Determinants of circadian blood pressure rhythm and blood pressure variability in obstructive sleep apnoea

SUMMARY  The prevalence of hypertension in patients with obstructive sleep apnoea (OSA) is high and blood pressure profile is characterized by nocturnal blood pressure (BP) elevation and increased nocturnal BP variability. Ambulatory 24-hour-biood pressure monitoring (ABPM) is a valid, non-invasive method to describe circadian BP variation. Circadian BP profile and nocturnal BP variability were related to OSA severity (apnoea-hypopnoea index, mean low O₂), age and body mass index (BMI) in 73 patients with OSA. Prevalence of hypertension was 75%, and in 59% BMI was greater than 30 kg m^-2. A nocturnal decline of at least 10% from daytime mean BP values (night/day BP ratio <0.9; dipper) was found in only 25% of hypertensive patients and 39% of normotensive patients. Comparison between dippers and non-dippers showed significant differences in apnoea severity (apnoea-hypopnoea index 32 + 19 vs. 50 + 23/h, P <0.01; mean low O₂ 84.5 + 4 vs. 80.2 + 5.8%, P< 0.01) but not for age and BMI. In multiple regression analyses with age, body mass index, apnoea-hypopnoea index and mean low O₂ as independent and BP ratios and BP variability as dependent variables, sleep apnoea severity was the only independent predictor for circadian BP rhythm and nocturnal BP variability. The results presented here suggest that independent of age and obesity the severity of sleep apnoea is an important determinant of circadian BP variation and nocturnal BP variability.     

Circadian blood pressure patterns and life stress

BACKGROUND: Scarce data are available on the influence of psychological aspects on 24-hour ambulatory blood pressure patterns either in normotensive or hypertensive subjects. This study was designed to evaluate the relationship between psychological profile and changes in daytime/nighttime blood pressure rhythm. METHODS: Nocturnal dipping was defined as the night/day ratio of ambulatory mean systolic and/or diastolic blood pressure < or =0.87. Three-hundred and two outpatients (M/F = 174/128; mean age = 49.8 years, SD = 13.6; range, 16-80 years) underwent 24-hour ambulatory blood pressure monitoring. They were administered a self-rating scale, the Psychosocial Index, as an indicator of stress, psychological distress, sleep disturbances, well-being, abnormal illness behavior and quality of life. There were 242 patients taking antihypertensive medication (146 adequately controlled and 96 not controlled) and 60 who were drug free (33 never-treated hypertensive and 27 normotensive subjects). Patients were divided according to the presence (n = 125) or absence (n = 177) of night blood pressure dipping. The two groups were compared using analysis of covariance, with age as a covariate. RESULTS: Dippers had lower (p < 0.001) nocturnal systolic and diastolic blood pressure than nondippers, and higher (p < 0.05) daytime diastolic blood pressure. Patients with nocturnal blood pressure decline had a markedly higher (p < 0.001) level of stress than nondippers. When the sample was divided according to the presence or absence of hypertension, only subjects with normal blood pressure showed nocturnal dipping associated with increased stressful life circumstances. CONCLUSIONS: Our findings indicate that dippers experience stressful life circumstances, both in terms of life events and chronic stress. This suggests that stress-reducing techniques may be particularly helpful in the setting of hypertension characterized by nighttime blood pressure dipping.     

The effect of melatonin on circadian blood pressure in patients with type 2 diabetes and essential hypertension

Introduction

The aim of this study was to evaluate the effect of melatonin on blood pressure in patients with essential hypertension receiving medical treatment and with type 2 diabetes in good metabolic control.

Material and methods

The study lasted 8 weeks. Patients were equipped with a 24-hour ambulatory blood pressure monitor and took melatonin (3 mg a day in the evening) for 4 weeks. The patients were divided into four groups: group 1 (n = 32) including dippers, group 2 (n = 34) non-dippers treated with melatonin; and two control groups: group 3 (n = 28) including dippers and group 4 (n = 30) non-dippers treated without melatonin. After 4 weeks patients took melatonin for the next 4 weeks (5 mg a day). In each visit were analyzed: systolic, diastolic and mean blood pressure in both day and night time.

