Investigation On The Relationship Between Arterial Blood Pressure Changes And Acute Mountain Sickness And Their Related Mechanisms Upon High-altitude Exposure1

ObjectiveThis prospective and observational research aimed to elucidate BP changes induced byexposure to high-altitude hypoxia in different conditions (time courses, sleep quality andexercise), and their relationships with acute mountain sickness (AMS), Lake Louise Score andAMS severity. We further discussed the association among plasma renin-angiotensin systemconcentration changes, BP and AMS in healthy Chinese young men.Methods1. The investigation on blood pressure changes of the subjects upon high-altitudeexposure in different conditionsWe enrolled a total number of931male young adults first exposed to high-altitude3700m (Lhasa) from low altitude (LA,500m). Thereamong,396healthy young men living atlow altitude were randomly selected as the control group. The rest would arrive athigh-altitude3700m by air in2.5h. A total of204healthy young men were randomly selectedon day1,62healthy young men were randomly selected on day3,56healthy young men wererandomly selected on day5, and60healthy young men were randomly on day7. Bloodpressure measurement was performed at LA and on day1,3,5,7of exposure to high-altitude3700m. Athens Insomnia Scale (AIS) and Epworth Sleepiness Scale (ESS) were filled out atLA and on day1,3,7of exposure to high-altitude3700m.At high-altitude3700m (Day2, Day7), before the first step test, the measure of bloodpressure was recorded (Pre-exercise). According to the velocity control of the metronome with30times per minute, subjects began to do the first step test at0.3-meter-high steps for5minutes and then the first measure of blood pressure was recorded immediately after exercise [Post-exercise (1)]. After a rest for5minutes, subjects continued to do the second step test at0.3-meter-high steps for5minutes and then the second measure of blood pressure wasrecorded immediately after exercise [Post-exercise (2)].2. The investigation on the relationship of blood pressure changes and acutemountain sickness upon high-altitude exposureWe randomly selected a total of778male young adults first exposed to high-altitude3700m (Lhasa) from low altitude (LA,500m). Acute mountain sickness (AMS) symptomsQuestionnaire was performed at LA and on day1,3,5,7of exposure to high-altitude3700m.Likewise, Athens Insomnia Scale (AIS) and Epworth Sleepiness Scale (ESS) were filled out atLA and on day1,3,7of exposure to high-altitude3700m.We evaluated the significance ofblood pressure in the diagnosis of AMS.3. The investigation on the relationship of low-altitude blood pressure and thesusceptibility of acute mountain sicknessA total of204healthy lowlanders were randomly selected as the observation group.Arterial blood pressure (a wrist sphygmomanometer) was determined in these subjects withfirst exposure to3700m-altitude (Lhasa) from plain (500m) by air. Compared the low-altitudeblood pressure related indicators of two groups (AMS and non-AMS).4. The investigation on the relationship of RAS, blood pressure changes and AMSupon high-altitude exposureA total of71healthy lowlanders were randomly selected as the observation group.Arterial blood pressure (a wrist sphygmomanometer) was determined in these subjects withfirst exposure to3700m-altitude (Lhasa) from plain (500m) by air. Blood samples for theanalysis of plasma renin, angiotensinⅡ, angiotensin-(1-7), angiotensin converting enzyme,angiotensin converting enzyme2were collected at low altitude and on day1of high-altitude3700m.Results1. The investigation on blood pressure changes of the subjects upon high-altitudeexposure in different conditions: time courses, sleep quality and exercise condition(1) Blood pressure changes of3700m on different time coursesOn day1of3700m, SBP (121.25±12.69mmHg) was significantly higher than that at LA (115.15±10.53mmHg)(P=0.000), and then slightly descended on Day3(P>0.05), and again itbegan to elevate.On day1of3700m, DBP (79.41±9.45mmHg) and MABP (93.36±9.55mmHg) weresignificantly higher than those at LA (72.50±9.56mmHg;86.71±8.93mmHg)(P=0.000;P=0.000), and hereafter remained elevated gradually and persistently, but above the level ofLA until Day7(P<0.05).On day1of3700m, Pulse BP (41.84±9.98mmHg) was below the level of LA(42.65±8.06mmHg)(P=0.000) and last until Day5(P<0.05).(2) Blood pressure changes of3700m and sleep qualityOn day1,3,7of altitude-3700m, no difference of SBP, MABP and Pulse BP were foundbetween insomnia and non-insomnia group and between sleepiness and non-sleepinessgroup(P>0.05, respectively).On day1,3of altitude-3700m, DBP in insomnia group was apt to be higher than that innon-insomnia group (P=0.049; P=0.024, respectively).(3) Blood pressure changes of3700m and exercise conditionOn day2of altitude-3700m, compared with low altitude (EG1), Post-exercise(2) SBP,Pulse BP rose significantly (P=0.001; P=0.000). Post-exercise(1) and Post-exercise(2) SBP,MABP, Pulse BP surpassed Pre-exercise (P=0.006, P=0.000; P=0.031, P=0.038; P=0.042,P=0.000). On day7of altitude-3700m, compared with low altitude (EG2), Pre-exercise,Post-exercise(1) and Post-exercise(2) SBP, MABP increased (P=0.045, P=0.001, P=0.000;P=0.016, P=0.001, P=0.000). Post-exercise(2) SBP, Pulse BP exceeded Pre-exercise (P=0.009;P=0.017).On day2of altitude-3700m, no difference of DBP was found among low altitude(EG1),Pre-exercise, Post-exercise(1) and Post-exercise(2)(P>0.05). On day7of altitude-3700m,compared with low altitude (EG2), Pre-exercise, Post-exercise(1) and Post-exercise(2) DBPincreased (P=0.021, P=0.003, P=0.009).2. The investigation on the relationship of blood pressure changes and AMS, LakeLouise Score criteria, AMS severity upon high-altitude exposure in different conditions:time courses, sleep quality(1) Blood pressure changes and AMS on different time coursesThere exist no differences of SBP, DBP and Pulse BP between AMS and non-AMS group at any period of3700m (P>0.05, respectively). MABP on day1of altitude-3700m wasprone to be much higher in AMS group (P=0.028).