| Background:Pulmonary arterial hypertension(PAH)is a progressive disease characterized by increased pulmonary arterial pressure and pulmonary vascular resistance,can result in right heart failure even death.PAH is a common and serious complication of connective tissue diseases(CTDs).Identifying predictive indicators for development and prognosis of connective tissue disease associated pulmonary arterial hypertension(CTD-PAH)has important clinical significance,contributing to early recognition of patients with high risk,close monitoring and providing corresponding treatment to those patients,which can be helpful to improve the prognosis.Anti-U1 ribonucleoprotein(RNP)antibody can be detected in patients with various CTDs and has been reported to be associated with development and prognosis of CTD-PAH,it is probably the appropriate clinical indicator for early diagnosis and prognosis evaluation which we are seeking for.However,there are still some controversies lie in existing researches,thus there is no consensus on relationship between anti-U1RNP antibody and CTD-PAH.Purpose:A systematic review and meta-analysis was performed to find out the role of anti-U1 RNP antibody in CTD-PAH,make clear whether anti-U1RNP antibody positivity is a risk factor and whether it is a prognostic factor of survival for CTD-PAH.We aimed at seeking out a clinical indicator suitable for predicting onset and mortality risk of CTD-PAH,which can benefit early recognition of high-risk patients,providing active screening and strict monitoring in order to improve prognosis of CTD-PAH.Methods:We searched databases including PubMed,Embase,Cochrane Library,Scopus,CNKI,WanFang,VIP,and CBM for studies related with anti-U1 RNP antibody and CTD-PAH,quality evaluation and data extraction were conducted in eligible researches.Cohort and case-control studies were assessed using Newcastle-Ottawa scales while cross-sectional studies were assessed by Agency for Healthcare Research and Quality indicators.All statistical analysis was performed by Stata 15.0 software.Odds ratio(OR)was adopted as a measure of effect in risk factor analysis,and hazard ratio(HR)was adopted for prognostic factor analysis.Outcomes of meta-analysis were presented by pooled effect size and 95%confidence intervals(CI).Heterogeneity between the included studies were evaluated by Q statistic and I2 statistic,outcomes were synthesized using random effects model when significant heterogeneity was detected;otherwise,a fixed effects model would be selected.Sensitivity analysis and subgroup analysis would be applied for exploring potential sources of heterogeneity.Publication bias was evaluated through Egger’s test.Results:Totally 12 studies were finally included,covering 1005 CTD patients with PAH and 5049 patients without PAH.All researches included were of high quality.According to the our meta-analysis,the risk of PAH in anti-UIRNP antibody positive CTD patients was significantly higher than antibody negative ones,suggesting anti-U1RNP-positivity as a risk factor for PAH among CTD patients(OR=3.94,95%CI 2.00-7.78,P<0.05),the heterogeneity mainly came from difference in ethnic background,sample size and study type;mortality risk of anti-UIRNP antibody positive CTD-PAH patients was significantly lower than antibody negative ones,anti-U1RNP antibody positivity was also proved as a protective factor against mortality among CTD-PAH patients(HR=0.66,95%CI 0.48-0.91,P<0.05),diverse ethnic background contributed to the heterogeneity.No considerable publication bias was found by Egger’s test.Conclusion:The outcome of our systemic review and meta-analysis indicated that Anti-U1RNP antibody has close connection with development and prognosis of CTD-PAH,therefore monitoring the antibody level is of great importance for early diagnosis and prognosis evaluation.CTD patients with positive anti-U1RNP antibodies are at high risk for PAH,so routine screening examination is recommended.Additionally,anti-U1RNP-negative patients are at high risk of poor prognosis,thus close monitoring is necessary. |
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