Circadian Blood Pressure Rhythm in Primary and Secondary Hypertension

Circadian blood pressure variability was recorded in patients with primary hypertension and with different forms of secondary hypertension using ambulatory 24-h blood pressure measurement. A group of 20 patients with different forms of secondary hypertension was compared with a matched group of patients with primary hypertension. Although the mean 24-h blood pressure was not different between the two groups, the patients with secondary hypertension had significantly higher systolic blood pressure during sleep and higher systolic and diastolic blood pressure in the early morning, compared with the primary hypertension group. This nocturnal blood pressure fall was then investigated in various groups of patients with different forms of secondary hypertension and compared with normotensives and patients with primary hypertension. Patients with mild primary hypertension (n = 152) and with severe primary hypertension (n = 30) had the same blood pressure fall (14–16 mm Hg systolic and diastolic) during the night (23:OO–05:OO h) as normotensives (n = 20). However, in patients with renoparenchymal hypertension (n = 29), renovascular hypertension (n = 20), hyperaldosteronism (n = 6), and hyperthyroidism (n = 14), the nocturnal blood pressure fall was significantly (p < 0.01) reduced. One patient with coarctation ofthe aorta and nine patients with primary hyperparathyroidism and elevated blood pressure had a normal circadian blood pressure profile with a normal nocturnal blood pressure fall. The heart rate decrease during the night was equal in all patient groups. Ambulatory blood pressure measurement allows blood pressure recording under everyday conditions, including nighttime. In primary hypertension the blood pressure variability exhibits the same circadian variation as in normotension, showing a marked nocturnal fall. However, in different forms of secondary hypertension, blood pressure shows a blunted circadian curve. This could have important diagnostic and therapeutic implications.     

原发性高血压患者血压昼夜节律与靶器官损害的关系研究

目的:研究原发性高血压患者血压昼夜节律异常是否与靶器官损害存在关联。方法:将2015年2~11月份在我院治疗的94例原发性高血压病人按照血压昼夜节律是否正常分为节律正常组52例和异常组42例。比较两组患者的24h、白天、夜间的收缩压(SBP)与舒张压(DBP)及血压负荷,并且比较两组患者心脏、脑、肾损伤相关指标。结果:异常组全天24h、白天、夜间SBP及DBP,血压负荷均高于正常组,差异具有统计学意义(P0.05)。异常组患者左室重量(LVM)和左室重量指数(LVMI)、发生心肌缺血次数及持续时间、发生脑梗死几率均明显高于正常组,差异有统计学意义(P0.05)。异常组尿微量白蛋白(MAU)、尿酸(UA)水平均高于正常组,差异有统计学意义(P0.05)。结论:原发性高血压患者出现昼夜节律异常,可能对相关靶器官造成损伤。     

原发性高血压患者心率变异性及血压变异性与血管损害的相关性研究

目的:探讨原发性高血压患者心率变异性(HRV)及血压变异性(BPV)与血管损害的相关性。方法:选取2014年12月到2017年12月期间在我院接受治疗的原发性高血压患者94例,根据脉搏波传导速度(PWV)的不同分为对照组(60例)和血管受损组(34例)。比较两组患者的HRV、BPV指标,并分析PWV与HRV、BPV指标的相关性。结果:血管受损组的5 min心搏R-R间期平均值的标准差(SDANN)低于对照组,低频(LF)、高频(HF)、低高频之比(LF/HF)高于对照组,差异均有统计学意义(P0.05);血管受损组的24h平均收缩压(24h SBP)、24h平均脉压(24h PP)、白天平均收缩压(dSBP)、白天平均脉压(dPP)、夜间平均收缩压(nSBP)、夜间平均脉压(nPP)高于对照组,差异均有统计学意义(P0.05);PWV与LF、HF、LF/HF、24h SBP、24h PP、dSBP、dPP、nSBP、nPP均呈正相关(P0.05)。结论:原发性高血压患者部分HRV、BPV指标与PWV呈明显的相关性,说明HRV和BPV与患者的血管损害密切相关。     

Circadian Rhythm of Blood Pressure: Internal and External Time Triggers

Diurnal blood pressure (BP) fluctuations are superimposed by a 24-h rhythm with usually lower levels during the night and higher levels during the day. In contrast to other rhythmic bioparameters, the diurnal BP rhythm is largely dependent on activity and sleep rather than on clock time. This has been demonstrated by the BP characteristics after shifted sleeping and working phases, during transition from sleep to wakefulness, and by the influence of sleep and activities on the 24-h BP curve during normal daily routines. Whereas the circadian rhythm of BP is predominantly governed by external time triggers, endogenous rhythmic-ity can only be detected by time microscopic analysis or in conditions where effects of external time triggers are almost excluded.     

