Construct A Risk Assessment Model For Ischemic Stroke Recurrence Based On Constitution

1 BackgroundThe risk of recurrent ischemic stroke is far greater than first ischemic stroke.The risk of recurrent ischemic stroke is 40%higher than first ischemic stroke,and the risk of disability and death in recurrent ischemic stroke is 9.4 times as higer as the first ischemic stroke.Because the severity of recurrent ischemic stroke,world countries take more attention to the stroke's secondary prevention,and a number of guidelines and consensus have been issued or updated.In 2014,the American Heart Association and the American Association(AHA/ASA)published the latest "Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack",which systematically summarized the latest advances in the risk factors associated with the recurrent ischemic stroke,and emphasized the effective control of hypertension,glucose metabolism disorder,diabetes,obesity,smoking and drinking,these called classical risk factors.Such as maintaining a reasonable diet and moderate physical activity can prevent the recurrent ischemic stroke.Combined with China's national conditions and clinical status,the Chinese Medical Association neurology branch also collectively revised the "guidelines for the secondary prevention of ischemic stroke and transient ischemic attack in China(2014)".Secondary prevention of ischemic stroke is a necessary measure to assess the risk of recurrence of ischemic stroke.The current long-term risk assessment tools for the recurrent ischemic stroke are mainly based on the ESSEN score in 1996 and the SPI-II score in 1991.The two risk assessment tools have no more new or improved versions since they were constructed,and were based on the clinical trials of foreign demographic characteristics.In 2016,Chinese medical association neurology branch.,published the expert consensus on the Chinese ischemic stroke risk assessment scale,recommended the clinical use of the ESSEN scale or the SPI-II scale to assess the risk of long-term recurrence of ischemic stroke,but at the same time,it was pointed out that these scales predictive effect are limited.It is suggested that the secondary prevention risk assessment scale suitable for Chinese people should be further established and perfected.Establishing the risk assessment model for the recurrent ischemic stroke,find and control the accurate risk factors are fundmental points.Therefore,it is of great clinical value to find the risk factors of recurrent ischemic stroke.This study further explored the risk factors for recurrent ischemic stroke,and provided more theoretical evidence for the prevention of ischemic stroke recurrence.The early stage of the research team has studied the predictive function of TCM syndrome in the recurrent ischemic stroke and concluded that the syndrome of phlegm dampness god is the risk factor of the recurrent ischemic stroke,so this research focuses on the constitution in the ischemic stroke recurrence.Under the guidance of "preventive treatment of disease"theories in TCM,based on the national demographic characteristics,combined with the above risk factors,and constitution in chinese medicine,social life ablity,psychological factor,constructing multi-dimensional risk assessment model of recurrent ischemic stroke.In order to provide more suitable for chinese to predict the ischemic stroke recurence.2 Objective:To construct a risk assessment model for the recurrent ischemic stroke3 Method:3.1 Study designRegistration study3.2 Study populationAccording to the history and CT/MRI examination,the TOAST classification was LAA and SA.The age is more than 35 years old and is less than 85 years old;The patient or legal guardian sign the informed consent.The study group participated in the Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing Tiantan Hospital affiliated to Capital Medical University and Guangzhou in the "research and development and demonstration application of the recurrent risk assessment system of ischemic stroke in the health management of traditional Chinese medicine in 2015" November 2016,"research and development and demonstration application of TCM characteristic health management of ischemic stroke disease"(No.201507003-8).The Second Affiliated Hospital of the Medical University and the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,1384 cases of the first diagnosed patients with atherosclerotic ischemic stroke were diagnosed in 13 hospitals.Study population from November 2016 to January 2018 to participate in the "2015 TCM industry research projects-Development and demonstration application of ischemic stroke recurrence risk assessment system with TCM characteristic health management(No.201507003-8)".Clinical data acquisition units include Dongzhimen Hospital Beijing Unversity of Chinese Medicine,Beijing Tian Tan Hospital,Capital Medical University,etal.Finally,1384 cases of first diagnosed atherosclerotic ischemic stroke were included from 13 hospitals.3.3 observation index3.3.1 Primary outcome--recurrent ischemic stroke3.3.2 secondary outcome--death3.4 judgement of recurrent eventsIn general,the recurrent events of ischemic apoplexy include cerebral infarction,cerebral hemorrhage and TIA,which must be based on reliable imaging indicators and clinical evaluation of doctors,combined with imaging events and clinical events.Ischemic stroke was defined as an acute focal infarction of the brain or retina with one of the following:sudden onset of a new focal neurologic deficit,with clinical or imaging evidence of infarction lasting 24 hours or more and not attributable to a nonischemic cause(i.e.,not associated with brain infection,trauma,tumor,seizure,severe metabolic disease,or degenerative neurologic disease);a new focal neurologic deficit lasting for less than 24 hours and not attributable to a nonischemic cause but accompanied by neuroimaging evidence of new brain infarction;or rapid worsening of an existing focal neurologic deficit lasting more than 24 hours and not attributable to a nonischemic cause,accompanied by new ischemic changes on MRI or CT of the brain and clearly distinct from the index ischemic event.Hemorrhagic stroke was defined as acute extravasation of blood into the brain parenchyma or subarachnoid space with associated neurologic symptoms.Recurrent stroke was considered to be disabling