis:a Meta-analysis

Objective:Antineutrophil cytoplasmic antibody associated vasculitis(AAV)is a systemic vasculitis that mainly affects small blood vessels,involving the lungs、kidneys、skin、gastrointestinal tract,nerves and other systems.Among them,thromboembolic events are not uncommon.Thromboembolic events are mainly manifested as cardiovascular disease(CVD)and venous thromboembolism(VTE).CVD includes ischemic heart disease(IHD),cerebrovascular accident(CVA)and peripheral vascular disease(PVD).There is evidence that AAV is related to thromboembolism,but the risk of AAV combined with thromboembolic events is difficult to quantify.Meta-analysis was used to analyze the risk of thromboembolic events in AAV.Methods:We searched PubMed,Embase,Cochrane,VIP,Wanfang,CNKI,China biomedical databases until January 2021 on AAV combined with thromboembolism.The literatures were screened and evaluated by applying PRISMA declaration and the Newcastle-Ottawa Scale(NOS),which is used to observe studies as a quality assessment tool.And then use Stata 14.0 software for Meta-analysis.Statistical indicators are collected by reading the full text,including the extraction of OR,RR,HR,and CI,as well as obtaining the original incident rate as much as possible.Explore the source of heterogeneity through subgroup analysis and sensitivity analysis.Explore the source of publication bias through Begg.Results:1.A total of 1021 articles were found by searching the database and searching for related references.After screening and evaluation,11 articles were finally included.A total of 16530 cases were included in the test group,including 5097 AAV patients with thromboembolism,and a total of 30004 cases in the control group(including chronic kidney disease and general healthy control).Nine of them are prospective cohort studies.The 11 studies are all high-quality studies after the NOS quality assessment.2.Eleven studies included showed an increased risk of AAV associated with thromboembolic events(OR=1.70,95%CI:1.43-2.01,P<0.0001),which is significantly different from the control group.The results show that the study has heterogeneity I~2=55.6%,P=0.013.The heterogeneity is explored through subgroup analysis,and it is estimated from the control group,the female gender percentage and the follow-up of the study.According to the OR,taking CKD as the control group(OR=1.64,95%CI:0.83～3.25,P=0.153),which intersecting with the invalid line OR=1,indicating that there is no correlation between the increased risk of thromboembolic events between the groups.The healthy population as the control group(OR=1.71,95%CI:1.42～2.05,P<0.0001)increased the risk of thromboembolic events.In addition,the study with follow-up time(≥5 years)(OR=2.11,95%CI:1.64～2.72,P<0.0001)had a significantly higher risk of thromboembolic events,compared with the study of follow-up time(<5 years)(OR=1.48,95%CI:1.11～1.98,P=0.008).Studies with few women(OR=2.03,95%CI:1.31～3.15,P=0.002)had a significantly higher risk of thromboembolic events than those with more women(OR=1.72,95%CI:1.36～2.16,P<0.0001).Through sensitivity analysis and detection,it was found that the two studies of Zoller and Li may be the source of heterogeneity,but the results are still significant,so the results obtained in the included studies are stable and reliable.Through Begg chart analysis,the included study was used to explore publication bias,and the result P=0.35,indicating that the included literature in this study has no publication bias.3.Eight studies reported IHD,and the analysis showed an increased risk of AAV combined with IHD(OR=1.51,95%CI:1.46-1.55,P<0.0001).Seven studies reported CVA,and the analysis showed an increased risk of AAV combined with CVA(OR=1.67,95%CI:1.11-2.51,P<0.0001).There was a statistical difference compared with the control group.The included 3 studies all reported PVD,and the analysis showed that the risk of AAV combined with PVD did not increase significantly(OR=1.06,95%CI:0.58～1.96,P=0.841),and there was no statistical difference compared with the control group;Seven studies all reported VTE,and the analysis showed that the risk of AAV combined with VTE was significantly increased(OR=4.03,95%CI:2.95-5.50,P<0.0001),which was significantly different from the control group.Conclusion:The risk of AAV combined with thromboembolic events is 1.70 times that of the general population.Among them,the risk of AAV combined with IHD,CVA,and VTE is higher than that of ordinary people,and VTE is the highest.There is no difference in the risk of AAV combined with PVD compared with the general population.