Study On The Cardiovascular Response Characteristics And Its Early Warning Role In Acute Mountain Sickness

Background:The high altitude areas in China have great potential with vast area and abundant resources.Nowadays,more and more people ascend to high altitude areas to engage in regional construction,national defense development,resources exploitation,commercial trade,high altitude tourism and other activities.However,the harsh environment of the highlands poses a serious challenge to both the local residents and visitors,it even causes a series of high altitude diseases,which seriously affects their normal work and life.In recent years,high altitude medicine researches have made great progress and their results have been reported and applied to reduce the incidence and mortality of high altitude diseases.However,there are still many unresolved issues.Hypobaric hypoxic will trigger a series of physiological changes in human body at high altitude areas.The adjustment process during which the body itself adapts to the high altitude environment gradually through these changes is called acclimatization.However,when the body cannot acclimatize well,various discomfort symptoms often appear and even develop into high altitude diseases.Acute mountain sickness（AMS）is one of the most common high altitude diseases.It is a clinical syndrome with series of discomfort symptoms in which the body fails to acclimatize well to the environment when people ascend rapidly from the sea level to high altitude or from high altitude areas to higher altitudes.Headache is the most predominant clinical symptom of AMS,usually accompanied by other symptoms such as insomnia,fatigue,dizziness,anorexia and nausea.In a few severe cases,the condition may develop into high altitude cerebral edema and/or high altitude pulmonary edema,which often leads to death if not treated timely and effectively.Therefore,it is important to study the early warning and effective treatment of AMS.The cardiovascular system is one of the first and foremost systems to react after high altitude exposure.After acute high altitude exposure,sympathetic activities increase,which causes vasoconstriction in pulmonary vascular and peripheral resistance vessels.Peripheral and pulmonary arterial pressure increase and heart rate accelerates,but stroke volume decreases.Cardiac output increases in the first few days and falls with acclimatization while the systolic function of the heart was generally maintained.The plasma volume and ventricular volume decrease,and diastolic filling pattern altered.These adjustments and changes in the cardiovascular system play an important role in the body’s rapid adaptation to the hypoxic environment of high altitude.In most cases,the cardiovascular response following acute high altitude exposure helps individuals tolerate and adapt to the hypoxic environment.However,in some cases,poor cardiovascular response may causes high altitude sickness such as AMS.Up to now,studies on the relationship between the response of the cardiovascular system following acute high altitude exposure and AMS are rare.Whether the baseline cardiovascular function of plain population influence the progression of AMS and whether the response of cardiovascular system after acute high altitude exposure involved in the development of AMS still need to be further explored.Therefore,this study will be divided into three parts to investigate the relationship between the response of cardiovascular system after acute high altitude exposure and AMS.The specific contents of the three parts are as follows:1.Epidemiological features of AMS;2.Characteristics of left ventricular response after acute high altitude exposure and its value in identifying AMS;3.The role of cardiac functional indexes in the early warning of AMS in plain population.Objectives:1.To identify the dynamic changes in the prevalence,clinical characteristics and relative risk of AMS based on the old and new versions of the Lake Louise scoring system in healthy plain population with different ascent patterns and different levels of acclimatization.2.To examine the effects of acute high altitude exposure on basic physiological parameters and left ventricular function in plain population.Screening for left ventricular functional parameters with discriminatory value for AMS and analyze the correlation and contribution among left ventricular functional parameters to explore the effects of acute high altitude exposure on left ventricular function and its potential associations with the occurrence of AMS.3.Screening for baseline cardiac functional parameters of early warning value for the onset of AMS in plain population and analyze its predictive value for AMS to explore the impact of baseline cardiac function in plain population on the progression of AMS,and further explore the potential associations of changes in cardiac function after acute high altitude exposure and the progression of AMS.Methods:1.1283 and 346 volunteers were respectively enrolled in Chengdu（500 m above sea level）in June 2012 and Chongqing（400 m above sea level）in June 2013.The fast ascent cohort consists of volunteers enrolled in 2012 who flew to Lhasa（3700 m above sea level）within 2hours.After stayed in Lhasa for 7 days,they further ascend to Yangbajing,Tibet（4400 m）by bus.The slow ascent cohort consist of volunteers enrolled in 2013 who ascend to Xinduqiao,Sichuan（3450 m）by bus within 4 days.After stayed in Xinduqiao for 3 days,they further ascend to Litang,Sichuan（4100m above sea level）by bus.Demographic data and the occurrence of symptoms were collected from volunteers on the plain,after acute high altitude exposure and further ascent to higher altitudes after short-term acclimatization respectively.AMS was diagnosed according to Lake Louise scoring system in old version and new version respectively.The occurrence of AMS and major symptoms