Circadian Rhythm of Blood Pressure: Internal and External Time Triggers

Diurnal blood pressure (BP) fluctuations are superimposed by a 24-h rhythm with usually lower levels during the night and higher levels during the day. In contrast to other rhythmic bioparameters, the diurnal BP rhythm is largely dependent on activity and sleep rather than on clock time. This has been demonstrated by the BP characteristics after shifted sleeping and working phases, during transition from sleep to wakefulness, and by the influence of sleep and activities on the 24-h BP curve during normal daily routines. Whereas the circadian rhythm of BP is predominantly governed by external time triggers, endogenous rhythmicity can only be detected by time microscopic analysis or in conditions where effects of external time triggers are almost excluded.     

血压昼夜节律特征及其分子调控机制

正常血压具有典型的昼夜节律特征。血压昼夜节律异常与高血压靶器官损害和心血管事件发生呈明显相关关系,是独立于血压水平的重要致病因素。血压昼夜节律的产生和维持与时钟基因的周期性表达有关。时钟基因bmal1、per2是体内生物钟系统运行的关键基因,其表达水平和节律变化直接调节血压的昼夜节律。     

Circadian Rhythm of Blood Pressure in Congestive Heart Failure and Effects of ACE Inhibitors

In 33 patients with heart failure (NYHA 11-III), the 24-h blood pressure rhythm was examined before and after the titration period of two ACE inhibitors. Blood pressure was measured by the oscillometric method using the blood pressure monitor 90202 from SpaceLabs, Inc. The measurements were taken from 06:OO to 22:OO h every 20 min and from 22:00 to 06:00 h every hour. Patients were randomized to therapy with either captopril (group 1, n = 17) or enalapril (group 2, n = 16). The average daily dosage of captopril was 41 ± 3 mg given in three divided doses (08:00, 12:00, and 17:00 h). The mean dose of enalapril was 8 ± 1 mg once daily (08:00 h). Serum electrolytes, serum creatinine, and plasma renin activity were measured before and during therapy with both ACE inhibitors. Twenty-four-hour blood pressure measurements were taken before and on the fifth day of treatment with ACE inhibitors. Both groups were not different with respect to the degree of heart failure, the concomitant medication, and the 24-h profiles of blood pressure and heart rate before initiation of ACE inhibition. The 24-h blood pressure values on day 5 were consistently below the pretreatment values (p < 0.005) in both groups. Both groups did not differ significantly during ACE inhibition in their 24-h blood pressure and heart rate profiles. In both groups, the mesor of the systolic and diastolic blood pressure decreased significantly by the same degree (by 4.7/5.1 mmg Hg in group 1 and 6.4/4.1 mm Hg in group 2). The systolic/diastolic blood pressure amplitude decreased slightly in both groups. Before treatment, serum sodium, potassium, and creatinine were within the normal range. The increase in potassium (0.5 ± 0.1 mmol/L) reached statistical significance (p < 0.01) only in the captopril group, whereas it was not significant in the enalapril group (0.1 ± 0.1 mmol/L). Serum creatinine was not significantly altered by both ACE inhibitors. No relationship could be found between the changes in serum potassium or creatinine and the mean of the 24-h blood pressure values during ACE inhibition. Captopril and enalapril showed comparable blood pressure profiles and similar effects on renal function at the end of the titration on day 5. It can therefore be concluded that the effects on blood pressure rhythm and renal function are similar with a single daily dose of enalapril compared to captopril given three times daily.     