Results

We observed that 29.5% non-dippers (n = 10) treated with melatonin in a dose of 3 mg/day achieved features of dippers compared to control group (p < 0.05). Five mg of melatonin per day restored normal diurnal blood pressure rhythm in 32.4% non-dippers (n = 11, p < 0.05). In non-dippers treated with melatonin significant decreases of diastolic, systolic and mean night blood pressure values (p < 0.05) were observed.

Conclusions

More than 30% of non-dippers with type 2 diabetes treated with melatonin were restored to the normal circadian rhythm of blood pressure. The effect of melatonin in both doses (3 mg and 5 mg) was significant for non-dippers only and included nocturnal systolic, diastolic and mean arterial pressure.     

焦虑抑郁障碍与血压变异性研究

高血压与焦虑抑郁障碍之间密切相关。焦虑、抑郁可以引起血压昼夜节律变化,促发并加重高血压,降低降压药物的疗效,并可能导致难治性高血压。血压变异性作为新的血压监测参数,能更好地反应血压全天的总体水平、变化规律、昼夜的波动状况,能更好地评估降压治疗的疗效。随着血焦虑抑郁障碍引起异常的血压波动也越来越受重视,现就焦虑障碍与血压变异性之间关系的进行综述。     

Morning versus evening administration of nifedipine gastrointestinal therapeutic system in the management of essential hypertension

The nifedipine gastrointestinal therapeutic system (GITS) is a recently developed controlled-release formulation for once-a-day dosing. We evaluated the influence of morning versus evening administration of the drug in a randomized double-blind cross-over study including 15 essential hypertensives. Five patients had to be excluded from blood pressure analysis because of noncompliance (three cases) or intolerable side effects (two cases). To assess the exact duration of the antihypertensive efficacy noninvasive automatic ambulatory blood pressure monitoring was performed. After a placebo period patients were given 30 mg nifedipine GITS either at 1000 or 2200 hours. Twenty-four-hour systolic and diastolic blood pressure profiles documented a sustained antihypertensive effect of both nifedipine regimens throughout the whole period without affecting the circadian rhythm. Statistical analysis revealed no significant difference between morning and evening administration. Two patients stopped their medication because of intolerable side effects (fatigue and muscle cramps, respectively). Two more cases suffered from mild reversible headache which provoked no discontinuation of the drug. In conclusion our results document a sustained antihypertensive efficacy of 30 mg nifedipine GITS in patients with moderate essential hypertension. Time of administration has no impact on day- and nighttime blood pressure control.Abbreviation GITS gastrointestinal therapeutic system     

Plasma free 3-methoxy-4-hydroxyphenylglycol circadian rhythm in sleep-deprived subjects: 5-methoxypsoralen effect

In order to determine whether 5-methoxypsoralen (5-MOP) (which bears resemblance to serotonin) restores the circadian rhythm of plasma 3-methoxy-4-hydroxyphenylglycol (MHPG), the metabolite of noradrenaline (NA), plasma free MHPG, was analyzed in blood samples obtained every hour over 24 h for six sleep-deprived healthy subjects, three of whom had taken 5-MOP the previous evening. Although 5-MOP had no demonstrable effect on the plasma NA circadian rhythm in a previous study, it may preserve a weak free MHPG circadian rhythm, by preventing the nocturnal increase in MHPG.     

Study of the reference values and nyctohemeral cycle of serum iron

Marked variations in the same individual of serum iron levels may be due to a circadian rhythm. We determined the reference values of serum iron in a population of blood donors who had no blood disease. The very wide reference interval found (0.47 to 1.75 mg/l in man and 0.36 to 1.66 mg/l in women) was due to physiological variations rather than analytical variations. We also demonstrated in individuals with a normal life rhythm, a circadian rhythm for iron with maximal levels in the morning (8 to 12) and minimal levels in the evening (8 p.m. to midnight) the ratio of these levels is usually between 1.5 and 2, but may reach much higher figures. On the other hand, the total fixation capacity varies little over 24 hours. In night workers, one may note a displacement of the cycle with a maximum towards 8 p.m. a minimum at 8 a.m. In diabetics, the circadian rhythm exists but with a lower amplitued than in healthy subjects. In a few cases a hemochromatosis, one may note disappearance of the cycle.     

