| Objective:The fluctuation of human blood pressure has a circadian rhythm,which is characterized by"two peaks and one tough".There are two peak periods of daytime blood pressure,which are early morning and late afternoon(or called early evening),respectively.The incidence of cardiovascular events(such as stroke,myocardial infarction,sudden cardiac death)is parallel and consistent with the fluctuation of human blood pressure,and there are also two peak periods during the day.It has been confirmed that morning blood pressure(BP)and morning hypertension are associated with cardiovascular events.However,there are few studies on the relationship between the second peak of BP and cardiovascular risks.Thus,the first purpose of this study was whether the morning BP can be replaceable with the second peak of blood pressure(late afternoon blood pressure)in terms of absolute blood pressure value and the link between BP and target organ damage.Large-scale epidemiological evidence shows that there is an independent and continuous positive correlation between clinic blood pressure and cardiovascular risk when it reaches 115/75mm Hg.In addition,previous studies have shown that target organ damage and even idiopathic atrial fibrillation exist in the currently defined non-hypertensive population.One of previous studies have reported that about 8.7%of non-hypertensive people have left ventricular hypertrophy,which is related to the increase in early morning BP assessed by ambulatory blood pressure monitoring,but the increase in early morning BP does not account for all left ventricular hypertrophy in this population.Therefore,the second purpose of this study was to investigate the relationship between the late afternoon blood pressure and left ventricular hypertrophy in non-hypertensive population.In addition,left ventricular hypertrophy is an important pathophysiological mechanism of atrial fibrillation.In normotensive people with atrial fibrillation,whether the increase of diurnal peak BP is related to the occurrence of atrial fibrillation,and the correlation between the two daytime peak blood pressures and the changes of left atrial matrix need to be further studied.Materials and Methods:The newly diagnosed and untreated hypertensive subjects who completed ambulatory blood pressure monitoring in the ambulatory blood pressure room of West China Hospital from January 1,2015 to December 31,2015,the non-hypertensive population who completed ambulatory blood pressure monitoring in the ambulatory blood pressure room of West China Hospital from January 1,2015 to December 31,2019,and non-hypertensive patients with paroxysmal atrial fibrillation scheduled for radiofrequency ablation in the Department of Cardiology of West China Hospital from September 2019 to January 2021,were sequentially included.Demographic data were collected,they were all performed clinic blood pressure measurement,ambulatory blood pressure monitoring,echocardiography,blood biochemistry and other examinations.Patients with atrial fibrillation needed to perform three-dimensional reconstruction enhanced scanning and retain dynamic images of transthoracic echocardiography under sinus rhythm before operation.Left ventricular end-diastolic diameter,interventricular septum thickness and left ventricular posterior wall thickness were measured by transthoracic echocardiography,and left ventricular mass index(LVMI,standardized by body surface area),was calculated to evaluate left ventricular hypertrophy(LVH,≥115g/m~2 for male,≥95g/m~2 for female).For patients with atrial fibrillation,two-dimensional speckle tracking technique was used to evaluate the global longitudinal axial strain(GLS)of the left ventricle on the apical three-chamber,four-chamber and two-chamber views,and the phasic function of the left atrium(reservoir function,conduit function,booster pump function)on the apical four-chamber and two-chamber views.Three-dimensional reconstruction of the heart CT enhanced scanning through the post-processing software to make the use of volume imaging,three-dimensional reconstruction of the left atrium to measure left atrial volume(LAV).24-hour ambulatory blood pressure monitoring evaluated morning BP and late afternoon BP.Morning blood pressure was defined as the average blood pressure within 2 hours after getting up.Afternoon blood pressure was defined as the average blood pressure for 2 consecutive hours from 16:00 to 18:00,including the highest systolic blood pressure.The normal thresholds of both were defined as135/85mm Hg.Results:A total of 1274 untreated essential hypertensive patients,579 normotensives and231 normotensives with paroxysmal atrial fibrillation were included in this study.The results of each population were shown as follows.Results among hypertensive patients:1.The 24-hour BP fluctuation of human body had circadian rhythm and daytime rhythm,which was not affected by BP level,age and sex.It was characterized by lower BP at night than the daytime,and double peaks of BP during the day.The first daytime BP peak was in the early morning,that was,between 6:00 and 10:00,and the second daytime BP peak was in the late afternoon,that was,between 16:00 and 18:00.However,the dipper shape of nocturnal blood pressure could significantly affect the diurnal BP rhythm.Dipper,non-dipper and extreme dipper were still the characteristics of diurnal BP bimodal,and there was no significant difference