血压昼夜节律特征及其分子调控机制

正常血压具有典型的昼夜节律特征。血压昼夜节律异常与高血压靶器官损害和心血管事件发生呈明显相关关系,是独立于血压水平的重要致病因素。血压昼夜节律的产生和维持与时钟基因的周期性表达有关。时钟基因bmal1、per2是体内生物钟系统运行的关键基因,其表达水平和节律变化直接调节血压的昼夜节律。     

Variability in the Period of the Blood Pressure Orcadian Rhythm in Human Beings

In studies and assessments of human beings done in natural settings, it is assumed that the period τ of circadian rhythms, including ones of systolic (SBP) and diastolic (DBP) blood pressure, is equal to 24 hours. To test this hypothesis, SBP and DBP rhythms were studied in 112 medication-free, non-hospitalized subjects (62 males, 47.1 + 2.0 years [χ ± SEM], and 50 females, 54.5 ± 2.1 years) by 48h ambulatory blood pressure monitoring (ABPM). Of these, 26 were hypertensive (diurnal SBP> 140 mmHg and diurnal DBP> 90 mmHg) and 86 normotensive. All subjects were synchronized by their habitual daytime activities from ?08:00h to ?23:00h ± lh and by sleep at night. The BP was assessed at 15-minute intervals during a continuous 48h span using a Spacelabs model #90207 ABPM. The time series data of each subject were individually evaluated by power spectra analysis for the prominent x of the SBP and DBP rhythms. The prominent X differed from 24 hours in 22/112 subjects for SBP and in 16/112 subjects for DBP. Generally, in these individuals the τ was less than 24 hours. The occurrence of non-24h τ's was more frequent in hypertensive than normotensive subjects; the difference between the groups in the distribution of the prominent τ's by class (τ = 24h, >=12, 12h<24h, etc.) was statistically significant (χ² test =19.1; p < 0.001). No difference in the distribution of x's of blood pressure was detected according to the subject's age and gender. These findings suggest that ABPM done only for a duration of 24h may be too short to characterize accurately the features of the day-night variation in human BP, including the precise period of its rhythm. (Chronobiology International, 14(3), 307–317, 1997)     

Circadian Rhythm of Blood Pressure and Heart Rate in Cardiopathic Patients Before and After Heart Transplantation

The aim of this study was to investigate the natural history of the circadian rhythm of blood pressure (BP) and heart rate (HR) in 10 patients with heart failure (class IV of the New York Heart Association), who underwent heart transplantation because of primary congestive cardiomyopathy. The control group was 10 age-matched clinically healthy subjects. The BP and HR monitor-ings were performed before and after transplantation. Preoperatively, analysis of variance and cosinor methods validated the occurrence of a statistically significant BP and HR circadian rhythm in cardiopathic patients. Over the 4 days after surgery, both the cosinor method and serial section analysis were unable to validate a 24-h periodicity for BP and HR in patients with heart transplants. Six months after surgery, the BP and HR circadian rhythm was not detected as well. One year after transplantation. the BP and HR circadian rhythm was statistically validated. The recovery of the BP and HR circadian rhythm 1 year after heart transplantation can be regarded as a clinical sign of a reacquired susceptibility to neurovegetative chronoregulation.     

Circadian Rhythm of Blood Pressure and Heart Rate in Healthy Persons and Kidney Transplant Patients: Correlations with Activity

Fourteen diurnally active (07: 00–22: 39 h) normotensive healthy control subjects and 14 kidney transplant patients were studied by ambulatory blood pressure monitoring and wrist actigraphy simultaneously during one 24-h period. In the control group, circadian rhythms in systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressure, heart rate (HR), and wrist activity were documented by cosinor analysis with comparable afternoon peak times. In contrast, circadian rhythms with afternoon acrophases were detected only in HR and wrist activity in the patient group. The correlation of wrist activity with HR in controls and patients was comparable. Wrist activity and blood pressure were associated (r = 0.65 DBP and 0.54 SBP; p < 0.05) in controls, while in patients the relationship was weak or absent (r ranging from 0.02 SBP to 0.22 DBP). In 6 of 14 patients, BP and wrist activity were negatively correlated, reflecting the existence of nocturnal hypertension. In eight others, the correlation was small but positive. The 24-h pattern in BP and wrist activity in controls was comparably phased; however, this was not the case for the transplant patients, indicating the day-night pattern in blood pressure in this group is strongly dependent on pathologic phenomena rather than activity level and pattern.     