Influence of head-down bed rest on the circadian rhythms of hormones and electrolytes involved in hydroelectrolytic regulation

We investigated in six men the impact of a 17-day head-down bed rest (HDBR) on the circadian rhythms of the hormones and electrolytes involved in hydroelectrolytic regulation. This HDBR study was designed to mimic an actual spaceflight. Urine samples were collected at each voiding before, during and after HDBR. Urinary excretion of aldosterone, arginine vasopressin (AVP), cyclic guanosine monophosphate (cGMP), cortisol, electrolytes (Na⁺ and K⁺) and creatinine were determined. HDBR resulted in a significant reduction of body mass (P<0.01) and of caloric intake [mean (SEM) 2,778 (37) kcal·24 h^–1 to 2,450 (36) kcal·24 h^–1, where 1 kcal·h^–1=1.163 J·s^–1; P<0.01]. There was a significant increase in diastolic blood pressure [71.8 (0.7) mmHg vs 75.6 (0.91) mmHg], with no significant changes in either systolic blood pressure or heart rate. The nocturnal hormonal decrease of aldosterone was clearly evident only before and after HDBR, but the day/night difference did not appear during HDBR. The rhythm of K⁺ excretion was unchanged during HDBR, whereas for Na⁺ excretion, a large decrease was shown during the night as compared to the day. The circadian rhythm of cortisol persisted. These data suggest that exposure to a 17-day HDBR could induce an exaggeration of the amplitude of the Na⁺ rhythm and abolition of the aldosterone rhythm. Electronic Publication     

Impact of evening alcohol consumption on nocturnal autonomic and cardiovascular function in adult men and women: a dose–response laboratory investigation

Study ObjectivesTo investigate the dose-dependent impact of moderate alcohol intake on sleep-related cardiovascular (CV) function, in adult men and women.MethodsA total of 26 healthy adults (30–60 years; 11 women) underwent 3 nights of laboratory polysomnographic (PSG) recordings in which different doses of alcohol (low: 1 standard drink for women and 2 drinks for men; high: 3 standard drinks for women and 4 drinks for men; placebo: no alcohol) were administered in counterbalanced order before bedtime. These led to bedtime average breath alcohol levels of up to 0.02% for the low doses and around 0.05% for the high doses. Autonomic and CV function were evaluated using electrocardiography, impedance cardiography, and beat-to-beat blood pressure monitoring.ResultsPresleep alcohol ingestion resulted in an overall increase in nocturnal heart rate (HR), suppressed total and high-frequency (vagal) HR variability, reduced baroreflex sensitivity, and increased sympathetic activity, with effects pronounced after high-dose alcohol ingestion (p’s < 0.05); these changes followed different dose- and measure-dependent nocturnal patterns in men and women. Systolic blood pressure showed greater increases during the morning hours of the high-alcohol dose night compared to the low-alcohol dose night and placebo, in women only (p’s < 0.05).ConclusionsAcute evening alcohol consumption, even at moderate doses, has marked dose- and time-dependent effects on sleep CV regulation in adult men and women. Further studies are needed to evaluate the potential CV risk of repeated alcohol-related alterations in nighttime CV restoration in healthy individuals and in those at high risk for CV diseases, considering sex and alcohol dose and time effects.     

Diurnal variation in uterine artery blood flow in post-menopausal women on oestrogen hormone replacement therapy.

Doppler ultrasound was used to investigate circadian variations in uterine artery blood flow in 20 post-menopausal women in the oestrogen-only phase of combined oestrogen hormone replacement therapy with cyclical oral norethisterone or dydrogesterone. All women were examined between 0800 and 0830 h and then again between 1800 and 1830 h on the same day. Mean arterial blood pressure, heart rate and a blood sample for measurement of serum oestradiol were taken at each visit. Indices of uterine artery blood flow included the pulsatility index, resistance index, peak systolic velocity and time-averaged maximum velocity. No significant differences in the mean arterial blood pressure, pulse rate and oestradiol concentrations were detected between morning and evening visits. Significant fluctuation was observed in the pulsatility index (P < 0. 001), resistance index (P < 0.001) and time-averaged maximum velocity (P < 0.01). The assessment of uterine artery blood flow in post-menopausal women should take into account the presence of circadian variations to ensure accuracy and reproducibility of Doppler investigations.     