(2) Blood pressure changes and Lake Louise Score criteria on different time coursesIn the light of LLS, SBP, DBP and Pulse BP at high-altitude3700m were not correlatedwith LLS (P>0.05, respectively). Mean arterial blood pressure (MABP) at high-altitude3700m was related to LLS (r=0.138, P=0.048). MABP level for diagnosis of AMS athigh-altitude3700m has an cut-off point of98.5mmHg with a positive predictive value of of67.7%and specificity of73.7%(P<0.05).(3) Blood pressure changes and AMS severity on different time coursesOn day1of altitude-3700m, SBP was apt to be higher in severe AMS group than that inmild or moderate AMS group (P=0.033; P=0.013, respectively). DBP had no differencesamong three AMS subgroups (P>0.05). MABP was apt to be higher in severe AMS groupthan that in mild AMS group (P=0.000). Pulse BP was prone to be lower in severe AMS groupthan that in moderate AMS group (P=0.017).(4) Blood pressure changes and AMS on sleep qualityIn accordance with AIS, ESS, in the insomnia group, SBP, DBP and MABP on day1ofaltitude-3700m tended to be higher in AMS group (P=0.037; P=0.042; P=0.03, respectively),while in the non-insomnia group, BP showed no discrepancy between AMS and non-AMSgroup (P>0.05, respectively).In the sleepiness group and non-sleepiness group, BP showed no discrepancy betweenAMS and non-AMS group (P>0.05, respectively).(5) Blood pressure changes and Lake Louise Score criteria on sleep qualityOn day1,3,7, there were no associations between BP and Lake Louise Score criteria inthe insomnia group and non-insomnia group or in the sleepiness group and non-sleepinessgroup (P>0.05, respectively).(6) Blood pressure changes and AMS severity on sleep qualityOn day1,3,7, no associations of BP and AMS severity were found in the insomniagroup and non-insomnia group or in the sleepiness group and non-sleepiness group (P>0.05,respectively).3. The investigation on the relationship of low-altitude blood pressure and thesusceptibility of acute mountain sickness DBP and MABP in the AMS group are higher than those in the non-AMS group(P=0.009; P=0.019). Low-altitude DBP levels for diagnosis of AMS at high-altitude3700mhave an area under curve (AUC)=0.598, P<0.05, sensitivity56.3%, specificity63.2%, andcut-off point of72.5mmHg.4. The investigation on the relationship of plasma renin-angiotensin system andhigh-altitude blood pressure, AMS(1) Renin-angiotensin system changes after exposure to high altitudeCompared with low altitude, plasma renin, AngⅡ, Ang-(1-7), ACE2concentration withsubjects after acute exposure to high-altitude3700m were higher than those at low altitude(P<0.05, respectively), but plasma ACE concentration didn’t change (P>0.05).(2) Renin-angiotensin system changes and BPThere exist no associations between renin、Ang-(1-7)、ACE and BP after acute exposureto high-altitude3700m(Day1). Plasma AngⅡconcentration was positively correlated withSBP、DBP and MABP (Spearman’s ρ=0.312, P=0.008; ρ=0.251, P=0.035; ρ=0.302, P=0.01,respectively), and plasma ACE2concentration was negatively linked with DBP (r=-0.267,P=0.024).(3) Renin-angiotensin system changes and AMSAccording to LLS, there exist no differences of renin、AngⅡ、Ang-(1-7)、ACE2betweenAMS and non-AMS group after acute exposure to high-altitude3700m (P>0.05, respectively).ACE on day1of altitude-3700m was prone to be much higher in AMS group (P=0.017).In the light of LLS, rennin, AngⅡ, Ang-(1-7), ACE2at high-altitude3700m were notcorrelated with LLS (P>0.05, respectively). ACE at high-altitude3700m (Day1) wascorrelated with LLS (r=0.241, P=0.043).There exist no differences of renin、AngⅡ、Ang-(1-7)、ACE、ACE2between mild AMSand moderate AMS group after acute exposure to high-altitude3700m (P>0.05, respectively).Conclusions:1. Blood pressure changes in different conditions of high altitude (time courses, sleepquality and exercise): after acute exposure to high altitude, BP increased significantly, andfluctuated with time. SBP began to rise and then decrease. DBP and MABP escalatedgradually and continually. Pulse BP decreased. DBP in insomnia group was higher than that in non-insomnia group. Post-exercise(2) SBP and Pulse BP were significantly higher than thoseof low altitude and Pre-exercise.2. The value of blood pressure after high-altitude exposure in the diagnosis of AMS:subjects with AMS had higher MABP. SBP, MABP in severe AMS group were higher.Subjects with AMS and with insomnia had higher SBP, DBP and MABP. MABP may be oneof sensitive index of AMS.3. A higher baseline DBP may be considered as a potential risk factor for AMS and maytestify to be a useful screening tool for AMS.4. The effect of RAS changes on BP and their roles in the development of AMS: afteracute exposure to high-altitude3700m, plasma renin, AngⅡ, Ang-(1-7), ACE2concentrationrose significantly. AngⅡrose significantly with the increasement of SBP, DBP and MABP.ACE2decreased with the increasement of DBP. Subjects with AMS had higher plasma ACEconcentration.