Relationship Between Metabolic Syndrome,Circadian Treatment Time,and Blood Pressure Non-Dipping Profile in Essential Hypertension

There is a strong association between metabolic syndrome (MS) and increased cardiovascular risk. Moreover, elevated nighttime blood pressure (BP) and non-dipping (subjects with <10% decline in the asleep relative to the awake BP mean) have been also linked to increased cardiovascular morbidity and mortality. We investigated the relation between MS, circadian time of hypertension treatment, and impaired nighttime BP decline in a cross-sectional study on 3352 (1576 men/1776 women) non-diabetic hypertensive subjects, 53.7?±?13.1 (mean?±?SD) yrs of age. Among them, 2056 were ingesting all their prescribed hypertension medication upon awakening, and 1296 were ingesting at least one of their BP medications at bedtime. BP was measured by ambulatory monitoring for 48 consecutive hours to substantiate reproducibility of the dipping pattern. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate mean BP when awake and asleep for each subject. MS was present in 52.6% of the subjects. The prevalence of an altered non-dipper BP profile was significantly higher among subjects with MS (52.0% vs. 39.5% in subjects without MS, p < .001). Non-dipping was significantly more prevalent among subjects ingesting all BP-lowering medications upon awakening (56.8%) than among those ingesting at least one of their BP medications at bedtime (29.1%; p < .001). Subjects with MS had significantly higher values of uric acid (6.0 vs. 5.3?mg/dL, p < .001), plasma fibrinogen (331 vs. 315?mg/dL, p < .001), and erythrocyte sedimentation rate (14.8 vs. 12.4?mm, p < .001). Non-dipping was significantly associated with the presence of MS and treatment upon awakening in a multiple logistic regression model adjusted by significant confounding factors, including age, creatinine, erythrocyte sedimentation rate, and cigarette smoking. This cross-sectional study documents a significant increase of a blunted sleep-time BP decline in treated hypertensive subjects with MS. Even in the presence of MS, treatment at bedtime is significantly associated with lower prevalence of a high-risk non-dipper BP profile. (Author correspondence: rhermida@uvigo.es)     

SRC-2 Is an Essential Coactivator for Orchestrating Metabolism and Circadian Rhythm

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Effects of Different Once-a-Day Medications on 24-Hour Blood Pressure Recordings in Hypertensives

Compliance with antihypertensive treatment can be increased by using medications that are taken only once daily. There is, however, concern as to whether the efficacy of such drugs is sufficient to cover 24 h. Ambulatory blood pressure monitoring (ABPM) is an ideal technique to assess the effect of this kind of drug and to determine over- or undertreatment. In this study three drugs were examined as once-a-day preparations. Thirty-six patients were treated with three different doses of bisoprolol, as an example of the β,-selective beta-blockers; 12 patients were treated with a combination of the AChE-inhibitor enalapril and hydrochlorothiazide; eight patients were treated with nifedipine once per day, a new galenic form of nifedipine, as an example of the calcium-channel blockers. In each group we saw a significant downward shift over the entire 24-h curve. Our results also show that using 24-h blood pressure monitoring devices can help establish an appropriate dose, avoid over- and undertreatment, and control the total burden of the patient.     

时钟节律与细胞周期

昼夜节律和细胞周期是生命有机体中两种主要的节律性、周期性的活动,参与机体代谢与生理节律．在分子水平上,它们的周期性活动是由一种周期性振荡的网络构成的,这种网络由一系列节律性表达的蛋白所形成．研究发现,多种节律因子通过调节周期蛋白的表达影响细胞周期进程,如G ₁-S期,REV-ERBa抑制p21促进细胞进程,RORα激活p21抑制细胞进程,DEC1抑制cyclinD1,CLOCK/BMAL1负调控c-Myc;G ₂-M期,BMAL1/CLOCK、BMAL1/NPAS2或Cry1作用于Wee1抑制或激活G_2-M期进程．此外,昼夜节律钟蛋白也参与了DNA损伤修复及细胞死亡的过程：Per1、Tim分别作用于ATM、ATR,因而促进细胞周期停滞,p53缺失的细胞中敲除Cry促进细胞凋亡过程,抑制了肿瘤的形成,DEC1以p53依赖的方式促细胞衰老等．同时,节律因子的紊乱引起多种疾病的产生．因此,阐明昼夜节律对细胞周期及死亡的影响,将为肿瘤的治疗提供分子理论基础．     