Self-report of circadian type reflects the phase of the melatonin rhythm.

This study examined the relationship between circadian rhythm characteristics of the pineal hormone melatonin and individual differences in circadian type and mood. 95 healthy young men and 22 women were assessed each hour (00:00-07:00 h) for blood levels of melatonin throughout one night in the laboratory. Each subject was assessed for circadian type (morning, afternoon, or evening type) and morning mood (PANAS). Circadian type was strongly related to the melatonin acrophase but not to amplitude or time of year of assessment. Also, morning types evidenced a more rapid decline in melatonin levels after the peak than did evening types. Evening types were younger than were morning types. Female morning types reported more positive affect upon waking than did female afternoon or evening types. Males showed no such discrimination. Age was related to both melatonin acrophase and circadian type but did not explain the relationship between them. The results replicate and extend findings on circadian type and psychological and physiological variables.     

The effect of resistance training on blood pressure in normotensive women

The purpose of the present study was to determine whether conventional resistance training alters 24-h ambulatory and manually determined casual blood pressure of normotensive women. Seven individuals (23 +/- 2 years old) trained 2 days week-1 for 20 weeks emphasizing the hip and knee extensor muscle groups. Three sets to exhaustion of the knee extension, squat, knee flexion and leg press exercises were performed. The load for each exercise represented approximately 80-85% of the one-repetition maximum. Average values for 24-h ambulatory blood pressure were not different (P greater than 0.05) pre- and post-training (systolic, 107 +/- 4 vs. 109 +/- 1 mmHg; diastolic, 73 +/- 2 vs. 71 +/- 2 mmHg). Ambulatory values over 8-h segments of the 24 h (day, evening, night) and casual resting determinations of blood pressure were also not affected. The lack of change in blood pressure cannot be explained by an insufficient training response. Knee extensor strength during dynamic or isokinetic actions increased (approximately 43%, P less than 0.05). In addition, biopsies from the vastus lateralis muscle showed an increase (P less than 0.05) in average muscle fibre cross-sectional area of 32%. This hypertrophic response was further substantiated by an increase (P less than 0.05) in lean body mass (41.2 +/- 1.3 kg to 43.4 +/- 1.5 kg). These results indicate that resistance training, which increases muscular strength, muscle fibre area and lean body mass, does not alter ambulatory or casual blood pressure. Thus, the concern that conventional resistance training may chronically elevate blood pressure does not appear warranted, at least in normotensive women.     

高血压病血压昼夜节律与心肌缺血的关系

目的 探讨高血压病患者血压昼夜节律改变与心肌缺血之间的关系及临床意义。方法对90例高血压病患者,根据动态心电图上有无心肌缺血(MI)分为MI组(40例)和无MI组(50例),并与20例健康体检者进行对照,观察3组的动态血压变化,同时分析血压昼夜节律正常组和异常组的心肌缺血的发生情况。结果 高血压病伴有MI的患者中,除dSBP、24hDBPL、dSBPL、dDBPL与无MI组比较无统计学差异外,其余各项动态血压指标均明显高于无MI组(P<0.01);高血压病血压昼夜节律异常组发生MI者明显高于血压昼夜节律正常组(P<0.05)。结论 高血压病患者中伴有血压昼夜节律异常者更易导致心肌缺血的发生。对高血压病患者的治疗,除积极控制血压外,还应注意检测和逆转异常的昼夜血压节律,对减少心肌缺血的发生和靶器官损害具有重要意义。     