were compared among groups.Logistic regression analysis was conduct to screening risk factors for the occurrence of AMS.2.589 volunteers were enrolled in Chengdu（500 m above sea level）in June 2012,and all the volunteers flew to Lhasa（3700 m above sea level）within 2 hours.Demographic data,basic physiological parameters,occurrence of symptoms and echocardiographic indexes were collected from the volunteers on the plain and after acute high altitude exposure respectively.Demographic data,physiological parameters,and indexes of left ventricular function detected by echocardiography of the volunteers were compared between groups before and after high altitude exposure.AMS was diagnosed according to the new version of Lake Louise scoring system,and all the volunteers were grouped into AMS+group and AMS-group according to whether they suffered AMS or not.And demographic data,physiological parameters,and indexes of left ventricular function were compared between the AMS+and AMS-groups.ROC curves analysis were conducted to screen echocardiographic indexes with AMS identification value.Then volunteers were further grouped according to the echocardiographic index with optimal AMS differential value.Indexes of left ventricular function,the occurrence of AMS and its scoring symptoms were compared between the groups.Linear regression analysis was also performed between the indexes of left ventricular function respectively.3.106 volunteers were enrolled in Chongqing（400 m above sea level）in June 2013,and all the volunteers ascent to Litang,Sichuan（4100 m above sea level）by bus within 7 days.Demographic data,basic physiological parameters,occurrence of symptoms and echocardiographic indexes were collected from volunteers on the plain and after acute high altitude exposure respectively.AMS was diagnosed according to the new version of Lake Louise scoring system,and all the volunteers were grouped in to AMS+group and AMS-group according to whether they suffered AMS or not.Between-group comparisons and logistic regression analyses were performed to find out baseline echocardiographic indexes of early warning value for the occurrence of AMS,ROC curves were used to find a cut-off value of the screened indexes and all the volunteers were further grouped according to the cut-off value.The occurrence of AMS and its scoring symptoms were compared between groups and the predictive value of the screened indexes for the occurrence of AMS was explored.The changes of echocardiographic indexes after acute high altitude exposure were also compared between groups.Results:1.As diagnosed by the old LLS and new LLS,the prevalence of AMS was 68.4%and56.1%at 3700 m,respectively,which decreased to 21.4%and 14.3%after further ascending to4400 m in the fast ascent cohort;the prevalence of AMS was 30.3%and 25.7%at 3450 m,which increased to 36.6%and 32.2%after further ascending to 4100 m in the slow ascent cohort.Except for the fast ascent cohort at 4400 m,headache,dizziness and fatigue were the leading symptoms in the other situations.Fast ascending mode was a risk factor during the initial ascent but became a protective factor after a further ascent to a higher altitude.2.The oxygen saturation,end-systolic volume index,end-diastolic volume index（EDVi）,stroke volume index（SVi）,E-wave velocity and E/A ratio decreased,whereas the heart rate（HR）,ejection fraction,cardiac index and A-wave velocity increased after high altitude exposure.AMS patients showed higher HR,lower EDVi,SVi,Ci,E-wave velocity and E/A ratio than AMS-free subjects.SVi mainly correlated with the changes of EDVi（R2=0.757,p<0.001）and EDVi mainly correlated with the changes of E-wave velocity（R2=0.522,p<0.001）.SVi was the most valuable factor associated with AMS incidence following receiver-operator characteristic curves（AUC:0.804,95%CI:0.767-0.842）,linear and Poisson regression.Compared with subjects in the highest SVi tertile,subjects in the middle SVi tertile showed higher multivariable Incidence Rate Ratios（IRR）for AMS（IRR:1.958,95%CI:1.333-2.876）with higher incidences of mild headache and gastrointestinal symptoms,whereas subjects in the lowest SVi tertile showed even higher multivariable IRR（IRR:4.710,95%CI:3.375-6.572）with higher incidences of all the symptoms.3.After acute high altitude exposure（AHAE）,33 subjects（31.1%）were diagnosed with AMS,who exhibited a lower lateral mitral valve tissue motion annular displacement(MV TMAD_lateral)at SL than that in subjects free of AMS（13.09 vs.13.89 mm,p=0.022）.Regression analysis demonstrated that MV TMAD_lateral at SL was significantly correlated with AMS occurrence（OR=0.717,CI:0.534～0.964,p=0.028）.Subjects with MV TMAD_lateral<13.30mm showed significant higher risk for suffering AMS in comparison to subjects with MV TMAD_lateral≥13.30 mm（OR:4.046,95%CI:1.648-9.933）.After AHAE,the increase of HR（64vs.74 bpm,p=0.001）and RV MPI（0.54 vs.0.69,p=0.009）,and the decrease of LV GLS（21.50vs.20.23%,p=0.002）,TV E/A（2.11 vs.1.89,p=0.019）as well as MV EDT（169.60 vs.156.90ms,p=0.035）were only found in subjects in MV TMAD_lateral<13.30 mm group.Conclusion:1.According to different LLS systems,modes of ascent,and levels of acclimatization,the incidence of AMS in the population ranged from 14.3%to 68.4%.Headache,dizziness and fatigue are the most prevalent symptoms after acute high altitude exposure.Fast ascending mode is a risk factor for AMS.2.After acute high altitude exposure,a decrease in SVi is significantly associated with the incidence and clinical severity of AMS.And alteration in SVi is associated with alteration in left ventricular filling pattern.3.Baseline MV TMAD_lateral level is a potential marker for predicting the occurrence of AMS in plains population,which may be related to differential alterations in biventricular systolic and diastolic function in subjects with different baseline MV TMAD_lateral levels after acute high altitude exposure.