高血压患者动态血压变异与中医体质分类的相关性研究及中医干预

目的：以中山市石岐区退休干部为样本,探讨高血压患者动态血压变异与中医体质分类的相关性,并观察中医干预对血压变异的影响。方法：选取部分中山市石岐区退休干部进行血压测量,筛查出原发性高血压患者465例进行24 h动态血压监测,根据24 h动态血压昼夜节律变化,分为杓型组和非杓型组,比较2组患者中医体质分类。观察非杓型患者经中医干预前后的血压昼夜节律变化情况。结果：比较杓型组与非杓型组的中医体质分类,差异有统计学意义（P＜0．05）,杓型组多见湿热质、痰湿质,非杓型组多见阴虚质、气虚质和阳虚质。通过适当的中医干预有助于改善血压昼夜节律变化,有助于使非杓型血压向杓型血压转归（P＜0．05）。结论：中医体质分类与高血压患者动态血压变异有相关性,可为临床观察高血压患者动态血压变异做客观依据,为高血压患者实施个体化中医干预提供客观依据。     

Circadian Blood Pressure Variability in Normotensive Pregnant Women as a Function of Parity,Maternal Age,and Stage of Gestation

Studies based on conventional office blood pressure (BP) measurements concluded that both maternal age and parity have significant effects on BP during pregnancy. Previous results have also indicated predictable trends of BP variability with gestational age. Accordingly, we have evaluated possible differences in the circadian pattern of ambulatory BP as a function of parity, maternal age, and stage of gestation in normotensive women who were systematically studied by ambulatory BP monitoring during their pregnancies. We analyzed 1408 BP profiles obtained from 126 nulliparous and 109 multiparous pregnant women sampled for 48 consecutive h every 4 weeks from the first obstetric visit (usually within the first trimester of pregnancy) until delivery. Data were divided for comparative analysis according to parity (nulliparous versus multiparous), age (≤25, 26–30, 31–35, and ≥36 yrs), and trimester of gestation. Circadian BP parameters established by population multiple‐components analysis were compared between groups using a nonparametric test. A highly statistically significant circadian pattern described by a model that includes components with periods of 24 and 12 h is demonstrated for systolic and diastolic BP for all groups of pregnant women in all trimesters (always p<0.001). There was no significant difference in the 24 h mean among groups divided by parity at any age or stage of pregnancy. A trend of increasing BP with age was found for diastolic but not for systolic BP. Although statistically significant, differences in the 24 h mean of diastolic BP among groups divided by age were always less than 2 mm Hg. Data obtained from systematic ambulatory monitoring in normotensive pregnant women indicate the lack of differences in BP according to parity. The small, although significant, increase in diastolic BP with age may have scarce influence in the proper identification of women with gestational hypertension. Reference thresholds for BP to be used in the early identification of hypertensive complications in pregnancy could thus be developed as a function of the rest‐activity cycle and gestational age only, and independently of parity or maternal age.     

Circadian Rhythm in Serum Iron Levels

This study was aimed at assessing the circadian rhythm of serum iron levels in Chinese healthy subjects. The project was conducted in 19 healthy, Chinese male subjects following a 4-day diet equilibration. Blood samples were collected on day 5 at 0800, 1000, 1200, 1400, 1600, 1800, 2000, and 2400 hours to determine endogenous serum iron concentrations. Iron concentrations were determined using an inductively coupled plasma mass spectrometry. Iron concentration was decreased from morning to afternoon. The minimum value of iron level was 1,987 μg/L at 2000 hours while the maximum was 2,229 μg/L at 1000 hours, and 2,278 μg/L at 1400 hours, respectively, the amplitude was 291 μg/L. This study indicates that when assessing the bioequivalence of iron formulations, baseline levels of iron (obtained before dosing) should not be subtracted simply from the amount obtained on the drug dosing day to yield the net effect of iron formulation administration. More valid methods to optimize the design of such bioequivalence studies should be taken into consideration.     

Circadian Rhythm in Pineal Methionine S-Adenosyltransferase

Abstract: The circadian rhythm of methionine S -adenosyltransferase, which catalyzes the formation of S -adenosylmethionine, a cosubstrate for melatonin in the pineal gland, follows the pattern of hydroxyindole- O -methyltransferase. Around the middle of the dark period, methionine S -adenosyltransferase and hydroxyindole- O -methyltransferase appear to be elevated by 2.5- and 1.5-fold, respectively, and tend to fall back during the light period.