血压负荷,血压昼夜节律及心率变异性与左室肥厚的关系

目的：观察高血压左心室肥厚患者血压负荷，血压昼节律和心率变异性及其相关性。方法：选择伴有左室肥厚的高血压患者31例（I组），不伴左心室肥厚的高血压患者33例（Ⅱ组），选择年龄与患者可比的健康人30例作为对照组（Ⅲ组），进行动态血压与动态心电图同步监测，分析24小时血压负荷，血压昼夜节律及24小时心率变异性时域指标。结果：（1）血压负荷，血压昼节律：I、Ⅱ组24小时血压负荷，日间血压及夜间血压显著高于Ⅲ组，I组与Ⅱ组间血压负荷有显著差异；I与Ⅱ组非构型血压显著高于Ⅲ组，I与Ⅱ组二者间的非构型高血压出现率有显著差异。（2）心率变异性：I、Ⅱ组心率变异性各参数显著低于Ⅲ组，I与Ⅱ组间心率变异性也有显著差异。（3）四个指标的相关性：I组HRV与24小时血压负荷，非构型出现率及左室肥厚呈负相关。结论：高血压左室肥厚患者昼夜节律消失，血压负荷增加，心率变异性降低。副交感神经调节功能减弱可能与上述变化有关。高血压治疗中应注意改变心率变异性，恢复血压昼夜节律，减少血压负荷。     

Circadian characteristics of urinary melatonin from clinically healthy young women at different civilization disease risks

Rhythm characteristics in the about-daily (circadian) and about-yearly (circannual) frequency ranges were assessed for urinary melatonin. Clinically healthy women in Minnesota, USA, and Kyushu, Japan, were sampled around the clock once in 1-4 seasons. Possible differences that could reflect the large difference in breast cancer incidence in these two geographic locations were investigated. Each subject's risk of developing breast cancer, cardiovascular diseases resulting from an elevated blood pressure, and emotional conditions was numerically evaluated according to epidemiologic questionnaires. A prominent circadian rhythm characterizes urinary melatonin in both populations, peaking in the middle of the night. The American women exhibit a larger circadian rhythm-adjusted mean (mesor) than do the Japanese women. A circannual rhythm is also apparent in the North American women, but not in the Japanese women. The circadian mesor of urinary melatonin correlates negatively with the risk score of emotional depression and positively with that of developing cardiovascular diseases.     

Increased ambulatory arterial stiffness index and blood pressure load in normotensive obese patients

ObjectivesIt has been shown that blood pressure (BP) values measured in obese subjects are higher than the individuals with normal weight, even in normotensive limits. However, data concerning the Ambulatory Arterial Stiffness Index (AASI) and blood pressure load in normotensive obese subjects is lacking. This study was aimed to compare the ambulatory arterial stiffness index and blood pressure load in normotensive obese and healthy controls.MethodsOne hundred normotensive obese and one hundred normal weight subjects were included in this study. All subjects underwent 24-hour ambulatory blood pressure monitoring. Ambulatory arterial stiffness index was calculated from 24-hour ambulatory blood pressure monitoring records. Ambulatory arterial stiffness index was defined as one minus the regression slope of unedited 24-h diastolic on systolic blood pressures. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) load values were calculated from 24-hour ambulatory blood pressure monitoring analysis.ResultsAmbulatory arterial stiffness index of the obese subjects was significantly higher than the healthy controls (0.48±0.2 vs. 0.33±0.11, p<0.001). 24-hours systolic blood pressure and diastolic blood pressure loads were significantly higher in obese subjects. Logistic regression analysis revealed that body mass index (BMI) was an independent predictor for an abnormal ambulatory arterial stiffness ındex (≥0.50) (OR: 1.137, 95% CI: 0.915-1.001, p=0.004).ConclusionBlood pressure load and ambulatory arterial stiffness index are increased in normotensive obese patients. Moreover, body mass index is an independent predictor for an abnormal ambulatory arterial stiffness index. Our results indicate that obese subjects are at higher risk for future cardiovascular events despite normal office BP levels.     