in the period of bimodal BP,but in the reverse dipper group,the blood pressure in the early morning was lower than that at night,losing the characteristics of daytime bimodal blood pressure.2.Following analysis was performed after excluding nocturnal dipper with hypertension.In people with hypertension,the consistency of morning systolic blood pressure(SBP)and late afternoon SBP was poor(Mc Nemar’s ~2=6.42;P=0.014),that was,the increase of early morning SBP did not represent the increase of late afternoon SBP,and the normal early morning SBP did not mean that the afternoon SBP was normal.The 95%consistency ranges of morning SBP/diastolic blood pressure(DBP)and afternoon SBP/DBP were in the range of(-19.4mm Hg,22.8mm Hg),(-13.9mm Hg,14.6mm Hg),respectively.In normotensives,the 95%consistency ranges of early morning SBP/DBP and late afternoon SBP/DBP were in the range of(-21.5mm Hg,18.6mm Hg),(-15.4mm Hg,13mm Hg),respectively.These confidence intervals of consistency were too broad to be accepted clinically.Therefore,in the individual,the two BP components did not show a completely parallel and consistent increase and decrease relationship,but the morning BP was more significant,or the afternoon blood pressure is more significant.3.The patients were further divided into two groups according to the relationship between morning SBP and afternoon SBP:morning SBP>afternoon SBP group,morning SBP≤afternoon SBP group.Through subgroup analysis,the effects of morning SBP,afternoon SBP and pre-bedtime SBP on LVMI and left ventricular hypertrophy were compared.It was found that in the above two groups,pre-bedtime SBP could not affect LVMI and left ventricular hypertrophy independently of morning SBP and afternoon SBP.In the morning SBP>afternoon SBP group,morning SBP could influence LVMI independently of afternoon SBP,bedtime SBP and 24-hour SBP.In addition,morning SBP could affect left ventricular hypertrophy independently of afternoon SBP.In the morning SBP≤afternoon SBP group,afternoon SBP could influence LVMI independently of morning SBP,bedtime SBP and 24-hour SBP.In addition,afternoon SBP could affect left ventricular hypertrophy independently of morning SBP.Results among normotensive population:1.In the normotensive population,about 29.7%of the population showed elevated BP in the early morning and 19.3%in the afternoon;62.7%of the population showed normal morning BP and afternoon BP,11.7%of the population showed elevated BP in the morning and afternoon.In addition,in the population,there was a significant difference in the consistency of morning BP and afternoon BP(Mc Nemar’s=24.32,P<0.0l),and the Kappa consistency coefficient was only 0.319(P<0.01).After excluding people with elevated morning BP,10.8%(44/407)showed elevated BP in the afternoon.2.In the normotensive population,about 9.67%(56/579)had left ventricular hypertrophy.The increase of BP in the morning and afternoon was correlated with left ventricular hypertrophy.The OR of elevated morning BP was 4.696(95%CI:2.642-8.346).After excluding people with elevated morning B,there was still a correlation between afternoon BP and left ventricular hypertrophy,with an OR of 3.663(95%CI:1.342-10.000).3.24-hour BP fluctuation maps were drawn according to left ventricular hypertrophy group and non-left ventricular hypertrophy group.The difference in BP level was caused by SBP,rather than DBP.In addition,the difference in SBP in the afternoon(about 17:00)was significantly significant,followed by SBP in the morning and SBP in the night.4.In order to exclude the effect of early morning BP on LVMI and left ventricular hypertrophy,people with elevated early morning blood pressure were excluded for follow-up analysis.In Pearson correlation analysis,we studied the correlation between BP,BP variability and LVMI,and found that LVMI was mainly correlated with SBP,but not DBP,blood pressure morning peak-SBP,blood pressure morning peak-DBP.In addition,LVMI was correlated with SD/CV of daytime SBP/DBP,24-hour SBP and SD of nocturnal SBP,but not with blood pressure variability in other periods.Through the analysis of the ROC curve and the area under the calculated curve,it was found that the BP variability indexes of SBP and daytime DBP could distinguish left ventricular hypertrophy,while DBP,blood pressure variability index and morning peak of blood pressure could not distinguish left ventricular hypertrophy.The best cut-off points of afternoon SBP and daytime average SBP for identifying left ventricular hypertrophy were 120.5mm Hg and 114.5mm Hg,respectively.5.On Multiple linear regression analysis,afternoon SBP could influence LVMI independently of 24-hour SBP,daytime SBP,morning SBP,morning blood pressure peak and other blood pressure variability indexes.6.Binary logistic analysis showed that afternoon SBP could influence left ventricular hypertrophy independently of 24-hour SBP,daytime SBP,nighttime SBP/morning SBP,morning BP peak and other BP variability indexes.Results among normotensives with paroxysmal atrial fibrillation:1.In people with normal BP and paroxysmal atrial fibrillation,the proportion of elevated BP in the early morning and afternoon was 28.6%(66/231)and 22.5%(52/231)respectively.The proportion of both early morning BP and afternoon BP elevated was 13.0%(30/231).The 95%consistency range of afternoon SBP with morning SBP,afternoon DBP and morning DBP were respectively in the range of(-19.5mm