if the score on the modified Rankin scale was 2 or more.3.5 Quality controlIn order to improve the real,objective and effective data in the process of clinical data collection,improving patient compliance and reducing missing visits are the core issue.To this end,the team adopted various methods to improve the quality control of clinical trial plan and clinical trial standard operation standard.In the whole clinical trial,we adopted the quality control system of first level inspection,second level supervision and third level inspection.3.6 Data managementTo train the data entry personnel of the electronic data collection table,the independent double entry and double entry are carried out,and the data of one and two records are"discrepant check".If the data of the two entries are inconsistent,the revised data of the paper clinical data collection table will be checked and until the two records are consistent.The data administrator checks the exported database,uses the database of logic check,the differential checkout program and the manual retrieval method to carry on the data checklist.Based on the list of problems,it is necessary to combine the verification of the original record and organize the production data interrogative table when necessary.The interrogative table is checked,confirmed and corrected by the clinical inspector and the clinical unit quality controller and the data administrator.The database is modified and updated according to the results confirmed by the data.This process is repeated and repeated until all the questions in the electronic database are answered and solved,and then the electronic database lock is completed.3.7 statistical analysisThe counting data were checked with chi square,and the measurement data were use t test.The process of data analysis included screening risk factors using group Lasso,frailty model,and using two multiple factor logistc regression models to construct the risk assessment model of ischemic stroke based on constitution.4 Results4.1 Group-Lasso LogisticBy screening Group-Lasso Logistic of structural variables,we can see:The first group of demographic data in the general data of age,BMI index;second groups of primary hypertension,type 2 diabetes,coronary heart disease,hyperlipidemia,hyperlipidemia combined with type 2 diabetes;third family history of stroke,coronary heart disease,fourth groups of life and behavior are smoking,high fat diet,sleep state;Five groups of TCM constitution are Yang deficiency constitution,phlegm constitution,blood stasis constitution,sixth groups of nerve system NIHSS scale score,seventh groups of BI scale score;eighth groups of low density lipoprotein abnormality,high density lipoprotein may aggravate the risk of recurrent ischemic stroke.After taking exercise,combined treatment of clopidogrel with aspirin and taking Chinese medicine decoction,it will play a certain protective role in the recurrence of ischemic stroke patients.The anxiety self rating scale,the self rating depression scale,the patient's course and its subsection,hypertension at the onset of disease and the rehabilitation therapy were 0.In this study,the above factors have no significant influence on the recurrent ischemic stroke.4.2 Frailty modelThe results of combing recurrent and death outcomes frailty modelare:more than age 60,coronary heart history,hyperlipidemia,sleep abnormality and blood stasis constitution are the risk factors of the recurrent ischemic stroke.4.3 Multiple factor Logistic regression model4.3.1 Relative risk of risk factors and recurrent eventsThe relative risk of recurrent events is more than 60 years of age 2.722 times as much as less than 60 year old patients,95%CI(1.134,6.532);The relative risk of recurrent events in patients with hypertension was 2.454 times that of without hypertension patients,95%CI(1.072,5.671).The relative risk of recurrence in patients with type 2 diabetes was 2.201 times higher than that of without,95%CI diabetes(0.982,4.931).The relative risk of recurrent events in patients with hyperlipidemia was 2.817 times that of patients without,95%CI(1.024,7.752).The relative risk of recurrent events in patients with family history of coronary heart disease is 4.322 times that of patients without,95%CI(1.238,15.091).The relative risk of recurrent events in patients with continuous smoking history was 1.852 times higher than that non smokers,95%CI(0.921,3.722);The relative risk of recurrent events in patients with sleep apnea syndrome is 2.413 times that of patients without sleep disorders,95%CI(0.913,6.373).The relative risk of recurrence in patients with phlegm dampness constitution is 2.133 times that of non phlegm dampness constitution patients,95%CI(1.049,4.34).The relative risk of recurrence in patients with blood stasis constitution is 2.585 times that of non blood stasis constitution patients,95%CI(1.288,5.188).The relative risk of recurrence events in patients with moderate or severe BI scores was 2.097 times higher than those in patients without dependence or mild dependence,95%CI(0.955,4.605).4.3.2 Evaluation of risk assessment model forecasting abilityThe prediction ability of the risk assessment model was evaluated.First,the calculation only included the risk assessment model of conventional western medicine risk factors.The AUC value was 0.718;Second,based on constitution the risk assessment model recurrent ischemic stroke was 0.766.5 ConclusionThe risk assessment model of the recurrent ischemic stroke based on the constitution is more suitable for the national use.According to the national characteristics,the social environment,the natural environment,the constitution quality of the people and the law of the transformation of the disease.The risk assessment model of ischemic stroke based on constitution is more accurate and has important clinical value,timeliness and creativity.6 Innovation point6.1 build a physique based risk assessment model for ischemic stroke.Combining the conventional recurrent ischemnic stroke risk factors with constitution,using frailty model can fit the recurrence and death event screening to identify the core of the recurrenct ischemic stroke risk factors.Finally,construct the recurrent ischemic stroke risk assessment model.6.2 The application of frailty model to identify risk factors for ischemic stroke recurrence is innovative.