Blood pressure levels and variance assessed by ambulatory monitoring: Optimal parameters

We obtained multiple ambulatory blood pressure monitoring (ABPM) records over five years from two trained, normotensive subjects experienced in wearing the apparatus. The resulting time series data on systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were used to suggest optimal parameters for monitoring by two instruments (Colin Medical Instruments ABPM-630 and Del Mar Avionics Pressurometer) and to compare two indirect methods (auscultatory and oscillometric). A 10-min sampling interval day and night provided sufficient density of data to support spectral analysis for ultradian rhythms in the frequency range of one cycle per hour to one cycle per 9 h on a 24-h record. Rhythms with major periods of approximately 3, 6, and 9 h were variously found in 94 normotensive subjects, aged 20 to 95 years, including the two trained subjects. When the monitoring period was extended to 72 h, the circadian (∼24 h) rhythm could be more sharply defined, as well as a 12-h harmonic. In some studies the two trained subjects wore two monitors, one on each arm, set to read simultaneously. From the simultaneous measurements on both arms, it was shown that averaging across three points (30 min of record) reduced the coefficient of variation between the two simultaneous records to 6% or less. Auscultatory and oscillometric methods were equally reliable. Echocardiographic data were obtained in five normotensive subjects and compared to their ABPM data. The ABPM records provided additional information about cardiovascular function not merely duplicating that obtained by acute stress tests, such as exercise or cold pressor responses, or echocardiography. Standards for ABPM are suggested.     

Influence of obstructive sleep apnoea on circadian blood pressure profile

SUMMARY  A high prevalence of systemic hypertension in obstructive sleep apnoea (OSA) has been described but data on circadian blood pressure (BP) profile are limited and give inconsistent results. The present study examines 24-h BP in 106 patients referred because of loud snoring or excessive daytime sleepiness in combination with snoring. Patients were classified as OSA ( n = 62) or habitual snorers (HS) ( n = 44). Respiratory disturbance index (RDI) in OSA was 47 ± 24 vs. 2 ± 2 in HS. Mean age and body mass index in OSA was significantly higher.
BP was measured non-invasively at 15-min intervals during a 24-h period. Daytime and night-time BP was higher in OSA compared to HS. BP night/day ratio in OSA was 0.92 ± 0.07 vs. 0.86 ± 0.06 in HS ( P < 0.05). To investigate the influence of variables other than breathing abnormalities during sleep on our results we compared BP profiles of 25 OSA and 25 HS matched for sex, age and body weight. Again differences in daytime and night-time BP and BP night/day ratio were significant. Using a value of at least 10% fall in nocturnal BP to describe a regular BP profile (dipper) 68% of OSA were classified as non-dippers vs. 24% of HS.
Influence of short-term (2–4 days) nCPAP therapy on circadian BP profile was investigated in 34 patients with OSA. Systolic and diastolic nocturnal (but not daytime) BP was significantly reduced. The percentage of non-dippers was 79% before and 50% after treatment. In conclusion results of this study indicate a causal link between OSA and abnormal circadian BP profile.     

动态血压监测技术的临床应用价值

分析了58例原发性高血压患者治疗前后的动态血压监测,结果显示动态血压监测可真实、全面反映患者24小时血压状况,昼夜节律,治疗后降压疗效。因此,动态血压监测对高血压治疗、估计预后等方面,具有重要的临床价值。     

Overnight increases in haematocrit: additional evidence for a nocturnal fall in plasma volume

Talan , M. I., Engel , B. T. & Kawate , R. 1992. Overnight increases in haematocrit: additional evidence for a nocturnal fall in plasma volume. Acta Physiol Scand 144 , 473–476. Received 2 September 1 991 , accepted 20 November 1991. ISSN 0001–6722. National Institute on Aging, NIH, Gerontology Research Center, Baltimore, MD 21 224 , USA. Our previously published studies with monkeys describe a characteristic nocturnal haemodynamic pattern consisting of a monotonic decline in cardiac output and central venous pressure, and a concomitant rise in total peripheral resistance. These findings led us to hypothesize that there is a reduction in total plasma volume during the night. Since a fall in plasma volume should cause an increase in haemoglobin and plasma protein concentration, we designed this experiment to test the hypothesis that haematocrit levels would be significantly greater in the morning than in the evening. In a study of five monkeys, the levels of haematocrit were measured at 1700 h and at 0900 h the next morning for 14 days. The average morning haematocrit levels were 6_S0h higher than the average evening values. Lower plasma volume and possibly greater blood viscosity could contribute to the pathophysiology of the morning increase in the incidence of ‘silen’ ischaemia and catastrophic vascular events such as sudden cardiac death, myocardial infarctions and strokes in man.