Hg,15.2mm Hg),(-14.3mm Hg,12.0mm Hg).The Kappa consistency coefficient of morning BP and afternoon BP of the two categories was 0.343(P<0.01),but there was no significant difference in the consistency test(Mc Nemar’s 2=3.38,P<0.087).2.There was no significant difference in age,smoking,drinking and diabetes between the normal BP group with atrial fibrillation and the normal BP group without atrial fibrillation.The proportion of men in the atrial fibrillation group was higher than that in the non-atrial fibrillation group(68.0%vs.39.6%).In terms of BP,there was no significant difference in SBP between atrial fibrillation group and non-atrial fibrillation group in 24 hours,daytime,nighttime,morning and afternoon SBPs.In terms of DBP,the DBP of atrial fibrillation group was 1-2mm Hg higher than that of non-atrial fibrillation group(all P<0.01).In terms of LVH and anteroposterior diameter of the left atrium,the proportion of left ventricular hypertrophy in patients with atrial fibrillation was higher(24.2%vs.9.7%,P<0.01),and the anteroposterior diameter of the left atrium was larger(34.4±4.5mm vs.31.6±4.4 mm,P<0.01mm).3.On multivariate Logistic analysis of influencing factors of atrial fibrillation,among gender,age,BMI,smoking,drinking,diabetes,LDL-C,HDL-C,serum creatinine,uric acid,morning blood pressure,afternoon blood pressure and left ventricular hypertrophy,it was found that gender,age and left ventricular hypertrophy were independent predictors.The OR and 95%CI were 1.027(1.010-1.045),P<0.01,2.025(1.137-3.607),P=0.017,2.936(1.633-5.278),P<0.01,respectively.4.In patients with normal BP and paroxysmal atrial fibrillation,multivariate Logistic analysis of left ventricular hypertrophy showed that SBP in the morning and elevated blood pressure in the morning were independent predictors of left ventricular hypertrophy(both P<0.01),while afternoon SBP and elevated BP in the afternoon could not predict left ventricular hypertrophy(both P>0.05).5.By taking left atrial volume index,left atrial reserve pool function,left atrial conduit function,left atrial auxiliary pump function,LVMI,left ventricular longitudinal axial strain,E/e’as dependent variables,sex,age,BMI,smoking,drinking,diabetes,serum creatinine,uric acid,LCDL-C,HDL-C as covariates respectvivesly,stepwise linear regression was conducted.The SBP/DBP of morning,afternoon and morning peak of BP were substituted into the model,and SBP in the morning was the main influencing factor of myocardial injury.In the models of LAVI-CT,LA-Conduit,LVMI,LV-GLS and E/e’,the regression coefficientβwere 0.180,-0.079,0.237,0.036(all P<0.05),respectively.There was a negative correlation between morning SBP and left atrial conduit function,while there was a positive correlation between morning DBP,afternoon SBP,afternoon DBP and left atrial auxiliary pump function.6.Left atrial high density mapping was performed in 79 normotensives with paroxysmal atrial fibrillation,including 18 participants with LVH and 61 participants without LVH.Compared with patients wittout LVH,there was a higher percentage of subjects with voltage transition zone in left atrium among patients with LVH(44.4%vs.18.0%,P=0.047).Besides,local mean voltage was lower among patients with LVH in anterior,posterior,lateral and roof walls of left atrial,where voltage transition zones were frequently located.Conclusion:1.Circadian rhythm of human’s blood pressure fluctuation is characteristized with two daytime blood pressure peaks,which appear in the morning and late afternnon,respectively.And this fluctuation chanracteristics of blood pressure is not altered by age,sex,and blood pressure level.While,normal daytime blood pressure rhythm disappears among nocturnal dippers.2.Morning blood pressure and late afternoon blood pressure posses different clinical significance in terms of blood pressure aspect and association with target organ damage,regardless of hypertensives or normotensives.It is often manifested as the daytime peak blood pressure characteristics with more significant blood pressure in the morning or more significant blood pressure in the afternoon.Late afternoon blood pressure might require exclusive monitoring and intervention.Monitroing late afternoon blood pressure shoud be guided daytime blood pressure fluctuation rhythm,and should avoid eating,drinking,bating and other factors.3.Among normotensives without atrial fibrillation,late afternoon blood pressure is associated with LVMI and LVH,independent of other undelying confounders.Elevated late afternoon blood pressure might be a kind of manifestations of masked hypertension.4.Among normotensives with atrial fibrillation,elevated morning blood pressure might be an independent risk factor for LVH,and LVH might be an independent risk factor for atrial fibrillation.Elevated morning blood pressure might trigger atrial fibrillation,via LVH and subsequent diastolic dysfunction,which enhance left atrial pressure.5.Compared with normotensives in subclinical stage,clinical significance of late afternoon blood pressure is worse among normotensives in clinical stage.To further explore the association between late afternoon blood pressure and left atrial remodeling,atrial fibrillation,more normotensives with atrial fibrillation should be collected in future research,after excluding thess subjects with isolated elevated morning blood pressure. |
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