Clinical And Experimental Study On Long-term Use Of Aspirin To Prevent Ischemic Stroke

Objective: Prospective clinical study to explore the safety and efficacy of long-term use of aspirin in the prevention of ischemic stroke.Exploring the mechanism of aspirin resistance through cell experiments.Expect to clarify the efficacy and safety of long-term antiplatelet therapy,To provide a research basis for the safety and efficacy of long-term use of aspirin in the prevention of ischemic stroke.Methods:（1）Clinical research,The included population came from the elderly population from the Chongqing Army Special Medical Center and the Physical Examination Center of the First Affiliated Hospital of Bengbu Medical College from January 6,2015 to April 28,2016,742 people were included at enrollment,53 people were lost to follow-up.At the end of the 5-year follow-up,a total of 689 subjects were included in the baseline analysis,with a mean age of 71.2 years,350 men（50.8%）and339 women（49.2%）.A total of 330 people were in the aspirin group（100 mg/day）and359 people in the non-aspirin group.The clinical data and serological indexes of the patients were collected,and the primary and secondary outcomes of the patients were observed through follow-up,The primary outcome observed was the ischemic stroke,including acute cerebral infarction and transient ischemic attack（TIA）,and secondary outcomes were angina,myocardial infarction,cardiovascular death,and all-cause death,Secondary outcomes were angina,myocardial infarction,cardiovascular death,and all-cause death.Safety includes gastrointestinal bleeding,intracranial bleeding,and bleeding from other sites.Estimation of the association between aspirin and ischemic stroke using a Cox proportional hazards model.（2）In vitro cell culture,Immortalized human brain microvascular endothelial cells（HCMEC/D3）were cultured in extracellular matrix（ECM）endothelial cells and randomly selected for cyclooxygenase 1（COX1）interference,COX1 The construction and transfection of the overexpression plasmid vector,And use real-time fluorescence quantitative PCR（quantitative real-time polymerase chain reaction,q RT-PCR）to verify the interference effect and screen the most suitable samples,Then it was used to detect the expression levels of miR-34b-3p and Thromboxane A Synthase 1 m RNA（TBXAS1）.Results:（1）The clinical study showed that among the 689 people included,at the end of the 5-year follow-up,121 people in the aspirin group and 158 people in the non-aspirin group developed ischemic stroke,and there was a significant difference between the two groups（P<0.05）.Gastrointestinal bleeding（4.2% vs 1.8%）and gastrointestinal adverse reactions（20.0% vs 8.1%）in the aspirin group were higher than those in the non-aspirin group（P<0.05）.Compared with the non-aspirin group,the aspirin group had a significantly lower risk of ischemic stroke from 12 months to 48months（P<0.05）,while there was no significant difference in the incidence of ischemic stroke from 49 to 60 months（P>0.05）.（2）Cell experiments showed that the expression level of miR-34b-3p in vascular endothelial cells in COX1 interference group was lower than that in control group,and the expression level of miR-34b-3p in COX1 overexpression group was higher than that in control group.COX1 affected the expression level of miR-34b-3p.Moreover,miR-34b-3p was positively correlated with the expression level of thromboxane A synthase m RNA（r =0.8909,P<0.001）.Conclusion: Long-term use of aspirin to reduce the incidence of ischemic stroke effectiveness gradually decreased,and increased the risk of gastrointestinal bleeding;In the COX1 overexpression group,the expression level of miR-34b-3p in the cerebrovascular endothelial cell group was increased,and the miR-34b-3p could regulate the expression of TBXAS1 gene,suggesting that miR-34b-3p could be used as a biomarker of aspirin resistance.